Modulating oral microbiota ameliorates hypobaric hypoxia-induced anxiety- and depression-like behaviors in mice.

Abstract

Background: Hypobaric hypoxia exposure (HHE) often causes neuropsychiatric disorders. Due to its complex mechanism, efficient strategies for alleviating HHE-induced anxiety- and depression-like behaviors remain limited.

Aim: To characterize alterations in the oral and gut microbiota following HHE and to explore a potential microbiota-based intervention to mitigate associated psychiatric symptoms.

Methods: C57BL/6J mice were exposed to simulated high-altitude hypoxia (5000 m) for 1, 3, 5, or 7 days. Behavioral assessments, including the open field test, elevated plus maze, and forced swim test, were conducted to evaluate anxiety- and depression-like behaviors. Oral and fecal microbiota were analyzed using 16S rRNA sequencing to assess changes in microbial composition and diversity. Immunofluorescence staining was performed to examine c-Fos expression in brain nuclei. A probiotic formulation containing Lactobacillus rhamnosus (L. rhamnosus) DSM17648, Lactobacillus acidophilus DDS-1, and L. rhamnosus UALR-06 was administered to mice subjected to one day of HHE (HH1) to evaluate its therapeutic efficacy.

Results: Behavioral tests revealed that HHE caused anxiety- and depression-like behaviors, which were most pronounced after 1 day of exposure. The IF data revealed significantly increased expression of c-Fos in various brain nuclei after HHE, including the anterior cingulate cortex, paraventricular thalamic nucleus, lateral habenula nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, and periaqueductal gray. The 16S rRNA sequencing results demonstrated a sharp decline in the abundance of Lactobacillus in the oral microbiota of mice exposed to HH1 and a marked decrease in the abundance of Lactobacillus and Bifidobacterium in the fecal microbiota of mice exposed to three days of HHE. Finally, oral administration and gavage of Lactobacillus significantly alleviated anxiety- and depression-like behaviors in HH1 mice.

Conclusion: HHE caused significant variations in the oral and fecal microbiota of mice. Lactobacillus supplementation alleviated anxiety- and depression-like behaviors in mice. Improving oral flora may relieve HHE-induced psychiatric disorders.