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

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.

Ileal Mucosa-Associated Microbiota Overgrowth Associated with Diagnosis and Pathogenesis of Primary Biliary Cholangitis

Background The gut microbiota has potential implications in the pathogenesis of primary biliary cholangitis (PBC). However, little is known about the significance of small intestinal mucosa-associated microbiota (MAM) in PBC. We aimed to investigate the ileal MAM profile and identify its association with liver pathology in patients with PBC. Methods Forty-three patients with PBC and 24 healthy controls who underwent colonoscopy at our hospital between March 2018 and January 2020 were enrolled in a cross-sectional study. We performed 16S ribosomal RNA gene sequencing of MAM samples obtained from the mucosa of the terminal ileum of all subjects. We also examined the relationship between the abundance of ileal MAM and chronic nonsuppurative destructive cholangitis using liver specimens from patients with PBC. Results 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. Moreover, the abundance of Sphingomonadaceae was associated with chronic nonsuppurative destructive cholangitis in PBC. Conclusions Overgrowth of Sphingomonadaceae and Pseudomonas in ileal MAM is an independent association factor for diagnosing PBC. Sphingomonadaceae may be particularly associated with the pathological development of PBC.

Novel Approach to Bile Duct Damage in Primary Biliary Cirrhosis: Participation of Cellular Senescence and Autophagy

Primary biliary cirrhosis (PBC) is characterized by antimitochondrial autoantibodies (AMAs) in patients' sera and histologically by chronic nonsuppurative destructive cholangitis in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. The autoimmune-mediated pathogenesis of bile duct lesions, including the significance of AMAs, triggers of the autoimmune process, and so on remain unclear. We have reported that cellular senescence in biliary epithelial cells (BECs) may be involved in bile duct lesions and that autophagy may precede the process of biliary epithelial senescence in PBC. Interestingly, BECs in damaged bile ducts show characteristicsof cellular senescence and autophagy in PBC. A suspected causative factor of biliary epithelial senescence is oxidative stress. Furthermore, senescent BECs may modulate the microenvironment around bile ducts by expressing various chemokines and cytokines called senescence-associated secretory phenotypes and contribute to the pathogenesis in PBC.

Chronic Lymphocytic Cholangitis in Three Cats

Wedge biopsy of the liver during episodic clinical illness in three male cats showed chronic lymphocytic cholangitis. Principal clinical findings were increased serum alkaline phosphatase activity and hepatomegaly (two cats) associated with anorexia, pyrexia, and weight loss; these signs of illness were intermittent with asymptomatic periods. The hepatic lesions were characterized by lymphoid aggregate or follicle formation, diffusely dispersed lymphocytes and plasma cells, and abnormal bile ducts and ductules. Lymphoid aggregates and diffusely scattered lymphocytes were seen in the pancreas also. The spectrum of hepatic lesions in three cats seemed to represent a progression in the development of the disease. Similarities and dissimilarities between the findings in the three cats and human primary biliary cirrhosis or chronic nonsuppurative destructive cholangitis are discussed. During a prospective search for cats with this disease, other hepatic lesions were found, and it was concluded that cats may be affected by more than one pathogenic mechanism culminating in chronic cholangitis or cholangiohepatitis.