Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy

Tang, Ruqi; Wei, Yiran; Li, Yanmei; Chen, Weihua; Chen, Haoyan; Wang, Qixia; Yang, Fan; Miao, Qi; Xiao, Xiao; Zhang, Haiyan; Lian, Min; Jiang, Xiang; Zhang, Jun; Cao, Qing; Fan, Zhimin; Wu, Maoying; Qiu, Dekai; Fang, Jing‐Yuan; Ansari, Aftab A.; Gershwin, M. Eric; Ma, Xiong

doi:10.1136/gutjnl-2016-313332

Cited by 351 publications

(350 citation statements)

References 44 publications

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“…In their study, Lv et al observed that early stage PBC patients had reductions of several potentially beneficial gut microbiota (such as Acidobacteria, Lachnobacterium sp, etc), and the enrichment of some opportunistic pathogens (such as γ‐Proteobacteria, Enterobacteriaceae, etc) . Tang and co‐workers observed reduced species richness and a lower level of microbial diversity in patients with PBC and partial restoration of these changes after UDCA treatment . However, these investigators did not report gut microbiota in relation to pruritus associated with PBC.…”

Section: Discussionmentioning

confidence: 96%

Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus

Hegade

Pechlivanis

McDonald

et al. 2019

Liver International

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Background and Aims Pruritus is a common symptom in patients with primary biliary cholangitis (PBC) for which ileal bile acid transporter (IBAT) inhibition is emerging as a potential therapy. We explored the serum metabonome and gut microbiota profile in PBC patients with pruritus and investigated the effect of GSK2330672, an IBAT inhibitor. Methods We studied fasting serum bile acids (BAs), autotaxin and faecal microbiota in 22 PBC patients with pruritus at baseline and after 2 weeks of GSK2330672 treatment. Control group included 31 asymptomatic PBC patients and 18 healthy volunteers. BA profiling was done by ultra performance liquid chromatography coupled to a mass spectrometry (UPLC‐MS). Faecal microbiomes were analysed by 16S ribosomal RNA gene sequencing. Results In PBC patients with pruritus, serum levels of total and glyco‐conjugated primary BAs and autotaxin were significantly elevated. Autotaxin activity correlated significantly with tauro‐ and glyco‐conjugated cholic acid (CA) and chenodeoxycholic acid (CDCA), both at baseline and after GSK2330672. GSK2330672 significantly reduced autotaxin and all tauro‐ and glyco‐ conjugated BAs and increased faecal levels of CA (P = 0.048) and CDCA (P = 0.027). Gut microbiota of PBC patients with pruritus was similar to control groups. GSK2330672 increased the relative abundance of Firmicutes (P = 0.033) and Clostridia (P = 0.04) and decreased Bacteroidetes (P = 0.033) and Bacteroidia (P = 0.04). Conclusions Pruritus in PBC does not show a distinct gut bacterial profile but is associated with elevated serum bile acid and autotaxin levels which decrease after IBAT inhibition. In cholestatic pruritus, a complex interplay between BAs and autotaxin is likely and may be modified by IBAT inhibition.

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Section: Discussionmentioning

confidence: 96%

Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus

Hegade

Pechlivanis

McDonald

et al. 2019

Liver International

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“…26 Individual variation in Gammaproteobacteria has been directly linked with susceptibility to fatty liver disease. 12,30 This indicates that these alterations might be rather unspecific features of chronic liver disease. 28,29 For eight taxa across different taxonomic levels we demonstrated a consistently increased abundance in patients with PSC.…”

Section: Diet Has Minor Impact On Microbial Community Alterations Imentioning

confidence: 99%

“…Both genera comprise butyrate-producing species, which provide an important energy source for intestinal epithelia and display an array of beneficial immunological properties 33. This finding further underlines its potential importance for the understanding of the pathophysiology and development of novel therapeutic approaches in inflammatory intestinal and liver diseases, where depletion of Faecalibacterium is a frequently observed common trait 11,30. This finding further underlines its potential importance for the understanding of the pathophysiology and development of novel therapeutic approaches in inflammatory intestinal and liver diseases, where depletion of Faecalibacterium is a frequently observed common trait 11,30.…”

mentioning

confidence: 96%

Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis

Rühlemann¹,

Liwinski²,

Heinsen³

et al. 2019

Aliment Pharmacol Ther

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Summary Background Single‐centre studies reported alterations of faecal microbiota in patients with primary sclerosing cholangitis (PSC). As regional factors may affect microbial communities, it is unclear if a microbial signature of PSC exists across different geographical regions. Aim To identify a robust microbial signature of PSC independent of geography and environmental influences. Methods We included 388 individuals (median age, 47 years; range, 15‐78) from Germany and Norway in the study, 137 patients with PSC (n = 75 with colitis), 118 with ulcerative colitis (UC) and 133 healthy controls. Faecal microbiomes were analysed by 16S rRNA gene sequencing (V1‐V2). Differences in relative abundances of single taxa were subjected to a meta‐analysis. Results In both cohorts, microbiota composition (beta‐diversity) differed between PSC patients and controls (P < 0.001). Random forests classification discriminated PSC patients from controls in both geographical cohorts with an average area under the curve of 0.88. Compared to healthy controls, many new cohort‐spanning alterations were identified in PSC, such as an increase of Proteobacteria and the bile‐tolerant genus Parabacteroides, which were detected independent from geographical region. Associated colitis only had minor effects on microbiota composition, suggesting that PSC itself drives the faecal microbiota changes observed. Conclusion Compared to healthy controls, numerous microbiota alterations are reproducible in PSC patients across geographical regions, clearly pointing towards a microbiota composition that is shaped by the disease itself and not by environmental factors. These reproducibly altered microbial populations might provide future insights into the pathophysiology of PSC.

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“…In a recent study, a reduction in several potentially beneficial microbes and an enrichment in several opportunistic pathogens was observed in the GM of early‐stage PBC patients . Another paper reported that an observed reduction in species richness and a significant shift in the overall microbial diversity in PBC patients could be partially ameliorated after ursodeoxycholic acid (UDCA) treatment . Taken together, it is clear that the GM is directly involved in the pathogenesis of autoimmune cholestatic liver diseases.…”

Section: Gut Microbiome and Bas In Liver Diseasesmentioning

confidence: 96%

“…104 Another paper reported that an observed reduction in species richness and a significant shift in the overall microbial diversity in PBC patients could be partially ameliorated after ursodeoxycholic acid (UDCA) treatment. 105 Taken together, it is clear that the GM is directly involved in the pathogenesis of autoimmune cholestatic liver diseases. Targeting this cross-talk between BAs and GM could offer exciting new perspectives for the treatment of cholestatic liver diseases like PSC and PBC.…”

Section: Autoimmune Liver Diseasesmentioning

confidence: 99%

Reciprocal interactions between bile acids and gut microbiota in human liver diseases

Ikegami

Honda

2018

Hepatology Research

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The gut microbiota (GM) play a central role in their host's metabolism of bile acids (BAs) by regulating deconjugation, dehydroxylation, dehydrogenation, and epimerization reactions to generate unconjugated free BAs and secondary BAs. These BAs generated by the GM are potent signaling molecules that interact with BA receptors, such as the farnesoid X receptor and Takeda G-protein-coupled receptor 5. Each BA has a differential affinity to these receptors; therefore, alterations in BA composition by GM could modify the intensity of receptor signaling. Bile acids also act as antimicrobial agents by damaging bacterial membranes and as detergents by altering intracellular macromolecular structures. Therefore, BAs and the GM reciprocally control each other's compositions. In this review, we discuss the latest findings on the mutual effects of BAs and GM on each other; we also describe their roles in the pathophysiology of liver disease progression and potential therapeutic applications of targeting this cross-talk.

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Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy

Abstract: This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

Cited by 351 publications

References 44 publications

Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus

Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus

Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis

Reciprocal interactions between bile acids and gut microbiota in human liver diseases

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