Commensal microbiota modulate murine behaviors in a strictly contamination‐free environment confirmed by culture‐based methods

Abstract

Background There is increasing evidence suggesting the existence of an interaction between commensal microbiota, the gut and the brain. The aim of this study was to examine the influence of commensal microbiota on the host behaviors in a contaminationfree environment, which was verified by culture-based methods. Methods Open-field and marble-burying tests were used to analyze anxiety-like behaviors and locomotor activity in gnotobiotic BALB/c mice with a common genetic background in a sterile isolator. The monoamine levels in several regions of the brain were measured in germfree (GF) mice and commensal fecal microbiota-associated mice (EX-GF). Key Results A 24-h exposure to the environment outside the sterile isolators rendered GF mice less anxious than those not contaminated, while there was no change in the locomotion. EX-GF mice, the gnotobiotic mice with normal specific pathogen-free microbiota, were less anxious and active than GF mice using open-field and marble-burying tests. The norepinephrine, dopamine, and serotonin turnover rates were higher in the EX-GF mice than in the GF mice in most regions of the brain, suggesting that monoaminergic neurotransmission might increase in the EX-GF mice comparing the GF mice. Monoassociation with Brautia coccoides reduced the anxiety level, but it did not affect the locomotor activity. In contrast, colonization with Bifidobacterium infantis decreased the locomotor activity, while having little effect on the anxiety level. Conclusions & Inferences These results strongly support the current view that gut microorganisms modulate brain development and behavior.

Effect of Probiotics on Central Nervous System Functions in Animals and Humans: A Systematic Review

“…9,29,30,35,37,45,[78][79][80][81][82] In humans, we are not able to adapt most of these models for ethical reasons. Ten of the animal studies included in our review used probiotics in animals whose health state had been disturbed by various manipulations, which included antibiotic treatment, gene knockout, inflammation, infection, maternal immune activation, hyperammonemia, and diabetic induction, and depression induced by myocardial infarction.…”

Impact of the gut microbiota on the neuroendocrine and behavioural responses to stress in rodents

“…Such discrepancies could result from methodological differences but the genetic background also plays an important role in the anxious behaviour (Griebel et al, 2000). Interestingly, the F344 rat strain we used, as well as the BALB/c mouse strain chosen by Nishino et al (2013) are both sensitive to stress, while the mice strains chosen in the other studies (Swiss, NMRI) are reported to be moderately emotive. Accordingly, we hypothesize that the gut microbiota has a buffering effect on the behavioural response to an acute stress.…”

“…2). Only in one study (Nishino et al, 2013) did GF mice show a greater anxiety-like behaviour than their SPF counterparts, when subjected to the open-field or the marble-burying test (Fig. 2).…”

Vaccinating against depression or anxiety: is it plausible?

“…Conversely, mono-association with enteropathogenic Escherichia coli enhanced the response to stress [4]. Mono-association with Blautia (Clostridium) coccoides (the most dominant inhabitant of the human gut) reduced the anxiety level [5].…”

“…The intestinal microbiota has been found to modulate anxiety-like behavior in rodents [4,5], but a literature search (PubMed and ClinicalTrials.gov) found no vaccine tested in animal models of anxiety or undergoing clinical trials in anxiety disorders.…”