Zheng Jia, Zhang Ling, Gao Ying, Wu Honghua, Zhang Junqing
Department of Endocrinology, Peking University First Hospital, Beijing, China.
Front Nutr. 2022 Jul 28;9:941969. doi: 10.3389/fnut.2022.941969. eCollection 2022.
Dysbiosis of gut microbiota can contribute to the progression of diabetes and obesity. Previous studies have shown that maternal high-fat (HF) diet during the perinatal period can alter the microbiota and induce metabolic disorders at weaning. However, whether dysbiosis of gut microbiota and metabolism could be recovered by a normal diet after weaning and the dynamic changes of gut microbiota have not been fully studied. In this study, C57BL/6J female mice were fed with a normal chow (NC) or HF diet for 4 weeks preconception, during gestation, and until pup weaning. After weaning, male offspring were fed with an NC diet until 9 weeks of age. The microbiota of offspring at weaning and 9 weeks of age was collected for 16S rRNA gene amplicon sequencing. We found that dams fed with an HF diet showed glucose intolerance after lactation. Compared with the offspring from NC dams, the offspring from HF dams exhibited a higher body weight, hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia, and leptin resistance and lower adiponectin at weaning. Fecal analysis indicated altered microbiota composition between the offspring of the two groups. The decrease in favorable bacteria (such as ) and increase in unfavorable bacteria (such as and ) were strongly associated with a disturbance of glucose and lipid metabolism. After 6 weeks of normal diet, no difference in body weight, glucose, and lipid profiles was observed between the offspring of the two groups. However, the microbiota composition of offspring in the HF group was still different from that in the NC group, and microbiota diversity was lower in offspring of the HF group. The abundance of was lower in the offspring of the HF group. In conclusion, a maternal HF diet can induce metabolic homeostasis and gut microbiota disturbance in offspring at weaning. Gut microbiota dysbiosis can persist into adulthood in the offspring, which might have a role in the promotion of susceptibility to obesity and diabetes in the later life of the offspring.
肠道微生物群失调可能会促进糖尿病和肥胖的发展。先前的研究表明，围产期母体高脂（HF）饮食会改变微生物群，并在断奶时诱发代谢紊乱。然而，断奶后正常饮食能否恢复肠道微生物群失调和代谢，以及肠道微生物群的动态变化尚未得到充分研究。在本研究中，C57BL/6J雌性小鼠在受孕前、妊娠期直至幼崽断奶期间，喂食正常饲料（NC）或HF饮食4周。断奶后，雄性后代喂食NC饮食直至9周龄。收集断奶时和9周龄后代的微生物群进行16S rRNA基因扩增子测序。我们发现，喂食HF饮食的母鼠在哺乳期后出现葡萄糖不耐受。与NC母鼠的后代相比，HF母鼠的后代在断奶时体重更高、血糖升高、葡萄糖不耐受、高胰岛素血症、高胆固醇血症和瘦素抵抗，脂联素水平更低。粪便分析表明两组后代的微生物群组成发生了改变。有益细菌（如 ）的减少和有害细菌（如 和 ）的增加与葡萄糖和脂质代谢紊乱密切相关。正常饮食6周后，两组后代在体重、血糖和血脂谱方面未观察到差异。然而，HF组后代的微生物群组成仍与NC组不同，且HF组后代的微生物群多样性较低。HF组后代中 的丰度较低。总之，母体HF饮食可在断奶时诱导后代代谢稳态和肠道微生物群紊乱。肠道微生物群失调可在后代中持续至成年，这可能在促进后代成年后肥胖和糖尿病易感性方面发挥作用。
