Gut microbiota and NASH course

Hepatitis

A study recently demonstrated a link between gut microbiota and inflammatory state that promotes progression of non-alcoholic fatty liver disease to steatohepatitis through the production of short-chain fatty acids.

About this article

Created 26 March 2019

Updated 06 October 2021

Together with insulin resistance, non-alcoholic fatty liver disease (NAFLD) has become the most frequent hepatic disorder in Western countries, with a prevalence of around 25%. The first stage is fatty liver disease, which progresses to non-alcoholic steatohepatitis (NASH) in some patients under the influence of several factors, including a proinflammatory state. A German team recently published a study comparing three parameters from 32 patients with NAFLD (of which 18 with NASH) and 27 healthy volunteers: gut microbiota, fecal short-chain fatty acids (SCFA) and Th17/rTreg ratio in blood.

NASH-specific microbiota

Compared to patients with a less advanced stage of non-alcoholic fatty liver disease, those with NASH have a greater abundance of species from the Fusobacteriaceae family and Fusobacterium, Prevotella and Eubacterium genera, as well as a higher content of Fusobacteriaceae and Prevotellacea, two bacterial groups that probably produce SCFAs, compared to control subjects. The observed microbiotic profile thus characterizes two different subgroups corresponding to patients with or without NASH in the NAFLD group, and it is correlated to the results of hepatic biopsies. This could open the way to a new non-invasive method to monitor the disease, since hepatic biopsy is currently the only way to diagnose NASH. Moreover, fecal levels of acetate, propionate and butyrate–three SCFAs produced by the fermentation of dietary fiber in the GI tract–are higher in the NAFLD group than in the control group. A significantly higher level of butyrate is also observed in the NASH group compared to the control group.

The controversial role of SCFAs

Finally, the study focused on the comparison between levels of specific blood lymphocytes: anti-inflammatory resting Treg cells (rTreg) and pro-inflammatory Th17 cells. A study published by the same team had shown that the Th17/rTreg ratio was higher in the NASH subgroup than in patients with NAFLD. The current study brought to light a positive correlation between Th17/rTreg ratio and fecal levels of acetate and propionate. SCFAs are also known for their anti-inflammatory properties, but several studies, including this one, have raised the question of their proinflammatory role in some pathologies and under certain conditions.

Sources

^{Rau et al., Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease, United European Gastroenterology Journal 2018, Vol. 6(10) 1496–1507}

^{He et al., The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice, BMC Immunol. 2017; 18: 33}

^{Yoon et al., Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease, World J Hepatol. 2014 Nov 27;6(11):800-11}

^{Gariani et al., Diabète et stéatose hépatique non alcoolique, Rev Med Suisse 2012 Jun 6;8(344):1211-4.}