The Co-Regulation of the Gut Microbiome and Host Genes Might Play Important Roles in Metformin Intolerance
Research Square (Research Square)(2021)
摘要
Abstract Background Metformin is commonly considered the first-line therapy for type 2 diabetes (T2D) and also had potential treating utility in other areas; however, ~20% of patients experience intolerance with unclear underlying mechanisms. In the present study, we performed the full-length 16S rRNA (V1-V9) for the fecal samples and bioinformatics analysis to study the mechanisms of the metformin intolerance combining the gut flora and host. Results The results showed that Barnesiella (p=0.046) and Parabacteroides goldsteinii (p=0.016), which transforming primary into secondary bile acid (SBA), were higher in the TS than T group, and were eliminated in the TSa group, which might lead to the accumulation of primary bile acids (PBA) such as cholic acid (CA), the change of GLI1 gene, and following diarrhea in the TSa group. Lactobacillus brevis (p=0.024) and Lactobacillus plantarum (p=0.026) were up-regulated in TSa than TS group. The two flora might cause the changes of genes including FOXA2, HTR7, GADPH, and intolerance relief, which might be a worthwhile future direction for preventing metformin intolerance. Conclusions These results hinted that the differential flora and co-regulation of them with the host might be intolerance-related. Our results partly provided theoretical support for intolerance prevention.
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关键词
metformin,gut microbiome,host genes,co-regulation
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