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Orlistat, an anti‐obesity remedy as a competitive lipase inhibitor, enhanced inflammatory reaction in the intestine

Secondary gut metabolites derived from microbial fermentation of food in the gut have broad impacts on various aspects of host physiology. Our recent studies on obese mice treated with Orlistat, an anti‐obesity treatment, showed significantly altered gut microbial profile marked by an overabundance of Proteobacteria and possible alterations in secondary gut metabolites. Consequently, aqueous fecal extracts from treated and untreated mice groups were analyzed for anti‐oxidant and mitochondrial altering function using HCT‐116‐ARE and Caco2 cells under oxidative stress. The results of this study showed that fecal extracts in groups containing increased cecal concentraations of butyrate and propionate had reduced fold change in luciferase activity, thus, alleviating oxidative stress. Conversely, fecal extracts from high fat/orlistat treated mice resulted in a significant increase in fold change in the luciferase activity and maximal ATP production of cells under oxidative stress. Changes in secondary gut metabolites during obesity treatment may provide the necessary insight into the possible side effects seen during intervention.