Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response

• Published in: Free radical biology & medicine 2016-04, Vol.93, p.155-164
• Main Authors: Beaumont, Martin, Andriamihaja, Mireille, Lan, Annaïg, Khodorova, Nadezda, Audebert, Marc, Blouin, Jean-Marc, Grauso, Marta, Lancha, Luciana, Benetti, Pierre-Henri, Benamouzig, Robert, Tomé, Daniel, Bouillaud, Frédéric, Davila, Anne-Marie, Blachier, François
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; Animals; Colon - metabolism; Colon - microbiology; Colonocyte; DNA Damage - drug effects; Energy Metabolism; Fermentation - drug effects; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - genetics; Gene Expression Regulation - drug effects; Genotoxicity; High-protein diet; Hydrogen sulfide; Hydrogen Sulfide - metabolism; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; Inflammation; Interleukin-6 - biosynthesis; Intestine, Large - metabolism; Intestine, Large - microbiology; Life Sciences; Microbiota; Mitochondria; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - biosynthesis; Oxygen Consumption - drug effects; Rats; Sulfides - pharmacology
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2016.01.028

Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1α (Hif-1α) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the γH2AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite. [Display omitted] •H2S in excess reversibly inhibits colonocyte respiration and increases inflammatory genes expression.•H2S detoxification capacity in colonocytes is impaired in the presence of excessive nitric oxide concentration.•High-protein diet markedly increases sulfide content in the large intestine.•Increased luminal bulk and increased expression of SQR represent adaptive responses to excessive H2S exposition.