背景:生酮饮食在解决肥胖方面越来越受欢迎,但它们对肠道微生物群和代谢组的影响仍不清楚。本文旨在研究生酮饮食对肥胖患者肠道微生物和代谢产物的影响。
方法:为雄性小鼠提供以下饮食方案之一:正常饮食,高脂肪饮食,生酮饮食,或者高脂肪饮食转变为生酮饮食。每周使用高精度电子天平和微型身体成分分析仪测量体重和脂肪量。使用宏基因组学和非靶向代谢组学数据来分析肠道内容物的差异。
结果:生酮饮食的肥胖小鼠在体重和体脂方面表现出显著的改善。然而,这些伴随着肠道微生物多样性的显著减少,以及Firmicutes丰度的增加和Firmicutes/拟杆菌比率的247%的增加。生酮饮食也改变了肠道的多种代谢途径,包括葡萄糖,脂质,能源,碳水化合物,氨基酸,酮体,丁酸酯,和甲烷途径,以及细菌分泌和定植途径。这些变化与肥胖小鼠肠道炎症和生态失调增加有关。此外,生酮饮食增强了肥胖小鼠胆汁的分泌和氨基糖苷类抗生素的合成,这可能会损害肠道微生物群,并与肠道炎症和免疫力有关。
结论:研究表明,生酮饮食具有不利的风险-收益权衡,并可能损害肥胖小鼠的代谢稳态。
BACKGROUND: Ketogenic diets are increasingly popular for addressing obesity, but their impacts on the gut microbiota and metabolome remain unclear. This paper aimed to investigate how a ketogenic diet affects intestinal microorganisms and metabolites in obesity.
METHODS: Male mice were provided with one of the following dietary regimens: normal chow, high-fat diet, ketogenic diet, or high-fat diet converted to ketogenic diet. Body weight and fat mass were measured weekly using high-precision electronic balances and minispec body composition analyzers. Metagenomics and non-targeted metabolomics data were used to analyze differences in intestinal contents.
RESULTS: Obese mice on the ketogenic diet exhibited notable improvements in weight and body fat. However, these were accompanied by a significant decrease in intestinal microbial diversity, as well as an increase in Firmicutes abundance and a 247% increase in the Firmicutes/Bacteroidetes ratio. The ketogenic diet also altered multiple metabolic pathways in the gut, including glucose, lipid, energy, carbohydrate, amino acid, ketone body, butanoate, and methane pathways, as well as bacterial secretion and colonization pathways. These changes were associated with increased intestinal inflammation and dysbiosis in obese mice. Furthermore, the ketogenic diet enhanced the secretion of bile and the synthesis of aminoglycoside antibiotics in obese mice, which may impair the gut microbiota and be associated with intestinal inflammation and immunity.
CONCLUSIONS: The study suggest that the ketogenic diet had an unfavorable risk-benefit trade-off and may compromise metabolic homeostasis in obese mice.