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High-fat Diet-Mediated Dysbiosis Exacerbates NSAID-induced Small Intestinal Damage Through the Induction of interleukin-17A

High-fat Diet-Mediated Dysbiosis Exacerbates NSAID-induced Small Intestinal Damage Through the Induction of interleukin-17A

Naoki Sugimura, Koji Otani, Toshio Watanabe, Geicho Nakatsu, Sunao Shimada, Kosuke Fujimoto, Yuji Nadatani, Shuhei Hosomi, Fumio Tanaka, Noriko Kamata, Koichi Taira, Yasuaki Nagami, Tetsuya Tanigawa, Satoshi Uematsu, etc.

Sci Rep. 2019 Nov 14;9(1):16796.

PMID: 31727909

Abstract:

Non-steroidal anti-inflammatory drugs (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. 16S rRNA gene analysis revealed that the population of Bifidobacterium spp. significantly decreased by fold change of individual operational taxonomic units in the small intestine of mice fed HFD for 8 weeks. HFD increased intestinal permeability, as indicated by fluorescein isothiocyanate-dextran absorption and serum lipopolysaccharide levels, accompanied by a decrease in the protein expressions of ZO-1 and occludin and elevated mRNA expression of interleukin (IL)-17A in the small intestine. HFD-fed mice exhibited increased susceptibility to indomethacin-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 against IL-17A to HFD-fed mice reduced intestinal permeability and prevented exacerbation of indomethacin-induced damage. Thus, HFD-induced microbial dysbiosis in small intestine caused microinflammation through the induction of IL-17A and increase in intestinal permeability, resulting in the aggravation of NSAID-induced small intestinal damage.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP60842468	Fluorescein isothiocyanate-dextran		60842-46-8	Price

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