Abstract
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.
Highlights
The gut is critical to host health and disease development through interactions with microbes that colonize the gut and establishment of the gut epithelial barrier [1,2]
We focused on genes involved in gut barrier function, integrity, and development to establish how maternal malnutrition may impact the maternal gut and, by consequence, fetal gut and enteric nervous system (ENS) development (Table 1). mRNA expression data were normalized to the geometric mean of the three stably-expressed reference genes: TATA-Box Binding Protein (Tbp), Tyrosine
Malnutrition Was Associated with Reduced Gut Barrier Function and Integrity In UN mothers, small intestine (SI) mRNA expression levels of antimicrobial peptides (AMP) genes Lyz2 (p = 0.02, Figure 1B) and Reg3g (p = 0.003, Figure 1C) were decreased compared to control diet (CON)
Summary
The gut is critical to host health and disease development through interactions with microbes that colonize the gut and establishment of the gut epithelial barrier [1,2]. The gut is involved in vitamin synthesis [4], nutrient metabolism [5], and protection against pathogens [1,6]. Microbes that reside in the gut, their metabolites [8], hormones [9], and immune factors [10], have been shown to affect gut and brain function through this axis in humans and animals [7]. Since microbes and the metabolites they produce can activate host immune, metabolic, and stress pathways once they
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