The following is a summary of ”Metabolites mediate the causal associations between gut microbiota and NAFLD: a Mendelian randomization study,” published in the July 2024 issue of Gastroenterology by Ouyang et al.

Gut bacteria and blood chemical makeup changes occur in patients with non-alcoholic fatty liver disease (NAFLD), but past studies have yielded conflicting results.

Researchers conducted a retrospective study investigating the association between gut bacteria, blood chemicals, and NAFLD, but due to potential confounding factors and reverse causation, Mendelian randomization (MR) was employed to establish a link.

They conducted a 2-step MR analysis using genome-wide association study (GWAS) data from MiBioGen and UK Biobank. False Discovery Rate (FDR) correction and linkage disequilibrium score regression (LDSC) analysis were applied to address potential errors. Sensitivity analyses, including cML-MA and bidirectional MR, confirmed the result’s robustness.

The results showed that 9 gut microbiota and 7 metabolites were significantly linked to NAFLD. The MR analysis identified a link between Ruminococcus2 and cysteine-glutathione disulfide (OR = 1.17, 95% CI = 1.006–1.369, P=0.041) and between Ruminococcus2 and 3-indoleglyoxylic acid (OR = 1.18, 95% CI = 1.011–1.370, P=0.036). A 26% decrease in NAFLD risk was observed with each incremental standard deviation of Ruminococcus2 (OR = 0.74, 95% CI = 0.61–0.89, P=0.0012), while cysteine-glutathione disulfide levels increased by 17% (OR = 1.17, 95% CI = 1.01–1.37, P=0.041) and 3-indoleglyoxylic acid levels rose by 18% (OR = 1.18, 95% CI = 1.00–1.37, P=0.036). Cysteine-glutathione disulfide mediated 11.2% of the effect, and 3-indoleglyoxylic acid mediated 7.5%.

Investigators concluded that higher levels of specific gut bacteria may lower NAFLD risk, possibly through blood chemical changes.

Source: bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-024-03277-w