Wang Yao, Zhuang Kai, Yi Qiuxia, Wu Yalan, Luo Yi, Ouyang Yulin, Li Liang, Li Chun, Luo Huanhuan
State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Chinese Medicine Guangdong Laboratory, Hengqin, Guangdong, China.
Front Immunol. 2025 Aug 27;16:1625609. doi: 10.3389/fimmu.2025.1625609. eCollection 2025.
Climate and environmental changes pose significant threats to human metabolic health; however, the specific effects of individual environmental factors on metabolic diseases remain poorly understood. This study aimed to investigate the impact of a high humidity environment (HH) on fasting blood glucose (FBG), intestinal barrier integrity, and gut microbiota composition.
We analyzed clinical samples collected during HH exposure and performed a controlled male mouse experiment. FBG and hormone levels were assessed, and intestinal barrier integrity was evaluated using western blot and immunofluorescence staining. Gut microbiota composition was profiled via 16S rDNA sequencing. Mechanistic insights were obtained through fecal microbiota transplantation (FMT), Mendelian randomization (MR) analysis, and metabolomic profiling. An antibiotic cocktail (ABX) intervention was applied to determine the reversibility of HH-induced effects.
Clinical samples collected under HH conditions showed elevated FBG, increased glucagon (GC) levels, impaired intestinal barrier function, and decreased serum gamma-aminobutyric acid (GABA) concentrations. 16S rDNA sequencing revealed increased abundances of , and . Metabolomic analysis demonstrated reduced serum GABA levels, which correlated with intestinal barrier disruption and activation of the MDP-NOD2 pathway in pancreatic β-cells. HH exposure also downregulated GAD67 expression, reducing GABA synthesis and leading to enhanced GC secretion from islet α-cells. FMT suggested that gut microbiota alterations mediated HH-induced FBG elevation. ABX treatment effectively reversed these metabolic and microbial changes.
Our findings demonstrate that a high humidity environment disrupts gut microbiota homeostasis, impairs the intestinal barrier, and reduces GABA synthesis in pancreatic β-cells, thereby promoting the development of type 2 diabetes mellitus (T2DM).
气候和环境变化对人类代谢健康构成重大威胁；然而，个体环境因素对代谢性疾病的具体影响仍知之甚少。本研究旨在调查高湿度环境（HH）对空腹血糖（FBG）、肠道屏障完整性和肠道微生物群组成的影响。
我们分析了在HH暴露期间收集的临床样本，并进行了一项对照雄性小鼠实验。评估了FBG和激素水平，并使用蛋白质免疫印迹法和免疫荧光染色评估肠道屏障完整性。通过16S rDNA测序分析肠道微生物群组成。通过粪便微生物群移植（FMT）、孟德尔随机化（MR）分析和代谢组学分析获得了机制性见解。应用抗生素鸡尾酒（ABX）干预来确定HH诱导效应的可逆性。
在HH条件下收集的临床样本显示FBG升高、胰高血糖素（GC）水平增加、肠道屏障功能受损以及血清γ-氨基丁酸（GABA）浓度降低。16S rDNA测序显示 、 和 的丰度增加。代谢组学分析表明血清GABA水平降低，这与肠道屏障破坏和胰腺β细胞中MDP-NOD2途径的激活相关。HH暴露还下调了GAD67表达，减少了GABA合成，并导致胰岛α细胞GC分泌增强。FMT表明肠道微生物群改变介导了HH诱导的FBG升高。ABX治疗有效逆转了这些代谢和微生物变化。
我们的研究结果表明，高湿度环境会破坏肠道微生物群稳态，损害肠道屏障，并减少胰腺β细胞中的GABA合成，从而促进2型糖尿病（T2DM）的发展。
