Review article: emerging role of the gut microbiome in the progression of nonalcoholic fatty liver disease and potential therapeutic implications

Abstract

Summary Background Nonalcoholic fatty liver disease (NAFLD) is a prevalent disorder associated with obesity and diabetes. Few treatment options are effective for patients with NAFLD, but connections between the gut microbiome and NAFLD and NAFLD‐associated conditions suggest that modulation of the gut microbiota could be a novel therapeutic option. Aim To examine the effect of the gut microbiota on pathophysiologic causes of NAFLD and assess the potential of microbiota‐targeting therapies for NAFLD. Methods A PubMed search of the literature was performed; relevant articles were included. Results The composition of bacteria in the gastrointestinal tract can enhance fat deposition, modulate energy metabolism and alter inflammatory processes. Emerging evidence suggests a role for the gut microbiome in obesity and metabolic syndrome. NAFLD is often considered the hepatic manifestation of metabolic syndrome, and there has been tremendous progress in understanding the association of gut microbiome composition with NAFLD disease severity. We discuss the role of the gut microbiome in NAFLD pathophysiology and whether the microbiome composition can differentiate the two categories of NAFLD: nonalcoholic fatty liver (NAFL, the non‐progressive form) vs nonalcoholic steatohepatitis (NASH, the progressive form). The association between gut microbiome and fibrosis progression in NAFLD is also discussed. Finally, we review whether modulation of the gut microbiome plays a role in improving treatment outcomes for patients with NAFLD. Conclusions Multiple pathophysiologic pathways connect the gut microbiome with the pathophysiology of NAFLD. Therefore, therapeutics that effectively target the gut microbiome may be beneficial for the treatment of patients with NAFLD.

Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms

“…Soderborg et al also found that these colonized mice had increased periportal inflammation, which correlated with an increased modified pediatric NAFLD histological score [ 121 ] and increased collagen disposition around the portal triad [ 122 ] compared with mice colonized with stool from 2-week-old infants from normal-weight mothers. In the liver, LPS infiltration leads to pro-inflammatory cytokine production and liver Kupffer cell (KC) activation, which can lead to the activation of hepatic stellate cells and fibrosis [ 123 ]. These results support the concept that early maternal microbial dysbiosis contributes to the detrimental effects on offspring immune function that can drive hepatic inflammation.…”

Gut microbiota in non‐alcoholic fatty liver disease and alcohol‐related liver disease: Current concepts and perspectives

“…Importantly, these pathways can influence disease phenotype in a diverse fashion, thus determining disease heterogeneity . Several studies have highlighted the role of the gut microbiota in NAFLD . Preclinical studies have shown that germ‐free mice are protected against obesity and hepatic steatosis .…”

Fermented Foods in Medicine: An Evaluation of Their Uses and Effects on the Human Gut Microbiota

“…Comparative metagenomics aims to study the diversity of microbes through large-scale sequencing of microbial communities; in the case of this study, the communities studied were part of the gut microbiota (Huson et al 2009, Turnbaugh et al 2008. Similar studies conducted in children and adults have shown correlations between gut microbe composition and diseases, such as type-2 diabetes, obesity, IBS, and inflammation (Lambert et al 2015, Durack and Lynch 2019, Jayakumar and Loomba 2019, Cooper et al 2017.…”

“…The study of the human gut microbiome has increasingly become a topic of interest for researchers worldwide, including the effects of fermented products on the composition of the gut microbiome. Gut microbiota can be correlated to IBDs such as Crohn's Disease (CD), and other diseases such as Non-Alcoholic Fatty Liver Disease, and diabetes (Lambert et al 2015, Durack and Lynch 2019, Jayakumar and Loomba 2019. Dysbiosis is increasingly being implicated in varying forms of IBD, where the loss of enteric bacterial diversity and an expansion in the relative abundance of family Enterobacteriaceae has been associated with the onset of CD (Durack and Lynch 2019).…”