Antioxidants maintain Butyrate production by Human GutClostridiain the presence of Oxygen

Abstract

BackgroundOxygen diffused from the human gut mucosa and shape the microbiota with a radial gradient of microbes according to their oxygen tolerance, while microbial and chemical oxygen consumption maintains the lumen in a deeply anaerobic state. Uncontrolled oxidative stress and hyperoxygenation have been reported as a pathogenic mechanism in Salmonella or Citrobacter rodentium infection, in patients with HIV and in severe acute malnutrition. We recently found that antioxidants allow strict anaerobes, including methanogenic archaea, to thrive in an oxidative environment (aerobic). Here, we tested the metabolomics switching of the 3 most odorous anaerobic microbes isolated from human gut when grown in aerobiosis with antioxidants. MethodsThree human gut Clostridia, Clostridium sporogenes, Clostridium lituseburense and Clostridium subterminale, isolated by culturomics, were grown in anaerobiosis or in aerobiosis with antioxidants. Gaz and liquid chromatography-Mass spectrometry (GC/MS and LC/MS) were used for metabolomics analysis. ResultsAn unexpected global dichotomic metabolomic switching from thiols, alcohols and shortchain fatty acid esters to a specific aerobic metabolic repertoire with the production of alkanes, cycloheptatriene and, paradoxically, increased butyrate production, was observed.Analysis of polar metabolites confirmed the discovery of an unexplored aerobic metabolic repertoire, including the production of specific dipeptides and several lysophospholipids, thus unraveling unsuspected human gut microbiome capacities. Conclusions 3Antioxidants unraveled an unexplored aerobic metabolic repertoire of human gut Clostridia.The increased production of butyrate suggests that antioxidants contribute to the maintenance and the active resilience of the human gut microbiome against oxidative aggression, as during Salmonella infection.