Minibioreactor arrays to model microbiome response to alcohol and tryptophan in the context of alcohol-associated liver disease
Year: 2024
Type: article
Abstract: Intestinal microbiota (IM) plays a role in the severity of alcohol-associated liver disease. Hence, modifying severe alcohol-associated hepatitis (AH) dysbiosis improves liver injury through tryptophan (Trp) metabolites and aryl hydrocarbon receptor (AhR). However, the effect of Trp on IM in alcohol use disorder (AUD) patients remains unclear. Here, we used an in vitro microbiota modeling system named Minibioreactor arrays (MBRAs) to study IM in continuous and controlled-flow cultures. Feces from AUD patients with or without AH were transferred to MBRAs and treated with low, normal, or high Trp concentrations and in the presence of alcohol or not. 16s IM sequencing and AhR activity were studied. We showed that microbial communities from donors were maintained in MBRA. High and low Trp increased the abundance of pathogen Escherichia/Shigella in AH and AUD IM. High Trp decreased the Shannon index in AH IM. In the absence of alcohol, Trp changed more bacteria in AUD IM compared to AH IM. Compared to low Trp, normal Trp increased the AhR activity, whereas high Trp activated AhR only in AUD IM. Overall, it appears that maintaining normal Trp levels is relevant to prevent dysbiosis in AUD or AH, which should be confirmed through in vivo experimentation.
Source: npj Biofilms and Microbiomes
Institutions: Inserm, Université Paris-Saclay, Assistance Publique – Hôpitaux de Paris, Inflammation, Microbiome and Immunosurveillance, Centre National de la Recherche Scientifique, Université Paris Cité, Institut Cochin, Fédération Hospitalo-Universitaire, Paris Center for Microbiome Medicine, Hôpital Antoine-Béclère, Institut Pasteur
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,990
Funders: Fondation de l'Avenir pour la Recherche Médicale Appliquée, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, China Scholarship Council, Association Française pour l'Etude du Foie, Université Paris-Sud, Société Nationale Française de Gastro-Entérologie
Awards: EMULBIONT: Impact of dietary food additive EMULsifiers on pathoBIONT’s pathogenic potential in chronic inflammatory diseases: from mechanism to prevention, Target the intestinal microbiota by prebiotics to improve alcoholic hepatitis progression: from molecular mechanisms to bedside, G2522628222, G3186420570, Dynamique de la REsistance aux Antibiotiques dans le Microbiote intestinal humain: combinaison d'une cohorte informée sur nutrition à des études quantitatives sur un modèle in vitro d'intestin, G4180218856, G434337789
OpenAlex ID: W4404545261