Dataset Information

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

ABSTRACT:

Background

Human body microbiotas are influenced by several factors, including the interaction of the host with the environment and dietary preferences. The role of host genetics in modulating the liver microbiota in the context of NAFLD remains unknown. To address this gap, we examined the interplay between the liver metataxonomic profile and host genetics.

Methods

We obtained 16S rRNA gene sequences from liver biopsies and genotypes by Taqman-assays in 116 individuals. We compared taxon abundance at the genus level across host genotypes using dominant models of inheritance. We focused the analysis on variants influencing the risk/ protection against NAFLD-histological severity (PNPLA3-rs738409, TM6SF2-rs58542926, MBOAT7-rs641738, and HSD17B13-rs72613567) and a variant influencing macronutrient intake (FGF21-rs838133). We also explored the variants' combined effect via a polygenic risk score (PRS).

Findings

We identified at least 18 bacterial taxa associated with variants in the selected loci. Members of the Gammaproteobacteria class were significantly enriched in carriers of the rs738409 and rs58542926 risk-alleles, including Enterobacter (fold change [FC]=6.2) and Pseudoalteromonas (FC=2) genera, respectively. Lawsonella (1.6-FC), Prevotella_9 (FC=1.5), and Staphylococcus (FC=1.3) genera were enriched in rs838133-minor allele carriers, which is linked to sugar consumption and carbohydrate intake. Tyzzerella abundance (FC=2.64) exhibited the strongest association (p = 0.0019) with high PRS values (>4 risk alleles). The percentage of genus-level taxa variation explained by the PRS was ∼7.4%, independently of liver steatosis score and obesity.

Interpretation

We provided evidence that genetic variation may influence the liver microbial DNA composition. These observations may represent potentially actionable mechanisms of disease.

Funding

This study was partially supported by grants PICT 2018-889, PICT 2019-0528, PICT2016-0135 and PICT 2018-0620 (Agencia Nacional de Promoción Científica y Tecnológica, FONCyT), CONICET Proyectos Unidades Ejecutoras 2017, PUE 0055.

SUBMITTER: Pirola CJ

PROVIDER: S-EPMC8803595 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Pirola Carlos Jose CJ Salatino Adrian A Quintanilla Maria Florencia MF Castaño Gustavo Osvaldo GO Garaycoechea Martin M Sookoian Silvia S

EBioMedicine 20220126

<h4>Background</h4>Human body microbiotas are influenced by several factors, including the interaction of the host with the environment and dietary preferences. The role of host genetics in modulating the liver microbiota in the context of NAFLD remains unknown. To address this gap, we examined the interplay between the liver metataxonomic profile and host genetics.<h4>Methods</h4>We obtained 16S rRNA gene sequences from liver biopsies and genotypes by Taqman-assays in 116 individuals. We compar ...[more]

PMID: 35092912

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Dataset Information

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

Background

Methods

Findings

Interpretation

Funding

Publications

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

Similar Datasets

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