MATERNAL FIBER AND GUT MICROBIOTA SHAPE LONG-TERM METABOLIC AND AUTONOMIC HEALTH IN OFFSPRING

The rising prevalence of obesity and type 2 diabetes raises a fundamental question: why does maternal nutrition so powerfully increase offspring metabolic disease risk, even before differences in lifestyle or diet emerge? Evidence suggests that vulnerability to metabolic disease is programmed in utero, yet signals linking maternal nutrition to the development of offspring metabolic control systems remains poorly defined. Western-style diets rich in ultra-processed foods, characterized by high fat, sugar, and low fiber, disrupt the maternal gut microbiota and reduce fermentable substrates, impairing gut-brain signaling pathways vital for metabolic regulation. Consequently, bacterial production of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, is reduced. These metabolites regulate glucose homeostasis, energy expenditure, and autonomic function via the gut-brain axis. However, their role in programming the gut-brain axis during early life remains unclear and a comprehensive characterization of this regulation is needed.
Here, we determined whether maternal nutrition programs offspring brown adipose tissue (BAT) thermogenesis through alterations in adipose tissue morphology and autonomic regulation. Using maternal dietary interventions, we performed metabolic phenotyping of offspring alongside analyses of BAT structure, and autonomic regulation across embryonic development and adulthood. We show that maternal fiber intake and SCFA production during offspring development may protect against metabolic dysfunction, accompanied by preserved BAT morphology and thermogenic capacity. In contrast, disruption of the maternal gut microbiota by western diet increased susceptibility to impaired BAT thermogenesis and metabolic dysfunction. These findings highlight nutrition and gut-derived metabolites as key mediators of programming neuro-metabolic as early as in the womb.