期刊
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
卷 49, 期 -, 页码 44-51出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2015.10.040
关键词
Calcium-sensing receptor; Diarrhea; Intestinal inflammation; Intestinal permeability; Microbiota; Polyamines
资金
- National Institute of Allergy and Infectious Diseases [RO1 AI093370]
- Department of Defense [CA111002]
- Ocala Royal Dames for Cancer Research
- Gatorade Foundation
- Florida Breast Cancer Foundation to the University of Florida [UL1 PRO29890]
- NIH/NCRR Clinical and Translational Science Award
- CDNHF/NASPGHAN [00102979]
- NICHD [K08HD079674]
- Children's Miracle Network
- National Institute of Allergy and Infectious Diseases [RO1 AI093370]
- Department of Defense [CA111002]
- Ocala Royal Dames for Cancer Research
- Gatorade Foundation
- Florida Breast Cancer Foundation to the University of Florida [UL1 PRO29890]
- NIH/NCRR Clinical and Translational Science Award
- CDNHF/NASPGHAN [00102979]
- NICHD [K08HD079674]
- Children's Miracle Network
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [K08HD079674] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI093370] Funding Source: NIH RePORTER
The gastrointestinal (GI) tract must balance the extraction of energy and metabolic end-products from ingested nutrition and resident gut microbes and the maintenance of a symbiotic relationship with this microbiota, with the ability to mount functional immune responses to pathogenic organisms to maintain GI health. The gut epithelium is equipped with bacteria-sensing mechanisms that discriminate between pathogenic and commensal microorganisms and regulate host responses between immunity and tolerance. The epithelium also expresses numerous nutrient-sensing receptors, but their importance in the preservation of the gut microbiota and immune homeostasis remains largely unexplored. Observations that a deficiency in the extracellular calcium-sensing receptor (CaSR) using intestinal epithelium-specific receptor knockout mice resulted in diminished intestinal barrier integrity, altered composition of the gut microbiota, modified expression of intestinal pattern recognition receptors, and a skewing of local and systemic innate responses from regulatory to stimulatory, may change the way that this receptor is considered as a potential immunotherapeutic target in gut homeostasis. These findings suggest that pharmacologic CaSR activators and CaSR-based nutrients such as calcium, polyamines, phenylalanine, tryptophan, and oligo-peptides might be useful in conditioning the gut microenvironment, and thus, in the prevention and treatment of disorders such as inflammatory bowel disease (IBD), infectious enterocolitis, and other inflammatory and secretory diarrheal diseases. Here, we review the emerging roles of the CaSR in intestinal homeostasis and its therapeutic potential for gut pathology. (C) 2015 Elsevier Ltd. All rights reserved.
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