Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes

Abstract

Antidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed to characterize the spatial variation of the gut microbiome in response to metformin treatment by using a high-fat diet-induced type 2 diabetes mouse model of both sexes. Four intestinal parts, each at the luminal and mucosal layer level, were analyzed in this study by performing 16S rRNA sequencing covering six variable regions (V1-V6) of the gene and thus allowing to obtain in-depth information about the microbiome composition. We identified significant differences in gut microbiome diversity in each of the intestinal parts regarding the alpha and beta diversities. Metformin treatment altered the abundance of different genera in all studied intestinal sites, with the most pronounced effect in the small intestine, where Lactococcus increased remarkably. The abundance of Lactobacillus was substantially lower in male mice compared to female mice in all locations, in addition to an enrichment of opportunistic pathogens. Diet type and intestinal layer had significant effects on microbiome composition at each of the sites studied. We observed a different effect of metformin treatment on the analyzed subsets, indicating the multiple dimensions of metformin’s effect on the gut microbiome.

Dextran sodium sulfate-induced colitis alters the proportion and composition of replicating gut bacteria

“…68,69 In contrast, Group 2 bacterial taxa Erysipelatoclostridium and E. fissicatena persistently increase after colitis development, as reported elsewhere. 70–87 While the mechanisms behind this increase are unclear, our data align with the literature while also contributing a finer time scale regarding their changes in abundance during colitis.…”

“…What allows Erysipelatoclostridium to benefit from perturbations can only be speculated, since its metabolism is not well described, 70 despite being a dominant gut Clostridial taxon. 131 The best described member of this genus is C. ramosum , which is reported to produce low amounts of acetate and possibly butyrate, and can significantly increase the number and function of anti-inflammatory Treg cells.…”

Integrated Analysis of Gut Microbiome and Adipose Transcriptome Reveals Beneficial Effects of Resistant Dextrin from Wheat Starch on Insulin Resistance in Kunming Mice

“…Total genomic DNA of the gut microbiome was extracted from cecum content samples using previously described methods [24]. The hypervariable region V3-V4 of the bacterial 16S rRNA gene was amplified with primer pairs 338F (5 ′ -ACTCCTACGGGAGGCAGCAG-3 ′ ) and 806R (5 ′ -GGACTACHVGGGTWTCTAAT-3 ′ ), employing an ABI GeneAmp ® 9700 PCR thermocycler (ABI, Foster, CA, USA).…”

“…However, the specific changes in gut microbiota may vary, possibly due to differences in the methods of preparation or the raw materials of RD [52].The abundances of these prominent bacteria enriched by either the RD or metformin-supplemented groups have been associated with the improvement in glucose-lipid metabolism disorders, as well as the well-known ability of Bacteroides, Muribaculum, and Bifidobacterium to produce short-chain fatty acids. Some articles suggest that metformin has a limited impact on the regulation of gut microbiota in the cecum of high-fat diet-induced diabetic mice, primarily influencing the small intestine's flora composition [24]. However, numerous studies increasingly emphasize the role of cecum flora, which can directly impact metabolism [53][54][55].…”

“…Metformin is widely recognized as a hypoglycemic agent, known for its ability to reduce blood glucose levels by inhibiting hepatic glucose production [23]. Recent studies have presented compelling evidence that metformin exerts notable effects on the gut microbiota, influencing both the small and large intestines [24,25]. In a rat model subjected to a high-fat diet, metformin demonstrated its capacity to modulate glucose-sensing pathways in the upper small intestine.…”