Impact of maternal high-fat diet on offspring gut microbiota during short-term high-fat diet exposure in mice

Abstract

Alterations in the gut microbiome have been linked to obesity, with maternal high-fat diet (HF) playing a role in shaping offspring microbiome composition. However, the sex-specific responses to maternal HF diet and the impact of subsequent dietary challenges remain unclear. This study investigated the effects of maternal HF diet on offspring gut microbiota structure and predicted functional profile in response to short-term postnatal HF diet exposure with a focus on sex-specific responses. Female and male offspring of maternal control (C) diet or maternal HF diet were weaned onto C diet or HF diet. Offspring were euthanized at 13 weeks of age and cecal contents were collected for bacterial taxonomic profiling. Maternal HF diet reduced α-diversity, notably in male offspring weaned onto HF diet. Sex-specific differences were observed in the gut microbial composition and predicted functional potential. Furthermore, the influence of maternal diet on bacterial community structure and functional potential varied depending on postnatal diet. Maternal HF diet led to increased relative abundance of Corynebacterium in female offspring and decreased abundance of Akkermansia and Roseburia in male offspring. These findings underscore the sexually dimorphic nature of maternal HF diet effects on gut microbiota composition and function, with implications for developmental programming and metabolic health.

Keywords: diversity; functional profile; gut microbiota; maternal high‐fat diet; offspring; sexual dimorphism.

FIGURE 1

Maternal diet impacts alpha‐ and beta‐diversity metrics in a sex‐dependent manner. Alpha‐diversity metrics including observed features, Pielou's index, and the Shannon index at the (a, b, c) phylum and (d, e, f) genus levels. Two‐dimensional principal coordinate analysis (PCoA) plots based on weighted UniFrac distances for (g) female and (h) male offspring. Numbers in parentheses represent the percent of the variation accounted for the principal‐component axes and ellipses define the 95% confidence level. Three‐way ANOVA and PERMANOVA (maternal diet (MD), offspring diet (OD), sex (S), and interactions) were used to evaluate alpha‐diversity metrics and beta‐diversity, respectively. Pairwise comparisons are presented in Table S1. CC = offspring of control diet‐fed dams weaned onto control diet (female n = 6 and male n = 5), CHF = offspring of control diet‐fed dams weaned onto high‐fat diet (female n = 5 and male n = 6), HFC = offspring of high‐fat‐fed dams weaned onto control diet (female n = 6 and male n = 5), HFHF = offspring of high‐fat‐fed dams weaned onto high‐fat diet (female n = 5 and male n = 6).

FIGURE 2

Sexual dimorphic effect of maternal diet on phylum and genus level profiles. Stacked bar chart of the relative abundance at phylum level from the cecal bacterial communities of murine (a) female and (b) male offspring. (c) Bubble plot of the relative abundance at genus level from the cecal bacterial communities of murine female and male offspring. Circle size is proportional to the average relative abundance. Genera with relative abundance >0.5% are represented. (d–g) Maternal diet effect at genus level on female and male offspring. C = control diet, HF = high‐fat diet. p values from the Wilcoxon rank sum test.

FIGURE 3

Effects of maternal diet on predicted functional profiles differ by sex. (a) Two‐dimensional principal coordinate analysis (PCoA) plot based on Bray‐Curtis dissimilarities from PICRUSt2‐predicted functional profiles. Numbers in parentheses represent the percent of the variation accounted for the principal‐component axes and ellipses define the 95% confidence level. (b) Heatmaps displaying distinct functional profiles. (c) Correlations between genus and pathway abundances. Three‐way PERMANOVA (maternal diet (MD), offspring diet (OD), sex (S), and interactions). Pairwise comparisons are presented in Table S1. CC = offspring of control diet‐fed dams weaned onto control diet (female n = 6 and male n = 5), CHF = offspring of control diet‐fed dams weaned onto high‐fat diet (female n = 5 and male n = 6), HFC = offspring of high‐fat‐fed dams weaned onto control diet (female n = 6 and male n = 5), HFHF = offspring of high‐fat‐fed dams weaned onto high‐fat diet (female n = 5 and male n = 6).