Association Between Gut Microbiota And Metabolic Sydrome Induced By Imbalanced Early-life Nutrition

The evidences from epidemiological studies indicate that imbalancedearly-life nutrition, including in utero malnutrition and postnatal overfeeding,is a risk factor for obesity and related metabolic disorders in later life. Andemerging evidence has supported that gut microbiota dysbiosis induced byimbalance diet play a predominant role in the development of obesity andinsulin resistance. In this study, we used the postnatal overfeeding ICR micemodels with normal birth weight and low birth weight to investigate theassociation between gut microbiota and metabolic disease induced byimbalanced early-life nutrition.We randomly assigned the male pups with normal birth weight to eithera normal feeding (NF) or an overfeeding (OF) group at4days of age. OFgroup had a significantly increased body weight, epididymal fat pad,perinephric fat pad and susceptibility to insulin resistance compared with NFat weaning. Postnatal overfeeding significantly increased the amount ofendotoxin-producing Enterobacteriaceae and gut barrier-dysfunctioningsulfate reducting bacteria which was significantly positively correlated withvisceral fat gain according to spearman correlation analysis.We compared two ways to induce intrauterine growth retardation ofmice according to the previous reports. One is reducing50%food intake ofdams covering the whole pregnancy, the other is giving the restriction after11days of ad libitum during gestation. The former led dams to abortion, whilethe later made dams give birth to the low birth weight pups.And then we compared the obesity phenotype and structure of gutmicrobiota of catch-up growth mice (UO) and control mice (CC). Compared with its control counterpart, UO mice showed a significant lower birth weightand a similar body weight at3days of life. The body weight, epididymal fatpad and perinephric fat pad were significantly increased in UO group,indicating that the mice in this group had catch-up growth. Fasting bloodglucose and area under curve of oral glucose tolerance test (OGTT)decreased in UO group, which suggested catch-up growth induced severeinsulin resistance. Real-time PCR analysis showed that the amount of gutbarrier-protecting Bifidobacterium was significantly decreased in UO groupcompared with CC group. There was a significant negative correlationbetween the amount of Bifidobacterium and visceral fat according tospearman correlation analysis.In conclusion, our findings suggested that postnatal overfeedingincreased the amount of opportunistic pathogens or decrease the beneficialbacteria in normal birth weight and low birth weight (catch-up growth)subject. These bacteria were significantly associated with obesity and insulinresistance in the early-life. Our work provides a solid foundation for furtherresearch on the interaction of early-life nutrition, gut microbiota andmetabolic disease.