10 results on '"Latousakis D"'
Search Results
2. Ruminococcus gnavus ATC29149 endo-beta-1,4-galactosidase (RgGH98)
- Author
-
Owen, C.D., primary, Wu, H., additional, Crost, E.H., additional, van Bakel, W., additional, Gascuena, A.M., additional, Latousakis, D., additional, Hicks, T., additional, Walpole, S., additional, Urbanowicz, P.A., additional, Ndeh, D., additional, Monaco, S., additional, Salom, L.S., additional, Griffiths, R., additional, Colvile, A., additional, Spencer, D.I.R., additional, Walsh, M.A., additional, Angulo, J., additional, and Juge, N., additional
- Published
- 2022
- Full Text
- View/download PDF
3. Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.
- Author
-
Paone P, Latousakis D, Terrasi R, Vertommen D, Jian C, Borlandelli V, Suriano F, Johansson MEV, Puel A, Bouzin C, Delzenne NM, Salonen A, Juge N, Florea BI, Muccioli GG, Overkleeft H, Van Hul M, and Cani PD
- Subjects
- Animals, Mice, Humans, Milk, Human metabolism, Milk, Human chemistry, Intestinal Mucosa metabolism, Proteome metabolism, Proteome analysis, Mucus metabolism, Male, Mice, Inbred C57BL, Mucins metabolism, Diet, High-Fat adverse effects, Obesity metabolism, Obesity microbiology, Obesity prevention & control, Gastrointestinal Microbiome drug effects, Trisaccharides metabolism, Feces microbiology, Feces chemistry
- Abstract
Objective: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system., Results: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides , different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice., Conclusion: Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders., Competing Interests: Competing interests: PDC is an editor of the journal. PDC is inventor on patent applications dealing with the use bacteria on metabolic disorders. PDC was cofounders of The Akkermansia company SA and Enterosys., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)
- Published
- 2024
- Full Text
- View/download PDF
4. Role of mucin glycosylation in the gut microbiota-brain axis of core 3 O-glycan deficient mice.
- Author
-
Coletto E, Savva GM, Latousakis D, Pontifex M, Crost EH, Vaux L, Telatin A, Bergstrom K, Vauzour D, and Juge N
- Subjects
- Animals, Mice, Brain-Gut Axis, Glycosylation, Brain, Polysaccharides, Mucins, Gastrointestinal Microbiome
- Abstract
Alterations in intestinal mucin glycosylation have been associated with increased intestinal permeability and sensitivity to inflammation and infection. Here, we used mice lacking core 3-derived O-glycans (C3GnT
-/- ) to investigate the effect of impaired mucin glycosylation in the gut-brain axis. C3GnT-/- mice showed altered microbial metabolites in the caecum associated with brain function such as dimethylglycine and N-acetyl-L-tyrosine profiles as compared to C3GnT+/+ littermates. In the brain, polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive granule cells showed an aberrant phenotype in the dentate gyrus of C3GnT-/- mice. This was accompanied by a trend towards decreased expression levels of PSA as well as ZO-1 and occludin as compared to C3GnT+/+ . Behavioural studies showed a decrease in the recognition memory of C3GnT-/- mice as compared to C3GnT+/+ mice. Combined, these results support the role of mucin O-glycosylation in the gut in potentially influencing brain function which may be facilitated by the passage of microbial metabolites through an impaired gut barrier., (© 2023. Springer Nature Limited.)- Published
- 2023
- Full Text
- View/download PDF
5. Correction: Biochemical and structural basis of sialic acid utilization by gut microbes.
- Author
-
Bell A, Severi E, Owen CD, Latousakis D, and Juge N
- Published
- 2023
- Full Text
- View/download PDF
6. Biochemical and structural basis of sialic acid utilization by gut microbes.
- Author
-
Bell A, Severi E, Owen CD, Latousakis D, and Juge N
- Subjects
- Infant, Humans, Sialic Acids metabolism, Mucins metabolism, Polysaccharides metabolism, N-Acetylneuraminic Acid metabolism, Gastrointestinal Microbiome
- Abstract
The human gastrointestinal (GI) tract harbors diverse microbial communities collectively known as the gut microbiota that exert a profound impact on human health and disease. The repartition and availability of sialic acid derivatives in the gut have a significant impact on the modulation of gut microbes and host susceptibility to infection and inflammation. Although N-acetylneuraminic acid (Neu5Ac) is the main form of sialic acids in humans, the sialic acid family regroups more than 50 structurally and chemically distinct modified derivatives. In the GI tract, sialic acids are found in the terminal location of mucin glycan chains constituting the mucus layer and also come from human milk oligosaccharides in the infant gut or from meat-based foods in adults. The repartition of sialic acid in the GI tract influences the gut microbiota composition and pathogen colonization. In this review, we provide an update on the mechanisms underpinning sialic acid utilization by gut microbes, focusing on sialidases, transporters, and metabolic enzymes., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
7. Biochemical Basis of Xylooligosaccharide Utilisation by Gut Bacteria.
- Author
-
Singh RP, Bhaiyya R, Thakur R, Niharika J, Singh C, Latousakis D, Saalbach G, Nepogodiev SA, Singh P, Sharma SC, Sengupta S, Juge N, and Field RA
- Subjects
- Bacteria genetics, Bacteria metabolism, Glucuronates, Humans, Oligosaccharides, Phylogeny, Substrate Specificity, Xylans metabolism, Xylosidases metabolism
- Abstract
Xylan is one of the major structural components of the plant cell wall. Xylan present in the human diet reaches the large intestine undigested and becomes a substrate to species of the gut microbiota. Here, we characterised the capacity of Limosilactobacillus reuteri and Blautia producta strains to utilise xylan derivatives. We showed that L. reuteri ATCC 53608 and B. producta ATCC 27340 produced β-D-xylosidases, enabling growth on xylooligosaccharide (XOS). The recombinant enzymes were highly active on artificial ( p -nitrophenyl β-D-xylopyranoside) and natural (xylobiose, xylotriose, and xylotetraose) substrates, and showed transxylosylation activity and tolerance to xylose inhibition. The enzymes belong to glycoside hydrolase family 120 with Asp as nucleophile and Glu as proton donor, as shown by homology modelling and confirmed by site-directed mutagenesis. In silico analysis revealed that these enzymes were part of a gene cluster in L. reuteri but not in Blautia strains, and quantitative proteomics identified other enzymes and transporters involved in B. producta XOS utilisation. Based on these findings, we proposed a model for an XOS metabolism pathway in L. reuteri and B. producta strains. Together with phylogenetic analyses, the data also revealed the extended xylanolytic potential of the gut microbiota.
- Published
- 2022
- Full Text
- View/download PDF
8. Lipopolysaccharide associated with β-2,6 fructan mediates TLR4-dependent immunomodulatory activity in vitro.
- Author
-
Young ID, Nepogodiev SA, Black IM, Le Gall G, Wittmann A, Latousakis D, Visnapuu T, Azadi P, Field RA, Juge N, and Kawasaki N
- Subjects
- Animals, Cell Line, Cytokines biosynthesis, Erwinia chemistry, Fructans chemistry, Humans, Immunologic Factors chemistry, Lipopolysaccharides chemistry, Mice, Mice, Inbred C57BL, Mice, Knockout, Toll-Like Receptor 4 deficiency, Fructans pharmacology, Immunologic Factors pharmacology, Lipopolysaccharides pharmacology, Toll-Like Receptor 4 immunology
- Abstract
Levan, a β-2,6 fructofuranose polymer produced by microbial species, has been reported for its immunomodulatory properties via interaction with toll-like receptor 4 (TLR4) which recognises lipopolysaccharide (LPS). However, the molecular mechanisms underlying these interactions remain elusive. Here, we investigated the immunomodulatory properties of levan using thoroughly-purified and characterised samples from Erwinia herbicola and other sources. E. herbicola levan was purified by gel-permeation chromatography and LPS was removed from the levan following a novel alkali treatment developed in this study. E. herbicola levan was then characterised by gas chromatography-mass spectrometry and NMR. We found that levan containing LPS, but not LPS-depleted levan, induced TLR4-mediated cytokine production by bone marrow-derived dendritic cells and/or activated TLR4 reporter cells. These data indicated that the immunomodulatory properties of the levan toward TLR4-expressing immune cells were mediated by the LPS. This work also demonstrates the importance of LPS removal when assessing the immunomodulatory activity of polysaccharides., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
9. The role of the mucin-glycan foraging Ruminococcus gnavus in the communication between the gut and the brain.
- Author
-
Coletto E, Latousakis D, Pontifex MG, Crost EH, Vaux L, Perez Santamarina E, Goldson A, Brion A, Hajihosseini MK, Vauzour D, Savva GM, and Juge N
- Subjects
- Animals, Mice, N-Acetylneuraminic Acid metabolism, Polysaccharides metabolism, Brain metabolism, Clostridiales, Gastrointestinal Microbiome, Mucins metabolism
- Abstract
Ruminococcus gnavus is a prevalent member of the human gut microbiota, which is over-represented in inflammatory bowel disease and neurological disorders. We previously showed that the ability of R. gnavus to forage on mucins is strain-dependent and associated with sialic acid metabolism. Here, we showed that mice monocolonized with R. gnavus ATCC 29149 ( Rg -mice) display changes in major sialic acid derivatives in their cecum content, blood, and brain, which is accompanied by a significant decrease in the percentage of sialylated residues in intestinal mucins relative to germ-free (GF) mice. Changes in metabolites associated with brain function such as tryptamine, indolacetate, and trimethylamine N -oxide were also detected in the cecal content of Rg -mice when compared to GF mice. Next, we investigated the effect of R. gnavus monocolonization on hippocampus cell proliferation and behavior. We observed a significant decrease of PSA-NCAM immunoreactive granule cells in the dentate gyrus (DG) of Rg -mice as compared to GF mice and recruitment of phagocytic microglia in the vicinity. Behavioral assessments suggested an improvement of the spatial working memory in Rg -mice but no change in other cognitive functions. These results were also supported by a significant upregulation of genes involved in proliferation and neuroplasticity. Collectively, these data provide first insights into how R. gnavus metabolites may influence brain regulation and function through modulation of granule cell development and synaptic plasticity in the adult hippocampus. This work has implications for further understanding the mechanisms underpinning the role of R. gnavus in neurological disorders.
- Published
- 2022
- Full Text
- View/download PDF
10. The human gut symbiont Ruminococcus gnavus shows specificity to blood group A antigen during mucin glycan foraging: Implication for niche colonisation in the gastrointestinal tract.
- Author
-
Wu H, Crost EH, Owen CD, van Bakel W, Martínez Gascueña A, Latousakis D, Hicks T, Walpole S, Urbanowicz PA, Ndeh D, Monaco S, Sánchez Salom L, Griffiths R, Reynolds RS, Colvile A, Spencer DIR, Walsh M, Angulo J, and Juge N
- Subjects
- ABO Blood-Group System immunology, Blood Group Antigens immunology, Clostridiales genetics, Clostridiales physiology, Gastrointestinal Microbiome, Gastrointestinal Tract, Glycoside Hydrolases metabolism, Humans, Mucins metabolism, Oligosaccharides metabolism, Polysaccharides metabolism, Ruminococcus genetics, Ruminococcus metabolism, Substrate Specificity, Tandem Mass Spectrometry methods, Clostridiales metabolism, Mucin-1 metabolism
- Abstract
The human gut symbiont Ruminococcus gnavus displays strain-specific repertoires of glycoside hydrolases (GHs) contributing to its spatial location in the gut. Sequence similarity network analysis identified strain-specific differences in blood-group endo-β-1,4-galactosidase belonging to the GH98 family. We determined the substrate and linkage specificities of GH98 from R. gnavus ATCC 29149, RgGH98, against a range of defined oligosaccharides and glycoconjugates including mucin. We showed by HPAEC-PAD and LC-FD-MS/MS that RgGH98 is specific for blood group A tetrasaccharide type II (BgA II). Isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR confirmed RgGH98 affinity for blood group A over blood group B and H antigens. The molecular basis of RgGH98 strict specificity was further investigated using a combination of glycan microarrays, site-directed mutagenesis, and X-ray crystallography. The crystal structures of RgGH98 in complex with BgA trisaccharide (BgAtri) and of RgGH98 E411A with BgA II revealed a dedicated hydrogen network of residues, which were shown by site-directed mutagenesis to be critical to the recognition of the BgA epitope. We demonstrated experimentally that RgGH98 is part of an operon of 10 genes that is overexpresssed in vitro when R. gnavus ATCC 29149 is grown on mucin as sole carbon source as shown by RNAseq analysis and RT-qPCR confirmed RgGH98 expression on BgA II growth. Using MALDI-ToF MS, we showed that RgGH98 releases BgAtri from mucin and that pretreatment of mucin with RgGH98 confered R. gnavus E1 the ability to grow, by enabling the E1 strain to metabolise BgAtri and access the underlying mucin glycan chain. These data further support that the GH repertoire of R. gnavus strains enable them to colonise different nutritional niches in the human gut and has potential applications in diagnostic and therapeutics against infection., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.