A50 IMPACT OF SHORT CHAIN FATTY ACIDS ON PATHOGENICTY OF COMMENSAL BACTERIA IN PEDIATRIC INFLAMMATORY BOWEL DISEASES

Abstract

Abstract Background Dietary fibers are fermented by microbiota into many different compounds including short-chain fatty acids (SCFA). The gut microenvironment is essential not only for human health but also in maintaining a rich biodiversity of bacterial species. It is well known that the microbiome is altered in Inflammatory Bowel Diseases (IBD), which likely changes the microenvironment and has other health effects on individuals with IBD. Pathobionts are organisms that can induce pathology under specific conditions, and several have already been associated with IBD, such as adherent invasive Escherichia coli (AIEC) and Helicobacter hepaticus. Although these bacteria have been associated with IBD, it is still largely unknown what conditions make these bacteria become pathogenic. Aims Determine the role of SCFA composition on the pathogenic potential of commensal bacteria isolated from non-IBD and IBD pediatric patients. Methods Anaerobic bacteria were isolated during colonoscopy from pediatric IBD and non-IBD patients and identified using 16S sequencing. PMA-activated human monocytes (THP-1) and colonic epithelial cells (Caco2) were grown in the presence of SCFA (acetate, butyrate, formate, propionate, and succinate). The ability of commensal bacteria ( Bacteroides fragilis, Clostridium innocuum, Ruminococcus, Parabacteroides merdae, Bifidobacterium infantis and E. coli HB101) and the pathobiont AIEC to invade cells was assessed using a gentamicin protection assay. Immune activation was quantified with IL-1b and IL-6 by ELISA, as well as reactive oxygen species (ROS) using DCFDHA. Results The SCFA propionate and formate significantly decreased invasion for HB101 and LF82 into macrophages but not epithelial cells. Bacteria isolated from an IBD environment had a higher invasion potential independent of the addition of SCFA, compared to bacteria from a non-IBD environment. However, butyrate was found to significantly increase invasion of non-IBD B. fragilis into Caco2 cells but not macrophages. Bacteria isolated from IBD patients tended to have a higher inflammatory response with both elevated IL-1b as well as ROS production. Conclusions Microenvironment changes, such as in SCFA concentrations, during a disease state can affect the host response to microbes including commensals. Commensal bacteria from IBD patients tend to be more proinflammatory, suggesting that they play a role in driving inflammation. SCFA are beneficial factors for gut health; however, what is still unknown is the interaction between microbes and the host after microenvironmental shifts that likely causes bacterial stress. Understanding the host-microbe interactions and the role diet can have on this dynamic relationship has the potential for discovering new therapeutic options for those suffering from IBD. Funding Agencies CIHRWeston Family Foundation