2. Academic Validation
  3. Skatole regulates intestinal epithelial cellular functions through activating aryl hydrocarbon receptors and p38

Skatole regulates intestinal epithelial cellular functions through activating aryl hydrocarbon receptors and p38

  • Biochem Biophys Res Commun. 2019 Mar 19;510(4):649-655. doi: 10.1016/j.bbrc.2019.01.122.
Koichi Kurata 1,  Hideaki Kawahara 1,  Kohji Nishimura 2,  Mitsuo Jisaka 3,  Kazushige Yokota 3,  Hidehisa Shimizu 4
Affiliations

Affiliations

  • 1 Graduate School of Life and Environmental Science, Shimane University, Matsue, Shimane, 690-8504, Japan.
  • 2 Interdisciplinary Center for Science Research, Shimane University, Matsue, Shimane, 690-8504, Japan; Raman Project Center for Medical and Biological Applications, Shimane University, Matsue, Shimane, 690-8504, Japan; Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, Matsue, Shimane, 690-8504, Japan.
  • 3 Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, Matsue, Shimane, 690-8504, Japan.
  • 4 Raman Project Center for Medical and Biological Applications, Shimane University, Matsue, Shimane, 690-8504, Japan; Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, Matsue, Shimane, 690-8504, Japan; Estuary Research Center, Shimane University, Matsue, Shimane, 690-8504, Japan. Electronic address: hideshmz@life.shimane-u.ac.jp.
PMID: 30739789 DOI: 10.1016/j.bbrc.2019.01.122
Abstract

Intestinal bacteria produce skatole (3-methylindole) from tryptophan in dietary proteins and ingesting large quantities of animal protein is associated with increased fecal skatole concentrations. Although possibly associated with disrupted intestinal homeostasis, the influence of skatole on intestinal epithelial cellular function has not been characterized in detail. The present study aimed to determine whether skatole induces intestinal epithelial cell (IEC) dysfunction. We found that skatole dose-dependently caused IEC death and time-dependently induced IEC Apoptosis. Since skatole directly interacts with aryl hydrocarbon receptors (AhR), we investigated whether these receptors influence the skatole-induced death of IEC. In addition to increased AhR transcriptional activity induced by skatole, the AhR antagonist CH223191 partially suppressed of skatole-induced IEC death. Extracellular signal-related kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) are mitogen-activated protein kinases (MAPK) induced by skatole. None of them were repressed by CH223191, whereas the p38 inhibitor SB203580 promoted skatole-induced IEC death. These findings together indicated that skatole induces both AhR-dependent activation pathways and the AhR-independent activation of p38, consequently regulating the amount of IEC death. Accumulating evidence indicates that consuming large amounts of animal protein is associated with the pathogenesis and progression of inflammatory bowel diseases (IBD). Thus, intestinal skatole production induced by large amounts of dietary animal protein might be associated via IEC death with intestinal pathologies such as IBD.

Keywords

Bacterial metabolites; Caco-2 cell; Meat; Microbiome; Probiotics; Tryptophan metabolites.

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