The enteric microbiome in hepatobiliary health and disease

Abstract

Increasing evidence points to the contribution of the intestinal microbiome as a potentially key determinant in the initiation and/or progression of hepatobiliary disease. While current understanding of this dynamic is incomplete, exciting insights are continually being made and more are expected given the developments in molecular and high-throughput omics techniques. In this brief review, we provide a practical and updated synopsis of the interaction of the intestinal microbiome with the liver and its downstream impact on the initiation, progression and complications of hepatobiliary disease.

Pathobiology of biliary epithelia

“…Gut-derived bacterial products, such as LPS, activate the inflammatory cascade in immune cells, modulate the function of liver parenchymal cells, and contribute to chronic liver diseases [171,172]. Recently, it was showed that the expression of NLR pyrin domain-containing protein 3 (Nlrp3) inflammasome is increased in reactive cholangiocytes of both in vitro and in vivo models of a PSC, leading to the secretion of IL-18 and alteration of the epithelial barrier function of cholangiocytes with significantly decreased the expression of zonulin-1 and e-cadherin [173].…”

Популяційні Зміни Порожнинної Мікробіоти Товстої Кишки Хворих На Хронічний Вірусний Гепатит С

“…Гепатит С залишається однією з провідних проблем внутрішньолікарняних інфекцій, пов'язаних із гемо-трансфузіями, введенням препаратів крові, медичними інвазивними маніпуляціями з діагностичною та ліку-вальною метою [1,2]. Більше ніж 2 % населення світу заражено цим вірусом.…”

The Microbiome and Immune Regulation After Transplantation

“…PRRs, which include toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs), (3–5) are plasma membrane and/or intracytoplasmic proteins that sense and respond to pathogen-associated molecular patterns (PAMPs) such as microbial lipid, protein and nucleic acid moieties (6) as well as microbial metabolites (eg bile acids, (7) short-chain fatty acids, (8) and phosphatidylcholine. (7, 9) …”

“…This induces signal transduction cascades which involve recruitment of adaptor proteins and activation of a multitude of downstream signaling molecules, thus culminating in: i) nuclear translocation of transcription factors, ii) biosynthesis of interleukins, interferons, and/or chemokines, eg tumor necrosis factor (TNF-α) and interleukin (IL-1β), and iii) regional and recruited cell responses, including those of the adaptive immune system (Figure 1). (5) NLRs function similarly to and often in conjunction with TLRs.…”

“…(53) With respect to the microbiome and the underlying disease (eg indication for liver transplantation), a recent report described successful treatment of recurrent primary sclerosing cholangitis, an idiopathic disease with emerging links to microbial dysbiosis. (5, 54, 55) Variation of gut microbiota was found to predict early acute cellular rejection after liver transplantation in a rat model, (56) suggesting that a microbiota profile or alterations therein might hold promise as a predictor of acute rejection posttransplantation. Additionally, gut microbiota have been linked to the development of new-onset diabetes mellitus postliver transplantation through alterations of host metabolic homeostasis by as yet unclear gut-liver axis mechanisms.…”