Probiotics may help reduce stress-induced intestinal barrier dysfunction in newborn rats

The intestinal epithelium is considered a novel target for addressing several acute and chronic gastrointestinal conditions. It also could have a potential role in targeting systemic diseases. It is an active component of the mucosal immune system. When considering the complex ecosystem combining the gastrointestinal epithelium, immune cells and resident microbiota, several probiotics like Lactobacillus fermentum exhibit immunoregulatory effects in healthy adults (here; here). However, little is known about their effects in newborns.

A new study, led by Dr. Michel Neunlist from the French Institute of Health and Medical Research (INSERM) and Université de Nantes (Nantes, France), has found that the probiotic L. fermentum could prevent and/or treat gastrointestinal disorders related to intestinal epithelium dysfunction in newborn rats.

The researchers administered either L. fermentum (10⁹ colony forming units /100 g body weight/day) or water to newborn rats. Intestinal permeability was measured following maternal separation and water avoidance stress. Zonula occludens-1 (ZO-1) distribution and expression analysis was also performed, together with assessment of anxiety-like behaviour, ethological parameters, and locomotor activity using the elevated plus maze test. Cytokine secretion of activated splenocytes was evaluated in addition.

L. fermentum prevented intestinal epithelium dysfunction induced by both maternal separation and water avoidance stress, in vivo. Besides this, it reduced intestinal permeability to both fluorescein sulfonic acid and horseradish peroxidase in the small intestine (in particular in the ileum), but not in the colon, of newborn rats.

Regarding mechanisms involved in mediating reduction of epithelial permeability, it was found that L. fermentum reduced water avoidance stress-induced changes in intestinal permeability and corticosteronemia. Specifically, when assessing the impact of L. fermentum and water avoidance stress upon the organization and distribution of the key tight junction-associated protein ZO-1 in intestinal epithelial cells, the researchers found that L. fermentum increased in vivo ZO-1 expression and prevented stress-induced ZO-1 disorganization in intestinal epithelial cells.

For studying whether L. fermentum could modulate the immune system, production of interferon-g (IFNg), a key cytokine of T helper 1 (Th1) responses, and interleukin-4 (IL-4), a marker of Th2 responses, were assessed in splenocytes following T cell activation. In activated splenocytes, L. fermentum increased IFNg secretion and decreased IL-4 secretion. This Th1-skewing phenotype could contribute to the preventive effect of L. fermentum against Th2-driven pathologies including allergies and asthma; however, further follow-up studies are needed to determine this effect.

Besides modulating systemic immune response, L. fermentum increased exploratory behaviour in newborn rats as measured using the elevated plus maze test, while it did not exert any effect on anxiety-like behaviour, as measured by differences between open and closed arm exploration.

In conclusion, L. fermentum CECT 5716 could help manage gastrointestinal disorders related to an altered intestinal epithelium in newborn rats.

Reference:

Vanhaecke T, Aubert P, Grohard PA, et al. L. fermentum CECT 5716 prevents stress-induced intestinal barrier dysfunction in newborn rats. Neurogastroenterol Motil. 2017; 29(8). doi: 10.1111/nmo.13069.