Effect of gut microbiota and PNPLA3 polymorphisms on nonalcoholic fatty liver disease in lean and obese individuals

Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity but is also found in non-obese individuals. The PNPLA3 gene variant (rs738409) is by far the most important genetic determinant of NAFLD. To date, there is no study exploring the differences and associations between gut microbiota and PNPLA3 genotype on lean and obese NAFLD patients. Thus, the aim of this study was to evaluate the association between gut microbiota and lean and obese NAFLD, while considering the role of PNPLA3 variants. This prospective study took place at Kaohsiung Chang Gung Memorial Hospital from December 2019 to November 2020. We recruited 35 lean NAFLD patients, 70 obese NAFLD patients, and 35 healthy individuals. Fecal samples were collected to analyze the V4 region of the 16S rRNA gene for intestinal bacteria composition. Although lean and obese NAFLD groups did not differ in PNPLA3 variant abundance, the lean NAFLD group had a higher percentage of the G allele variant (82.9% vs. 72.9%) than obese NAFLD group. Alpha diversity for gut microbiota was not significantly different among the three groups. Microbiota differed significantly between lean and obese NAFLD groups in a multi-response permutation procedure analysis (p = .005). Although, there were no significant differences between PNPLA3 G and C in alpha and beta diversity, the same phylum, family, and genus dominant microbiota differed between lean and obese NAFLD. Lean and obese NAFLD patients have different predominant gut microbiota, as do PNPLA3 C and G variants, indicating that lean NAFLD patients may be associated with PNPLA3 G allele variant.