Epidemiological Study on the Interaction between the PNPLA3 (rs738409) and Gut Microbiota in Metabolic Dysfunction-Associated Steatotic Liver Disease

Many factors are associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, genetics and gut microbiota are representative factors. Recent studies have highlighted the link between host genes and the gut microbiota. Although there have been many studies on the separate effects of single nucleotide polymorphisms (SNPs) and gut bacteria on MASLD, few epidemiological studies have examined how SNPs and gut bacteria interact in the development and progression of MASLD. This study aimed to investigate the association between <i>PNPLA3</i> rs738409, a representative MASLD-related SNP, and gut bacteria in MASLD using a cross-sectional study of the general population. The 526 participants (318 normal and 208 MASLD groups) were grouped into the <i>PNPLA3</i> rs738409 SNP, CC, CG, and GG genotypes, and the differences in the gut microbiota were investigated in each group. The <i>PNPLA3</i> rs738409 CC and CG genotypes were associated with decreased <i>Blautia</i> and <i>Ruminococcaceae</i> in the MASLD group. They were negatively correlated with controlled attenuation parameter levels, body mass index, serum blood glucose, and triglycerides. In contrast, there was no association between the normal and MASLD groups and the gut bacteria in the <i>PNPLA3</i> rs738409, the GG genotype group. This finding implies that dietary interventions and probiotics may be more effective in preventing and treating MASLD in individuals with the <i>PNPLA3</i> rs738409 CC and CG genotypes. In contrast, their efficacy may be limited in those with the GG genotype.