Gut Microbiota Dysbiosis and Chronic Intestinal Inflammation

Abstract Background Host tp53 mutations are frequently found during the early stages of colitis-associated colorectal cancer (CAC), but whether such mutations induce gut microbiota dysbiosis and chronic intestinal inflammation that contributes to the development of CAC, remains unknown. Results We found that zebrafish tp53 mutant larvae exhibited elevated intestinal inflammation, by monitoring the NFκB activity in the mid-distal intestines of zebrafish larvae using an NFκB:EGFP transgenic reporter line in vivo as well as neutrophil infiltration into the intestine. This inflammation was due to dysbiotic gut microbiota with reduced diversity, revealed using both 16S rRNA amplicon sequencing and a germfree larva model. In this dysbiosis, Aeromonas spp. were aberrantly enriched as major pathobionts and exhibited the capacity for aggressive colonization in tp53 mutants. Importantly, the ex-germfree experiments supported the causality of the host tp53 mutation for inducing the inflammation. Transcriptome and high-performance liquid chromatography analyses of the host gastrointestinal tracts identified dysregulated sialic acid (SA) metabolism concomitant with increased host Neu5Gc levels as the key determinant of aberrant inflammation, which was reversed by the sialidase inhibitors oseltamivir and Philippin A. Conclusions These results demonstrate a crucial role for host tp53 in maintaining symbiosis and immune homeostasis via SA metabolism. Disturbed SA metabolism via a tp53 mutation may be exploited by specific elements of the gut microbiome, eliciting both dysbiosis and inflammation. Manipulating sialometabolism may therefore provide an efficacious therapeutic strategy for tp53 mutation-induced dysbiosis, inflammation, and ultimately, related cancers.

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Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽

10.3390/cells8060517 ◽

2019 ◽

Vol 8 (6) ◽

pp. 517 ◽

Cited By ~ 12

Author(s):

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Angeli Dominique Macandog ◽

Angelica Diaz-Basabe ◽

Fulvia Milena Cribiù ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Immune Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

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Protective effect and mechanism of Monascus-fermented red yeast rice against colitis caused by Salmonella enterica serotype Typhimurium ATCC 14028

Food & Function ◽

10.1039/d0fo01017k ◽

2020 ◽

Vol 11 (7) ◽

pp. 6363-6375

Author(s):

Ya-ping Huang ◽

Ping Li ◽

Ting Du ◽

Xin-jun Du ◽

Shuo Wang

Keyword(s):

Gut Microbiota ◽

Protective Effect ◽

Salmonella Enterica ◽

Intestinal Inflammation ◽

Underlying Mechanism ◽

Red Yeast Rice ◽

Red Yeast ◽

Gut Microbiota Dysbiosis

The effect of red yeast rice on Salmonella enterica-induced intestinal inflammation and gut microbiota dysbiosis in mice as well as the underlying mechanism.

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Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis

10.1101/2021.08.24.21262265 ◽

2021 ◽

Author(s):

Ryan Marsh ◽

Helen Gavillet ◽

Liam Hanson ◽

Christabella Ng ◽

Mandisa Mitchell-Whyte ◽

...

Keyword(s):

Cystic Fibrosis ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Age Groups ◽

Gastrointestinal Symptoms ◽

List Type ◽

Microbiota Composition ◽

Community Function ◽

Gut Function ◽

Gut Microbiota Dysbiosis

AbstractBackgroundMost people with cystic fibrosis (pwCF) suffer from gastrointestinal symptoms and are at risk of gut complications. Gut microbiota dysbiosis is apparent within the CF population across all age groups, with evidence linking dysbiosis to intestinal inflammation and other markers of health. This pilot study aimed to investigate the potential relationships between the gut microbiota and gastrointestinal physiology, transit, and health.Study DesignFaecal samples from 10 pwCF and matched controls were subject to 16S rRNA sequencing. Results were combined with clinical metadata and MRI metrics of gut function to investigate relationships.ResultspwCF had significantly reduced microbiota diversity compared to controls. Microbiota compositions were significantly different, suggesting remodelling of core and rarer satellite taxa in CF. Dissimilarity between groups was driven by a variety of taxa, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. The core taxa were explained primarily by CF disease, whilst the satellite taxa were associated with pulmonary antibiotic usage, CF disease, and gut function metrics. Species-specific ordination biplots revealed relationships between taxa and the clinical or MRI-based variables observed.ConclusionsAlterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa. Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon.HighlightsFaecal microbiota significantly differs between pwCF and healthy controlsKey SCFA producers contributed to microbiota dissimilarity between groupsPulmonary antibiotic treatment heavily impacted gut microbiotaIntestinal physiology and transit impacted satellite microbiota composition

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Dietary Composition and Effects in Inflammatory Bowel Disease

Nutrients ◽

10.3390/nu11061398 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1398 ◽

Cited By ~ 2

Author(s):

Fernando Castro ◽

Heitor S. P. de Souza

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Dietary Habits ◽

Intestinal Inflammation ◽

Dietary Factors ◽

Food Components ◽

Increased Risk ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.

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Chronic cereulide exposure causes intestinal inflammation and gut microbiota dysbiosis in mice

Environmental Pollution ◽

10.1016/j.envpol.2021.117814 ◽

2021 ◽

pp. 117814

Author(s):

Ruqin Lin ◽

Danyang Li ◽

Yangyang Xu ◽

Mengyao Wei ◽

Qingmei Chen ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Gut Microbiota Dysbiosis

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DIETARY FIBER DEPRIVATION QUELLS COLONIC INFLAMMATION BY TARGETING GUT PATHOBIONTS IN A NEW MODEL OF CROHN’S DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.097 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S39-S39

Author(s):

Roberta Caruso ◽

Peter Kuffa ◽

Naohiro Inohara ◽

Gabriel Nunez

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

Dietary Intervention ◽

Intestinal Inflammation ◽

Mucosal Immune Response ◽

Inflammatory Disorder ◽

Mucus Layer ◽

Experimental Conditions ◽

Chronic Intestinal Inflammation

Abstract Crohn’s disease (CD) is a chronic intestinal inflammatory disorder that results from a dysregulated mucosal immune response to symbiotic bacteria in genetically susceptible individuals. While genetic predispositions to CD have been well documented, the overall contribution of genetic factors to disease development remains unclear. Indeed, abnormal interactions between microbes and the immune system have been identified as the core defect leading to chronic intestinal inflammation. We used a “multi-hit” genetic approach to study the complex interplay between host immunity and microbes in the context of CD. We have found that the combined deficiency of NOD2 and phagocyte NADPH oxidase (i.e. CYBB), two CD susceptibility genes, triggers microbiota-dependent and spontaneous TH1-type colitis in mice that is accompanied by the pathological hallmarks seen in CD patients. Disease was induced by Mucispirillum schaedleri, a gram-negative mucus-dwelling anaerobe. The absence of the two anti-microbial genes (i.e. NOD2 and CYBB) resulted in a marked accumulation of M. schaedleri in the gut lumen, the colonic mucus layer and ultimately a focal penetration of the intestinal wall. Accumulation of M. schaedleri was associated with impaired recruitment of neutrophils in the intestine and subsequently inefficient elimination of the bacterium. Among the environmental factors associated with CD, diet shapes the composition of the gut microbiota and can be used to manage disease symptoms. Our experiments have shown that consumption of a fiber-free diet leads to a depletion of the colonic mucus layer and increased proximity between microbes and the gut epithelium. Interestingly, these experimental conditions are effective at inhibiting intestinal inflammation observed in our model of CD-like colitis when used both as a preventive and as a therapeutic approach. In addition to shaping the overall gut microbiota composition, this dietary intervention specifically alters the abundance and/or localization of the disease-causing M. schaedleri in the double mutant mice. Our results provide direct evidence that a specific intestinal microbe can, in conjunction with impaired bacterial clearance, trigger CD-like disease. Our results also indicate that dietary approaches can be successfully used to target microbial-driven intestinal pathology.

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