An orally active carbon monoxide-releasing molecule enhances beneficial gut microbial species to combat obesity in mice

• DOI: 10.1016/j.redox.2024.103153
• Publication Date: 2024-04-09T08:50:34Z
• Authors: Djamal Eddine Ben...; Shruti Mohan; Matija Trickovic; Florence Anne Cas...; Ghida Alloul; Arielle Sobngwi; Rosa Abdiche; Silas Kieser; Vanessa Demontant; Elisabeth Trawinski; Céline Chollet; Christophe Rodriguez; Hiroaki Kitagishi; François Fenaille; Mirko Trajkovski; Roberto Motterlini; Roberta Foresti
• Keywords: Akkermansia muciniphila; Metabolic pathway

Carbon monoxide (CO), a gaseous signaling molecule, has shown promise in preventing body weight gain and metabolic dysfunction induced by high fat diet (HFD), but the mechanisms underlying these effects are largely unknown. An essential component response to HFD is gut microbiome, which significantly altered during obesity represents target for developing new therapeutic interventions fight diseases. Here, we show that CO delivered oral administration with CO-releasing molecule (CORM-401) accumulates faeces enriches variety of microbial species were perturbed regimen. Notably, Akkermansia muciniphila, exerts salutary mice humans, was strongly depleted most abundant detected after CORM-401 treatment. Analysis bacterial transcripts revealed restoration functional activity, partial or full recovery Krebs cycle, β-oxidation, respiratory chain glycolysis. Mice treated exhibited normalization several plasma fecal metabolites disrupted dependent on muciniphila's including indoles tryptophan derivatives. Finally, treatment led an improvement morphology as well reduction inflammatory markers colon cecum profiles tissues. Our findings provide insights efficacy potential prebiotic combat obesity, identifying microbiota crucial CO-mediated pharmacological activities against disorders.