Ileal mucosa-associated microbiota overgrowth associated with pathogenesis of primary biliary cholangitis

Shogo Kitahata,Yoshio Tokumoto,Yoshiou Ikeda,Yasunori Yamamoto,Teru Kumagi,Eiji Takeshita,Shinya Furukawa,Yoichi Hiasa,Tomoe Kawamura,Masanori Abe,Osamu Yoshida,Masashi Hirooka

doi:10.1038/s41598-021-99314-9

Shogo Kitahata, Yoshio Tokumoto + Show 10 more

Open Access

https://doi.org/10.1038/s41598-021-99314-9

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Journal: Scientific Reports	Publication Date: Oct 5, 2021
Citations: 11	License type: open-access

Affiliation: Ehime University, Ehime University Hospital

Abstract

The small intestinal mucosa-associated microbiota (MAM) can potentially impact the etiology of primary biliary cholangitis (PBC). Herein, we investigate the MAM profile to determine its association with liver pathology in patients with PBC. Thirty-four patients with PBC and 21 healthy controls who underwent colonoscopy at our hospital were enrolled in our study. We performed 16S ribosomal RNA gene sequencing of MAM samples obtained from the mucosa of the terminal ileum and examined the relationship between the abundance of ileal MAM and chronic nonsuppurative destructive cholangitis using liver specimens from patients with PBC. There was a significant reduction in microbial diversity within individuals with PBC (P = 0.039). Dysbiosis of ileal MAM was observed in patients with PBC, with a characteristic overgrowth of Sphingomonadaceae and Pseudomonas. Multivariate analysis showed that the overgrowth of Sphingomonadaceae and Pseudomonas is an independent association factor for PBC (P = 0.0429, P = 0.026). Moreover, the abundance of Sphingomonadaceae was associated with chronic nonsuppurative destructive cholangitis in PBC (P = 0.00981). The overgrowth of Sphingomonadaceae and Pseudomonas in ileal MAM was found in patients with PBC. Sphingomonadaceae may be associated with the pathological development of PBC.

Highlights

The small intestinal mucosa-associated microbiota (MAM) can potentially impact the etiology of primary biliary cholangitis (PBC)
The levels of γ-glutamyl transpeptidase, alkaline phosphatase (ALP), total bile acid, and immunoglobulin M were higher in patients with PBC than in those of the healthy controls (HCs)
We evaluated the relative abundance of Sphingomonadaceae and Pseudomonas in 27 patients who had undergone liver biopsy to investigate whether these bacteria are associated with the pathology of PBC

Summary

Introduction

The small intestinal mucosa-associated microbiota (MAM) can potentially impact the etiology of primary biliary cholangitis (PBC). We investigate the MAM profile to determine its association with liver pathology in patients with PBC. Primary biliary cholangitis (PBC) is a chronic liver disease resulting from progressive, immune-mediated destruction of the small interlobular bile ducts. It leads to progressive intrahepatic cholestasis and eventually fibrosis and cirrhosis of the liver[1,2]. Fecal microbiota profiles of patients with PBC have a significant reduction in microbial diversity compared with healthy controls (HCs), suggesting gut microbiota as a potential therapeutic target and diagnostic biomarker for PBC10,11.

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