Clinical Management Unit of Endocrinology and Nutrition, Laboratory of the Biomedical Research Institute of Málaga, Virgen de la Victoria University Hospital, Universidad de Málaga, Málaga, Spain; University of Málaga, Program in Biomedicine, Translational Research and New Technologies, Spain.
Clinical Management Unit of Endocrinology and Nutrition, Laboratory of the Biomedical Research Institute of Málaga, Virgen de la Victoria University Hospital, Universidad de Málaga, Málaga, Spain.
Biomed Pharmacother. 2022 Jan;145:112448. doi: 10.1016/j.biopha.2021.112448. Epub 2021 Nov 26.
Metformin modifies the gut microbiome in type 2 diabetes and gastrointestinal tolerance to metformin could be mediated by the gut microbiome.
We enrolled 35 patients with type 2 diabetes not receiving treatment with metformin due to suspected gastrointestinal intolerance. Metformin was reintroduced at 425 mg, increasing 425 mg every two weeks until reaching 1700 mg per day. According to the occurrence of metformin-related gastrointestinal symptoms, patients were classified into three groups: early intolerance, non-tolerant, and tolerant. Gut microbiota was profiled with 16 S rRNA. This sequencing aimed to determine the differences in the baseline gut microbiota in all groups and prospectively in the tolerant and non-tolerant groups.
The classification resulted in 15 early intolerant, 10 tolerant, and 10 non-tolerant subjects. Early tolerance was characterized by a higher abundance of Subdoligranulum; while Veillonella and Serratia were higher in the non-tolerant group. The tolerant group showed enrichment of Megamonas, Megamonas rupellensis, and Phascolarctobacterium spp; Ruminococcus gnavus was lower in the longitudinal analysis. At the end point Prevotellaceae, Prevotella stercorea, Megamonas funiformis, Bacteroides xylanisolvens, and Blautia producta had a higher relative abundance in the tolerant group compared to the non-tolerant group. Subdoligranulum, Ruminococcus torques_1, Phascolarctobacterium faecium, and Eubacterium were higher in the non-tolerant group. The PICRUSt analysis showed a lower activity of the amino acid biosynthesis pathways and a higher sugar degradation pathway in the intolerant groups.
Gut microbiota of subjects with gastrointestinal intolerance depicted taxonomic and functional differences compared to tolerant patients, and this changed differently after metformin administration.
二甲双胍可改变 2 型糖尿病患者的肠道微生物群，而胃肠道对二甲双胍的耐受性可能由肠道微生物群介导。
我们招募了 35 名因疑似胃肠道不耐受而未接受二甲双胍治疗的 2 型糖尿病患者。以 425mg 起始二甲双胍剂量，每两周增加 425mg，直至达到每天 1700mg。根据二甲双胍相关胃肠道症状的发生情况，将患者分为三组：早期不耐受、不耐受和耐受。采用 16S rRNA 对肠道微生物群进行分析。本研究旨在确定所有组患者基线肠道微生物群的差异，以及前瞻性确定耐受组和不耐受组的差异。
分类得到 15 例早期不耐受、10 例耐受和 10 例不耐受患者。早期耐受的特征是 Subdoligranulum 的丰度较高，而不耐受组中 Veillonella 和 Serratia 的丰度较高。在纵向分析中，耐受组显示出 Megamonas、Megamonas rupellensis 和 Phascolarctobacterium spp 的富集，而 Ruminococcus gnavus 的丰度较低。在终点时，与不耐受组相比，耐受组 Prevotellaceae、Prevotella stercorea、Megamonas funiformis、Bacteroides xylanisolvens 和 Blautia producta 的相对丰度更高。不耐受组 Subdoligranulum、Ruminococcus torques_1、Phascolarctobacterium faecium 和 Eubacterium 的丰度较高。PICRUSt 分析显示不耐受组的氨基酸生物合成途径活性较低，糖降解途径活性较高。
与耐受患者相比，胃肠道不耐受患者的肠道微生物群在分类和功能上存在差异，并且在接受二甲双胍治疗后，这些差异发生了不同的变化。
