The programming effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in adult mice

Abstract

Substantial evidence indicated that catch-up growth could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes mellitus in adulthood. However, investigations into the "programming" effects of catch-up growth on gut microbiota in the offspring are limited. C57/BL6 mice were fed on either low protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the offspring were randomly weaned to either NC or high fat (HF) diet until 32weeks of age, generating four experimental groups: NC-NC, NC-HF, LP-NC, and LP-HF. Metabolic parameters and gut microbiota were examined in the offspring. It showed that the NC-HF and LP-HF offspring displayed higher body weight (P<0.05), impaired glucose tolerance (P<0.001), and elevated serum lipids (P<0.05) at 32weeks of age. Both the operational taxonomic units (OTUs) and the Shannon indexes (P<0.05) showed significantly lower microbial diversity in NC-HF and LP-HF offspring. There were significant variations in the compositions of gut microbiota in the NC-HF and LP-HF offspring, compared with NC-NC offspring (P<0.05). Furthermore, it indicated Lactobacillus percentage was negatively associated with blood glucose concentrations of intraperitoneal glucose tolerance test (r=-0.886, P=0.019). In conclusion, catch-up growth predisposes the offspring to gut microbiota perturbation, obesity, impaired glucose tolerance, insulin resistance, and dyslipidemia. Our study is novel in showing the "programming" effects of nutrition-induced catch-up growth on gut microbiota and metabolic diseases in later life. Our work is novel in showing the "programming" effects of maternal nutrition imbalance on gut microbiota and metabolic diseases in adult mice. It is suggested that therapeutic interventions targeting gut microbiota may be a new theoretical basis for preventing the onset of such metabolic diseases in individuals with previous episodes of growth restriction.