Abstract

Substantial studies demonstrated that maternal nutrition can significantly determine the susceptibility to developing some metabolic diseases in offspring. However, investigations into the later-life effects of these diets on gut microbiota in the offspring are limited. Our objective was to explore the effects of maternal and post-weaning diet interaction on offspring's gut microbiota and glucose metabolism in later life. The male offspring of dams fed on either a high-fat (HF) diet or control (C) diet and then weaned to either a HF or C diet, generating four groups: C-C, HF-C, C-HF and HF-HF (n=8in each group). The C-C offspring had lower body weight than C-HF group at 16weeks of age (P<0.01) and both C-HF and HF-HF offspring had higher body weight than C-C group at 24 and 32weeks of age (P<0.001 respectively). The blood glucose (BG) levels of the male offspring from the C and HF dams weaned HF diet were significantly higher at 30min, 60min and 120min (P<0.001) after intraperitoneal glucose administration compared with those of the C-C group. The C-HF group had higher BG at 30min than HF-HF group (P<0.01). Furthermore, area under the curve (AUC) in C-HF and HF-HF groups was also significantly larger than C-C group (P<0.001). Fasting BG and homoeostasis model assessment of insulin resistance (HOMA-IR) of the offspring were significantly higher in C-HF and HF-HF groups than C-C group at 32weeks of age (P<0.05). Operational taxonomic unit (OTU), Chao and Shannon indexes showed a significantly lower diversity in C-HF offspring compared with HF-C and C-C groups (P<0.05). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria, which also showed significantly different percentages in the group (P<0.05). Furthermore, it is indicated that Lactobacillus and Bacteroides were significantly associated with glucose response to a glucose load (P<0.05). In conclusion, maternal and post-weaning diet interaction predisposes the offspring to aberrant glucose metabolism and alterations of gut microbiota in later life. Our study is novel in focusing on the effects of maternal and post-weaning diet interaction on offspring gut microbiota and glucose metabolism in later life.

Highlights

  • The developmental origins of health and disease (DOHaD) hypothesis, firstly formulated in the early 1990s, proposes that imbalanced diet during early life plays a critical role in determining the risks of developing some metabolic diseases such as obesity, insulin resistance and diabetes mellitus in offspring [1]

  • Glucose response The blood glucose (BG) levels of the male offspring from the C and HF dams weaned HF diet were significantly higher at 30 min (P < 0.001 and P < 0.01 respectively), 60 min (P < 0.001) and 120 min (P < 0.001) after intraperitoneal glucose administration compared with those of the C–C group

  • In order to determine the effects on microbial composition in the offspring exposed to different maternal diets during pregnancy and lactation, we compared the microbial composition between HF–C and C–C groups

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Summary

Introduction

The developmental origins of health and disease (DOHaD) hypothesis, firstly formulated in the early 1990s, proposes that imbalanced diet during early life plays a critical role in determining the risks of developing some metabolic diseases such as obesity, insulin resistance and diabetes mellitus in offspring [1]. Previous and recent studies have indicated that a maternal high-fat (HF). Diet [2] and/or a postnatal weaning diet rich in fat [3] can increase susceptibility to obesity, glucose intolerance and insulin resistance in the adult offspring. The mechanisms underlying maternal imbalanced nutrition and such metabolic diseases in the offspring remain unclear. Gut microbiota, which can affect numerous biological functions throughout the body, has become a major and promising research area in biomedicine.

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