Chen Lu, Xu Shuo, Zhou Qiankun, Zhao Tianming, Zhao Yuanyi, Chen Xinyu, Zhu Wenlong, Ding Jing, Zheng Haining, Jiang Mingzuo, Zhao Si, Zhu Hanlong, Yang Miaofang, Wang Fangyu
Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Department of Gastroenterology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Free Radic Biol Med. 2025 Sep;237:600-614. doi: 10.1016/j.freeradbiomed.2025.05.420. Epub 2025 May 31.
Hyperbaric oxygen therapy (HBOT) has been validated as a potential treatment for metabolic dysfunction, but its effect on metabolic dysfunction-associated steatohepatitis (MASH) has not been well elucidated. This study aims to determine the effect of HBOT on diet-induced MASH in mice.
HBOT (2.2 ATA, 60 min per day for 4 weeks) was administrated in mice fed with 12-week high-fat, high-cholesterol (HFHC) and 4-week methionine- and choline-deficient (MCD) diets to explore the therapeutic effects on MASH. 16S rRNA sequencing, oral broad-spectrum antibiotic cocktail (Abx) administration and non-targeted metabolomics were employed to further investigate the modulatory effect of HBOT on gut microbiota and liver metabolism.
Dyslipidemia, liver dysfunction, hepatic steatosis, inflammation and fibrosis were markedly attenuated by HBOT intervention in HFHC-fed mice. In parallel, HBOT showed similar therapeutic effects in MCD-fed mice. Furthermore, 16S rRNA sequencing revealed that the MASH-associated community diversity reduction of gut microbiota was reversed by HBOT, which also improved gut dysbiosis and increased the relative level of beneficial bacteria, such as Alloprevotella and Akkermansia. Removal of gut microbiota by Abx obviously abolished the therapeutic effect of HBOT. Additionally, HBOT significantly changed liver metabolism and ameliorated the changes of sphingolipids, which were significantly correlated with gut microbiota changes.
In summary, HBOT protects against diet-induced steatohepatitis in mice by remodeling the gut microbiota and improving the liver metabolic profile, indicating promising therapy for MASH.
高压氧疗法（HBOT）已被确认为代谢功能障碍的一种潜在治疗方法，但其对代谢功能障碍相关脂肪性肝炎（MASH）的影响尚未得到充分阐明。本研究旨在确定HBOT对饮食诱导的小鼠MASH的影响。
对喂食12周高脂肪、高胆固醇（HFHC）饮食和4周蛋氨酸及胆碱缺乏（MCD）饮食的小鼠进行HBOT治疗（2.2ATA，每天60分钟，共4周），以探究其对MASH的治疗效果。采用16S rRNA测序、口服广谱抗生素鸡尾酒（Abx）以及非靶向代谢组学进一步研究HBOT对肠道微生物群和肝脏代谢的调节作用。
在喂食HFHC的小鼠中，HBOT干预显著减轻了血脂异常、肝功能障碍、肝脏脂肪变性、炎症和纤维化。同时，HBOT在喂食MCD的小鼠中也显示出类似的治疗效果。此外，16S rRNA测序显示，HBOT逆转了与MASH相关的肠道微生物群落多样性降低，还改善了肠道生态失调，并增加了有益细菌（如别普雷沃菌属和阿克曼氏菌属）的相对水平。通过Abx清除肠道微生物群明显消除了HBOT的治疗效果。此外，HBOT显著改变了肝脏代谢，并改善了鞘脂的变化，这些变化与肠道微生物群的变化显著相关。
总之，HBOT通过重塑肠道微生物群和改善肝脏代谢谱来保护小鼠免受饮食诱导的脂肪性肝炎，表明其对MASH具有潜在的治疗前景。
