Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring

Abstract

Early-life adversity is a major risk factor for the development of diseases later in life. Maternal protein restriction (MPR) is associated with morbidities in offspring affecting multiple organs, but its impact on the gastrointestinal (GI) tract remains poorly studied. Using a rat model, we examined the consequences of MPR on GI function and on the enteric nervous system (ENS) in the offspring at postnatal d 35 under basal state and following a water avoidance stress (WAS). Compared with control rats, MPR rats exhibited greater colonic motility, permeability, and corticosteronemia. In contrast to controls, MPR rats presented a blunted functional and corticosteronemic response to WAS. Furthermore, MPR rats showed an increased proportion of choline acetyltransferase-immunoreactive (ChAT-IR) neurons and a reduced level of autophagy in colonic myenteric neurons. In ENS cultures, corticosterone treatment increased the proportion of ChAT-IR neurons and reduced autophagy level in enteric neurons. Inhibition of autophagy in ENS cultures resulted in a higher vulnerability of enteric neurons to a cellular stress. Altogether, this study suggests that MPR induced GI dysfunction and ENS alterations in offspring rats and that MPR-induced increased corticosteronemia might be involved in ENS remodeling and altered responsiveness of the gut to stressors later in life.-Aubert, P., Oleynikova, E., Rizvi, H., Ndjim, M., Le Berre-Scoul, C., Grohard, P. A., Chevalier, J., Segain, J.-P., Le Drean, G., Neunlist, M., Boudin, H. Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring.

Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention

“…For instance, in female offspring from undernourished pregnant rats (8% protein diet), colonic tight junction Zonula Occludens 1 mRNA expression was decreased, without impacting on permeability to lipopolysaccharides (LPS), in comparison to offspring of pregnant rats receiving the standard 20% diet [18]. Another study with the same level of maternal protein restriction reported an increased ex vivo colonic hyperpermeability to small molecules in 35 days aged offspring [19]. In offspring from undernourished pregnant rats (receiving a 6% protein diet), the disaccharidase activity (lactase and sucrase) was increased in different segments of the intestine [41].…”

The Effect of Dietary Protein Imbalance during Pregnancy on the Growth, Metabolism and Circulatory Metabolome of Neonatal and Weaned Juvenile Porcine Offspring

“…Low-protein diets fed during pregnancy have been shown to reduce offspring birth weight in several species [ 13 , 14 , 36 ]. Results from the current study show that exposure to a low-protein diet in utero significantly reduced the average birth weight of all live born, female and male piglets by 15%, compared to AP offspring.…”

“…However, it remains controversial whether these models adequately reflect the transgenerational effects of diet. Additionally, exposure has been conducted during both gestation and lactation [ 13 , 14 , 15 , 16 ], complicating analysis of how in utero exposure is linked to the onset of metabolic diseases later in life.…”

PDTC Alleviates Depressive Symptoms and Colon Tissue Injury via Inhibiting NO Overproduction in CUMS Rats

“…Stress has been shown to be associated with both the onset and maintenance of GI symptoms. Furthermore, patients with GI dysfunctions have been found to be more likely to develop psychiatric disorders before the onset of GI symptoms (Mayer et al, 2001;Donald et al, 2017;Aubert et al, 2018). However, the mechanisms underlying stress-gut dysfunctions have not yet been fully elucidated.…”