The dynamic effects of maternal high-calorie diet on glycolipid metabolism and gut microbiota from weaning to adulthood in offspring mice

Abstract

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 norank f Bacteroidales S24-7 group) and increase in unfavorable bacteria (such as Lachnoclostridium and Desulfovibrio) 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 Lactobacillus 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.

Keywords: glucose metabolism; gut microbiota; lipid metabolism; maternal high-fat diet; offspring.

FIGURE 1

Maternal HF diet impaired glucose metabolism in dams and damaged glycolipid metabolism in offspring at weaning. (A) Body weight of dams. (B) IPGTT of dams. (C) AUC of dams. (D) Body weight of offspring. (E) FBG of offspring. (F) IPGTT of offspring. (G) AUC of offspring. (H) Serum insulin of offspring. (I) Subcutaneous adipose tissue (%) of offspring. (J) Visceral adipose tissue (%) of offspring. (K) Serum T-CHO of offspring. (L) Serum LDL-C of offspring. (M) Serum HDL-C of offspring. (N) Serum leptin of offspring. (O) Serum adiponectin of offspring. (P) Ratio of adiponectin to leptin of offspring. Data are represented as mean ± SEM (F0-NC, n = 7; F0-HF, n = 8; NC-3w, n = 5–7; HF-3w, n = 6–7). *p < 0.05, ^**p < 0.01, ^***p < 0.001 vs. F0-NC, NC-3w. NC, normal chow diet; HF, high-fat diet; IPGTT, intraperitoneal glucose tolerance tests; AUC, the area under the glucose curve; FBG, fasting blood glucose; T-CHO, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.

FIGURE 2

Maternal HF feeding altered structures and composition of gut microbiota in offspring at weaning. (A) Venn diagram of the OUTs. (B) Relative abundance of the bacterial population at the phylum level. (C) Relative abundance of the bacterial population at the genus level. (D) PCoA plots of gut communities (NC-3w, n = 6; HF-3w, n = 6). NC, normal chow diet; HF, high-fat diet. OTUs, operational taxonomic units; PCoA, principal coordinate analysis.

FIGURE 3

Key bacteria were altered by the maternal HF diet in offspring at weaning. (A) Column chart of species abundance at the phylum level. (B) Column chart of top 20 species with significant differences at the genus level. (C,D) LEfSe analysis of the gut microbiota from the phylum level to the genus level, with LDA values of 2.0 (NC-3w, n = 6; HF-3w, n = 6). *p < 0.05, ^**p < 0.01 vs. NC-3w. NC, normal chow diet; HF, high-fat diet. LEfSe, linear discriminant analysis (LDA) effect size.

FIGURE 4

Heatmap of correlation analysis between the differential genera and glycolipid profiles in offspring at weaning. Heatmap of correlation analysis of offspring at weaning (NC-3w, n = 6; HF-3w, n = 6). *p < 0.05, **p < 0.01, ***p < 0.001 vs. NC-3w. NC, normal chow diet; HF, high-fat diet. BW, body weight; FBG, fasting blood glucose; BG15, blood glucose level at 15 min of IPGTTs; BG30, blood glucose level at 30 min of IPGTTs; BG60, blood glucose level at 60 min of IPGTTs; BG120, blood glucose level at 120 min of IPGTTs; AUC: the area under the glucose curve; T-CHO, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SAT, subcutaneous adipose tissue; VAT, visceral adipose tissue.

FIGURE 5

Functional predictions of bacterial communities by the KEGG pathway database in offspring at weaning. (A) KEGG pathway level 1. (B) KEGG pathway level 2 (NC-3w, n = 6; HF-3w, n = 6). *p < 0.05 vs. NC-3w. NC, normal chow diet; HF, high-fat diet.

FIGURE 6

Glycolipid metabolism disturbance induced by the maternal HF diet was recovered in offspring at 9 weeks of age. (A) Body weight. (B) FBG. (C) IPGTT. (D) AUC. (E) Subcutaneous adipose tissue. (F) Visceral adipose tissue. (G) Serum T-CHO. (H) Serum LDL-C. (I) Serum HDL-C. Data are represented as the mean ± SEM (NC-9w, n = 8; HF-9w, n = 8). NC, normal chow diet; HF, high-fat diet. IPGTT, intraperitoneal glucose tolerance tests; AUC, the area under the glucose curve; FBG, fasting blood glucose; T-CHO, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol.

FIGURE 7

Dysbiosis of gut microbiota was partly restored by a normal diet in offspring at 9 weeks of age. (A) Venn diagram of the OUTs. (B) Relative abundance of the bacterial population at the phylum level. (C) Relative abundance of the bacterial population at the genus level. (D) PCoA plots of gut communities (NC-9w, n = 6; HF-9w, n = 5). NC, normal chow diet; HF, high-fat diet. OTUs, operational taxonomic units; PCoA, principal coordinate analysis.

FIGURE 8

Dysbiosis of gut microbiota induced by the maternal HF diet was partly recovered in adult offspring. (A) Column chart of species with significant differences at the genus level. (B,C) LEfSe analysis of the gut microbiota from the phylum level to the genus level with LDA values of 2.0 (NC-9w, n = 6; HF-9w, n = 5). *p < 0.05, **p < 0.01 vs. NC-9w. NC, normal chow diet; HF, high-fat diet. LEfSe, linear discriminant analysis (LDA) effect size.

FIGURE 9

Functional predictions of bacterial communities by the KEGG pathway database in offspring at 9 weeks of age. (A) KEGG pathway level 1. (B) KEGG pathway level 2 (NC-9w, n = 6; HF-9w, n = 5). NC, normal chow diet; HF, high-fat diet.