Metabolic memory in the gut: The microbiota-epigenetic crosstalk orchestrating obesity onset and novel therapeutic landscapes

Figure 2 Intergenerational impact pathways of maternal obesogenic diets. This schematic illustrates the key mechanisms through which maternal high-fat high-sugar diets exert intergenerational effects on offspring metabolic health. Maternal diet-induced gut microbiota dysbiosis, characterized by reduced microbial diversity, elevated Firmicutes/Bacteroidetes ratio, and decreased beneficial taxa such as Bifidobacterium and Lactobacillus, is vertically transmitted to offspring via birth and breastfeeding. Altered breast milk composition, including increased saturated fatty acids and reduced butyrate, further disrupts offspring gut microbiota maturation and function. Concurrently, maternal chronic inflammation and epigenetic modifications (e.g., DNA methylation and histone acetylation) contribute to impaired intestinal barrier function and metabolic dysregulation in offspring, perpetuating a transgenerational cycle of obesity risk. Created in BioRender (Supplementary material). TNF: Tumor necrosis factor; IL: Interleukin; Fasn: Fatty acid synthase.