Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Shijiazhuang 050017, China.
College of Forensic Medicine, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medical University, Shijiazhuang 050017, China.
Int J Mol Sci. 2024 Jun 30;25(13):7250. doi: 10.3390/ijms25137250.
The glucose-lowering drug metformin alters the composition of the gut microbiome in patients with type 2 diabetes mellitus (T2DM) and other diseases. Nevertheless, most studies on the effects of this drug have relied on fecal samples, which provide limited insights into its local effects on different regions of the gut. Using a high-fat diet (HFD)-induced mouse model of T2DM, we characterize the spatial variability of the gut microbiome and associated metabolome in response to metformin treatment. Four parts of the gut as well as the feces were analyzed using full-length sequencing of 16S rRNA genes and targeted metabolomic analyses, thus providing insights into the composition of the microbiome and associated metabolome. We found significant differences in the gut microbiome and metabolome in each gut region, with the most pronounced effects on the microbiomes of the cecum, colon, and feces, with a significant increase in a variety of species belonging to , , , and . Metabolomics analysis showed that metformin had the most pronounced effect on microbiome-derived metabolites in the cecum and colon, with several metabolites, such as carbohydrates, fatty acids, and benzenoids, having elevated levels in the colon; however, most of the metabolites were reduced in the cecum. Thus, a wide range of beneficial metabolites derived from the microbiome after metformin treatment were produced mainly in the colon. Our study highlights the importance of considering gut regions when understanding the effects of metformin on the gut microbiome and metabolome.
二甲双胍等降糖药物可改变 2 型糖尿病（T2DM）及其他疾病患者的肠道微生物组成。然而，大多数关于该药物影响的研究都依赖粪便样本，这对其在肠道不同区域的局部影响提供的信息有限。我们采用高脂肪饮食（HFD）诱导的 T2DM 小鼠模型，对二甲双胍治疗后肠道微生物组及其相关代谢组的空间变异性进行了特征描述。我们使用全长 16S rRNA 基因测序和靶向代谢组学分析，对肠道的四个部分以及粪便进行了分析，从而深入了解微生物组和相关代谢组的组成。我们发现每个肠道区域的肠道微生物组和代谢组均存在显著差异，其中以盲肠、结肠和粪便中的微生物组变化最为显著，属于 、 、 和 的多种物种丰度显著增加。代谢组学分析表明，二甲双胍对盲肠和结肠中的微生物组衍生代谢物的影响最为显著，一些代谢物（如碳水化合物、脂肪酸和苯类）在结肠中的水平升高；而在盲肠中，大多数代谢物则减少。因此，在接受二甲双胍治疗后，主要在结肠中产生了广泛的有益的微生物组衍生代谢物。本研究强调了在理解二甲双胍对肠道微生物组和代谢组影响时，考虑肠道区域的重要性。
