Intervention in gut microbiota increases intestinal γ-aminobutyric acid and alleviates anxiety behavior: a possible mechanism via the action on intestinal epithelial cells.
Level 5 - mechanism / opinion, no new human data
Animal and in vitro mechanistic study without human data.
PubMed 39301289 · doi:10.3389/fcimb.2024.1421791
What was done
Mice were administered either neomycin or Bifidobacterium bifidum TMC3115 to evaluate changes in intestinal γ-aminobutyric acid (GABA) concentrations and anxiety behavior. Researchers assessed serum levels of serotonin, corticosterone, and GABA, examined GABA receptor subunit expression on intestinal epithelial cells, and evaluated mitogen-activated protein kinase (MAPK) signaling in vitro and in murine small intestinal and colonic epithelial cells.
What was found
Intestinal GABA concentrations increased in mice treated with neomycin or TMC3115. Administration of TMC3115 reduced anxiety-like behavior without altering serum concentrations of serotonin, corticosterone, or GABA. Intestinal epithelial cells expressed GABA receptor subunits and demonstrated MAPK signaling upon GABA stimulation. TMC3115 administration induced MAPK signaling in colonic epithelial cells but not in small intestinal epithelial cells. No numerical values or effect sizes were reported in the abstract.
Why it matters
This study provides evidence that gut microbiota-derived GABA can influence host behavior via local colonic epithelial receptor signaling rather than crossing into the bloodstream or past the blood-brain barrier.
Limits
The study is limited to mouse models and in vitro cell experiments, precluding direct clinical conclusions. The abstract does not report sample sizes, specific behavioral metrics, or quantitative effect sizes.
Cited by
- supports GABA produced in the gut does not cross the blood-brain barrier.