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dc.contributor.author
Pirola, Carlos José
dc.contributor.author
Salatino, Adrián Emanuel
dc.contributor.author
Quintanilla, María Florencia
dc.contributor.author
Castaño, Gustavo Osvaldo
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Garaycoechea, Martin Enrique
dc.contributor.author
Sookoian, Silvia Cristina
dc.date.available
2023-08-18T14:34:05Z
dc.date.issued
2022-02
dc.identifier.citation
Pirola, Carlos José; Salatino, Adrián Emanuel; Quintanilla, María Florencia; Castaño, Gustavo Osvaldo; Garaycoechea, Martin Enrique; et al.; The influence of host genetics on liver microbiome composition in patients with NAFLD; Elsevier; eBioMedicine; 76; 2-2022; 1-13
dc.identifier.issn
2352-3964
dc.identifier.uri
http://hdl.handle.net/11336/208721
dc.description.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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
FGF21
dc.subject
GENETICS
dc.subject
HSD17B13
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MBOAT7
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NASH
dc.subject
PNPLA3
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RISK SCORE
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TM6SF2
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Genética Humana
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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Gastroenterología y Hepatología
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Medicina Clínica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.subject.classification
Bioquímica y Biología Molecular
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
The influence of host genetics on liver microbiome composition in patients with NAFLD
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-06T11:06:37Z
dc.journal.volume
76
dc.journal.pagination
1-13
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Pirola, Carlos José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil
Fil: Salatino, Adrián Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil
Fil: Quintanilla, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.description.fil
Fil: Castaño, Gustavo Osvaldo. Gobierno de la Ciudad de Buenos Aires. Hospital "Dr. Abel Zubizarreta"; Argentina
dc.description.fil
Fil: Garaycoechea, Martin Enrique. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
dc.description.fil
Fil: Sookoian, Silvia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
dc.journal.title
eBioMedicine
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S2352396422000421
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ebiom.2022.103858
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