Association of Gut Microbiota-Derived Short-Chain Fatty Acids With Persistent Elevated Serum Transaminase Levels in Normal Weight and Obesity: A Pilot Study.

Abstract

Although obesity is the most common risk factor for hepatic steatosis, this disease may occur in normal-weight individuals. While gut microbial metabolites such as short-chain fatty acids (SCFAs) have been associated with obesity and metabolic disease, the relationship among fecal SCFA concentrations, SCFA-producing bacteria, and hepatic steatosis with and without obesity is not fully understood. This pilot study aimed to compare fecal SCFA concentrations and SCFA-producing gut bacteria in four study groups: 7 individuals with normal-weight and normal alanine aminotransferase levels (Nw-N ALT), 7 individuals with normal-weight and elevated ALT levels (Nw-E ALT), 12 individuals with obesity and normal ALT levels and (Ob-N ALT), and 18 individuals with obesity and elevated ALT levels (Ob-E ALT). Fecal SCFA concentrations were quantified using gas chromatography, and gut microbiota was characterized by sequencing 16S rRNA. Median fecal SCFA concentrations (propionate, butyrate, and valerate) were highest in the Ob-E ALT group and lowest in the Nw-N ALT group (p < 0.05). These SCFA concentrations were also higher in obese than in normal-weight individuals regardless of ALT levels (p < 0.05) and in elevated ALT individuals regardless of obesity status, although the difference lost significance after correction for multiple testing. Notably, the abundance of Roseburia was higher in Ob-N ALT and Ob-E ALT than in the Nw-N ALT group and correlated positively with fecal SCFA concentrations. In conclusion, this pilot study suggests that the presence of both obesity and persistent elevated serum ALT levels is associated with increased fecal SCFA concentrations and SCFA-producing bacteria, particularly Roseburia. However, a larger sample is required to define whether the associations of SCFA fecal levels with obesity and elevated ALT levels are independent.