Hyaluronan-induced alterations of the gut microbiome protects mice against Citrobacter rodentium infection and intestinal inflammation

AbstractThe gut microbiota is emerging as an important modulator of neurodegenerative diseases, and accumulating evidence has linked gut microbes to Parkinson’s disease (PD) symptomatology and pathophysiology. PD is often preceded by gastrointestinal symptoms and alterations of the enteric nervous system accompany the disease. Several studies have analyzed the gut microbiome in PD, but a consensus on the features of the PD-specific microbiota is missing. Here, we conduct a meta-analysis re-analyzing the ten currently available 16S microbiome datasets to investigate whether common alterations in the gut microbiota of PD patients exist across cohorts. We found significant alterations in the PD-associated microbiome, which are robust to study-specific technical heterogeneities, although differences in microbiome structure between PD and controls are small. Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, both important short-chain fatty acids producers, emerged as the most consistent PD gut microbiome alterations. This dysbiosis might result in a pro-inflammatory status which could be linked to the recurrent gastrointestinal symptoms affecting PD patients.

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The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis

Nutrients ◽

10.3390/nu13061780 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1780

Author(s):

Jean-Frédéric LeBlanc ◽

Jonathan P. Segal ◽

Lucia Maria de Campos Braz ◽

Ailsa L. Hart

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Faecal Microbiota ◽

Dietary Interventions ◽

Therapeutic Landscape ◽

Microbiome Diversity ◽

Inflammatory Bowel

The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem’s importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.

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An interventional Soylent diet increases the Bacteroidetes to Firmicutes ratio in human gut microbiome communities: a randomized controlled trial

10.1101/200881 ◽

2017 ◽

Cited By ~ 1

Author(s):

Ryan H. Hsu ◽

Dylan M. McCormick ◽

Mitchell J. Seitz ◽

Lauren M. Lui ◽

Harneet S. Rishi ◽

...

Keyword(s):

Gut Microbiome ◽

Intestinal Inflammation ◽

Controlled Trial ◽

Alpha Diversity ◽

Diet Group ◽

Positive Health ◽

Unifrac Distance ◽

Liquid Meal ◽

Regular Diet ◽

Rdna Sequencing

AbstractOur knowledge of the relationship between the gut microbiome and health has rapidly expanded in recent years. Diet has been shown to have causative effects on microbiome composition, which can have subsequent implications on health. Soylent 2.0 is a liquid meal replacement drink that satisfies nearly 20% of all recommended daily intakes per serving. This study aims to characterize the changes in gut microbiota composition resulting from a short-term Soylent diet. Fourteen participants were separated into two groups: 5 in the regular diet group and 9 in the Soylent diet group. The regular diet group maintained a diet closely resembling self-reported regular diets. The Soylent diet group underwent three dietary phases: A) a regular diet for 2 days, B) a Soylent-only diet (five servings of Soylent daily and water as needed) for 4 days, and C) a regular diet for 4 days. Daily logs self-reporting diet, Bristol stool ratings, and any abdominal discomfort were electronically submitted. Eight fecal samples per participant were collected using fecal sampling kits, which were subsequently sent to uBiome, Inc. for sample processing and V4 16S rDNA sequencing. Reads were clustered into operational taxonomic units (OTUs) and taxonomically identified against the GreenGenes 16S database. We find that an individual’s alpha-diversity is not significantly altered during a Soylent-only diet. In addition, principal coordinate analysis using the unweighted UniFrac distance metric shows samples cluster strongly by individual and not by dietary phase. Among Soylent dieters, we find a significant increase in the ratio of Bacteroidetes to Firmicutes abundance, which is associated with several positive health outcomes, including reduced risks of obesity and intestinal inflammation.

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Interleukin‐17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin‐25–Driven Intestinal Inflammation

Arthritis & Rheumatology ◽

10.1002/art.41169 ◽

2020 ◽

Vol 72 (4) ◽

pp. 645-657 ◽

Cited By ~ 8

Author(s):

Julia Manasson ◽

David S. Wallach ◽

Giuliana Guggino ◽

Matthew Stapylton ◽

Michelle H. Badri ◽

...

Keyword(s):

Gut Microbiome ◽

Intestinal Inflammation ◽

Interleukin 17 ◽

Interleukin 25

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The Essential Role of Selenoproteins in the Resolution of Citrobacter rodentium-Induced Intestinal Inflammation

Frontiers in Nutrition ◽

10.3389/fnut.2020.00096 ◽

2020 ◽

Vol 7 ◽

Author(s):

Shaneice K. Nettleford ◽

Luming Zhao ◽

Fenghua Qian ◽

Morgan Herold ◽

Brooke Arner ◽

...

Keyword(s):

Essential Role ◽

Intestinal Inflammation ◽

Citrobacter Rodentium

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A52 BUTYRATE SUPPLEMENTATION AMELIORATES DAMAGE CAUSED BY ENTERIC CITROBACTER RODENTIUM INFECTION

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.051 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 61-62

Author(s):

L S Celiberto ◽

G Healey ◽

J Xu ◽

L Xia ◽

B Vallance

Keyword(s):

Butyric Acid ◽

Tissue Damage ◽

Intestinal Inflammation ◽

Bacterial Colonization ◽

Clinical Signs ◽

Host Susceptibility ◽

Mucus Layer ◽

Citrobacter Rodentium ◽

Oral Gavage ◽

Intestinal Mucus

Abstract Background Patients with inflammatory bowel disease (IBD) often display a dysbiotic microbiome as well as a defective intestinal mucus layer, which appears thinner and more penetrable than the mucus layer of healthy subjects. Tributyrin (TB), a prodrug of butyric acid, has shown beneficial effects in models of IBD due to its anti-inflammatory effects. We previously showed that mice lacking the major intestinal mucin Muc2 (Muc2-/-) or lacking the “Core1” enzyme responsible for glycosylating Muc2 (C1galt1-/-) were highly susceptible to infection by Citrobacter rodentium, a murine model of intestinal inflammation. Aims The study explored the role of gut mucus in providing host defense against C. rodentium, as well as the effects of TB supplementation in the prevention of mucosal damage in this model. Methods Six to ten week old wildtype (WT), Muc2-/-, flox control (C1galt1f/f) and C1galt1-/- mice were infected with C. rodentium (∼2.5 × 108 CFU) by oral gavage. For TB supplementation experiments, mice received 100µL of TB or glycerol as a control by oral gavage every other day starting on day 1 post infection. Mice were monitored daily throughout the experiment and were euthanized at day 6 of infection. Several tissues of interest were collected to verify bacterial colonization in the gut and at systemic sites as well as histological tissue damage. Cecal contents were collected for the analysis of short chain fatty acids, while blood was collected by cardiac puncture after oral gavage with FITC-dextran to measure intestinal permeability. Results While WT and C1galt1f/f mice were only modestly susceptible to C. rodentium infection, Muc2-/- and C1galt1-/- mice displayed dramatically (100 fold) increased pathogen burdens, significantly greater intestinal macroscopic and histopathology scores, and heightened barrier disruption as compared to controls. Moreover, Muc2-/- and C1galt1-/- mice showed significantly lower levels of butyric acid as compared to control mice under baseline conditions. Interestingly, when supplemented with TB, Muc2-/- and C1galt1-/- proved less susceptible to C. rodentium infection, as indicated by reduced weight loss and clinical signs of colitis, while pathogen burdens were greatly reduced as was histological tissue damage, and epithelial barrier dysfunction. The same protection was conferred when TB was administered as a dietary supplementation, thus confirming its beneficial effect in protecting mice against C. rodentium infection. Conclusions These findings demonstrate that intestinal mucus controls host susceptibility to C. rodentium infection via control over butyrate levels, and highlight the need to explore the mechanisms by which gut mucus modulates the resident microbiota and its metabolites. Funding Agencies CCC, CIHR

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Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease

Microbiome ◽

10.1186/s40168-021-01135-5 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Grégoire Chevalier ◽

Arnaud Laveissière ◽

Guillaume Desachy ◽

Nicolas Barnich ◽

Adeline Sivignon ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiome ◽

Bacterial Adhesion ◽

Intestinal Inflammation ◽

Mucosal Inflammation ◽

Intestinal Epithelial ◽

E Coli ◽

Promising Therapeutic Approach ◽

Activity Dependent

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.

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Molecular and Microbial Signatures Predictive of Prebiotic Action of Neoagarotetraose in a Dextran Sulfate Sodium-Induced Murine Colitis Model

Microorganisms ◽

10.3390/microorganisms8070995 ◽

2020 ◽

Vol 8 (7) ◽

pp. 995

Author(s):

Fang Liu ◽

Jianan Liu ◽

Thomas T.Y. Wang ◽

Zhen Liu ◽

Changhu Xue ◽

...

Keyword(s):

Gut Microbiome ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Intestinal Inflammation ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Murine Colitis ◽

Bioactive Properties ◽

Rrna Gene Sequencing ◽

Colitis Model

Neoagarotetraose (NT), a hydrolytic product of agar by β-agarase, is known to possess bioactive properties. However, the mechanisms via which NT alleviates intestinal inflammation remain unknown. In this study, a dextran sulfate sodium (DSS)-induced murine model was developed to evaluate the effect of NT on gut microbiome and microbial metabolism using 16S rRNA gene sequencing and untargeted metabolomics. Our data demonstrate that NT ingestion improved gut integrity and inflammation scores. NT reversed the abundance of Proteobacteria from an elevated level induced by DSS and significantly increased the abundance of Verrucomicrobia. Further, NT significantly increased the abundance of Akkermansia and Lactobacillus and concomitantly decreased that of Sutterella, which were among the important features identified by random forests analysis contributing to classification accuracy for NT supplementation. A microbial signature consisting of Adlercreutzia (denominator) and Turicibacter (numerator) predicted the NT supplementation status. Moreover, NT significantly modulated multiple gut metabolites, particularly those related to histidine, polyamine and tocopherol metabolism. Together, our findings provided novel insights into the mechanisms by which NT modulated the gut microbiome and metabolome and should facilitate the development of NT as a potent prebiotic for colitis management.

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