The antimicrobial peptide CRAMP is essential for colon homeostasis by maintaining microbiota balance

Teizo Yoshimura, Mairi H. McLean, Amiran K. Dzutsev, Xiaohong Yao, Keqiang Chen, Jiaqiang Huang, Wanghua Gong, Jiamin Zhou, Yi Xiang, Jonathan H. Badger, Colm O'HUigin, Vishal Thovarai, Lino Tessarollo, Scott K. Durum, Giorgio Trinchieri, Xiu Wu Bian, Ji Ming Wang

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11 Citations (Scopus)

Abstract

Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in cathelin-related antimicrobial peptide (CRAMP) were defective in the development of colon mucosa and highly sensitive to dextran sulfate sodium (DSS)-elicited colitis, as well as azoxymethane-mediated carcinogenesis. Pretreatment of CRAMP -/- mice with antibiotics markedly reduced the severity of DSS-induced colitis, suggesting CRAMP as a limiting factor on dysbiosis in the colon. This was supported by observations that wild-type (WT) mice cohoused with CRAMP -/- mice became highly sensitive to DSS-induced colitis, and the composition of fecal microbiota was skewed by CRAMP deficiency. In particular, several bacterial species that are typically found in oral microbiota, such as Mogibacterium neglectum, Desulfovibrio piger, and Desulfomicrobium orale, were increased in feces of CRAMP -/- mice and were transferred to WT mice during cohousing. When littermates of CRAMP+/2 parents were examined, the composition of the fecal microbiota of WT pups and heterozygous parents was similar. In contrast, although the difference in fecal microbiota between CRAMP -/- and WT pups was small early on after weaning and single mouse housing, there was an increasing divergence with prolonged single housing. These results indicate that CRAMP is critical in maintaining colon microbiota balance and supports mucosal homeostasis, antiinflammatory responses, and protection from carcinogenesis.

Original languageEnglish
Pages (from-to)2174-2185
Number of pages12
JournalJournal of Immunology
Volume200
Issue number6
DOIs
Publication statusPublished - Mar 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yoshimura, T., McLean, M. H., Dzutsev, A. K., Yao, X., Chen, K., Huang, J., Gong, W., Zhou, J., Xiang, Y., Badger, J. H., O'HUigin, C., Thovarai, V., Tessarollo, L., Durum, S. K., Trinchieri, G., Bian, X. W., & Wang, J. M. (2018). The antimicrobial peptide CRAMP is essential for colon homeostasis by maintaining microbiota balance. Journal of Immunology, 200(6), 2174-2185. https://doi.org/10.4049/jimmunol.1602073