The influence of host genetics on liver microbiome composition in patients with NAFLD

GUSTAVO O CASTAÑO; CARLOS JOSE PIROLA; SILVIA SOOKOIAN; MARIA SILVINA LANDA; ADRIAN SALATINO; MARTIN E GARAYCOECHEA

Anaheim, CA

Congreso; The Liver Meeting 2021; 2021

The American Association for the Study of Liver Diseases

Background and aims: Several factors, including interaction among the environment, dietary preferences, and host genetics, influence human body microbiotas. The importance of genetics in contributing to the composition of the liver microbiota is unknown. We aimed to explore the association between liver microbiota and host genetics. Methods: We obtained 16S rRNA gene sequences by NGS from liver biopsies and host genotypes by Taqman genotyping in 116 individuals. Microbial operational taxonomic units and their taxonomic assignments were obtained by QIIME2. We selected the following genetic variants: rs838133 in FGF21 linked to food intake regulation, macronutrient preference (high carbohydrate) and central reward pathways, and ADH1B-rs1229984, which influences alcohol consumption through modulation of ethanol oxidation to acetaldehyde. Also, we included variants in loci influencing NAFLD-natural history (PNPLA3, TM6SF2, MBOAT7, and HSD17B13). We compared taxa abundance at the genus level across genotypes using dominant models by parametric and non-parametric statistical tests (FDR 4 risk alleles) showed associations with potential detrimental taxa linked to CV risk (Tyzzerella 2.64-FC, p=0.0019). Conclusion: In this study, we provide the first evidence that genetic variation in genes that modulate preferences in dietary components, alcohol consumption, and severe NAFLD risk might influence the liver microbial DNA profile´s composition.