摘要
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 depressionlike 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.
基金
by Guangdong Basic and Applied Basic Research Foundation,No.2023A1515012394.
