287 results on '"Nicolas Barnich"'
Search Results
2. ChiA: a major player in the virulence of Crohn’s disease-associated adherent and invasive Escherichia coli (AIEC)
- Author
-
Margot Fargeas, Frederic Faure, Clara Douadi, Caroline Chevarin, Aurélien Birer, Adeline Sivignon, Michael Rodrigues, Jérémy Denizot, Elisabeth Billard, Nicolas Barnich, and Anthony Buisson
- Subjects
Inflammatory bowel disease ,Crohn disease ,adherent-invasive e. coli ,ChiA ,virulence factor ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
We investigated the role of ChiA and its associated polymorphisms in the interaction between Crohn’s disease (CD)-associated adherent-invasive Escherichia coli (AIEC) and intestinal mucosa. We observed a higher abundance of chiA among the metagenome of CD patients compared to healthy subjects. In dextran sulfate sodium-induced colitis mice model, AIEC-LF82∆chiA colonization was reduced in ileal, colonic and fecal samples compared to wild-type LF82. The binding of ChiA to recombinant human CHI3L1 or mucus was higher with the pathogenic polymorphism. The strength of ChiA-mucin interaction was 300-fold stronger than ChiA-rhCHI3L1. ChiA was able to degrade mucin to promote its growth and enabled LF82 to get closer to epithelial cells. The pathogenic polymorphism of ChiA had a stronger impact on mucus degradation than on the binding capability of AIEC to adhere to the intestinal epithelium. We observed that ChiA could favor an efficient bacterial invasion of intestinal crypts, and that ChiA, especially its pathogenic polymorphism, gives LF82 an advantage to uptake within Peyer’s patches, macrophages and mesenteric lymph nodes. All together, these data support the role of ChiA in the virulence of AIEC and show that it could be a promising target to reduce AIEC colonization in patients with CD.
- Published
- 2024
- Full Text
- View/download PDF
3. The colibactin-producing Escherichia coli alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance
- Author
-
Nilmara de Oliveira Alves, Guillaume Dalmasso, Darja Nikitina, Amaury Vaysse, Richard Ruez, Lea Ledoux, Thierry Pedron, Emma Bergsten, Olivier Boulard, Lora Autier, Sofian Allam, Laurence Motreff, Pierre Sauvanet, Diane Letourneur, Pragya Kashyap, Johan Gagnière, Denis Pezet, Catherine Godfraind, Michel Salzet, Emmanuel Lemichez, Mathilde Bonnet, Imène Najjar, Christophe Malabat, Marc Monot, Denis Mestivier, Nicolas Barnich, Pankaj Yadav, Isabelle Fournier, Sean Kennedy, Amel Mettouchi, Richard Bonnet, Iradj Sobhani, and Mathias Chamaillard
- Subjects
Colibactin-producing Escherichia coli ,land’s cycle ,lipid droplet ,right-sided colorectal cancer ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
ABSTRACTIntratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8+ T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land’s cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5∆ClbQ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.
- Published
- 2024
- Full Text
- View/download PDF
4. Colibactin-producing Escherichia coli enhance resistance to chemotherapeutic drugs by promoting epithelial to mesenchymal transition and cancer stem cell emergence
- Author
-
Guillaume Dalmasso, Antony Cougnoux, Tiphanie Faïs, Virginie Bonnin, Benoit Mottet-Auselo, Hang TT Nguyen, Pierre Sauvanet, Nicolas Barnich, Marine Jary, Denis Pezet, Julien Delmas, and Richard Bonnet
- Subjects
Colorectal cancer ,colibactin ,pks ,chemotherapy resistance ,cancer stem cell ,microbiota ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
ABSTRACTHuman colorectal cancers (CRCs) are readily colonized by colibactin-producing E. coli (CoPEC). CoPEC induces DNA double-strand breaks, DNA mutations, genomic instability, and cellular senescence. Infected cells produce a senescence-associated secretory phenotype (SASP), which is involved in the increase in tumorigenesis observed in CRC mouse models infected with CoPEC. This study investigated whether CoPEC, and the SASP derived from CoPEC-infected cells, impacted chemotherapeutic resistance. Human intestinal epithelial cells were infected with the CoPEC clinical 11G5 strain or with its isogenic mutant, which is unable to produce colibactin. Chemotherapeutic resistance was assessed in vitro and in a xenograft mouse model. Expressions of cancer stem cell (CSC) markers in infected cells were investigated. Data were validated using a CRC mouse model and human clinical samples. Both 11G5-infected cells, and uninfected cells incubated with the SASP produced by 11G5-infected cells exhibited an increased resistance to chemotherapeutic drugs in vitro and in vivo. This finding correlated with the induction of the epithelial to mesenchymal transition (EMT), which led to the emergence of cells exhibiting CSC features. They grew on ultra-low attachment plates, formed colonies in soft agar, and overexpressed several CSC markers (e.g. CD133, OCT-3/4, and NANOG). In agreement with these results, murine and human CRC biopsies colonized with CoPEC exhibited higher expression levels of OCT-3/4 and NANOG than biopsies devoid of CoPEC. Conclusion: CoPEC might aggravate CRCs by inducing the emergence of cancer stem cells that are highly resistant to chemotherapy.
- Published
- 2024
- Full Text
- View/download PDF
5. Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life
- Author
-
Caroline Carlé, Delphine Boucher, Luisa Morelli, Camille Larue, Ekaterina Ovtchinnikova, Louise Battut, Kawthar Boumessid, Melvin Airaud, Muriel Quaranta-Nicaise, Jean-Luc Ravanat, Gilles Dietrich, Sandrine Menard, Gérard Eberl, Nicolas Barnich, Emmanuel Mas, Marie Carriere, Ziad Al Nabhani, and Frédérick Barreau
- Subjects
Perinatal period ,Foodborne TiO2 ,Intestinal barrier function ,Intestinal stem cells ,Microbiota ,Colitis ,Toxicology. Poisons ,RA1190-1270 ,Industrial hygiene. Industrial welfare ,HD7260-7780.8 - Abstract
Abstract Background Perinatal exposure to titanium dioxide (TiO2), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel diseases (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2′-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis. Results In pregnant and lactating mice, foodborne TiO2 was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO2 early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO2 also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO2 exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO2-induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring. Conclusions Our findings indicate that foodborne TiO2 consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis.
- Published
- 2023
- Full Text
- View/download PDF
6. Identification of autophagy receptors for the Crohn’s disease-associated adherent-invasive Escherichia coli
- Author
-
Alison Da Silva, Guillaume Dalmasso, Anaïs Larabi, My Hanh Thi Hoang, Elisabeth Billard, Nicolas Barnich, and Hang Thi Thu Nguyen
- Subjects
adherent-invasive E. coli (AIEC) ,autophagy ,Crohn’s disease ,p62 ,NDP52 ,Microbiology ,QR1-502 - Abstract
IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease, of which the etiology involves genetic, environmental and microbial factors. Adherent-invasive Escherichia coli (AIEC) and polymorphisms in autophagy-related genes have been implicated in CD etiology. Autophagy is a key process for the maintenance of cellular homeostasis, which allows the degradation of damaged cytoplasmic components and pathogens via lysosome. We have shown that a functional autophagy is necessary for AIEC clearance. Here, we aimed at identifying the autophagy receptor(s) responsible to target AIEC to autophagy for degradation.MethodsThe levels of autophagy receptors p62, NDP52, NBR1, TAX1BP1 and Optineurin were knocked down in human intestinal epithelial cells T84 using siRNAs. The NDP52 knock-out (KO) and p62 KO HeLa cells, as well as NDP52 KO HeLa cells expressing the wild-type NDP52 or the mutated NDP52Val248Ala protein were used.Results and discussionWe showed that, among the tested autophagy receptors (p62, NDP52, NBR1, TAX1BP1 and Optineurin), diminished expression of p62 or NDP52 increased the number of the clinical AIEC LF82 strain inside epithelial cells. This was associated with increased pro-inflammatory cytokine production. Moreover, p62 or NDP52 directly colocalized with AIEC LF82 and LC3, an autophagy marker. As the NDP52Val248Ala polymorphism has been associated with increased CD susceptibility, we investigated its impact on AIEC control. However, in HeLa cell and under our experimental condition, no effect of this polymorphism neither on AIEC LF82 intracellular number nor on pro-inflammatory cytokine production was observed. Together, our results suggest that p62 and NDP52 act as autophagy receptors for AIEC recognition, controlling AIEC intracellular replication and inflammation.
- Published
- 2024
- Full Text
- View/download PDF
7. Cytotoxic necrotizing factor 1 hinders colon tumorigenesis induced by colibactin-producing Escherichia coli in ApcMin/+ mice
- Author
-
Héloïse Chat, Guillaume Dalmasso, Catherine Godfraind, Virginie Bonnin, Racha Beyrouthy, Mathilde Bonnet, Nicolas Barnich, Amel Mettouchi, Emmanuel Lemichez, Richard Bonnet, and Julien Delmas
- Subjects
Colorectal cancer ,Escherichia coli ,colibactin ,CNF-1 ,CoPEC ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
ABSTRACTColorectal cancer (CRC) patients are frequently colonized by colibactin-producing Escherichia coli (CoPEC) (>40%), which enhances tumorigenesis in mouse models of CRC. We observed that 50% of CoPEC also contains the cnf1 gene, which encodes cytotoxic necrotizing factor-1 (CNF1), an enhancer of the eukaryotic cell cycle. The impact of its co-occurrence with colibactin (Clb) has not yet been investigated. We evaluated the impact of CNF1 on colorectal tumorigenesis using human colonic epithelial HT-29 cells and CRC-susceptible ApcMin/+ mice inoculated with the CoPEC 21F8 clinical strain (Clb+Cnf+) or 21F8 isogenic mutants (Clb+Cnf-, Clb-Cnf+ and Clb-Cnf-). Infection with the Clb+Cnf- strain induced higher levels of inflammatory cytokines and senescence markers both in vitro and in vivo compared to those induced by infection with the Clb+Cnf+ strain. In contrast, the Clb+Cnf- and Clb+Cnf+ strains generated similar levels of DNA damage in HT-29 cells and in colonic murine tissues. Furthermore, the ApcMin/+ mice inoculated with the Clb+Cnf- strain developed significantly more tumors than the mice inoculated with the Clb+Cnf+ strain or the isogenic mutants, and the composition of their microbiota was changed. Finally, rectal administration of the CNF1 protein in ApcMin/+ mice inoculated with the Clb+Cnf- strain significantly decreased tumorigenesis and inflammation. Overall, this study provides evidence that CNF1 decreases the carcinogenic effects of CoPEC in ApcMin/+ mice by decreasing CoPEC-induced cellular senescence and inflammation.
- Published
- 2023
- Full Text
- View/download PDF
8. Host-microbiota relationship in the pathophysiology of aseptic abscess syndrome: protocol for a multicentre case-control study (ABSCESSBIOT)
- Author
-
Nathalie Costedoat-Chalumeau, Patrick Jégo, Nicolas Barnich, Emilie Vazeille, Maria Nachury, Marc André, Stanislas Faguer, Laurent Sailler, Bruno Pereira, Olivier Chosidow, Alexandre Thibault Jacques Maria, Jean-François Viallard, Arnaud Hot, Jean-David Bouaziz, Jérôme Connault, Jean Schmidt, Ludovic Trefond, Felix Ackermann, Fabrice Bonnet, François Lifermann, Nicolas Limal, Guillaume Cadiot, Elisabeth Billard, Richard Bonnet, Romain Altwegg, Alexandra Audemard-Verger, Damien Richard, Elisabeth Aslangul, Fairouzé Bani Sadr, Sophie Besnard, Jean-François Bourgaux, Sebastien De Almeida, Amandine Dernoncourt, Hélène Desmurs Clavel, Amelie Dutheil, Jean-Marc Galempoix, Camille Hua, Estelle Jean, Wendy Jourde, Clemence Lepelletier, Jean Benoit Monfort, Yves Poinsignon, Marie Laure Rabilloux, Jerome Razatomaery, Clea Rouillon, Mihaela Saplacan, and Laure Swiader
- Subjects
Medicine - Abstract
Introduction Aseptic abscess (AA) syndrome is a rare disease whose pathophysiology is unknown. It is often associated with inflammatory bowel disease and characterised by sterile inflammation with collections of neutrophils affecting several organs, especially the spleen. Microbiota are known to influence local and systemic immune responses, and both gut and oral microbiota perturbations have been reported in diseases associated with AA syndrome. However, interactions between these factors have never been studied in AA syndrome. The purpose of this translational case-control study (ABSCESSBIOT) is to investigate gut and/or oral microbiota in patients with AA syndrome compared with healthy controls. Moreover, microbiota associated metabolites quantification and Treg/Th17 balance characterisation will give a mechanistic insight on how microbiota may be involved in the pathophysiology of AA syndrome.Methods and analysis This French multicentre case-control study including 30 French centres (University hospital or regional hospital) aims to prospectively enrol 30 patients with AA syndrome with 30 matched controls and to analyse microbiota profiling (in stools and saliva), microbial metabolites quantification in stools and circulating CD4+ T cell populations.Ethics and dissemination This study protocol was reviewed and approved by an independent French regional review board (n° 2017-A03499-44, Comité de Protection des Personnes Ile de France 1) on 10 October 2022, and declared to the competent French authority (Agence Nationale de Sécurité du Médicament et des produits de santé, France). Oral and written informed consent will be obtained from each included patient and the control participant. Study results will be reported to the scientific community at conferences and in peer-reviewed scientific journals.Trial registration number Clinical Trials web-based platform (NCT05537909).
- Published
- 2023
- Full Text
- View/download PDF
9. Adherent-invasive E. coli – induced specific IgA limits pathobiont localization to the epithelial niche in the gut
- Author
-
Rika Tanaka, Jin Imai, Hitoshi Tsugawa, Karl Bil Eap, Masaki Yazawa, Motoki Kaneko, Masashi Ohno, Kohei Sugihara, Sho Kitamoto, Hiroko Nagao-Kitamoto, Nicolas Barnich, Masashi Matsushima, Takayoshi Suzuki, Tatehiro Kagawa, Yasuhiro Nishizaki, Hidekazu Suzuki, Nobuhiko Kamada, and Katsuto Hozumi
- Subjects
inflammatory bowel disease ,Crohn’s disease ,host-pathogen interaction ,IgA ,adherent invasive E coli ,pathobiont ,Microbiology ,QR1-502 - Abstract
Background and aimAdherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn’s disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive.MethodsAntibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium.ResultsPersistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC – epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice.ConclusionThese results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.
- Published
- 2023
- Full Text
- View/download PDF
10. Determination of biomarkers associated with neoadjuvant treatment response focusing on colibactin-producing Escherichia coli in patients with mid or low rectal cancer: a prospective clinical study protocol (MICARE)
- Author
-
Nicolas Barnich, Philippe Rouanet, Marta Jarlier, Caroline Chevarin, Johan Gagniere, Mathilde Bonnet, Pierre-Emmanuel Colombo, Guillaume Carrier, Hélène de Forges, Christophe Taoum, Gwenaelle Roche, and Catherine Fiess
- Subjects
Medicine - Abstract
Introduction The management of mid and low rectal cancer is based on neoadjuvant chemoradiotherapy (CRT) followed by standardised surgery. There is no biomarker in rectal cancer to aid clinicians in foreseeing treatment response. The determination of factors associated with treatment response might allow the identification of patients who require tailored strategies (eg, therapeutic de-escalation or intensification). Colibactin-producing Escherichia coli (CoPEC) has been associated with aggressive colorectal cancer and could be a poor prognostic factor. Currently, no study has evaluated the potential association between intestinal microbiota composition and tumour response to CRT in mid and low rectal cancer. The aim of this study is to assess the association between response to neoadjuvant CRT and faecal intestinal microbiota composition and/or CoPEC prevalence in patients with mid or low rectal cancer.Methods and analysis This is a non-randomised bicentric prospective clinical study with a recruitment capacity of 200 patients. Three stool samples will be collected from participants with histological-proven adenocarcinome of mid or low rectum who meet eligibility criteria of the study protocol: one before neoadjuvant treatment start, one in the period between CRT end and surgery and one the day before surgery. In each sample, CoPEC will be detected by culture in special media and molecular (PCR) approaches. The global microbiota composition will be also assessed by the bacterial 16S rRNA gene sequencing. Neoadjuvant CRT response and tumour regression grade will be described using the Dworak system at pathological examination. Clinical data and survival outcomes will also be collected and investigated.Ethics and dissemination MICARE was approved by the local ethics committee (Comité de Protection des Personnes Sud-Est II, 18 December 2019. Reference number 2019-A02493-54 and the institutional review board. Patients will be required to provide written informed consent. Results will be published in a peer reviewed journal.Trial registration number NCT04103567.
- Published
- 2022
- Full Text
- View/download PDF
11. AhR/IL-22 pathway as new target for the treatment of post-infectious irritable bowel syndrome symptoms
- Author
-
Maëva Meynier, Elodie Baudu, Nathalie Rolhion, Manon Defaye, Marjolène Straube, Valentine Daugey, Morgane Modoux, Ivan Wawrzyniak, Frédéric Delbac, Romain Villéger, Mathieu Méleine, Esther Borras Nogues, Catherine Godfraind, Nicolas Barnich, Denis Ardid, Philippe Poirier, Harry Sokol, Jean-Marc Chatel, Philippe Langella, Valérie Livrelli, Mathilde Bonnet, and Frédéric Antonio Carvalho
- Subjects
post-infectious ibs ,colonic-associated microbiota ,citrobacter rodentium ,tryptophan ,ahr ,il-22 ,lactococcus lactis ,well-being disorders ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Alterations in brain/gut/microbiota axis are linked to Irritable Bowel Syndrome (IBS) physiopathology. Upon gastrointestinal infection, chronic abdominal pain and anxio-depressive comorbidities may persist despite pathogen clearance leading to Post-Infectious IBS (PI-IBS). This study assesses the influence of tryptophan metabolism, and particularly the microbiota-induced AhR expression, on intestinal homeostasis disturbance following gastroenteritis resolution, and evaluates the efficacy of IL-22 cytokine vectorization on PI-IBS symptoms. The Citrobacter rodentium infection model in C57BL6/J mice was used to mimic Enterobacteria gastroenteritis. Intestinal homeostasis was evaluated as low-grade inflammation, permeability, mucosa-associated microbiota composition, and colonic sensitivity. Cognitive performances and emotional state of animals were assessed using several tests. Tryptophan metabolism was analyzed by targeted metabolomics. AhR activity was evaluated using a luciferase reporter assay method. One Lactococcus lactis strain carrying an eukaryotic expression plasmid for murine IL-22 (L. lactisIL−22) was used to induce IL-22 production in mouse colonic mucosa. C. rodentium-infected mice exhibited persistent colonic hypersensitivity and cognitive impairments and anxiety-like behaviors after pathogen clearance. These post-infectious disorders were associated with low-grade inflammation, increased intestinal permeability, decrease of Lactobacillaceae abundance associated with the colonic layer, and increase of short-chain fatty acids (SCFAs). During post-infection period, the indole pathway and AhR activity were decreased due to a reduction of tryptophol production. Treatment with L. lactisIL−22 restored gut permeability and normalized colonic sensitivity, restored cognitive performances and decreased anxiety-like behaviors. Data from the video-tracking system suggested an upgrade of welfare for mice receiving the L.lactisIL−22 strain. Our findings revealed that AhR/IL-22 signaling pathway is altered in a preclinical PI-IBS model. IL-22 delivering alleviate PI-IBS symptoms as colonic hypersensitivity, cognitive impairments, and anxiety-like behaviors by acting on intestinal mucosa integrity. Thus, therapeutic strategies targeting this pathway could be developed to treat IBS patients suffering from chronic abdominal pain and associated well-being disorders.
- Published
- 2022
- Full Text
- View/download PDF
12. Epigenetic master regulators HDAC1 and HDAC5 control pathobiont Enterobacteria colonization in ileal mucosa of Crohn’s disease patients
- Author
-
Mélissa Chervy, Adeline Sivignon, Flavie Dambrine, Anthony Buisson, Pierre Sauvanet, Catherine Godfraind, Matthieu Allez, Lionel Le Bourhis, The Remind Group, Nicolas Barnich, and Jérémy Denizot
- Subjects
Histone deacetylases ,Adherent-InvasiveE. coli ,Crohn’s disease ,histone acetylation ,High-fat diet ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Adherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn’s disease (CD) patients, are known to contribute to the etiopathogenesis of CD. Molecular mechanisms favoring AIEC ileal colonization have not been completely characterized yet. The aim of this study was to investigate whether epigenetic regulators histone deacetylases (HDAC) expression in intestinal epithelial cells of CD patients regulate Enterobacteria and AIEC encroachment to intestinal mucosa. HDAC were inhibited in vitro and in CEABAC10 mice to decipher their involvement in the entry of AIEC within host cells. CD ileal samples from the REMIND cohort were used to study the relationship between HDAC expression level and Enterobacteria/AIEC colonization in patients. Mice were fed a westernized diet and orally challenged with AIEC to determine the impact of diet on HDAC expression. Global level of acetylated histone H3 is higher in patients colonized by AIEC bacteria compared to patients non-colonized by Enterobacteria and HDAC inhibition-mediated H3 hyperacetylation promotes the entry of AIEC bacteria within intestinal epithelial cells. HDAC1 and HDAC5 are central and antagonistic in the regulation of AIEC entry within host cells in vitro, in mouse models and in ileal mucosa of CD patients. In mice fed a western-type diet, AIEC infection decreases HDAC1 expression, inducing H3 hyperacetylation to favor their own colonization. CD patients under a western diet are more prone to be colonized by AIEC bacteria as such a diet affects intestinal homeostasis, enables AIEC access to intestinal mucosa where they then manipulate host-epigenome to their advantage.Abbreviations AIEC Adherent-Invasive Escherichia coli; BSA Bovine serum albumin; CD Crohn’s disease; CEABAC10 Carcinoembryonic antigen bacterial artificial chromosome 10; CEACAM Carcinoembryonic antigen-related cell adhesion molecule; FBS Fetal bovine serum; IBD Inflammatory Bowel Disease; HAT Histone acetyltransferase; HDAC Histone deacetylase; kDa KiloDalton; SAHA Suberoylanilide Hydroxamic Acid; Scr Scramble
- Published
- 2022
- Full Text
- View/download PDF
13. Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease
- Author
-
Grégoire Chevalier, Arnaud Laveissière, Guillaume Desachy, Nicolas Barnich, Adeline Sivignon, Marc Maresca, Cendrine Nicoletti, Eric Di Pasquale, Margarita Martinez-Medina, Kenneth William Simpson, Vijay Yajnik, Harry Sokol, MOBIDIC Study Investigators, Jonathan Plassais, Francesco Strozzi, Alessandra Cervino, Rachel Morra, and Christophe Bonny
- Subjects
Crohn’s disease ,Inflammation ,FimH ,Enterobacteriaceae ,Microbial ecology ,QR100-130 - Abstract
Abstract Background An Escherichia coli (E. coli) pathotype with invasive properties, first reported by Darfeuille-Michaud and termed adherent-invasive E. coli (AIEC), was shown to be prevalent in up to half the individuals with Crohn’s Disease (CD), suggesting that these bacteria could be involved in the pathophysiology of CD. Among the genes related to AIEC pathogenicity, fim has the potential to generate an inflammatory reaction from the intestinal epithelial cells and macrophages, as it interacts with TLR4, inducing the production of inflammatory cytokines independently of LPS. Therefore, targeting the bacterial adhesion of FimH-expressing bacteria seems a promising therapeutic approach, consisting of disarming bacteria without killing them, representing a selective strategy to suppress a potentially critical trigger of intestinal inflammation, without disturbing the intestinal microbiota. Results We analyzed the metagenomic composition of the gut microbiome of 358 patients with CD from two different cohorts and characterized the presence of FimH-expressing bacteria. To assess the pathogenic role of FimH, we used human intestinal explants and tested a specific FimH blocker to prevent bacterial adhesion and associated inflammation. We observed a significant and disease activity-dependent enrichment of Enterobacteriaceae in the gut microbiome of patients with CD. Bacterial FimH expression was functionally confirmed in ileal biopsies from 65% of the patients with CD. Using human intestinal explants, we further show that FimH is essential for adhesion and to trigger inflammation. Finally, a specific FimH-blocker, TAK-018, inhibits bacterial adhesion to the intestinal epithelium and prevents inflammation, thus preserving mucosal integrity. Conclusions We propose that TAK-018, which is safe and well tolerated in humans, is a promising candidate for the treatment of CD and in particular in preventing its recurrence. Video abstract
- Published
- 2021
- Full Text
- View/download PDF
14. An adherent-invasive Escherichia coli-colonized mouse model to evaluate microbiota-targeting strategies in Crohn's disease
- Author
-
Adeline Sivignon, Mélissa Chervy, Caroline Chevarin, Elia Ragot, Elisabeth Billard, Jérémy Denizot, and Nicolas Barnich
- Subjects
aiec ,ileal colonization ,mouse model ,crohn's disease ,ceacam6 ,Medicine ,Pathology ,RB1-214 - Published
- 2022
- Full Text
- View/download PDF
15. The Crohn’s disease-related bacterial strain LF82 assembles biofilm-like communities to protect itself from phagolysosomal attack
- Author
-
Victoria Prudent, Gaëlle Demarre, Emilie Vazeille, Maxime Wery, Nicole Quenech’Du, Antinéa Ravet, Julie Dauverd - Girault, Erwin van Dijk, Marie-Agnès Bringer, Marc Descrimes, Nicolas Barnich, Sylvie Rimsky, Antonin Morillon, and Olivier Espéli
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Prudent et al. show that intracellular bacteria related to the Crohn’s disease, LF82, produce an extra-bacterial matrix that acts as a biofilm and controls the formation of LF82 intracellular bacterial communities. This study provides insights into the strategies that adherent invasive E. coli use to establish their replicative niche within macrophages.
- Published
- 2021
- Full Text
- View/download PDF
16. Correction: Genes mcr improve the intestinal fitness of pathogenic E. coli and balance their lifestyle to commensalism
- Author
-
Guillaume Dalmasso, Racha Beyrouthy, Sandrine Brugiroux, Etienne Ruppé, Laurent Guillouard, Virginie Bonnin, Pierre Saint-Sardos, Amine Ghozlane, Vincent Gaumet, Nicolas Barnich, Julien Delmas, and Richard Bonnet
- Subjects
Microbial ecology ,QR100-130 - Published
- 2023
- Full Text
- View/download PDF
17. Exosomes transfer miRNAs from cell-to-cell to inhibit autophagy during infection with Crohn’s disease-associated adherent-invasive E. coli
- Author
-
Anaïs Larabi, Guillaume Dalmasso, Julien Delmas, Nicolas Barnich, and Hang Thi Thu Nguyen
- Subjects
crohn’s disease ,aiec ,exosomes ,mirna ,autophagy ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Adherent-invasive E. coli (AIEC), which abnormally colonize the intestinal mucosa of Crohn’s disease (CD) patients, are able to adhere to and invade intestinal epithelial cells (IECs), survive and replicate within macrophages and induce a pro-inflammatory response. AIEC infection of IECs induces secretion of exosomes that increase AIEC replication in exosome-receiving IECs and macrophages. Here, we investigated the mechanism underlying the increased AIEC replication in cells receiving exosomes from AIEC-infected cells. Exosomes released by uninfected human intestinal epithelial T84 cells (Exo-uninfected) or by T84 cells infected with the clinical AIEC LF82 strain (Exo-LF82), the nonpathogenic E. coli K12 strain (Exo-K12) or the commensal E. coli HS strain (Exo-HS) were purified and used to stimulate T84 cells. Stimulation of T84 cells with Exo-LF82 inhibited autophagy compared with Exo-uninfected, Exo-K12 and Exo-HS. qRT-PCR analysis revealed increased levels of miR-30c and miR-130a in Exo-LF82 compared to Exo-uninfected, Exo-K12 and Exo-HS. These miRNAs were transferred via exosomes to recipient cells, in which they targeted and inhibited ATG5 and ATG16L1 expression and thereby autophagy response, thus favoring AIEC intracellular replication. Inhibition of these miRNAs in exosome-donor cells infected with AIEC LF82 abolished the increase in miR-30c and miR-130a levels in the released Exo-LF82 and in Exo-LF82-receiving cells, thus suppressing the inhibitory effect of Exo-LF82 on ATG5 and ATG16L1 expression and on autophagy-mediated AIEC clearance in Exo-LF82-receiving cells. Our study shows that upon AIEC infection, IECs secrete exosomes that can transfer specific miRNAs to recipient IECs, inhibiting autophagy-mediated clearance of intracellular AIEC.
- Published
- 2020
- Full Text
- View/download PDF
18. Characterization of mucosa-associated Escherichia coli strains isolated from Crohn’s disease patients in Brazil
- Author
-
Rafaella F. A. Costa, Maria L. A. Ferrari, Marie-Agnès Bringer, Arlette Darfeuille-Michaud, Flaviano S. Martins, and Nicolas Barnich
- Subjects
Crohn’s disease ,Inflammatory bowel disease ,Mucosa-associated Escherichia coli ,Microbiology ,QR1-502 - Abstract
Abstract Background Crohn’s disease (CD) is characterized by chronic inflammation of the human intestine. Several studies have demonstrated that the intestinal mucosa of CD patients in Western countries is abnormally colonized by adherent-invasive Escherichia coli (AIEC) strains. However, no studies to date have focused on the involvement of such E. coli strains in CD patients in Brazil. Here, we characterized E. coli strains associated with the ileal mucosa of Brazilian CD patients (ileal biopsies from 35 subjects, 24 CD patients and 11 controls). Results The colonization level of adherent Enterobacteriaceae associated with the ileal mucosa of CD patients was significantly higher than that of the controls. The proportions of E. coli strains belonging to phylogroups B1 and B2 were two-fold higher in strains isolated from CD patients than in those isolated from controls. CD patients in the active phase harbored 10-fold more E. coli belonging to group B2 than CD patients in remission. Only a few E. coli isolates had invasive properties and the ability to survive within macrophages, but 25% of CD patients in Brazil (6/24) harbored at least one E. coli strain belonging to the AIEC pathobiont. However, fimH sequence analysis showed only a few polymorphisms in the FimH adhesin of strains isolated in this study compared to the FimH adhesin of AIEC collections isolated from European patients. Conclusions Mucosa-associated E. coli strains colonize the intestinal mucosa of Brazilian CD patients. However, the strains isolated from Brazilian CD patients have probably not yet co-evolved with their hosts and therefore have not fully developed a strong adherent-invasive phenotype. Thus, it will be crucial to follow in the future the emergence and evolution of AIEC pathobionts in the Brazilian population.
- Published
- 2020
- Full Text
- View/download PDF
19. Adaptation of adherent-invasive E. coli to gut environment: Impact on flagellum expression and bacterial colonization ability
- Author
-
Gwladys Sevrin, Sébastien Massier, Benoit Chassaing, Allison Agus, Julien Delmas, Jérémy Denizot, Elisabeth Billard, and Nicolas Barnich
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
The pathogenesis of Crohn's disease (CD) is multifactorial and involves genetic susceptibility, environmental triggers and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are flagellated bacteria more prevalent in CD patients than in healthy subjects and promote chronic intestinal inflammation. We aim at deciphering the role of flagella and flagellin modulation by intestinal conditions. AIEC flagellum expression is required for optimal adhesion to and invasion of intestinal epithelial cells. Interestingly, differential flagellin regulation was observed between commensal E. coli (HS) and AIEC (LF82) strains: flagellum expression by AIEC bacteria, in contrast to that of commensal E. coli, is enhanced under intestinal conditions (the presence of bile acids and mucins). Flagella are involved in the ability of the AIEC LF82 strain to cross a mucus layer in vitro and in vivo, conferring a selective advantage in penetrating the mucus layer and reaching the epithelial surface. In a CEABAC10 mouse model, a non-motile mutant (LF82-ΔfliC) exhibits reduced colonization that is restored by a dextran sodium sulfate treatment that alters mucus layer integrity. Moreover, a mutant that continuously secretes flagellin (LF82-ΔflgM) triggers a stronger inflammatory response than the wild-type strain, and the mutant's ability to colonize the CEABAC10 mouse model is decreased. Overexpression of flagellin in bacteria in contact with epithelial cells can be detrimental to their virulence by inducing acute inflammation that enhances AIEC clearance. AIEC pathobionts must finely modulate flagellum expression during the infection process, taking advantage of their specific virulence gene regulation to improve their adaptability and flexibility within the gut environment.
- Published
- 2020
- Full Text
- View/download PDF
20. The Role of OmpR in Bile Tolerance and Pathogenesis of Adherent-Invasive Escherichia coli
- Author
-
Valentina Lucchini, Adeline Sivignon, Michel Pieren, Marc Gitzinger, Sergio Lociuro, Nicolas Barnich, Christian Kemmer, and Vincent Trebosc
- Subjects
OmpR ,AIEC ,virulence ,CEABAC10 mice ,sodium deoxycholate ,tolerance ,Microbiology ,QR1-502 - Abstract
Gut microbiota dysbiosis toward adherent-invasive Escherichia coli (AIEC) plays an important role in Crohn’s disease (CD). The OmpR transcriptional regulator is required for the AIEC LF82 prototype strain to adhere and invade intestinal epithelial cells. In this study, we explored the role of OmpR in AIEC pathogenesis using a panel of eight Escherichia coli strains isolated from CD patients and identified as AIEC. The deletion of ompR together with the implementation of two cell-based assays revealed that the role of OmpR in adhesion in vitro was not conserved in AIEC clinical strains. Nevertheless, we showed that OmpR was required for robust gut colonization of transgenic mice expressing human CEACAM receptors, suggesting that OmpR is involved in alternative virulence mechanisms in AIEC strains. We found that deletion of ompR compromised the ability of AIEC strains to cope with the stress induced by bile salts, which may be key for AIEC pathogenesis. More specifically, we demonstrated that OmpR was involved in a tolerance mechanism toward sodium deoxycholate (DOC), one of bile salts main component. We showed that the misregulation of OmpF or the loss of outer membrane integrity are not the drivers of OmpR-mediated DOC tolerance, suggesting that OmpR regulates a specific mechanism enhancing AIEC survival in the presence of DOC. In conclusion, the newly discovered role of OmpR in AIEC bile tolerance suggests that OmpR inhibition would interfere with different aspects of AIEC virulence arsenal and could be an alternative strategy for CD-treatment.
- Published
- 2021
- Full Text
- View/download PDF
21. Beneficial Effects of Linseed Supplementation on Gut Mucosa-Associated Microbiota in a Physically Active Mouse Model of Crohn’s Disease
- Author
-
Claire Plissonneau, Adeline Sivignon, Benoit Chassaing, Frederic Capel, Vincent Martin, Monique Etienne, Ivan Wawrzyniak, Pierre Chausse, Frederic Dutheil, Guillaume Mairesse, Guillaume Chesneau, Nathalie Boisseau, and Nicolas Barnich
- Subjects
linseed ,mucosa-associated microbiota ,adherent-invasive E. coli ,butyrate ,inflammation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The Western diet, rich in lipids and in n-6 polyunsaturated fatty acids (PUFAs), favors gut dysbiosis observed in Crohn’s disease (CD). The aim of this study was to assess the effects of rebalancing the n-6/n-3 PUFA ratio in CEABAC10 transgenic mice that mimic CD. Mice in individual cages with running wheels were randomized in three diet groups for 12 weeks: high-fat diet (HFD), HFD + linseed oil (HFD-LS-O) and HFD + extruded linseed (HFD-LS-E). Then, they were orally challenged once with the Adherent-Invasive Escherichia coli (AIEC) LF82 pathobiont. After 12 weeks of diet, total energy intake, body composition, and intestinal permeability were not different between groups. After the AIEC-induced intestinal inflammation, fecal lipocalin-2 concentration was lower at day 6 in n-3 PUFAs supplementation groups (HFD-LS-O and HFD-LS-E) compared to HFD. Analysis of the mucosa-associated microbiota showed that the abundance of Prevotella, Paraprevotella, Ruminococcus, and Clostridiales was higher in the HFD-LS-E group. Butyrate levels were higher in the HFD-LS-E group and correlated with the Firmicutes/Proteobacteria ratio. This study demonstrates that extruded linseed supplementation had a beneficial health effect in a physically active mouse model of CD susceptibility. Additional studies are required to better decipher the matrix influence in the linseed supplementation effect.
- Published
- 2022
- Full Text
- View/download PDF
22. Propionate catabolism by CD-associated adherent-invasive E. coli counteracts its anti-inflammatory effect
- Author
-
Allison Agus, Damien Richard, Tiphanie Faïs, Emilie Vazeille, Mélissa Chervy, Virginie Bonnin, Guillaume Dalmasso, Jérémy Denizot, Elisabeth Billard, Richard Bonnet, Anthony Buisson, Nicolas Barnich, and Julien Delmas
- Subjects
crohn’s disease ,adherent-invasive e. coli ,propionate ,methyl-citrate pathway ,gpr43 agonist treatment ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Crohn’s disease (CD) is a chronic and disabling inflammatory disorder of the gut that is profoundly influenced by intestinal microbiota composition, host genetics and environmental factors. Several groups worldwide have described an imbalance of the gut microbiome composition, called dysbiosis, in CD patients, with an increase in Proteobacteria and Bacteroidetes and a decrease in Firmicutes. A high prevalence of adherent-invasive Escherichia coli (AIEC) pathobionts has been identified in the intestinal mucosa of CD patients. A significant loss in the bacteria that produce short-chain fatty acids (SCFAs) with anti-inflammatory properties, such as propionate, is also a consequence of dysbiosis in CD patients. Here, the AIEC reference strain LF82 was able to degrade propionate in the gut, which was sufficient to counteract the anti-inflammatory effect of propionate both in in vitro models and in mice with DSS-induced colitis. The consumption of propionate by AIEC pathobionts leads to an increase in TNF-α production by macrophages upon infection through the bacterial methyl-citrate pathway. To induce the protective effects of SCFAs on the inflamed gut, we used a G-protein-coupled receptor 43 agonist (GPR43 agonist) that is not metabolizable by intestinal bacteria. Interestingly, this agonist showed anti-inflammatory properties and decreased the severity of colitis in AIEC-infected mice, as assessed by an improvement in the disease activity index (DAI) and a decrease in AIEC pathobiont encroachment. Taken together, these results highlight the effectiveness of GPR43 agonist treatment in the control of gut inflammation and improved our understanding of the ability of AIEC to modulate propionate availability to create an infectious niche to its advantage.
- Published
- 2021
- Full Text
- View/download PDF
23. Association of Adherent-invasive Escherichia coli with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn’s disease
- Author
-
Zhilu Xu, Xiangqian Dong, Keli Yang, Caroline Chevarin, Jingwan Zhang, Yu Lin, Tao Zuo, Lok Cheung Chu, Yang Sun, Fengrui Zhang, Francis Kl Chan, Joseph Jy Sung, Jun Yu, Anthony Buisson, Nicolas Barnich, Jean-Frédéric Colombel, Sunny Hei Wong, Yinglei Miao, and Siew C Ng
- Subjects
adherent-invasive escherichia coli ,aiec ,crohn’s disease ,inflammatory bowel disease ,microbiota ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn’s disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.
- Published
- 2021
- Full Text
- View/download PDF
24. TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn’s disease
- Author
-
Manabu Nagayama, Tomonori Yano, Koji Atarashi, Takeshi Tanoue, Mariko Sekiya, Yasutoshi Kobayashi, Hirotsugu Sakamoto, Kouichi Miura, Keijiro Sunada, Takaaki Kawaguchi, Satoru Morita, Kayoko Sugita, Seiko Narushima, Nicolas Barnich, Jun Isayama, Yuko Kiridooshi, Atsushi Shiota, Wataru Suda, Masahira Hattori, Hironori Yamamoto, and Kenya Honda
- Subjects
crohn’s disease ,double-balloon enteroscopy ,microbiome ,escherichia coli ,ruminococcus gnavus ,th1 ,th17 ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Dysbiotic microbiota contributes to the pathogenesis of Crohn’s disease (CD) by regulating the immune system. Although pro-inflammatory microbes are probably enriched in the small intestinal (SI) mucosa, most studies have focused on fecal microbiota. This study aimed to examine jejunal and ileal mucosal specimens from patients with CD via double-balloon enteroscopy. Comparative microbiome analysis revealed that the microbiota composition of CD SI mucosa differs from that of non-CD controls, with an increased population of several families, including Enterobacteriaceae, Ruminococcaceae, and Bacteroidaceae. Upon anaerobic culturing of the CD SI mucosa, 80 bacterial strains were isolated, from which 9 strains representing 9 distinct species (Escherichia coli, Ruminococcus gnavus, Klebsiella pneumoniae, Erysipelatoclostridium ramosum, Bacteroides dorei, B. fragilis, B. uniformis, Parabacteroides distasonis, and Streptococcus pasteurianus) were selected on the basis of their significant association with CD. The colonization of germ-free (GF) mice with the 9 strains enhanced the accumulation of TH1 cells and, to a lesser extent, TH17 cells in the intestine, among which an E. coli strain displayed high potential to induce TH1 cells and intestinal inflammation in a strain-specific manner. The present results indicate that the CD SI mucosa harbors unique pro-inflammatory microbiota, including TH1 cell-inducing E. coli, which could be a potential therapeutic target.
- Published
- 2020
- Full Text
- View/download PDF
25. Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts
- Author
-
Hyungjun Yang, Hengameh Chloé Mirsepasi-Lauridsen, Carsten Struve, Joannie M. Allaire, Adeline Sivignon, Wayne Vogl, Else S. Bosman, Caixia Ma, Abbas Fotovati, Gregor S. Reid, Xiaoxia Li, Andreas Munk Petersen, Sébastien G. Gouin, Nicolas Barnich, Kevan Jacobson, Hong Bing Yu, Karen Angeliki Krogfelt, and Bruce A. Vallance
- Subjects
inflammatory bowel disease ,ulcerative colitis ,crohn’s disease ,intestinal microbiota ,in vivo mouse model ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Ulcerative colitis (UC) is a chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of E. coli strains related to extra-intestinal pathogenic E. coli. These “pathobionts” exhibit pathogenic properties, but their potential to promote UC is unclear due to the lack of relevant animal models. Here, we established a mouse model using a representative UC pathobiont strain (p19A), and mice lacking single immunoglobulin and toll-interleukin 1 receptor domain (SIGIRR), a deficiency increasing susceptibility to gut infections. Strain p19A was found to adhere to the cecal mucosa of Sigirr -/- mice, causing modest inflammation. Moreover, it dramatically worsened dextran sodium sulfate-induced colitis. This potentiation was attenuated using a p19A strain lacking α-hemolysin genes, or when we targeted pathobiont adherence using a p19A strain lacking the adhesin FimH, or following treatment with FimH antagonists. Thus, UC pathobionts adhere to the intestinal mucosa, and worsen the course of colitis in susceptible hosts.
- Published
- 2020
- Full Text
- View/download PDF
26. The Nutrition-Microbiota-Physical Activity Triad: An Inspiring New Concept for Health and Sports Performance
- Author
-
Nathalie Boisseau, Nicolas Barnich, and Christelle Koechlin-Ramonatxo
- Subjects
exercise ,training ,dysbiosis ,eubiosis ,diets ,supplements ,Nutrition. Foods and food supply ,TX341-641 - Abstract
The human gut microbiota is currently the focus of converging interest in many diseases and sports performance. This review presents gut microbiota as a real “orchestra conductor” in the host’s physio(patho)logy due to its implications in many aspects of health and disease. Reciprocally, gut microbiota composition and activity are influenced by many different factors, such as diet and physical activity. Literature data have shown that macro- and micro-nutrients influence gut microbiota composition. Cumulative data indicate that gut bacteria are sensitive to modulation by physical activity, as shown by studies using training and hypoactivity models. Sports performance studies have also presented interesting and promising results. Therefore, gut microbiota could be considered a “pivotal” organ for health and sports performance, leading to a new concept: the nutrition-microbiota-physical activity triad. The next challenge for the scientific and medical communities is to test this concept in clinical studies. The long-term aim is to find the best combination of the three elements of this triad to optimize treatments, delay disease onset, or enhance sports performance. The many possibilities offered by biotic supplementation and training modalities open different avenues for future research.
- Published
- 2022
- Full Text
- View/download PDF
27. Dietary Emulsifiers Directly Impact Adherent-Invasive E. coli Gene Expression to Drive Chronic Intestinal Inflammation
- Author
-
Emilie Viennois, Alexis Bretin, Philip E. Dubé, Alexander C. Maue, Charlène J.G. Dauriat, Nicolas Barnich, Andrew T. Gewirtz, and Benoit Chassaing
- Subjects
emulsifier ,adherent-invasive Escherichia coli ,intestinal inflammation ,flagellin ,microbiota ,pathobiont ,Biology (General) ,QH301-705.5 - Abstract
Summary: Dietary emulsifiers carboxymethylcellulose (CMC) and polysorbate-80 (P80) disturb gut microbiota, promoting chronic inflammation. Mice with minimal microbiota are protected against emulsifiers’ effects, leading us to hypothesize that these compounds might provoke select pathobionts to promote inflammation. Gnotobiotic wild-type (WT) and interleukin-10 (IL-10)−/− mice were colonized with Crohn’s-disease-associated adherent-invasive E. coli (AIEC) and subsequently administered CMC or P80. AIEC colonization of GF and altered Schaedler flora (ASF) mice results in chronic intestinal inflammation and metabolism dysregulations when consuming the emulsifier. In IL-10−/− mice, AIEC mono-colonization results in severe intestinal inflammation in response to emulsifiers. Exposure of AIEC to emulsifiers in vitro increases its motility and ability to adhere to intestinal epithelial cells. Transcriptomic analysis reveals that emulsifiers directly induce expression of clusters of genes that mediate AIEC virulence and promotion of inflammation. To conclude, emulsifiers promote virulence and encroachment of pathobionts, providing a means by which these compounds may drive inflammation in hosts carrying such bacteria.
- Published
- 2020
- Full Text
- View/download PDF
28. Pathogenicity Factors of Genomic Islands in Intestinal and Extraintestinal Escherichia coli
- Author
-
Mickaël Desvaux, Guillaume Dalmasso, Racha Beyrouthy, Nicolas Barnich, Julien Delmas, and Richard Bonnet
- Subjects
Escherichia coli ,pathogenicity islands ,genomic island ,virulence ,ExPEC ,AIEC ,Microbiology ,QR1-502 - Abstract
Escherichia coli is a versatile bacterial species that includes both harmless commensal strains and pathogenic strains found in the gastrointestinal tract in humans and warm-blooded animals. The growing amount of DNA sequence information generated in the era of “genomics” has helped to increase our understanding of the factors and mechanisms involved in the diversification of this bacterial species. The pathogenic side of E. coli that is afforded through horizontal transfers of genes encoding virulence factors enables this bacterium to become a highly diverse and adapted pathogen that is responsible for intestinal or extraintestinal diseases in humans and animals. Many of the accessory genes acquired by horizontal transfers form syntenic blocks and are recognized as genomic islands (GIs). These genomic regions contribute to the rapid evolution, diversification and adaptation of E. coli variants because they are frequently subject to rearrangements, excision and transfer, as well as to further acquisition of additional DNA. Here, we review a subgroup of GIs from E. coli termed pathogenicity islands (PAIs), a concept defined in the late 1980s by Jörg Hacker and colleagues in Werner Goebel’s group at the University of Würzburg, Würzburg, Germany. As with other GIs, the PAIs comprise large genomic regions that differ from the rest of the genome by their G + C content, by their typical insertion within transfer RNA genes, and by their harboring of direct repeats (at their ends), integrase determinants, or other mobility loci. The hallmark of PAIs is their contribution to the emergence of virulent bacteria and to the development of intestinal and extraintestinal diseases. This review summarizes the current knowledge on the structure and functional features of PAIs, on PAI-encoded E. coli pathogenicity factors and on the role of PAIs in host–pathogen interactions.
- Published
- 2020
- Full Text
- View/download PDF
29. When Adherent-invasive E. coli plays with host glycosylation: Does it open new perspectives for therapeutic strategies in Crohn's disease?
- Author
-
Jérémy Denizot and Nicolas Barnich
- Subjects
Medicine ,Medicine (General) ,R5-920 - Published
- 2020
- Full Text
- View/download PDF
30. The Crohn's disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages.
- Author
-
Gaëlle Demarre, Victoria Prudent, Hanna Schenk, Emilie Rousseau, Marie-Agnès Bringer, Nicolas Barnich, Guy Tran Van Nhieu, Sylvie Rimsky, Silvia De Monte, and Olivier Espéli
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Adherent Invasive Escherichia coli (AIEC) strains recovered from Crohn's disease lesions survive and multiply within macrophages. A reference strain for this pathovar, AIEC LF82, forms microcolonies within phagolysosomes, an environment that prevents commensal E. coli multiplication. Little is known about the LF82 intracellular growth status, and signals leading to macrophage intra-vacuolar multiplication. We used single-cell analysis, genetic dissection and mathematical models to monitor the growth status and cell cycle regulation of intracellular LF82. We found that within macrophages, bacteria may replicate or undergo non-growing phenotypic switches. This switch results from stringent response firing immediately after uptake by macrophages or at later stages, following genotoxic damage and SOS induction during intracellular replication. Importantly, non-growers resist treatment with various antibiotics. Thus, intracellular challenges induce AIEC LF82 phenotypic heterogeneity and non-growing bacteria that could provide a reservoir for antibiotic-tolerant bacteria responsible for relapsing infections.
- Published
- 2019
- Full Text
- View/download PDF
31. Beneficial Effects of High Intensity Interval Training and/or Linseed Oil Supplementation to Limit Obesity-Induced Oxidative Stress in High Fat Diet-Fed Rats
- Author
-
Carole Groussard, Claire Plissonneau, Laurie Josset, Fréderic Capel, Mathilde Mura, Etienne Gouraud, Guillaume Mairesse, Guillaume Chesneau, Nicolas Barnich, Vincent Pialoux, and Nathalie Boisseau
- Subjects
linseed oil supplementation ,high intensity interval training ,high fat diet ,obesity ,oxidative stress ,Nutrition. Foods and food supply ,TX341-641 - Abstract
High-intensity interval training (HIIT) and linseed oil (LO) supplementation are effective strategies to reduce obesity-induced oxidative stress. Our aim was to determine whether the HIIT + LO combination prevents obesity-induced oxidative stress in high fat diet (HFD)-fed rats. HFD-fed 8-week-old, male, Wistar rats were subdivided in four groups: HFD, LO (2% of sunflower oil replaced with 2% of LO in the HFD), HIIT (4 days/week for 12 weeks), and HIIT + LO. Wistar rats fed a low-fat diet (LFD) were used as controls. Epididymal and subcutaneous adipose tissue, gastrocnemius muscle, liver, and plasma samples were collected to measure oxidative stress markers (AOPP, oxLDL), antioxidant (SOD, CAT, and GPx activities) and pro-oxidant (NOx and XO) enzyme activities. Compared with the LFD, the HFD altered the pro/antioxidant status in different tissues (increase of AOPP, oxLDL, SOD and catalase activities in plasma, and SOD activity increase in liver and decrease in adipose tissues) but not in gastrocnemius. LO upregulated CAT activity and decreased NOx in liver. HIIT alleviated HFD negative effects in liver by reducing SOD and NOx activities. Moreover, the HIIT + LO combination potentiated SOD activity upregulation in subcutaneous tissue. HIIT and LO supplementation have independent beneficial effects on the pro/antioxidant balance. Their association promotes SOD activity in subcutaneous adipose tissue.
- Published
- 2021
- Full Text
- View/download PDF
32. When Pathobiont-Carbohydrate Interaction Turns Bittersweet!
- Author
-
Nicolas Barnich and Benoit Chassaing
- Subjects
Diseases of the digestive system. Gastroenterology ,RC799-869 - Published
- 2021
- Full Text
- View/download PDF
33. The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet
- Author
-
Marine Dupuit, Vivien Chavanelle, Benoit Chassaing, Fanny Perriere, Monique Etienne, Claire Plissonneau, Audrey Boscaro, Nicolas Barnich, Vincent Pialoux, Thierry Maugard, Florian Le Joubioux, Sébastien Peltier, Pascal Sirvent, Yolanda F. Otero, and Nathalie Boisseau
- Subjects
high-intensity interval training ,plant extract supplementation ,glycemic control ,body composition ,microbiota ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Obesity and prediabetes are the two strongest risk factors of type 2 diabetes. It has been reported that TOTUM-63, a polyphenol-rich plant extract, has beneficial effects on body weight (BW) and insulin resistance in mice fed a high fat diet (HFD). The study aim was to determine whether high-intensity interval training (HIIT) and/or TOTUM-63 supplementation improved body composition and glycemic control and gut microbiota composition in a Western diet-induced obesity rat model. Wistar rats received a standard diet (CTRL; control; n = 12) or HFD (HFD; n = 48) for 16 weeks. Then, HFD rats were divided in four groups: HFD, HFD + TOTUM-63 (T63), HFD + HIIT (HIIT), and HFD + HIIT +T63 (HIIT + T63). Training was performed 4 days/week for 12 weeks. TOTUM-63 was included in diet composition (2%). The HIIT + T63 combination significantly limited BW gain, without any energy intake modulation, and improved glycemic control. BW variation was correlated with increased α-diversity of the colon mucosa microbiota in the HIIT + T63 group. Moreover, the relative abundance of Anaeroplasma, Christensenellaceae and Oscillospira was higher in the HIIT + T63 group. Altogether, these results suggest that the HIIT and TOTUM-63 combination could be proposed for the management of obesity and prediabetes.
- Published
- 2021
- Full Text
- View/download PDF
34. High intensity interval training promotes total and visceral fat mass loss in obese Zucker rats without modulating gut microbiota.
- Author
-
Florie Maillard, Emilie Vazeille, Pierre Sauvanet, Pascal Sirvent, Lydie Combaret, Antoine Sourdrille, Vivien Chavanelle, Richard Bonnet, Yolanda Fernandez Otero, Geoffrey Delcros, Nicolas Barnich, and Nathalie Boisseau
- Subjects
Medicine ,Science - Abstract
AimsIncreased visceral adipose tissue and dysbiosis in the overweight and obese promote chronic inflammation. The aim of this study was to compare the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on the gut-adipose tissue cross-talk in obese Zucker rats.MethodsObese male Zucker rats (n = 36) were divided in three groups: MICT (12m.min-1 for 51min), HIIT (6 sets at 18 m.min-1 for 4min followed by 3min at 10m.min-1) and controls (CONT; no exercise). The animals ran on a treadmill 5 days/week for 10 weeks. Body composition, glycaemic control, lipid profile, inflammation, lipolysis signalling in subcutaneous and visceral adipose tissue, intestinal permeability (tight junctions and plasma lipopolysaccharide binding protein; LBP), and gut microbiota composition were assessed in the three groups.ResultsAfter 10 weeks of exercise, total and epididymal fat mass decreased only in the HIIT group. The α/β adrenergic receptor RNA ratio in subcutaneous adipose tissue increased only in the HIIT group. The expression level of phosphorylated hormone-sensitive lipase was not modified by training. Both HIIT and MICT decreased inflammation (plasma myeloperoxidase and keratinocyte-derived chemokine secretion in adipose tissue) and improved glucose metabolism. Zonula occludens-1 and occludin were upregulated in the HIIT group. Plasma LBP was similarly reduced in both training groups. HIIT and MICT did not affect gut microbiota composition.ConclusionIn obese Zucker rats, HIIT and MICT improved inflammation and glucose metabolism. In contrast, only HIIT decreased total and visceral fat mass. These adaptations were not associated with modifications in gut microbiota composition.
- Published
- 2019
- Full Text
- View/download PDF
35. Beneficial Effects of Natural Mineral Waters on Intestinal Inflammation and the Mucosa-Associated Microbiota
- Author
-
Nicolas Barnich, Michael Rodrigues, Pierre Sauvanet, Caroline Chevarin, Sylvain Denis, Olivier Le Goff, Danielle Faure-Imbert, Thierry Hanh, Christian F Roques, Benoit Chassaing, and Monique Alric
- Subjects
natural mineral water ,intestinal inflammation ,mucosa-associated microbiota ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Natural mineral water (NMWs) intake has been traditionally used in the treatment of various gastrointestinal diseases. We investigated the effect of two French NMWs, one a calcium and magnesium sulphate, sodium chloride, carbonic, and ferruginous water (NMW1), the other a mainly bicarbonate water (NMW2) on the prevention of intestinal inflammation. Intestinal epithelial cells stimulated with heat inactivated Escherichia coli or H2O2 were treated with NMWs to evaluate the anti-inflammatory effects. Moderate colitis was induced by 1% dextran sulfate sodium (DSS) in Balbc/J mice drinking NMW1, NWW2, or control water. General signs and histological features of colitis, fecal lipocalin-2 and pro-inflammatory KC cytokine levels, global mucosa-associated microbiota, were analyzed. We demonstrated that both NMW1 and NMW2 exhibited anti-inflammatory effects using intestinal cells. In induced-colitis mice, NMW1 was effective in dampening intestinal inflammation, with significant reductions in disease activity scores, fecal lipocalin-2 levels, pro-inflammatory KC cytokine release, and intestinal epithelial lesion sizes. Moreover, NMW1 was sufficient to prevent alterations in the mucosa-associated microbiota. These observations, through mechanisms involving modulation of the mucosa-associated microbiota, emphasize the need of investigation of the potential clinical efficiency of such NMWs to contribute, in human beings, to a state of low inflammation in inflammatory bowel disease.
- Published
- 2021
- Full Text
- View/download PDF
36. Yersiniabactin Siderophore of Crohn’s Disease-Associated Adherent-Invasive Escherichia coli Is Involved in Autophagy Activation in Host Cells
- Author
-
Guillaume Dalmasso, Hang Thi Thu Nguyen, Tiphanie Faïs, Sébastien Massier, Caroline Chevarin, Emilie Vazeille, Nicolas Barnich, Julien Delmas, and Richard Bonnet
- Subjects
Crohn’s disease ,AIEC ,autophagy ,HIF-1alpha ,siderophore ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Background: Adherent-invasive Escherichia coli (AIEC) have been implicated in the etiology of Crohn’s disease. The AIEC reference strain LF82 possesses a pathogenicity island similar to the high pathogenicity island of Yersinia spp., which encodes the yersiniabactin siderophore required for iron uptake and growth of the bacteria in iron-restricted environment. Here, we investigated the role of yersiniabactin during AIEC infection. Methods: Intestinal epithelial T84 cells and CEABAC10 transgenic mice were infected with LF82 or its mutants deficient in yersiniabactin expression. Autophagy was assessed by Western blot analysis for p62 and LC3-II expression. Results: Loss of yersiniabactin decreased the growth of LF82 in competitive conditions, reducing the ability of LF82 to adhere to and invade T84 cells and to colonize the intestinal tract of CEABAC10 mice. However, yersiniabactin deficiency increased LF82 intracellular replication. Mechanistically, a functional yersiniabactin is necessary for LF82-induced expression of HIF-1α, which is implicated in autophagy activation in infected cells. Conclusion: Our study highlights a novel role for yersiniabactin siderophore in AIEC–host interaction. Indeed, yersiniabactin, which is an advantage for AIEC to growth in a competitive environment, could be a disadvantage for the bacteria as it activates autophagy, a key host defense mechanism, leading to bacterial clearance.
- Published
- 2021
- Full Text
- View/download PDF
37. High-Intensity Interval Training and α-Linolenic Acid Supplementation Improve DHA Conversion and Increase the Abundance of Gut Mucosa-Associated Oscillospira Bacteria
- Author
-
Claire Plissonneau, Frederic Capel, Benoit Chassaing, Marine Dupuit, Florie Maillard, Ivan Wawrzyniak, Lydie Combaret, Frederic Dutheil, Monique Etienne, Guillaume Mairesse, Guillaume Chesneau, Nicolas Barnich, and Nathalie Boisseau
- Subjects
exercise ,linseed oil supplementation ,body composition ,microbiota ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether high-intensity interval training (HIIT) and/or α-linolenic acid supplementation (to equilibrate the n-6/n-3 polyunsaturated fatty acids (PUFA) ratio) might prevent obesity disorders, particularly by modulating the mucosa-associated microbiota. Wistar rats received a low fat diet (LFD; control) or high fat diet (HFD) for 16 weeks to induce obesity. Then, animals in the HFD group were divided in four groups: HFD (control), HFD + linseed oil (LO), HFD + HIIT, HFD + HIIT + LO. In the HIIT groups, rats ran on a treadmill, 4 days.week−1. Erythrocyte n-3 PUFA content, body composition, inflammation, and intestinal mucosa-associated microbiota composition were assessed after 12 weeks. LO supplementation enhanced α-linolenic acid (ALA) to docosahexaenoic acid (DHA) conversion in erythrocytes, and HIIT potentiated this conversion. Compared with HFD, HIIT limited weight gain, fat mass accumulation, and adipocyte size, whereas LO reduced systemic inflammation. HIIT had the main effect on gut microbiota β-diversity, but the HIIT + LO association significantly increased Oscillospira relative abundance. In our conditions, HIIT had a major effect on body fat mass, whereas HIIT + LO improved ALA conversion to DHA and increased the abundance of Oscillospira bacteria in the microbiota.
- Published
- 2021
- Full Text
- View/download PDF
38. Differential miRNA-Gene Expression in M Cells in Response to Crohn’s Disease-Associated AIEC
- Author
-
Anaïs Larabi, Laurène Salesse, Charlotte Cordonnier, Lucie Etienne-Mesmin, Nicolas Barnich, Guillaume Dalmasso, and Hang Thi Thu Nguyen
- Subjects
Crohn disease ,Adherent-invasive E. coli ,M cells ,MicroRNAs ,Transcriptomic analysis ,Biology (General) ,QH301-705.5 - Abstract
Adherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn’s disease (CD) patients, are able to invade intestinal epithelial cells (IECs) and translocate through M cells overlying Peyer’s patches. The levels of microRNA (miRNA) and gene expression in IECs and M cells upon AIEC infection have not been investigated. Here, we used human intestinal epithelial Caco-2 monolayers and an in vitro M-cell model of AIEC translocation to analyze comprehensive miRNA and gene profiling under basal condition and upon infection with the reference AIEC LF82 strain. Our results showed that AIEC LF82 translocated through M cells but not Caco-2 monolayers. Both differential gene expression and miRNA profile in M cells compared to Caco-2 cells were obtained. In addition, AIEC infection induces changes in gene and miRNA profiles in both Caco-2 and M cells. In silico analysis showed that certain genes dysregulated upon AIEC infection were potential targets of AIEC-dysregulated miRNAs, suggesting a miRNA-mediated regulation of gene expression during AIEC infection in Caco-2, as well as M cells. This study facilitates the discovery of M cell-specific and AIEC response-specific gene-miRNA signature and enhances the molecular understanding of M cell biology under basal condition and in response to infection with CD-associated AIEC.
- Published
- 2020
- Full Text
- View/download PDF
39. Adherent-Invasive E. coli: Update on the Lifestyle of a Troublemaker in Crohn’s Disease
- Author
-
Mélissa Chervy, Nicolas Barnich, and Jérémy Denizot
- Subjects
Crohn’s disease ,adherent-invasive Escherichia coli ,AIEC-host interaction ,virulence gene ,intestinal environment ,AIEC-targeting therapy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Besides genetic polymorphisms and environmental factors, the intestinal microbiota is an important factor in the etiology of Crohn’s disease (CD). Among microbiota alterations, a particular pathotype of Escherichia coli involved in the pathogenesis of CD abnormally colonizes the intestinal mucosa of patients: the adherent-invasive Escherichia coli (AIEC) pathobiont bacteria, which have the abilities to adhere to and to invade intestinal epithelial cells (IECs), as well as to survive and replicate within macrophages. AIEC have been the subject of many studies in recent years to unveil some genes linked to AIEC virulence and to understand the impact of AIEC infection on the gut and consequently their involvement in CD. In this review, we describe the lifestyle of AIEC bacteria within the intestine, from the interaction with intestinal epithelial and immune cells with an emphasis on environmental and genetic factors favoring their implantation, to their lifestyle in the intestinal lumen. Finally, we discuss AIEC-targeting strategies such as the use of FimH antagonists, bacteriophages, or antibiotics, which could constitute therapeutic options to prevent and limit AIEC colonization in CD patients.
- Published
- 2020
- Full Text
- View/download PDF
40. Emerging Role of Exosomes in Diagnosis and Treatment of Infectious and Inflammatory Bowel Diseases
- Author
-
Anaïs Larabi, Nicolas Barnich, and Hang Thi Thu Nguyen
- Subjects
exosomes ,bacterial infection ,immune response ,inflammatory bowel disease ,vaccine ,Cytology ,QH573-671 - Abstract
To communicate with each other, cells release exosomes that transfer their composition, including lipids, proteins and nucleic acids, to neighboring cells, thus playing a role in various pathophysiological processes. During an infection with pathogenic bacteria, such as adherent-invasive E. coli (AIEC) associated with Crohn disease, exosomes secreted by infected cells can have an impact on the innate immune responses of surrounding cells to infection. Furthermore, inflammation can be amplified via the exosomal shuttle during infection with pathogenic bacteria, which could contribute to the development of the associated disease. Since these vesicles can be released in various biological fluids, changes in exosomal content may provide a means for the identification of non-invasive biomarkers for infectious and inflammatory bowel diseases. Moreover, evidence suggests that exosomes could be used as vaccines to prime the immune system to recognize and kill invading pathogens, and as therapeutic components relieving intestinal inflammation. Here, we summarize the current knowledge on the role of exosomes in bacterial infections and highlight their potential use as biomarkers, vaccines and conveyers of therapeutic molecules in inflammatory bowel diseases.
- Published
- 2020
- Full Text
- View/download PDF
41. Prevalence of Yersinia Species in the Ileum of Crohn's Disease Patients and Controls
- Author
-
Guillaume Le Baut, Claire O'Brien, Paul Pavli, Maryline Roy, Philippe Seksik, Xavier Tréton, Stéphane Nancey, Nicolas Barnich, Madeleine Bezault, Claire Auzolle, Dominique Cazals-Hatem, Jérome Viala, Matthieu Allez, The REMIND GROUP, Jean-Pierre Hugot, and Anne Dumay
- Subjects
yersinia ,Crohn's disease ,gut microbiota ,ileal mucosa ,innate immunity ,mucosal immune system ,Microbiology ,QR1-502 - Abstract
Yersinia are common contaminants of food products, but their prevalence in the human gut is poorly documented. Yersinia have been implicated in Crohn's Disease (CD, an inflammatory bowel disease) however their role in CD is controversial. We performed highly sensitive PCR assays of specific sequences for the gyrB gene of Y. aldovae, Y. bercovieri, Y. enterocolitica, Y. intermedia, Y. mollaretii and the inv gene of Y. pseudotuberculosis. We analyzed a total of 470 ileal samples taken from 338 participants (262 CD patients and 76 controls) belonging to three independent cohorts. All patients and controls were phenotyped and genotyped for the main CD susceptibility variants: NOD2, ATG16L1, and IRGM. Yersinia were found in 7.7% of ileal samples (respectively 7.9 and 7.6% in controls and CD patients) corresponding to 10% of participants (respectively 11.8 and 9.5% in controls and CD patients). Y. enterocolitica, Y. pseudotuberculosis and Y. intermedia were the most frequently identified species. The bacteria were more frequent in resected specimens, lymph nodes and Peyer's patches. Yersinia were no more likely to be detected in CD tissues than tissues from inflammatory and non-inflammatory controls. CD patients treated with immunosuppressants were less likely to be Yersinia carriers. In conclusion, this work shows that Yersinia species are frequently found at low levels in the human ileum in health and disease. The role of Yersinia species in this ecosystem should now be explored.
- Published
- 2018
- Full Text
- View/download PDF
42. Macrophages Inability to Mediate Adherent-Invasive E. coli Replication is Linked to Autophagy in Crohn’s Disease Patients
- Author
-
Anthony Buisson, Clara Douadi, Lemlih Ouchchane, Marion Goutte, Jean-Pierre Hugot, Anaëlle Dubois, Régine Minet-Quinard, Damien Bouvier, Gilles Bommelaer, Emilie Vazeille, and Nicolas Barnich
- Subjects
crohn’s disease ,macrophages ,adherent-invasive e. coli ,irgm ,ulk-1 ,autophagy ,Cytology ,QH573-671 - Abstract
The macrophages from Crohn’s Disease (CD) patients are defective to control the replication of CD-associated adherent-invasive E. coli (AIEC). We aimed to identify the host factors associated with AIEC replication focusing on polymorphisms related to autophagy. Peripheral blood monocyte-derived macrophages (MDM), obtained from 95 CD patient, 30 ulcerative colitis (UC) patients and 15 healthy subjects, were genotyped for several CD-associated polymorphisms. AIEC bacteria survival increased within MDM from CD patients compared to UC (p = 0.0019). AIEC bacteria survival increased in patients with CD-associated polymorphism IRGM (p = 0.05) and reduced in those with CD-associated polymorphisms XBP-1 (p = 0.026) and ULK-1 (p = 0.033). AIEC infection led to an increase of pro-inflammatory cytokines IL-1β (p < 0.0001) and TNF-α (p < 0.0001) in CD macrophages. ULK-1 expression increased in AIEC-infected MDM from CD patients compared to MDM from UC patients or healthy subjects (p = 0.0056) and correlated with AIEC survival (p = 0.0013). Moreover, the expression of ULK-1 phosphorylation on Serine 757 decreased following to AIEC infection (p < 0.0001). Short-term silencing of ULK-1 and IRGM genes restricted and promote, respectively, AIEC survival within MDM (p = 0.0018 and p = 0.0291). In conclusion, the macrophage defect to mediate AIEC clearance in CD patients is linked to polymorphisms related to autophagy such as IRGM and ULK-1.
- Published
- 2019
- Full Text
- View/download PDF
43. Oligomannose-Rich Membranes of Dying Intestinal Epithelial Cells Promote Host Colonization by Adherent-Invasive E. coli
- Author
-
Tetiana Dumych, Nao Yamakawa, Adeline Sivignon, Estelle Garenaux, Stefania Robakiewicz, Bernadette Coddeville, Antonino Bongiovanni, Fabrice Bray, Nicolas Barnich, Sabine Szunerits, Christian Slomianny, Martin Herrmann, Sébastien G. Gouin, Alexander D. Lutsyk, Luis E. Munoz, Frank Lafont, Christian Rolando, Rostyslav Bilyy, and Julie M. J. Bouckaert
- Subjects
CEACAM6 ,adherent-invasive E. coli ,apoptotic cell-derived membranous vesicles ,oligomannose glycans ,Crohn's disease ,Microbiology ,QR1-502 - Abstract
A novel mechanism is revealed by which clinical isolates of adherent-invasive Escherichia coli (AIEC) penetrate into the epithelial cell layer, replicate, and establish biofilms in Crohn's disease. AIEC uses the FimH fimbrial adhesin to bind to oligomannose glycans on the surface of host cells. Oligomannose glycans exposed on early apoptotic cells are the preferred binding targets of AIEC, so apoptotic cells serve as potential entry points for bacteria into the epithelial cell layer. Thereafter, the bacteria propagate laterally in the epithelial intercellular spaces. We demonstrate oligomannosylation at two distinct sites of a glycoprotein receptor for AIEC, carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6 or CD66c), on human intestinal epithelia. After bacterial binding, FimH interacts with CEACAM6, which then clusters. The presence of the highest-affinity epitope for FimH, oligomannose-5, on CEACAM6 is demonstrated using LC-MS/MS. As mannose-dependent infections are abundant, this mechanism might also be used by other adherent-invasive pathogens.
- Published
- 2018
- Full Text
- View/download PDF
44. Efficient and reproducible experimental infections of rats with Blastocystis spp.
- Author
-
Manon Defaye, Céline Nourrisson, Elodie Baudu, Ivan Warwzyniak, Virginie Bonnin, Mathilde Bonnet, Nicolas Barnich, Denis Ardid, Frédéric Delbac, Frédéric Antonio Carvalho, and Philippe Poirier
- Subjects
Medicine ,Science - Abstract
Although Blastocystis spp. infect probably more than 1 billion people worldwide, their clinical significance is still controversial and their pathophysiology remains poorly understood. In this study, we describe a protocol for an efficient and reproducible model of chronic infection in rats, laying the groundwork for future work to evaluate the pathogenic potential of this parasite. In our experimental conditions, we were unable to infect rats using vacuolar forms of an axenically cultivated ST4 isolate, but we successfully established chronic infections of 4 week-old rats after oral administration of both ST3 and ST4 purified cysts isolated from human stool samples. The infection protocol was also applied to 4 week-old C57BL/9, BALB/C and C3H mice, but any mouse was found to be infected by Blastocystis. Minimal cyst inoculum required for rat infection was higher with ST3 (105) than with ST4 (102). These results were confirmed by co-housing experiments highlighting a higher contagious potential of ST4 in rats compared to ST3. Finally, experiments mimicking fecal microbiota transfer from infected to healthy animals showed that Blastocystis spp. could easily infect a new host, even though its intestinal microbiota is not disturbed. In conclusion, our results provide a well-documented and robust rat model of Blastocystis chronic infection, reproducing "natural" infection. This model will be of great interest to study host parasite interactions and to better evaluate clinical significance of Blastocystis.
- Published
- 2018
- Full Text
- View/download PDF
45. Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?
- Author
-
Romain Villéger, Amélie Lopès, Guillaume Carrier, Julie Veziant, Elisabeth Billard, Nicolas Barnich, Johan Gagnière, Emilie Vazeille, and Mathilde Bonnet
- Subjects
intestinal microbiota ,chemotherapy ,probiotics ,cancer ,radiotherapy ,anticancer treatment ,surgery ,microbiome ,adjuvant therapies ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.
- Published
- 2019
- Full Text
- View/download PDF
46. Crohn’s Disease-Associated Adherent-Invasive Escherichia coli Manipulate Host Autophagy by Impairing SUMOylation
- Author
-
Guillaume Dalmasso, Hang T.T. Nguyen, Tiphanie Faïs, Sébastien Massier, Nicolas Barnich, Julien Delmas, and Richard Bonnet
- Subjects
Crohn’s disease ,AIEC ,post-translational modifications ,SUMO ,autophagy ,Cytology ,QH573-671 - Abstract
The intestinal mucosa of Crohn’s disease (CD) patients is abnormally colonized with adherent-invasive Escherichia coli (AIEC) that are able to adhere to and to invade intestinal epithelial cells (IECs), to survive in macrophages, and to induce a pro-inflammatory response. AIEC persist in the intestine, and induce inflammation in CEABAC10 transgenic mice expressing human CAECAM6, the receptor for AIEC. SUMOylation is a eukaryotic-reversible post-translational modification, in which SUMO, an ubiquitin-like polypeptide, is covalently linked to target proteins. Here, we investigated the role of SUMOylation in host responses to AIEC infection. We found that infection with the AIEC LF82 reference strain markedly decreased the levels of SUMO-conjugated proteins in human intestinal epithelial T84 cells. This was also observed in IECs from LF82-infected CEABAC10 transgenic mice. LF82-induced deSUMOylation in IECs was due in part to increased level of microRNA (miR)-18, which targets PIAS3 mRNA encoding a protein involved in SUMOylation. Over-expression of SUMOs in T84 cells induced autophagy, leading to a significant decrease in the number of intracellular LF82. Consistently, a decreased expression of UBC9, a protein necessary for SUMOylation, was accompanied with a decrease of LF82-induced autophagy, increasing bacterial intracellular proliferation and inflammation. Finally, the inhibition of miR-18 significantly decreased the number of intracellular LF82. In conclusion, our results suggest that AIEC inhibits the autophagy response to replicate intracellularly by manipulating host SUMOylation.
- Published
- 2019
- Full Text
- View/download PDF
47. Development of Heptylmannoside-Based Glycoconjugate Antiadhesive Compounds against Adherent-Invasive Escherichia coli Bacteria Associated with Crohn's Disease
- Author
-
Adeline Sivignon, Xibo Yan, Dimitri Alvarez Dorta, Richard Bonnet, Julie Bouckaert, Etienne Fleury, Julien Bernard, Sébastien G. Gouin, Arlette Darfeuille-Michaud, and Nicolas Barnich
- Subjects
Microbiology ,QR1-502 - Abstract
ABSTRACT The ileal lesions of Crohn's disease (CD) patients are colonized by adherent-invasive Escherichia coli (AIEC) bacteria. These bacteria adhere to mannose residues expressed by CEACAM6 on host cells in a type 1 pilus-dependent manner. In this study, we investigated different antagonists of FimH, the adhesin of type 1 pili, for their ability to block AIEC adhesion to intestinal epithelial cells (IEC). Monovalent and multivalent derivatives of n-heptyl α-d-mannoside (HM), a nanomolar antagonist of FimH, were tested in vitro in IEC infected with the AIEC LF82 strain and in vivo by oral administration to CEACAM6-expressing mice infected with LF82 bacteria. In vitro, multivalent derivatives were more potent than the monovalent derivatives, with a gain of efficacy superior to their valencies, probably owing to their ability to form bacterial aggregates. Of note, HM and the multi-HM glycoconjugates exhibited lower efficacy in vivo in decreasing LF82 gut colonization. Interestingly, HM analogues functionalized with an isopropylamide (1A-HM) or β-cyclodextrin pharmacophore at the end of the heptyl tail (1CD-HM) exerted beneficial effects in vivo. These two compounds strongly decreased the amount of LF82 bacteria in the feces of mice and that of bacteria associated with the gut mucosa when administered orally at a dose of 10 mg/kg of body weight after infection. Importantly, signs of colitis and intestinal inflammation induced by LF82 infection were also prevented. These results highlight the potential of the antiadhesive compounds to treat CD patients abnormally colonized by AIEC bacteria and point to an alternative to the current approach focusing on blocking proinflammatory mediators. IMPORTANCE Current treatments for Crohn's disease (CD), including immunosuppressive agents, anti-tumor necrosis factor alpha (anti-TNF-α) and anti-integrin antibodies, focus on the symptoms but not on the cause of the disease. Adherent-invasive Escherichia coli (AIEC) bacteria abnormally colonize the ileal mucosa of CD patients via the interaction of the mannose-specific adhesin FimH of type 1 pili with CEACAM6 mannosylated proteins expressed on the epithelial cell surface. Thus, we decided to develop an antiadhesive strategy based on synthetic FimH antagonists specifically targeting AIEC bacteria that would decrease intestinal inflammation. Heptylmannoside (HM)-based glycocompounds strongly inhibit AIEC adhesion to intestinal epithelial cells in vitro. The antiadhesive effect of two of these compounds of relatively simple chemical structure was also observed in vivo in AIEC-infected CEACAM6-expressing mice and was associated with a reduction in the signs of colitis. These results suggest a new therapeutic approach for CD patients colonized by AIEC bacteria, based on the development of synthetic FimH antagonists.
- Published
- 2015
- Full Text
- View/download PDF
48. Colibactin: More Than a New Bacterial Toxin
- Author
-
Tiphanie Faïs, Julien Delmas, Nicolas Barnich, Richard Bonnet, and Guillaume Dalmasso
- Subjects
colibactin ,pks ,E. coli ,cancer ,toxin ,microbiota ,Medicine - Abstract
Cyclomodulins are bacterial toxins that interfere with the eukaryotic cell cycle. A new cyclomodulin called colibactin, which is synthetized by the pks genomic island, was discovered in 2006. Despite many efforts, colibactin has not yet been purified, and its structure remains elusive. Interestingly, the pks island is found in members of the family Enterobacteriaceae (mainly Escherichia coli and Klebsiella pneumoniae) isolated from different origins, including from intestinal microbiota, septicaemia, newborn meningitis, and urinary tract infections. Colibactin-producing bacteria induce chromosomal instability and DNA damage in eukaryotic cells, which leads to senescence of epithelial cells and apoptosis of immune cells. The pks island is mainly observed in B2 phylogroup E. coli strains, which include extra-intestinal pathogenic E. coli strains, and pks E. coli are over-represented in biopsies isolated from colorectal cancer. In addition, pks E. coli bacteria increase the number of tumours in diverse colorectal cancer mouse models. Thus, colibactin could have a major impact on human health. In the present review, we will focus on the biological effects of colibactin, the distribution of the pks island, and summarize what is currently known about its synthesis and its structure.
- Published
- 2018
- Full Text
- View/download PDF
49. Influenza A virus infection of intestinal epithelial cells enhances the adhesion ability of Crohn's disease associated Escherichia coli strains.
- Author
-
Marta Aleandri, Maria Pia Conte, Giovanna Simonetti, Simona Panella, Ignacio Celestino, Paola Checconi, Massimiliano Marazzato, Catia Longhi, Paola Goldoni, Mauro Nicoletti, Nicolas Barnich, Anna Teresa Palamara, Serena Schippa, and Lucia Nencioni
- Subjects
Medicine ,Science - Abstract
Modifications of intestinal glycoreceptors expression, in particular CEACAM6, typically found in ileal Crohn's disease (CD), favor, among the commensal species of microbiota, the enrichment in Escherichia coli. Removal of protein glycosidic residues by neuraminidase, a sialidase typical of influenza virus, increases adhesion ability of Escherichia coli to Caco-2 intestinal cells. In this study we investigated whether influenza virus infection of human intestinal epithelial cells could influence the adhesiveness of different Escherichia coli strains isolated from CD patients by altering surface glycoreceptors. Influenza virus infection of intestinal cells increased exposure of galactose and mannose residues on the cell surface. In particular, glycoreceptors Thomsen-Friedenreich and CEACAM6 were over-expressed in influenza virus infected cells. In the same experimental conditions, a significant increase in bacterial adhesiveness was observed, independently of their own adhesive ability. The increase was reverted by treatment with anti-TF and anti-CEACAM6 antibodies. Interestingly, influenza virus was able to efficiently replicate in human primary intestinal cells leading to TF exposure. Finally, intestinal infected cells produced high levels of pro-inflammatory cytokines compared to control. Overall these data suggest that influenza virus infection, could constitute an additional risk factor in CD patients.
- Published
- 2015
- Full Text
- View/download PDF
50. Microbiota, Inflammation and Colorectal Cancer
- Author
-
Cécily Lucas, Nicolas Barnich, and Hang Thi Thu Nguyen
- Subjects
colorectal cancer ,intestinal microbiota ,inflammation ,genotoxins ,host-pathogen interaction ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.