The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research in mice
PubMed 21683077 · doi:10.1053/j.gastro.2011.04.052
What was done
Specific pathogen-free (SPF) and germ-free BALB/c and NIH Swiss mice were used to examine the effect of intestinal microbiota on behavior and brain chemistry. SPF BALB/c mice—intact or following subdiaphragmatic vagotomy or chemical sympathectomy—received oral nonabsorbable antimicrobials (neomycin, bacitracin, and pimaricin) for 7 days. Controls included intraperitoneal antimicrobials in SPF mice and oral antimicrobials in germ-free mice. Germ-free BALB/c and NIH Swiss mice were colonized with microbiota from SPF NIH Swiss or BALB/c mice. Behavioral outcomes were tested via step-down and light preference tests. Microbiota were assessed by denaturing gradient gel electrophoresis and sequencing; gut inflammation, intestinal neurotransmitters, and brain-derived neurotrophic factor (BDNF) levels were measured.
What was found
The abstract reports no numerical values or confidence intervals. Oral antimicrobials in SPF mice transiently altered gut microbiota composition and increased exploratory behavior and hippocampal BDNF expression without altering inflammatory activity or gut neurotransmitter levels, and these changes persisted despite vagal or sympathetic denervation. Intraperitoneal antimicrobials in SPF mice and oral antimicrobials in germ-free mice did not alter behavior. Colonization of germ-free BALB/c mice with NIH Swiss microbiota increased exploratory behavior and hippocampal BDNF, whereas colonization of germ-free NIH Swiss mice with BALB/c microbiota reduced exploratory behavior.
Why it matters
This study demonstrates in rodents that gut microbial composition can influence central neurochemistry and behavior independently of autonomic innervation or local gut inflammation.
Limits
The study is entirely preclinical in mice and cannot be directly generalized to humans. The abstract does not report sample sizes, exact effect sizes, or variance metrics, and the precise non-autonomic molecular mechanism linking the gut to the brain remains undetermined.
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