Hyperbaric oxygen improves depression‐like behaviors in chronic stress model mice by remodeling gut microbiota and regulating host metabolism

Abstract

Aims: There is growing evidence that the gut microbiota plays a significant part in the pathophysiology of chronic stress. The dysbiosis of the gut microbiota closely relates to dysregulation of microbiota-host cometabolism. Composition changes in the gut microbiota related to perturbations in metabolic profiles are vital risk factors for disease development. Hyperbaric oxygen therapy is commonly applied as an alternative or primary therapy for various diseases. Therefore, a metabolic and gut bacteria perspective is essential to uncover possible mechanisms of chronic stress and the therapeutic effect of hyperbaric oxygenation. We determined that there were significantly disturbed metabolites and disordered gut microbiota between control and chronic stress group. The study aims to offer further information on the interactions between host metabolism, gut microbiota, and chronic stress.Methods: At present, chronic unpredictable mild stress is considered the most widespread method of modeling chronic stress in animals, so we used a chronic unpredictable mild stress mouse model to characterize changes in the metabolome and microbiome of depressed mice by combining 16S rRNA gene sequencing and UHPLC-MS/MS-based metabolomics. Pearson's correlation-based clustering analysis was performed with above metabolomics and fecal microbiome data to determine gut microbiota-associated metabolites. Results:We found that 18 metabolites showed a significant correlation with campylobacterota. Campylobacterota associated metabolites were significantly enriched mainly in the d-glutamate and d-glutamine metabolism. Hyperoxia treatment may improve depressionlike behaviors in chronic stress model mice through regulating the disrupted metabolites.Conclusions: Hyperbaric oxygen improves depression-like behaviors in chronic stress model mice by remodeling Campylobacterota associated metabolites.

Gut microbiota-associated metabolites and risk of ischemic stroke in REGARDS

“…Environmental and social factors may also influence risk for stroke, with recognition of the impact of commensal microorganisms on health and disease. 59,60 Emerging gut-brain-microbiome research using murine models, humanized mouse models, and human clinical trials 61,62 has shown that microbiome-related metabolic changes can be induced by stress, 63 exercise, 64 and even changes in the circadian rhythm. These alterations in metabolite composition have been shown across different brain regions, peripheral organs, and in circulation.…”

Clinical value and mechanistic analysis of HIIT on modulating risk and symptoms of depression: A systematic review

“…Several studies included in this systematic review reported a significant increase in the following factors: the maximal oxygen uptake capacity and the relief of depressive symptoms in subjects treated with HIIT ( Choi et al., 2018 ; Chrysohoou et al., 2015 ; Dall et al., 2015 ; Flemmen et al., 2014 ; Freyssin et al., 2012 ; Plag et al., 2020 ). This observation may be rationalized as follows: increased maximal oxygen uptake capacity enhances cardiorespiratory fitness, which in turn promotes cerebrovascular function, neuronal growth and connectivity, and gut flora metabolism ( Bang-Kittilsen et al., 2022 ; Chaddock-Heyman et al., 2013 ; Zhang et al., 2022 ). Additionally, higher maximal oxygen uptake was associated with greater brain volume and protein integrity ( Chaddock-Heyman et al., 2013 ).…”

“…Recent studies have reported a potential target for the treatment of depression, hypoxia inducible factor-1 (HIF-1), by mediating mitochondrial metabolism in response to the phenomenon of oxidative stress occasioned by insufficient oxygen levels in tissues ( Kang et al., 2021 ). Intermittent hypoxic acclimatization training with hyperbaric oxygen therapy could increase HIF-1 expression and alleviate depressive symptoms in subjects ( Kang et al., 2021 ; Zhang et al., 2022 ). It is noteworthy that HT treatment also increased HIF-1 expression in the body, which may also contribute to the alleviation of depressive symptoms via HIIT ( Holloway et al., 2015 ; Tryfonos et al., 2021 ).…”

The Impact of Chronic Stress on Behavior and Body Mass in New Animal Models

“…Furthermore, chronic unpredictable mild stress is currently considered the most widely used method for modeling chronic stress in animals. It has been employed to investigate the effects of chronic stress on various conditions, including colonic inflammation, gastric precancerous lesions, depression, and other systemic disease [36].…”