Gut Microbiota-Mediated Pleiotropic Effects of Fucose Can Improve Inflammatory Bowel Disease by Modulating Bile Acid Metabolism and Enhancing Propionate Production

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid–gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.

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Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease

Microbiome ◽

10.1186/s40168-019-0689-3 ◽

2019 ◽

Vol 7 (1) ◽

Cited By ~ 32

Author(s):

Almut Heinken ◽

Dmitry A. Ravcheev ◽

Federico Baldini ◽

Laurent Heirendt ◽

Ronan M. T. Fleming ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bile Acid ◽

Bowel Disease ◽

Acid Metabolism ◽

Bile Acid Metabolism ◽

Secondary Bile Acid ◽

Gut Microbes ◽

Systematic Assessment ◽

Inflammatory Bowel

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A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa021 ◽

2020 ◽

Vol 14 (7) ◽

pp. 935-947 ◽

Cited By ~ 7

Author(s):

Mohammed Nabil Quraishi ◽

Animesh Acharjee ◽

Andrew D Beggs ◽

Richard Horniblow ◽

Chris Tselepis ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Bowel Disease ◽

Bile Acid ◽

Gut Microbiota ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

16S Rrna Analysis ◽

Immune Infiltration ◽

Inflammatory Bowel

Abstract Background Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data. Methods Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration. Results The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD. Conclusions Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.

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Alterations in Bile Acid Metabolism Associated With Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa342 ◽

2021 ◽

Author(s):

Na Li ◽

Shukai Zhan ◽

Zhenyi Tian ◽

Caiguang Liu ◽

Zonglin Xie ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Gut Microbiota ◽

Bowel Disease ◽

Patient Characteristics ◽

Bile Acid Metabolism ◽

Inflammatory Disorder ◽

Sample Type ◽

Fecal Samples ◽

Inflammatory Processes ◽

Inflammatory Bowel

Abstract Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder closely related to gut dysbiosis, which is associated with alterations in an important bacterial metabolite, bile acids (BAs). Although certain findings pertinent to BA changes in IBD vary among studies owing to the differences in sample type, quantitated BA species, study methodology, and patient characteristics, a specific trend concerning variations of BAs in IBD has been identified. In elaborating on this observation, it was noted that primary BAs and conjugated BAs are augmented in fecal samples but there is a reduction in secondary BAs in fecal samples. It is not entirely clear why patients with IBD manifest these changes and what role these changes play in the onset and development of IBD. Previous studies have shown that IBD-associated BA changes may be caused by alterations in BA absorption, synthesis, and bacterial modification. The complex relationship between bacteria and BAs may provide additional and deeper insight into host-gut microbiota interactions in the pathogenesis of IBD. The characteristic BA changes may generate profound effects in patients with IBD by shaping the gut microbiota community, affecting inflammatory processes, causing BA malabsorption associated with diarrhea, and even leading to intestinal dysplasia and cancer. Thus, therapeutic strategies correcting the alterations in the composition of BAs, including the elimination of excess BAs and the supplementation of deficient BAs, may prove promising in IBD.

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The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease

United European Gastroenterology Journal ◽

10.1177/2050640617708953 ◽

2017 ◽

Vol 6 (1) ◽

pp. 112-122 ◽

Cited By ~ 23

Author(s):

J Torres ◽

C Palmela ◽

H Brito ◽

X Bao ◽

H Ruiqi ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bile Acid ◽

Gut Microbiota ◽

Bile Acids ◽

Primary Sclerosing Cholangitis ◽

Bowel Disease ◽

Sclerosing Cholangitis ◽

Colorectal Neoplasia ◽

Bile Acid Pool ◽

Inflammatory Bowel

Background Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

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Bile Acid Signaling in Inflammatory Bowel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22169096 ◽

2021 ◽

Vol 22 (16) ◽

pp. 9096

Author(s):

Mariusz A. Bromke ◽

Małgorzata Krzystek-Korpacka

Keyword(s):

Inflammatory Bowel Disease ◽

Immune System ◽

Bile Acid ◽

Bile Acids ◽

Bowel Disease ◽

Gut Microbiome ◽

Physiological Role ◽

Membrane Receptors ◽

Bile Acid Metabolism ◽

Inflammatory Bowel

Inflammatory bowel disease is a chronic, idiopathic and complex condition, which most often manifests itself in the form of ulcerative colitis or Crohn’s disease. Both forms are associated with dysregulation of the mucosal immune system, compromised intestinal epithelial barrier, and dysbiosis of the gut microbiome. It has been observed for a long time that bile acids are involved in inflammatory disorders, and recent studies show their significant physiological role, reaching far beyond being emulsifiers helping in digestion of lipids. Bile acids are also signaling molecules, which act, among other things, on lipid metabolism and immune responses, through several nuclear and membrane receptors in hepatocytes, enterocytes and cells of the immune system. Gut microbiota homeostasis also seems to be affected, directly and indirectly, by bile acid metabolism and signaling. This review summarizes recent advances in the field of bile acid signaling, studies of inflamed gut microbiome, and the therapeutic potential of bile acids in the context of inflammatory bowel disease.

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