The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and ex vivo tissue research
PubMed 23041323 · doi:10.1053/j.gastro.2012.09.055
What was done
Researchers investigated the role of the G protein-coupled bile acid receptor TGR5 (GPBAR1) in gastrointestinal motility. They assessed whole-gut and colonic transit, defecation frequency, and fecal water content across wild-type (tgr5-wt), knockout (tgr5-ko), and transgenic (tgr5-tg) mice. They also analyzed isolated colon tissue for muscle contractility, peristalsis, and release of peristaltic neurotransmitters (5-hydroxytryptamine and calcitonin gene-related peptide) in response to bile acids (deoxycholic acid, lithocholic acid) and a selective TGR5 agonist (oleanolic acid).
What was found
Deoxycholic acid inhibited longitudinal muscle contractility in tgr5-wt tissue but not in tgr5-ko tissue. In tgr5-wt mice, bile acids and oleanolic acid triggered 5-hydroxytryptamine and calcitonin gene-related peptide release and induced peristalsis; these responses were absent in tgr5-ko mice, although mechanically stimulated peristalsis remained intact. In vivo, whole-gut transit was 1.4-fold slower in tgr5-ko mice compared with tgr5-wt or tgr5-tg mice, and colonic transit was 2.2-fold faster in tgr5-tg mice. Defecation frequency was reduced 2.6-fold in tgr5-ko and elevated 1.4-fold in tgr5-tg mice relative to wild-type controls. Stool water content was 37% in tgr5-ko mice compared with 58% in tgr5-tg and 62% in tgr5-wt mice.
Why it matters
This study defines TGR5 as the molecular receptor mediating the prokinetic and laxative actions of luminal bile acids in the colon. It establishes a mechanistic framework for understanding bile acid-induced diarrhea or constipation and identifies TGR5 as a potential target for gastrointestinal motility disorders.
Limits
The study was conducted entirely in mouse models and ex vivo colonic tissues, so human physiological translation is unverified. Specific sample sizes and variance metrics are omitted from the abstract, and systemic or off-target effects of chronic TGR5 modulation were not evaluated.
Cited by
- supports A deficiency of concentrated bile salts entering the small intestine promotes constipation, as bile salts assist digestion and prevent constipation.