RESUMO
Microbial metabolites may influence the metabolic integrity of intestinal epithelial cells and induce mucosal immune responses. Therefore, we investigated the effects of the microbial metabolites butyrate, iso-valerate, and ammonium on Caco-2 cells and macrophages. Barrier functioning was determined by measuring transepithelial electrical resistance and basolateral recoveries of metabolites. The barrier function of Caco-2 cells remained intact after exposures. Basolateral recoveries ranged from 6.2% to 15.2%. Tumour necrosis factor-alpha and interleukin-10 were measured to determine immune reactions. The Caco-2 cells did not secrete both cytokines. Physiological concentrations of butyrate and iso-valerate stimulated the secretion of tumour necrosis factor-alpha and suppressed the secretion of interleukin-10 by macrophages that are not protected by an epithelial barrier. In contrast, ammonium concentrations as high as those produced by microbiotas of IBD patients suppressed the release of both cytokines when the barrier function is impaired.
Assuntos
Intestinos/imunologia , Intestinos/microbiologia , Macrófagos/imunologia , Macrófagos/microbiologia , Cloreto de Amônio/metabolismo , Cloreto de Amônio/farmacologia , Butiratos/metabolismo , Butiratos/farmacologia , Células CACO-2 , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Hemiterpenos , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Técnicas In Vitro , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Interleucina-10/metabolismo , Intestinos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Ácidos Pentanoicos/metabolismo , Ácidos Pentanoicos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Células U937RESUMO
The hypothesis was studied that intestinal microbial metabolites play a role in the pathogenesis of inflammatory bowel disease. For that purpose, an in vitro model of the colon was inoculated with fresh feces of six healthy individuals and eight inflammatory bowel disease patients. Samples were taken from the model over time to analyze metabolites from both saccharolytic and proteolytic fermentation. Microbiotas from inflammatory bowel disease patients produced significantly more short-chain fatty acids and ammonia than microbiotas from healthy individuals. Furthermore, the branched-chain fatty acid production was 25% higher after inoculation with microbiotas from patients than after inoculation with microbiotas from healthy individuals. Phenolic compounds were produced by all microbiotas, with large interindividual variation. The production of (potentially toxic) metabolites may play a role in the onset or chronicity of inflammatory bowel disease, because they were produced in higher amounts by microbiotas from these patients than by microbiotas from healthy individuals.
