关键词: 妊娠期糖尿病, 肠道微生态, 益生菌, 炎症反应, 妊娠结局

Abstract: BACKGROUND: Probiotics can help alleviate abnormal glucose and lipid metabolism and insulin resistance in patients with type 2 diabetes by remodeling the structure of the gut microbiota, affecting gut microbiota metabolites, and improving intestinal barrier function. Therefore, therapeutic approaches such as adjusting dietary structure, taking probiotic supplements, and fecal microbiota transplantation are expected to become new targets for the prevention and treatment of gestational diabetes mellitus.
OBJECTIVE: To investigate the effects of probiotic supplements on the structure of the gut microbiota, inflammatory response, and glucose and lipid metabolism in rats with gestational diabetes mellitus, providing experimental evidence for clinical application.
METHODS: A total of 62 SPF-grade female Sprague-Dawley rats and 42 male Sprague-Dawley rats were housed together at a ratio of 1.5:1 for mating. After successful mating, eight female rats were randomly selected using a random number table as the blank group. The remaining female rats were fed a high-fat and high-sugar diet combined with an intraperitoneal injection of streptozotocin (35 mg/kg) to establish a rat model of gestational diabetes mellitus. They were then randomly divided into a model control group, a probiotic group, a prebiotic group, a synbiotic group, and a metformin group, with eight rats in each group. The probiotic group was administered 418 mg/(kg·d) of Bifidobacterium quadruple viable tablets by gavage, the prebiotic group was administered 315 mg/(kg·d) of fructooligosaccharides by gavage, the synbiotic group was administered a combination of both drugs by gavage, the metformin group was administered 
52.5 mg/(kg·d) of metformin by gavage, and the blank group and model control group were administered an equal volume of normal saline by gavage, once daily for 14 consecutive days. After 14 days of administration, the serum levels of fasting blood glucose, fasting insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol, tumor necrosis factor alpha, interleukin-1β, interleukin-6, lipopolysaccharide, C-reactive protein, and glucagon-like peptide-1 were measured in the rats. Changes in the structure of the gut microbiota were analyzed based on 16S rRNA sequencing, and the levels of short-chain fatty acids in the colonic contents were detected by gas chromatography.
RESULTS AND CONCLUSION: (1) The serum levels of fasting blood glucose, fasting insulin, total cholesterol, lipopolysaccharide, C-reactive protein, interleukin-1β, and interleukin-6, as well as the relative abundance of Spirochaetota, Desulfobacteroae, Actinobactera, Proteobacteria, Cyanobacteria, and Campilobacteria in the gut microbiota of rats in the model control group were significantly higher than those in the blank group (all P < 0.05). (2) The serum levels of glucagon-like peptide 1, the relative abundance of beneficial bacterial phyla, and the levels of short-chain fatty acids (acetic acid, propionic acid, butyric acid, isobutyric acid, isovaleric acid, and isocaproic acid) in the colonic contents of rats in the model control group were significantly lower than those in the blank group (all P < 0.05). (3) The serum levels of fasting blood glucose, fasting insulin, total cholesterol, lipopolysaccharide, C-reactive protein, interleukin-1β, and interleukin-6 in the probiotic group, synbiotic group, and metformin group were significantly lower than those in the model control group (all P < 0.05). (4) The serum levels of glucagon-like peptide 1, the relative abundance of Verrucomicrobiota, Firmicutes, and Bacteroidota in the gut microbiota, and the levels of short-chain fatty acids (acetic acid, valeric acid, isobutyric acid, isovaleric acid, and isocaproic acid) in the colonic contents of rats in the probiotic group, synbiotic group, and metformin group were significantly higher than those in the model control group (all P < 0.05). To conclude, these findings suggest that probiotic supplements may significantly improve insulin resistance and glucose and lipid metabolism disorders in rats with gestational diabetes mellitus by activating the gut microbiota-short-chain fatty acid-glucagon-like peptide 1 regulatory axis, upregulating the abundance of beneficial bacteria, promoting short-chain fatty acid synthesis, enhancing intestinal mucosal barrier function, and alleviating systemic inflammatory responses.

Key words: gestational diabetes mellitus, intestinal microecology, probiotics, inflammatory response, pregnancy outcomes