The influence of host genetics on liver microbiome composition in patients with NAFLD
Summary: 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 t...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422000421 |
| _version_ | 1818715405888258048 |
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| author | Carlos Jose Pirola Adrian Salatino Maria Florencia Quintanilla Gustavo Osvaldo Castaño Martin Garaycoechea Silvia Sookoian |
| author_facet | Carlos Jose Pirola Adrian Salatino Maria Florencia Quintanilla Gustavo Osvaldo Castaño Martin Garaycoechea Silvia Sookoian |
| author_sort | Carlos Jose Pirola |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-17T19:02:51Z |
| format | Article |
| id | doaj.art-c8954f9e08874c89b89e623a6e35e5a9 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-17T19:02:51Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-c8954f9e08874c89b89e623a6e35e5a92022-12-21T21:36:05ZengElsevierEBioMedicine2352-39642022-02-0176103858The influence of host genetics on liver microbiome composition in patients with NAFLDCarlos Jose Pirola0Adrian Salatino1Maria Florencia Quintanilla2Gustavo Osvaldo Castaño3Martin Garaycoechea4Silvia Sookoian5University of Buenos Aires, School of Medicine, Institute of Medical Research A Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET)−University of Buenos Aires, Institute for Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Ciudad Autónoma de Buenos Aires, Argentina; Corresponding authors at: Instituto de Investigaciones Médicas, IDIM-CONICET, Combatientes de Malvinas 3150, CABA-1427, Argentina.University of Buenos Aires, School of Medicine, Institute of Medical Research A Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET)−University of Buenos Aires, Institute for Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Ciudad Autónoma de Buenos Aires, ArgentinaUniversity of Buenos Aires, School of Medicine, Institute of Medical Research A Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET)−University of Buenos Aires, Institute for Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET)−University of Buenos Aires, Institute for Medical Research (IDIM), Department of Clinical and Molecular Hepatology, Ciudad Autónoma de Buenos Aires, ArgentinaLiver Unit, Medicine and Surgery Department, Hospital Abel Zubizarreta, Ciudad Autónoma de Buenos Aires, ArgentinaDepartment of Surgery and CEMET, Hospital de Alta Complejidad en Red “El Cruce”, Florencio Varela, Buenos Aires, ArgentinaUniversity of Buenos Aires, School of Medicine, Institute of Medical Research A Lanari, Ciudad Autónoma de Buenos Aires, Argentina; National Scientific and Technical Research Council (CONICET)−University of Buenos Aires, Institute for Medical Research (IDIM), Department of Clinical and Molecular Hepatology, Ciudad Autónoma de Buenos Aires, Argentina; Corresponding authors at: Instituto de Investigaciones Médicas, IDIM-CONICET, Combatientes de Malvinas 3150, CABA-1427, Argentina.Summary: 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.http://www.sciencedirect.com/science/article/pii/S2352396422000421NASHGeneticsPNPLA3TM6SF2HSD17B13Risk score |
| spellingShingle | Carlos Jose Pirola Adrian Salatino Maria Florencia Quintanilla Gustavo Osvaldo Castaño Martin Garaycoechea Silvia Sookoian The influence of host genetics on liver microbiome composition in patients with NAFLD EBioMedicine NASH Genetics PNPLA3 TM6SF2 HSD17B13 Risk score |
| title | The influence of host genetics on liver microbiome composition in patients with NAFLD |
| title_full | The influence of host genetics on liver microbiome composition in patients with NAFLD |
| title_fullStr | The influence of host genetics on liver microbiome composition in patients with NAFLD |
| title_full_unstemmed | The influence of host genetics on liver microbiome composition in patients with NAFLD |
| title_short | The influence of host genetics on liver microbiome composition in patients with NAFLD |
| title_sort | influence of host genetics on liver microbiome composition in patients with nafld |
| topic | NASH Genetics PNPLA3 TM6SF2 HSD17B13 Risk score |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422000421 |
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