Search

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine., Competing Interests: Declaration of interests JA received research support from Pfizer, Janssen, and Merck; has been a speaker for BMS, AbbVie, and Janssen; and reports consultancy with Janssen, Pfizer, AbbVie, Seres Therapeutics, Ferring, GSK, Merck, Bristol Myer Squibb Roivant, and Adiso. JB received grants to institution from Bausch, Grifols, Mallinckrodt, Cosmo, and Sequana and received personal fees for acting as has consultant for Merz and Novo Nordisk. PDC was co-founder of The Akkermansia Company and Enterosys. WMdV was co-founder and shareholder of The Akkermansia Company (Belgium), Caelus Pharmaceuticals (Netherlands) and Alba Health (Copenhagen-Stockholm). EE is a scientific cofounder of DayTwo and BiomX and is an advisor to Purposebio, Aposense, Zoe, and MyGutly. FG has received personal fees for acting as speaker and consultant from Biocodex, Danone, BioGaia, Menarini, and Sanofi. CLH received lecture honoraria from Baxter, Janssen, BMS, and Tillotts. SK received research support from Rebioitx/Ferring, Vedanta, Finch, Seres, and Pfizer and served as consultant for ProbioTech, Takeda, and Rise. OK is a co-founder of Shela Accurate Diagnosis (Israel). JKu received travel support and speaker fees from Ferring, AbbVie, KRKA, Takeda, Janssen, Pfizer, and Ipsen. RL received research funding from Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, and McKusker Charitable Foundation and is an advisory board member for AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda. PM received speaker honoraria from Aboca, Alfasigma, Allergosan, Bayer, Biocodex, and Menarini and is a member of the advisory board of Aboca, Alfasigma, Allergosan, Bayer, Biocodex, and Menarini. JM has received consultancy fees from Cultech and EnterioBioti. SCN received personal fees for acting as speaker for Ferring, Tillotts, Menarini, Janssen, AbbVie, and Takeda; receives patent royalties through her affiliated institutions and is named inventors of patent applications held by The Chinese University of Hong Kong and Microbiota I-Center that cover the therapeutic and diagnostic use of microbiome; received research grants through her affiliated institutions from Olympus, Ferring, and AbbVie; is a founder member and shareholder of GenieBiome; and has served as an advisory board member for Pfizer, Ferring, Janssen, and AbbVie. SPa reports consultancy for Vedanta Biosciences and received personal fees for acting as speaker and for acting as advisory board member for AbbVie, Dr Falk Pharma, Ferring, Janssen, and Takeda. FRP received personal fees for acting as speaker or consultant for AbbVie, Gilead, Roche, Astra Zeneca, Ipsen MSD, Eisai, Kedrion, Bayer, and Alfasigma and is an advisory board member of AbbVie, Gilead, Roche, Astra Zeneca, Ipsen MSD, Eisai, Kedrion, Bayer, and Alfasigma. MRS received personal fees for acting as speaker or advisory board member for Hemofarm, Abela Pharm, and ADOC Pharma. HS reports lecture fee, board membership, or consultancy from Amgen, Fresenius, Ipsen, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, and AbbVie; has stocks from Enterome bioscience; and is co-founder of Exeliom Biosciences. HTu is a named inventor of patent applications held by the CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome. RKW received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico, and Ferring; received speaker's fees from MSD, AbbVie, and Janssen Pharmaceuticals; and acted as consultant for Takeda Pharmaceuticals. GZ is named inventor on a patent (EP2955232A1) and received personal fee as member of the scientific advisory board of Alpha Biomics. FZ conceived the concept of GenFMTer and trasnendoscopic enteral tubing and the devices related to them (FMT Medical) and is an advisory board participant for Ferring and Seres. NS reports consultancy or SAB contracts with Zoe, Roche, Ysopia, and Freya, and Alia Therapeutics; speaker fees by Illumina; and is cofounder of PreBiomics. AG reports personal fees for consultancy for Eisai, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie Board MRGE, and Sanofi; personal fees for acting as a speaker for Takeda, AbbVie, and Sandoz; and personal fees for acting on advisory boards for VSL3 and Eisai. GC has received personal fees for acting as advisor for Ferring Therapeutics. GI has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics, Illumina, and Tillotts Pharma and for acting as consultant or advisor for Ferring Therapeutics, Giuliani, Metagenics, and Tillotts Pharma. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Chronic pouchitis occurs in about 50% of patients undergoing a restorative proctocolectomy for ulcerative colitis. This affection represents a significant therapeutic challenge, particularly for symptomatic patients who do not respond to antibiotic treatments and biologic therapies. Several dietary approaches, including low FODMAP diets and the Mediterranean diet, have shown promising results in improving symptoms and disease burden. The rationale for dietary intervention lies in the reduction in inflammation and modulation of gut microbiota. However, conflicting results and methodological heterogeneity jeopardize the transition of these approaches from the field of research to clinical practice. Together with a nutritional approach, innovative methods of microbiota modulation, including probiotics and fecal microbiota transplantation, are emerging as safe and effective strategies in managing chronic pouchitis. This narrative review analyzes recent advancements in nutritional therapies and microbiota modulation as innovative and complementary approaches for managing chronic pouchitis. After examining microbiota modulation strategies, specifically the effectiveness of probiotics, prebiotics, and fecal microbiota transplantation in restoring microbial diversity and their potential role in alleviating symptoms, the review assesses the available clinical evidence concerning dietary interventions and their impact on gut microbiota. A comprehensive understanding of interventions aimed at modulating the microbiota is crucial for enhancing the effectiveness of conventional therapies. Such strategies may lead to significant improvements in patients' quality of life and their perception of the disease. However, the variability in microbiota composition, the use of restrictive diets, and the lack of standardized methods for evaluating these interventions remain significant challenges. Future research is essential to improve our understanding of the underlying mechanisms and optimize clinical application.

The gut microbiome, a collection of gut microorganisms, is crucial in the development and progression of inflammatory bowel diseases (IBD). Therefore, diet and dietary interventions are promising strategies to shape the gut microbiota for IBD management. Of all the diets studied in the IBD field, the Mediterranean diet has the least restrictive nature, promoting long-term adherence. The Mediterranean diet is rich in plants, with a high daily intake of fruits and vegetables (high in fiber, antioxidants, and vitamins), olive oil, whole grains, legumes, and nuts. It includes the moderate consumption of animal products such as oily fish (rich in mono- and polyunsaturated fatty acids), dairy products, and poultry, with a limited intake of red meat and processed foods. This diet is associated with a decreased risk of chronic diseases, including IBD. However, the mechanisms of specific nutrients behind these effects in the Mediterranean diet remain under investigation. Therefore, in this review, we aim to provide an overview of the nutrients that are abundant in the Mediterranean diet and their effects on IBD, with a main focus on preclinical evidence. While several nutrients like fructo-oligosaccharide, chitosan, plant-derived protein, polyphenols, omega-3 polyunsaturated fatty acids, and resveratrol have shown potential beneficial effects in preclinical models, clinical evidence is often limited. However, understanding the complex interactions between specific nutrients and IBD is essential to developing a tailored, multidisciplinary, and personalized approach for disease management; therefore, further research is required.

Background: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis., Methods: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively., Results: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells., Conclusions: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry., Results: At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs., Conclusions: The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract., (© 2024. The Author(s).)

Background and Aims: Several faecal microbial transplantation [FMT] approaches for ulcerative colitis [UC] have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet [UCED], compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function., Methods: Subjects recruited to the CRAFT UC study with available pre- and post-intervention faecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group 1 received single FMT by colonoscopy [Day 1] and enemas [Days 2 and 14] without donors' dietary conditioning [N = 11]. Group 2 received FMT but with donors' dietary pre-conditioning and UCED for the patients [N = 10]. Faecal samples were assessed by DNA shotgun metagenomic sequencing., Results: Following diet conditioning, donors showed depletion in metabolic pathways involved in biosynthesis of sulphur-containing amino acids. Only Group 2 showed significant shifts towards the donors' microbial composition [ADONIS: R2 = 0.15, p = 0.008] and significantly increased Eubacterium&#95;sp&#95;AF228LB post-intervention [β-coefficient 2.66, 95% confidence interval 2.1-3.3, q < 0.05] which was inversely correlated with faecal calprotectin [rho = -0.52, p = 0.035]. Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post-intervention in Group 2 and were significantly inversely correlated with faecal calprotectin., Conclusion: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favourable microbial profiles which correlated with decreased faecal calprotectin. Our findings support further exploration of the additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Malnutrition poses a critical challenge in inflammatory bowel disease, with the potential to detrimentally impact medical treatment, surgical outcomes, and general well-being. Parenteral nutrition is crucial in certain clinical scenarios, such as with patients suffering from short bowel syndrome, intestinal insufficiency, high-yielding gastrointestinal fistula, or complete small bowel obstruction, to effectively manage malnutrition. Nevertheless, research over the years has attempted to define the potential effects of parenteral nutrition on the intestinal barrier and the composition of the gut microbiota. In this narrative review, we have gathered and analyzed findings from both preclinical and clinical studies on this topic. Based on existing evidence, there is a clear correlation between short- and long-term parenteral nutrition and negative effects on the intestinal system. These include mucosal atrophic damage and immunological and neuroendocrine dysregulation, as well as alterations in gut barrier permeability and microbiota composition. However, the mechanistic role of these changes in inflammatory bowel disease remains unclear. Therefore, further research is necessary to effectively address the numerous gaps and unanswered questions pertaining to these issues.

Bowel strictures are well recognized as one of the most severe complications in Crohn's disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-β, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis' pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn's disease.

Background: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches., Methods: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis., Results: In the UC cohort, we reported the increase of Streptococcus , Bifidobacterium , Enterobacteriaceae, TM7-3, Granulicatella , Peptostreptococcus , Lactobacillus , Veillonella , Enterococcus , Peptoniphilus , Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia ; Ruminococcaceae; Ruminococcus ; Gemmiger ; Methanobrevibacter ; Oscillospira ; Coprococus ; Christensenellaceae ; Clavispora ; Vishniacozyma ; Quambalaria ; hexadecane; cyclopentadecane; 5-hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3-methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota. Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions., Conclusion: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Scanu, Toto, Petito, Masi, Fidaleo, Puca, Baldelli, Reddel, Vernocchi, Pani, Putignani, Scaldaferri and Del Chierico.)

The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions., (© 2023. The Author(s).)

Background: Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific personality traits. Despite this, there are few data about personality profiles' characterization in UC patients and about correlation of their psychopathological profile with their intestinal microbiota.The aim of our study is to analyze the psychopathological and personality profile of UC patients and correlate it with specific signatures of their gut microbiota., Methods: This is a prospective interventional longitudinal cohort study. We enrolled consecutive patients affected by UC attending to the IBD Unit of Center for Digestive Disease of "A. Gemelli" IRCCS Hospital in Rome and a group of healthy subjects, matched for specific characteristics. Each patient was evaluated by a gastroenterologist and a psychiatrist. Moreover, all participants underwent psychological tests and a collection of stool samples., Results: We recruited 39 UC patients and 37 healthy subjects. Most patients showed high level of alexithymia, anxiety symptoms, depressive symptoms, as well as neuroticism and hypochondria, with obsessive-compulsive features at the behavioral level, which significantly impaired their quality of life and abilities at work. Gut microbiota analysis in UC patients demonstrated an increase in actinobacteria, Proteobacteria and Saccharibacteria (TM7), with a reduction in verrucomicrobia, euryarchaeota and tenericutes., Conclusions: Our study confirmed the presence of high levels of psycho-emotional distress in UC patients, alongside alterations of the intestinal microbiota, and highlighted some families and genera of bacteria (Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae) as potential markers of an altered gut-brain axis in these patients., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors., Objective: To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices., Design: An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines., Results and Conclusions: Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gut microbiota (GM) modulation can be investigated as possible solution to enhance recovery after COVID-19. An open-label, single-center, single-arm, pilot, interventional study was performed by enrolling twenty patients recently recovered from COVID-19 to investigate the role of a mixed probiotic, containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus , on gastrointestinal symptoms, local and systemic inflammation, intestinal barrier integrity and GM profile. Gastrointestinal Symptom Rating Scale, cytokines, inflammatory, gut permeability, and integrity markers were evaluated before (T 0 ) and after 8 weeks (T 1 ) of probiotic supplementation. GM profiling was based on 16S-rRNA targeted-metagenomics and QIIME 2.0, LEfSe and PICRUSt computational algorithms. Multiple machine learning (ML) models were trained to classify GM at T 0 and T 1 . A statistically significant reduction of IL-6 ( p < 0.001), TNF-α ( p < 0.001) and IL-12RA ( p < 0.02), citrulline ( p value < 0.001) was reported at T 1 . GM global distribution and microbial biomarkers strictly reflected probiotic composition, with a general increase in Bifidobacteria at T 1 . Twelve unique KEGG orthologs were associated only to T 0 , including tetracycline resistance cassettes. ML classified the GM at T 1 with 100% score at phylum level. Bifidobacteriaceae and Bifidobacterium spp. inversely correlated to reduction of citrulline and inflammatory cytokines. Probiotic supplementation during post-COVID-19 may trigger anti-inflammatory effects though Bifidobacteria and related-metabolism enhancement.

Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer in Western countries. Inflammation is a well-known driver of colonic carcinogenesis; however, its role in CRC extends beyond colitis-associated cancer. Over the last decades, numerous associations between intestinal dysbiosis and CRC have been identified, with more recent studies providing mechanistic evidence of a causative relationship. Nonetheless, much remains to be discovered regarding the precise implications of microbiome alterations in the pathogenesis of CRC. Research confirms the importance of a bidirectional crosstalk between the gut microbiome and the mucosal immune system in which inflammasomes, multiprotein complexes that can sense "danger signals," serve as conduits by detecting microbial signals and activating innate immune responses, including the induction of microbicidal activities that can alter microbiome composition. Current evidence strongly supports an active role for this "inflammasome-microbiome axis" in the initiation and development of CRC. Furthermore, the gasdermin (GSDM) family of proteins, which are downstream effectors of the inflammasome that are primarily known for their role in pyroptosis, have been recently linked to CRC pathogenesis. These findings, however, do not come without controversy, as pyroptosis is reported to exert both anti- and protumorigenic functions. Furthermore, the multi-faceted interactions between GSDMs and the gut microbiome, as well as their importance in CRC, have only been superficially investigated. In this review, we summarize the existing literature supporting the importance of the inflammasome-microbiota axis, as well as the activation and function of GSDMs, to gain a better mechanistic understanding of CRC pathogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Privitera, Rana, Scaldaferri, Armuzzi and Pizarro.)

Nutritional deficiencies are common in inflammatory bowel diseases (IBD). In patients, magnesium (Mg) deficiency is associated with disease severity, while in murine models, dietary Mg supplementation contributes to restoring mucosal function. Since Mg availability modulates key bacterial functions, including growth and virulence, we investigated whether the beneficial effects of Mg supplementation during colitis might be mediated by gut microbiota. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, and fecal consistency. Gut microbiota were analyzed by 16S-rRNA based profiling on fecal samples. Mg supplementation improved microbiota richness in colitic mice, increased abundance of Bifidobacterium and reduced Enterobacteriaceae. KEEG pathway analysis predicted an increase in biosynthetic metabolism, DNA repair and translation pathways during Mg supplementation and in the presence of colitis, while low Mg conditions favored catabolic processes. Thus, dietary Mg supplementation increases bacteria involved in intestinal health and metabolic homeostasis, and reduces bacteria involved in inflammation and associated with human diseases, such as IBD. These findings suggest that Mg supplementation may be a safe and cost-effective strategy to ameliorate disease symptoms and restore a beneficial intestinal flora in IBD patients.

Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nardone, de Sire, Petito, Testa, Villani, Scaldaferri and Castiglione.)

Compositional and functional alterations of the gut microbiota are involved in the pathogenesis of several gastrointestinal diseases. Rifaximin is often used to induce disease remission due to its eubiotic effects on the gut microbiota. To investigate the correlation between changes in the gut microbiota composition and symptoms improvement in patients who present a clinical response to rifaximin treatment. Patients with ulcerative colitis (UC), Crohn's disease (CD), irritable bowel syndrome (IBS) and diverticular disease (DD) undergoing rifaximin treatment for clinical indication were enrolled in the study. Rifaximin was administered at the dose of 1,200 mg/day for 10 days. Faecal samples were collected at baseline and at the end of treatment; clinical improvement was assessed by Mayo score for UC, CD Activity Index (CDAI) for CD, IBS severity scoring system (IBS-SSS) for IBS and global symptomatic score (GSS) for DD. Twenty-five patients were included in the analysis and a clinical improvement was recorded for 10/25 (40%) of them. Microbial alpha diversity showed a slight increase in clinical responders ( P =0.271), while it decreased in patients who did not improved ( P =0.05). A significant post-treatment increase in Faecalibacterium abundance was observed in patients with a positive response (log 2 FC 1.959, P =0.042). Roseburia abundance decreased in both groups, whereas Ruminococcus decreased only in patients who clinically improved. Clinical improvement consequent to rifaximin treatment is associated with an increase in Faecalibacterium abundance. Achieving a positive shift in the gut microbiota composition seems a key event to obtain a clinical benefit from treatment.

Background: Gut microbiota exerts a crucial role in gastrointestinal (GI) and extra-intestinal (EI) disorders. In this context, Akkermansia muciniphila is pivotal for the maintenance of host health and has been correlated with several disorders., Aim: To explore the potential role of A. muciniphila as common dysbiotic marker linked to the disease status., Methods: A cohort of patients affected by GI and EI disorders was enrolled and compared to healthy controls (CTRLs). A targeted-metagenomics approach combined to unsupervised cluster and machine learning (ML) analyses provided microbiota signatures., Results: Microbiota composition was associated to disease phenotype, therapies, diet and anthropometric features, identifying phenotype and therapies as the most impacting variables on microbiota ecology. Unsupervised cluster analyses identified one cluster composed by the majority of patients. DESeq2 algorithm identified ten microbial discriminatory features of patients and CTRLs clusters. Among these microbes, Akkermansia muciniphila resulted the discriminating ML node between patients and CTRLs, independently of specific GI/EI disease or confounding effects. A. muciniphila decrease represented a transversal signature of gut microbiota alteration, showing also an inverse correlation with α-diversity., Conclusion: Overall, A. muciniphila decline may have a crucial role in affecting microbial ecology and in discriminating patients from healthy subjects. Its grading may be considered as a gut dysbiosis feature associated to disease-related microbiota profile., Competing Interests: Declaration of Competing Interest Authors do not have any competing interests to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract, characterized by an inflammatory process that requires lifelong treatment. The underlying causes of IBD are still unclear, as this heterogeneous disorder results from a complex interplay between genetic variability, the host immune system and environmental factors. The current knowledge recognizes diet as a risk factor for the development of IBD and attributes a substantial pathogenic role to the intestinal dysbiosis inducing an aberrant mucosal immune response in genetically predisposed individuals. This review focused on the clinical evidence available that considers the impact of some nutrients on IBD onset and the role of different diets in the management of IBD and their effects on the gut microbiota composition. The effects of the Specific Carbohydrate Diet, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, gluten free diet, anti-inflammatory diet and Mediterranean diet are investigated with regard to their impact on microbiota and on the evolution of the disease. At present, no clear indications toward a specific diet are available but the assessment of dysbiosis prior to the recommendation of a specific diet should become a standard clinical approach in order to achieve a personalized therapy.

Osteoarthritis (OA) is considered one of the most common joint disorders worldwide and its prevalence is constantly increasing due to the global longevity and changes in eating habits and lifestyle. In this context, the role of gut microbiota (GM) in the pathogenesis of OA is still unclear. Perturbation of GM biodiversity and function, defined as 'gut dysbiosis', might be involved in the development of inflammaging, one of the main risk factors of OA development. It is well known that physical exercise could play a key role in the prevention and treatment of several chronic diseases including OA, and it is recommended by several guidelines as a first line intervention. Several studies have shown that physical exercise could modulate GM composition, boosting intestinal mucosal immunity, increasing the Bacteroidetes-Firmicutes ratio, modifying the bile acid profile, and improving the production of short chain fatty acids. Moreover, it has been shown that low intensity exercise might reduce the risk of gastrointestinal diseases, confirming the hypothesis of a strict correlation between skeletal muscle and GM. However, up to date, there is still a lack of clinical trials focusing on this research field. Therefore, in this narrative, we aimed to summarize the state-of-the-art of the literature regarding the correlation between these conditions, supporting the hypothesis of a 'gut-joint axis' and highlighting the role of physical exercise combined with adequate diet and probiotic supplements in rebalancing microbial dysbiosis.

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice., Competing Interests: Competing interests: JRA received grants from, and consulted for, Finch Therapeutics and Merck and Co. GC, GI, FS and LM received grants in the field of faecal microbiota transplantation (FMT) from the Italian Ministry of Health. SPC received fees from Shire, Ferring, Microbiotica, Pfizer and Janssen. MF is consultant to Finch Therapeutics Group and DSMB member for Rebiotix. AH has served as consultant, advisory board member or speaker for AbbVie, Atlantic, Bristol-Myers Squibb, Celltrion, Falk, Ferring, Janssen, MSD, Napp Pharmaceuticals, Pfizer, Pharmacosmos, Shire and Takeda; she also serves on the Global Steering Committee for Genentech. ZK is an employee/shareholder at Finch Therapeutics and advisor/consultant at OpenBiome. JK and EJK received research grants from Vedanta Bioscences, Boston, USA. CPK is a clinical site for the PRISM FMT trial conducted by Finch Therapeutics. HS received unrestricted study grants: Danone, Biocodex, Enterome; board membership, consultancy or lecture fees: Carenity, Abbvie, Astellas, Danone, Ferring, Mayoly Spindler, MSD, Novartis, Roche, Tillots, Enterome, Maat, BiomX, Biose, Novartis, Takeda; co-funder of Exeliom Biosciences. All the remaining authors have nothing to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The gut microbiota is a changing ecosystem, containing trillions of bacteria, continuously shaped by many factors, such as dietary habits, seasonality, lifestyle, stress, antibiotics use, or diseases. A healthy host-microorganisms balance must be respected in order to optimally maintain the intestinal barrier and immune system functions and, consequently, prevent disease development. In the past several decades, the adoption of modern dietary habits has become a growing health concern, as it is strongly associated with obesity and related metabolic diseases, promoting inflammation and both structural and behavioral changes in gut microbiota. In this context, novel dietary strategies are emerging to prevent diseases and maintain health. However, the consequences of these different diets on gut microbiota modulation are still largely unknown, and could potentially lead to alterations of gut microbiota, intestinal barrier, and the immune system. The present review aimed to focus on the impact of single food components (macronutrients and micronutrients), salt, food additives, and different dietary habits (i.e., vegan and vegetarian, gluten-free, ketogenic, high sugar, low FODMAP, Western-type, and Mediterranean diets) on gut microbiota composition in order to define the optimal diet for a healthy modulation of gut microbiota., Competing Interests: The authors declare no conflicts of interest.

Objective: Gut microbiota has a key role in host metabolic regulation and immune response, and its dysbiosis represents one of the main causes of gastrointestinal diseases. In this scenario, Akkermansia muciniphila is a crucial player in keeping the integrity of the gastrointestinal tract., Materials and Methods: This review focuses on the correlation between gut microbiota and intestinal homeostasis, primarily exploring A. muciniphila and its involvement in the development of metabolic disorders and gastrointestinal diseases., Results: Akkermansia muciniphila belongs to the Verrucomicrobia phylum, and it colonizes the mucus layer in the gastrointestinal tract, representing 1 to 4% of the fecal microbiota. It stimulates mucosal microbial networks, and it improves intestinal barrier function, providing crucial host immunological responses. Several studies have demonstrated the possible involvement of A. muciniphila in the development of intestinal and metabolic disorders. Indeed, adipose and glucose metabolisms are influenced by A. muciniphila, and its levels inversely correlate to inflammatory conditions, such as inflammatory bowel disease, obesity, and diabetes. Conversely, its therapeutic administration decreases their development., Conclusions: A. muciniphila exerts a key role in the maintenance of intestinal health and in host metabolic modulation. Future studies could open new horizons towards its potential therapeutic applications in gastrointestinal and extra-intestinal diseases.

Background: Anti-tumor necrosis factor α (TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing., Aim: To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium (DSS) colitis., Methods: Eighty C57BL/6 mice were divided into four groups: "No DSS", "No DSS + anti-TNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and "DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score (Disease Activity Index), colon length and histology. Bacteria such as Bacteroides , Clostridiaceae , Enterococcaceae and Fecalibacterium prausnitzii ( F. prausnitzii ) were evaluated by quantitative PCR. Type 1 helper T lymphocytes (Th1), type 17 helper T lymphocytes (Th17) and CD4 + regulatory T lymphocytes (Treg) distributions in the mesenteric lymph node (MLN) were studied by flow cytometry., Results: Bacteria associated with a healthy state ( i.e ., such as Bacteroides , Clostridiaceae and F. prausnitzii ) decreased during colitis and increased in course of anti-TNFα treatment. Conversely, microorganisms belonging to Enterococcaceae genera, which are linked to inflammatory processes, showed an opposite trend. Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase (day 5 of the colitis) in Treg cells and a consequent decrease (day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5 th and 12 th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12., Conclusion: Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration., Competing Interests: Conflict-of-interest statement: Authors disclose no any conflict of interest.

Intestinal permeability is the property that allows solute and fluid exchange between intestinal lumen and intestinal mucosa. Many factors could have major impact on its regulation, including gut microbiota, mucus layer, epithelial cell integrity, epithelial junction, immune responses, intestinal vasculature, and intestinal motility. Any change among these factors could have an impact on intestinal homeostasis and gut permeability. Healthy condition is associated to normal intestinal permeability whereas several intestinal and extra intestinal disease, like inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease among others, are associated to increased intestinal permeability. This review aims to synthesize determinants on intestinal permeability and to report methodologies useful to the measurement of intestinal permeability in clinical practice as well as in research settings.

Objective: the role of microbes and chronic inflammation in the pathogenesis of Alzheimer' disease (AD) has been postulated by many authors. On the other hand, several studies have reported the main role of H. pylori infection and/or GUT microbiota alteration in promoting chronic inflammation, thus possibly influencing both occurrence and evolution of AD. In this article, we analyze the most important and recent studies performed on this field both on humans and animals and provide possible pathogenic explanations., Results: all main and most recent animal, human, epidemiological and in-silico studies, showed a role of H. pylori and/or dysbiosis in AD, mostly through the promotion of systemic chronic inflammation and/or by triggering molecular mimicry mechanisms. In particular, H. pylori infection seems to be related to a poorer cognitive performance., Conclusions: Indeed, bacteria have been shown to affect neurodegeneration by promoting inflammation, inducing molecular mimicry mechanisms and accumulation of Aβ into the brain. These findings open the way for H. pylori eradicating trials and/or GUT microbiota remodulating strategies. Therefore, further studies are now needed in order to test whether antibiotics, pre and/or probiotics may exert a beneficial effect in the prevention of AD.

Over the last few years, the gut microbiota has been the focus of countless studies conducted both on mouse models and human population, aimed at analyzing its functions and interactions with the host, including nutrition, metabolic homeostasis, protection from infections and development of systemic and mucosal immunity both in inflammatory bowel disease (IBD) as well as other intestinal and extra-intestinal diseases. In IBD microbiota is impaired in overall composition and biodiversity, stability as well as functions. Microbial signature of IBD can be considered also a decrease in F. prausnitzii, increase of Proteonbacteria as well as the described increase of Candida albicans, Basidiomycota/Ascomycota ratio over Saccharomyces cerevisiae and of the Caudovirales over Microviridae. The indirect (through antibiotics, probiotics) and direct (through fecal microbiota transplantation) modulation of gut microbiota has relevant clinical implication in IBD management. In the near future role and clinical implication of gut microbiota characterization in the therapeutic personalized approach to IBD patients will eventually become clear.

Introduction: Helicobacter pylori (Hp) infection produces drastic changes in the gastric microenvironment, which, in turn, influence the gastric microbiota composition and might be correlated with large intestinal microbiota changes. This excellent perturbing actor could trigger important modifications in the homeostatic functions exerted by gut commensals leading to a new gastrointestinal balance. At the same time, the therapeutic strategies used to eradicate Hp can modulate this physiological symbiosis, but can be also conversely affected by its properties. Area covered: The purpose of this review is to explore the reciprocal interplay between Hp infection and gut microbiota and analyze how microbial changes can influence the management of Hp eradication therapies. Expert commentary: While many studies have described Hp-dependent gut microbiota alterations, their clinical implications are only partially clear, as well as the mechanism of actions that sustain these processes. This represents a clear challenge for future research projects that will also need to understand which role is exerted by viruses, parasites, and yeasts.

Bacteroidetes are the largest phylum of Gram-negative bacteria inhabiting our gastrointestinal tract and are considered the leading players of the healthy state and sophisticated homeostasis safeguarded by gut microbiota. Furthermore, specific roles have been attributed to some Bacteroidetes genera in the development of immune dysregulation, systemic disease such as metabolic syndrome and also neurological disorders. Glycoproteins secretion, short fatty acids imbalance, toxins production and molecular mimicry are only a part of the functions exerted by these commensals interacting with the host. The aim of this review is to summarize the current knowledge on the recognized role of Bacteroidetes in physiological functions and pathological networks in order to define the needs for future research and clarify the potential role for targeted microbial therapies., (Copyright © 2018. Published by Elsevier Ltd.)

Few data exist on differences in gut microbiota composition among principal gastrointestinal (GI) diseases. We evaluated the differences in gut microbiota composition among uncomplicated diverticular disease (DD), irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD) patients. DD, IBS, and IBD patients along with healthy controls (CT) were enrolled in our Italian GI outpatient clinic. Stool samples were collected. Microbiota composition was evaluated through a metagenomic gene-targeted approach. GI pathology represented a continuous spectrum of diseases where IBD displayed one extreme, while CT displayed the other. Among Phyla, Biplot PC2/PC3 and dendogram plot showed major differences in samples from IBS and IBD. DD resembled species CT composition, but not for Bacteroides fragilis. In IBS, Dialister spp. and then Faecalibacterium prausnitzii were the most representative species. Ulcerative colitis showed a reduced concentration of Clostridium difficile and an increase of Bacteroides fragilis. In Crohn's disease, Parabacteroides distasonis was the most represented, while Faecalibacterium prausnitzii and Bacteroides fragilis were significantly reduced. Each disorder has its definite overall microbial signature, which produces a clear differentiation from the others. On the other hand, shared alterations constitute the "core dysbiosis" of GI diseases. The assessment of these microbial markers represents a parameter that may complete the diagnostic assessment., (© 2017 S. Karger AG, Basel.)

Major advances have occurred in the knowledge of the pathogenesis of inflammatory bowel disease (IBD) over the last decade, and perhaps the most major, and clinically advantageous of these advances has been the discovery of the microbiome as a key multifaceted component of inflammation. The gut microbiome is the largest known group of cells in the body, and is now recognized as an organ in its own right. Initial studies looking at a possible role of bacterial manipulation of the immune system in IBD, looked at identifying a specific bacterial species, and were not representative of a feasible model of inflammation in IBD overall. More recently there has been a shift towards the concept of dysbiosis, and the acceptance that a number of bacterial factors interact with the immune system in order for inflammation to occur. In the present review we will focus on past perspective of the role of microbiota in IBD, current evidences about dysbiosis in IBD and also the main therapeutic modalities to affect IBD by affecting gut microbiota: probiotics, prebiotics, fecal microbiota transplantation and emerging dietary intervention.

Gut microbiota is characterized by an inter-individual variability due to genetic and environmental factors. Among the environmental ones, dietary habits play a key role in the modulation of gut microbiota composition. There are main differences between the intestinal microbiota of subjects fed with prevalent Western diet and that of subjects with a diet rich in fibers. Specific changes in the composition of gut microbiota have been demonstrated among subjects according to a different dietary intake. A particular diet may promote the growth of specific bacterial strains, driving hosts to a consequent alteration of fermentative metabolism, with a direct effect on intestinal pH, which can be responsible for the development of a pathogenic flora. Moreover, a high-fat diet can promote the development of a pro-inflammatory gut microbiota, with a consequent increase of intestinal permeability and, consequently, of circulating levels of lipopolysaccharides. In this review, we discuss the direct role of the diet in the composition of gut microbiota and about the possible clinical consequences.

Introduction: The intestinal barrier is a complex system responsible for the host health. Many gastrointestinal and extra-intestinal diseases are associated to gut barrier disruption. An increasing interest on nutritional supplements and functional foods focused on the hypothesis that specific prebiotics and probiotics may modulate and interact with gut barrier, re-establishing gut homeostasis., Areas Covered: The application of preparations containing B. clausii in the treatment or prevention of gut phisiology impairment has been largely supported in the last years and has driven its clinical applications. This review focuses on B. clausii clinical applications and speculates on the possible interactions among B. clausii, gut barrier and immune system and on the consequences of this interplay in modulating human health. Expert commentary: Its favorable effects have been linked to several properties, such as antimicrobial and immunomodulatory activity, regulation of cell growth and differentiation, cell-cell signaling, cell adhesion, signal transcription and transduction, production of vitamins and gut protection from genotoxic agents. In this scenario, future studies will need to better clarify its mechanisms of action and focus on the possible role of B. clausii in modulating gut immune system.

Gut virome has been shown to yield some beneficial effects on humans, being deeply involved in physiology, inflammation, immunity, and disease. Together with transkingdom interactions, it can interplay with genetic variation in the host to establish specific phenotypes. These interactions can lead to phenotypes not observed with either the virus or the host variation alone. Unfavorable alteration of gut virome composition has been implicated in chronic, and perhaps also systemic, immune disorders, such as in the pathogenesis of inflammatory bowel disease. This review focuses on what is currently known regarding the role of commensal gut virome in chronic gut inflammation, and speculate on the important translational implications in regard to gut virome modulation in inflammatory bowel disease with the end goal of promoting gut health.

Background: Inflammatory bowel disease (IBD) is the results of a chronic inflammatory process deriving from disequilibrium between self-microbiota composition and immune response., Methods: New evidence, coming from Clostridium difficile infection, clearly showed that active and powerful modulation of microbiota composition by fecal microbiota composition (FMT) is safe, easy to perform, and efficacious, opening new frontiers in gastrointestinal and extra-intestinal diseases. FMT has been proposed also for IBD as well as other non-gastrointestinal conditions related to intestinal microbiota dysfunctions, with good preliminary data., Results: In this setting, ulcerative colitis (UC) represents one of the most robust potential indications for FMT after C difficile colitis., Conclusions: In the present review, we focus on FMT and its application on ulcerative colitis, clarifying mechanisms of actions and efficacy data, trough completion of a meta-analysis on available randomized, controlled trial data in UC. Because microbiota is so crucially involved in this topic, a short review of microbial alterations in UC will also be performed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Mucosal healing (MH) represents a crucial factor for maintaining gut homeostasis. Indeed, in inflammatory bowel disease, MH has become the standard therapeutical target, because it is associated with more effective disease control, more frequent steroid-free remission, lower rates of hospitalization and surgery, and improved quality of life. In this scenario, gut microbiota is a crucial player in modulating intestinal repair and regeneration process. It can act on the tumor necrosis factor-α production, modulation of reactive oxygen and nitrogen species, activity of matrix metalloproteinases and on many other mechanisms strictly involved in restoring gut health. In this review, we analyze and review the literature on the role of gut microbiota in sustaining mucosal injury and achieving MH., (© 2016 S. Karger AG, Basel.)

Antibiotics are mainly used in clinical practice for their activity against pathogens, but they also alter the composition of commensal gut microbial community. Rifaximin is a non-absorbable antibiotic with additional effects on the gut microbiota about which very little is known. It is still not clear to what extent rifaximin can be able to modulate gut microbiota composition and diversity in different clinical settings. Studies based on culture-dependent techniques revealed that rifaximin treatment promotes the growth of beneficial bacteria, such as Bifidobacteria and Lactobacilli. Accordingly, our metagenomic analysis carried out on patients with different gastrointestinal and liver diseases highlighted a significant increase in Lactobacilli after rifaximin treatment, persisting in the short time period. This result was independent of the disease background and was not accompanied by a significant alteration of the overall gut microbial ecology. This suggests that rifaximin can exert important eubiotic effects independently of the original disease, producing a favorable gut microbiota perturbation without changing its overall composition and diversity., (© 2016 S. Karger AG, Basel.)

The gastrointestinal tract is a complex and dynamic network where an intricate and mutualistic symbiosis modulates the relationship between the host and the microbiota in order to establish and ensure gut homeostasis. Every day, thousands of compounds derived from food and microorganisms come in contact with the intestinal mucosa. This interaction requires a complex defense system that separates intestinal contents from the host tissues, regulates nutrient absorption, and allows tolerance between the resident bacterial flora and the mucosal immune system, while inhibiting translocation of infectious agents to the inner tissues. Unfavorable alteration of microbiota composition has been implicated in hepatic, gastrointestinal, and perhaps also systemic disorders. In this scenario, gut microbiota modulation represents an intriguing field and can be obtained by several approaches, including antibiotics, pro- and pre-biotics supplementation. Among antibiotics, Rifaximin seems to be a promising antibiotic to treat conditions related to gut microbiota imbalance and to potentially modulate intestinal homeostasis. This review focuses on what is currently known regarding the possible role of Rifaximin in restoring normal gut immune physiology and a healthy gut-liver axis. Detailed mechanistic studies will improve the development of targeted therapies that may shape gut microflora composition with the end goal of promoting gut health.