Intestinal Microbiome Shifts, Dysbiosis, Inflammation, and Non-alcoholic Fatty Liver Disease

Abstract

Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions, like the metabolic syndrome (MetS) and it's hepatic manifestation, non-alcoholic fatty liver disease (NAFLD). The intestinal microbial community of obese compared to lean subjects has been shown to undergo configurational shifts in various genera, including but not limited to increased abundances of Prevotella, Escherichia, Peptoniphilus, and Parabacteroides and decreased levels of Bifidobacteria, Roseburia, and Eubacteria genera. At the phylum level, decreased Bacteroidetes and increased Firmicutes have been reported. The intestinal microbiota therefore presents an important target for designing novel therapeutic modalities that target extra-intestinal inflammatory disorders, such as NAFLD. This review hypothesizes that disruption of the intestinal–mucosal macrophage interface is a key factor in intestinal-liver axis disturbances. Intestinal immune responses implicated in the manifestation, maintenance and progression of NAFLD provide insights into the dialogue between the intestinal microbiome, the epithelia and mucosal immunity. The pro-inflammatory activity and immune imbalances implicated in NAFLD pathophysiology are reported to stem from dysbiosis of the intestinal epithelia which can serve as a source of hepatoxic effects. We posit that the hepatotoxic consequences of intestinal dysbiosis are compounded through intestinal microbiota-mediated inflammation of the local mucosa that encourages mucosal immune dysfunction, thus contributing important plausible insight in NAFLD pathogenesis. The administration of probiotics and prebiotics as a cure-all remedy for all chronic diseases is not advocated, instead, the incorporation of evidence based probiotic/prebiotic formulations as adjunctive modalities may enhance lifestyle modification management strategies for the amelioration of NAFLD.

The Gut Microbiome in Patients with Intestinal Failure: Current Evidence and Implications for Clinical Practice

“…It normally penetrates the intestinal mucosa in trace amounts, enters the portal circulation, and becomes cleared in the liver. LPS has been involved in the pathogenesis of nonalcoholic fatty liver disease, leading to activation of toll‐like receptors, promoting inflammation and fibrogenesis . It is therefore possible that the increased abundance of Proteobacteria in patients with IF in conjunction with a compromised intestinal barrier function expose the liver to higher than normal concentrations of LPS .…”

“…LPS has been involved in the pathogenesis of nonalcoholic fatty liver disease, leading to activation of toll-like receptors, promoting inflammation and fibrogenesis. 75,76 It is therefore possible that the increased abundance of Proteobacteria in patients with IF in conjunction with a compromised intestinal barrier function expose the liver to higher than normal concentrations of LPS. [77][78][79] Another group of bacteria that may cause liver damage are species belonging to Lactobacillus that may promote liver steatosis via excessive bile acid deconjugation.…”

Microbiome diurnal rhythmicity and its impact on host physiology and disease risk

“…Through the portal vein that connects the liver to the gastrointestinal tract, the liver is exposed to the influence of the gut microbiome. Perturbations of the gut microbiome, coupled with disturbances in gut barrier function, have been associated with common liver disorders, such as non-alcoholic fatty liver disease [138][139][140], non-alcoholic steatohepatitis [139,[141][142][143][144][145][146][147][148][149][150][151][152], alcoholic liver disease [139,140,142,145,147,148,150,151,[153][154][155][156][157][158][159][160][161][162][163][164], and liver cirrhosis [165][166][167][168][169][170]. Thus, the microbiome serves as a modulator of liver rhythmic functions.…”

What is Needed for Evidence‐Based Dietary Recommendations for Migraine: A Call to Action for Nutrition and Microbiome Research

“…102,103 The impact of SCFAs on broader health and metabolism is increasingly appreciated, including reduced risk for cardiovascular disease and regulation of appetite. 110,111 The more permeable intestine allows bacterial translocation from the lumen into extraintestinal sites, along with their lipopolysaccharide (LPS) endotoxins, 112,113 triggering a cascade of immune responses at both local and distant sites, including systemic elevation of proinflammatory cytokines. The gut microbiota are also differentially capable of biotransforming numerous bioactive compounds found in diet, including various polyphenols, 105 and parent compounds and metabolites may have differing potential to impact host metabolism and physiology.…”

“…109 Consequences of this imbalanced gut microbiota include disturbance of the multiple roles of the gut microbiome, such as disruption of tight junction integrity and increased permeability of the intestinal epithelium. 110,111 The more permeable intestine allows bacterial translocation from the lumen into extraintestinal sites, along with their lipopolysaccharide (LPS) endotoxins, 112,113 triggering a cascade of immune responses at both local and distant sites, including systemic elevation of proinflammatory cytokines. 112,114,115 Additionally, LPS can activate dendritic cells, which influences the secretion and storage of serotonin.…”