NSAIDs cause damage in the small intestine in a bacteria-dependent manner. As high-fat diet (HFD) is a potent inducer of gut dysbiosis, we investigated the effects of HFD on bacterial flora in the small intestine and NSAID-induced enteropathy. HFD-fed mice exhibited increased susceptibility to NSAID-induced damage in the small intestine; this phenotype was observed in normal diet-fed mice that received small intestinal microbiota from HFD-fed mice. Administration of neutralizing antibodies to HFD-fed mice reduced intestinal permeability and prevented exacerbation of NSAID-induced damage. Thus, HFD-induced microbial dysbiosis in small intestine caused microinflammation and increase in intestinal permeability, resulting in the aggravation of NSAID-induced small intestinal damage.
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