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 language | English |
|---|---|
| Pages (from-to) | 2174-2185 |
| Number of pages | 12 |
| Journal | Journal of Immunology |
| Volume | 200 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 15 2018 |
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ASJC Scopus subject areas
- Immunology
Cite this
The antimicrobial peptide CRAMP is essential for colon homeostasis by maintaining microbiota balance. / Yoshimura, Teizo; McLean, Mairi H.; Dzutsev, Amiran K.; Yao, Xiaohong; Chen, Keqiang; Huang, Jiaqiang; Gong, Wanghua; Zhou, Jiamin; Xiang, Yi; Badger, Jonathan H.; O'HUigin, Colm; Thovarai, Vishal; Tessarollo, Lino; Durum, Scott K.; Trinchieri, Giorgio; Bian, Xiu Wu; Wang, Ji Ming.
In: Journal of Immunology, Vol. 200, No. 6, 15.03.2018, p. 2174-2185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The antimicrobial peptide CRAMP is essential for colon homeostasis by maintaining microbiota balance
AU - Yoshimura, Teizo
AU - McLean, Mairi H.
AU - Dzutsev, Amiran K.
AU - Yao, Xiaohong
AU - Chen, Keqiang
AU - Huang, Jiaqiang
AU - Gong, Wanghua
AU - Zhou, Jiamin
AU - Xiang, Yi
AU - Badger, Jonathan H.
AU - O'HUigin, Colm
AU - Thovarai, Vishal
AU - Tessarollo, Lino
AU - Durum, Scott K.
AU - Trinchieri, Giorgio
AU - Bian, Xiu Wu
AU - Wang, Ji Ming
PY - 2018/3/15
Y1 - 2018/3/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85044739106&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044739106&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1602073
DO - 10.4049/jimmunol.1602073
M3 - Article
C2 - 29440355
AN - SCOPUS:85044739106
VL - 200
SP - 2174
EP - 2185
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -