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Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high fat diet (HF). At day 18.5 (term = 19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g ) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin ( Muc2 ) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9 , associated with reduced expression of maturation markers ( Cdx2 , Muc2 ), and increased expression of tight junctions (TJ; Cldn-7 ). HF fetuses had increased mRNA expression of EGC markers ( S100b , Bfabp , Plp1 ), AMP ( Lyz1 , Defa1 , Reg3g ), and TJ ( Cldn-3 , Cldn-7 ), and reduced expression of an AMP-activator ( Tlr4 ). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

Impact of Maternal Malnutrition on Gut Barrier Defense: Implications for Pregnancy Health and Fetal Development