The gut microbial influence on cholestatic liver disease

Abstract

Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.

Adverse Effects of Proton Pump Inhibitors—Evidence and Plausibility

“…The underlying mechanism may be similar to that of HE, SBP, and alcohol-induced liver damage, whereby bacterial overgrowth [116] results in increased portal venous concentrations of several proposed harmful substances, including secondary bile acids [117]. In general, there is considerable interest in the role of intestinal microbiome in the pathogenesis of chronic liver diseases [118] that cannot be reviewed in depth here.…”

Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice

“…The changes described at genera level differ among studies 9–12 and include the enrichment in Veillonella , Akkermansia , Ruminococcaceae (undefined genus) and Clostridium 9 and the decrease in Prevotella 10 , overall supporting the association between changes in the microbiome and cholestatic disease. Few studies have investigated the composition of the microbiome in PBC patients and importantly show some similarities with those observed in PSC 13,14 .…”

“…Recent studies have further supported the association between changes in the microbiome and the progression of cholestatic liver disease in patients 9–14 . Cholestasis occurs when the natural flux of bile acids from the liver to the gut is impaired, mainly as a result of damage in the biliary ducts, causing accumulation of toxic bile acids in the liver that promote cell death, inflammation, fibrogenesis and ultimately cirrhosis and cancer 15 .…”

Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach

“…Therefore, alterations in bile composition may reveal the presence of different hepatobiliary and pancreatic disorders as well as the impairment of enterohepatic circulation [3,4]. Moreover, abnormal bile composition can also contribute to disease progression along the biliary and digestive tracts [3,[5][6][7].…”