Gut Microbiome-Targeted Modulations Regulate Metabolic Profiles and Alleviate Altitude-Related Cardiac Hypertrophy in Rats

Hu, Yichen; Pan, Zhiyuan; Huang, Zongyu; Li, Yan; Han, Ni; Zhuang, Xiaomei; Peng, Hui; Gao, Quansheng; Wang, Qing; Lee, B. J. Yang; Zhang, Heping; Bi, Yujing; Xu, Zhenjiang Zech

doi:10.1128/spectrum.01053-21

Cited by 17 publications

(15 citation statements)

References 57 publications

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“…In addition, acute hypoxia exposure leads to changes in intestinal barrier permeability 22 and gut microbiota composition 23 , resulting in host maladaption to high altitude and incidence of AMS 24 . Increased Parabacteroides , Akkermansia , Lactobacillus , Bacteroides , and decreased Prevotella were also found in human and animal models of AHH exposure 25 – 28 . Bacteroides , Parabacteroides , Butyricimonas , Lactobacillus , Phascolarctobacterium , and Akkermansia are intestinal commensal bacteria, most of whom are SCFAs producing bacteria 28 – 30 .…”

Section: Discussionmentioning

confidence: 89%

Association analysis of gut microbiota-metabolites-neuroendocrine changes in male rats acute exposure to simulated altitude of 5500 m

Wang¹,

Liu²,

Xie³

et al. 2023

Sci Rep

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Hyperactivation of hypothalamic–pituitary–adrenal (HPA) axis and hypothalamic–pituitary–thyroid (HPT) axis were found in acute high altitude challenge, but the role of gut microbiota and metabolites is unknown. We utilized adult male Sprague–Dawley rats at a simulated altitude of 5500 m for 3 days in a hypobaric-hypoxic chamber. ELISA and metabolomic analyses of serum and 16S rRNA and metabolomic analyses of fecal samples were then performed. Compared with the normoxic group, serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), and thyroxine (tT4) were increased in the hypoxia group, whereas thyrotropin-releasing hormone (TRH) was decreased. Bacteroides, Lactobacillus,Parabacteroides,Butyricimonas,SMB53,Akkermansia,Phascolarctobacterium, and Aerococcus were enriched in hypoxia group, whereas [Prevotella], Prevotella,Kaistobacter,Salinibacterium, and Vogesella were enriched in normoxic group. Metabolomic analysis indicated that acute hypoxia significantly affected fecal and serum lipid metabolism. In addition, we found five fecal metabolites may mediate the cross-talk between TRH, tT4, and CORT with [Prevotella], Kaistobacter,Parabacteroides, and Aerococcus, and 6 serum metabolites may mediate the effect of TRH and tT4 on [Prevotella] and Kaistobacter by causal mediation analysis. In conclusion, this study provides new evidence that key metabolites mediate the cross-talk between gut microbiota with HPA and HPT axis under acute hypobaric hypoxia challenge.

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Section: Discussionmentioning

confidence: 89%

Association analysis of gut microbiota-metabolites-neuroendocrine changes in male rats acute exposure to simulated altitude of 5500 m

Wang¹,

Liu²,

Xie³

et al. 2023

Sci Rep

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“…Specifically, Lactobacillaceae probiotics possess antitumor, antitoxic, cholesterol-lowering, antibacterial, and antiviral activity ( Nazir et al, 2018 ). Hu et al (2022) found that the abundance of Lactobacillaceae changed with prolonged hypoxic exposure in a hypoxic environment. Based on the above studies, we believe that changes in the abundance of Lactobacilli may be a defining feature after hypobaric hypoxia exposure, which is of great significance for future studies.…”

Section: Discussionmentioning

confidence: 99%

Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice

Zhao

Cui

et al. 2022

Front. Microbiol.

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BackgroundThe widely accepted microbiome-gut-brain axis (MGBA) hypothesis may be essential for explaining the impact of high-altitude exposure on the human body, especially brain function. However, studies on this topic are limited, and the underlying mechanism remains unclear. Therefore, this study aimed to determine whether high-altitude-induced working memory dysfunction could be exacerbated with gut microbiota disruption.Methods and resultsC57BL/6 mice were randomly divided into three groups: control, high-altitude exposed (HAE), and high-altitude exposed with antibiotic treatment (HAE-A). The HAE and HAE-A groups were exposed to a low-pressure oxygen chamber (60–65 kPa) simulating the altitude of 3,500–4,000 m for 14 days, The air pressure level for the control group was maintained at 94.5 kPa. Antibiotic water (mixed with 0.2 g/L of ciprofloxacin and 1 g/L of metronidazole) was provided to the HAE-A group. Based on the results of the novel object test and P300 in the oddball behavioral paradigm training test, working memory dysfunction was aggravated by antibiotic treatment. We determined the antioxidant capacity in the prefrontal cortex and found a significant negative influence (p < 0.05) of disturbed gut microbiota on the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The same trend was also observed in the apoptosis-related functional protein content and mRNA expression levels in the prefrontal cortex, especially the levels of bcl-2, Bax, and caspase-3. The high-altitude environment and antibiotic treatment substantially affected the richness and diversity of the colonic microbiota and reorganized the composition and structure of the microbial community. S24-7, Lachnospiraceae, and Lactobacillaceae were the three microbial taxa with the most pronounced differences under the stimulation by external factors in this study. In addition, correlation analysis between colonic microbiota and cognitive function in mice demonstrated that Helicobacteraceae may be closely related to behavioral results.ConclusionDisrupted gut microbiota could aggravate working memory dysfunction induced by high-altitude exposure in mice, indicating the existence of a link between high-altitude exposure and MGBA.

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“…For instance, plateau pikas and plateau pikas are rich in members of the families Lachnospiraceae and Clostridiaceae, which not only may enhance energy acquisition from food but also convert dietary fibers into SCFA ( Wang et al, 2022 ). SCFAs primarily suppress inflammation by inhibiting the NF-κB pathway and/or histone deacetylase (HDAC) functionality, thereby downregulating pro-inflammatory cytokines ( Hu et al, 2022 ). Similar phenomena have been observed in other high-altitude species.…”

Section: Impact Of Intestinal Microbiota Alterations On Organismal He...mentioning

confidence: 99%

“…The adverse conditions present in high-altitude environments have driven natural selection among populations ( Bai et al, 2022 ). Factors such as hypobaric hypoxia, low temperatures, and high radiation not only impact organismal reproduction and survival but also accelerate population-level evolution and physiological adaptations ( Hu et al, 2022 ). These conditions may also precipitate high-altitude reactions or illnesses in susceptible individuals, potentially leading to dysbiosis in the intestinal microbiota ( Lan et al, 2017 ; Zuo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

High-altitude-induced alterations in intestinal microbiota

Liu,

Chen,

Xiao

et al. 2024

Front. Microbiol.

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In high-altitude environments characterized by low pressure and oxygen levels, the intestinal microbiota undergoes significant alterations. Whether individuals are subjected to prolonged exposure or acute altitude changes, these conditions lead to shifts in both the diversity and abundance of intestinal microbiota and changes in their composition. While these alterations represent adaptations to high-altitude conditions, they may also pose health risks through certain mechanisms. Changes in the intestinal microbiota induced by high altitudes can compromise the integrity of the intestinal mucosal barrier, resulting in gastrointestinal dysfunction and an increased susceptibility to acute mountain sickness (AMS). Moreover, alterations in the intestinal microbiota have been implicated in the induction or exacerbation of chronic heart failure. Targeted modulation of the intestinal microbiota holds promise in mitigating high-altitude-related cardiac damage. Dietary interventions, such as adopting a high-carbohydrate, high-fiber, low-protein, and low-fat diet, can help regulate the effects of intestinal microbiota and their metabolic byproducts on intestinal health. Additionally, supplementation with probiotics, either through dietary sources or medications, offers a means of modulating the composition of the intestinal microbiota. These interventions may offer beneficial effects in preventing and alleviating AMS following acute exposure to high altitudes.

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Gut Microbiome-Targeted Modulations Regulate Metabolic Profiles and Alleviate Altitude-Related Cardiac Hypertrophy in Rats

Cited by 17 publications

References 57 publications

Association analysis of gut microbiota-metabolites-neuroendocrine changes in male rats acute exposure to simulated altitude of 5500 m

Association analysis of gut microbiota-metabolites-neuroendocrine changes in male rats acute exposure to simulated altitude of 5500 m

Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice

High-altitude-induced alterations in intestinal microbiota

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