Maternal Western diet increases inflammatory markers and decreases barrier function of offspring in Papio anubis

The Western diet (WD) has been associated with various pathologies, largely due to chronic inflammatory responses triggered by insulin spikes and excess cholesterol. However, the effects of maternal WD on offspring are currently understudied. We hypothesize that maternal WD consumption in baboons induces a hyperinflammatory state in offspring, leading to compromised intestinal barrier function. Intestinal tissue was harvested from olive baboon (Papio anubis) 0.9 gestation fetuses and juveniles (age 2-3 yr), whose mothers were fed either a high-fat/high-sugar WD or a control diet (CD) of standard monkey chow. RNA and protein were isolated and analyzed for markers of inflammation and apoptosis. Intestinal organoids (enteroids) were generated from these bowel samples and subsequently subjected to hypoxia and LPS to simulate necrotizing enterocolitis (NEC). RNA was extracted and similarly examined for inflammatory markers and markers of apoptosis. Enteroids were plated onto TransWellTM plates to evaluate barrier function. Immunohistochemistry and immunofluorescence were used to evaluate barrier proteins. The intestinal tissue of baboon fetuses and juveniles of mothers fed a Western diet exhibited evidence of a hyperinflammatory state. Although not all cytokines reached our significance set a priori at P < 0.05, interleukin-8 (IL-8) and Interferon γ (IFNγ) were significantly elevated. This trend was stable across generations. Offspring from the Western diet group exhibited decreased barrier function based on transepithelial resistance measurements. Maternal consumption of a Western diet during gestation in olive baboons leads to a generalized inflammatory state and weakened intestinal barrier function in offspring, with potential long-term health implications.NEW & NOTEWORTHY Our research examines a currently understudied area of the maternal/fetal relationship. This is especially pertinent, given the rampant access to high-fat/high-sugar foods in the Western diet. It is also noteworthy due to the findings of decreased barrier function among those in the Western diet group. This decreased function and hyperinflammatory state can prime neonates for various pathologies, such as necrotizing enterocolitis.