Probiotic lactobacilli as a promising strategy to ameliorate disorders associated with intestinal inflammation induced by a non-steroidal anti-inflammatory drug

María José Martínez Monteros,Silvia Inés Cazorla,Ricardo Weill,Juan Andrés De Paula,María Florencia Balcells,Carolina Maldonado Galdeano,Gabriela Perdigón

doi:10.1038/s41598-020-80482-z

Abstract

Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. Hence, we investigated whether probiotics can control the onset of this severe condition in a murine model of intestinal inflammation induced by the NSAID, indomethacin. Probiotic supplementation to mice reduce the body weight loss, anemia, shortening of the small intestine, cell infiltration into the intestinal tissue and the loss of Paneth and Goblet cells associated with intestinal inflammation. Furthermore, a high antimicrobial activity in the intestinal fluids of mice fed with probiotics compared to animals on a conventional diet was elicited against several pathogens. Interestingly, probiotics dampened the oxidative stress and several local and systemic markers of an inflammatory process, as well as increased the secretion of IL-10 by regulatory T cells. Even more importantly, probiotics induced important changes in the large intestine microbiota characterized by an increase in anaerobes and lactobacilli, and a significant decrease in total enterobacteria. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis.

Highlights

Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist
Probiotic bacteria ameliorate clinical signs of intestinal inflammation induced by indometha‐ cin in mice
Animals fed with L. casei CRL 431 (Lc 431), L. paracasei CNCM I-1518 (Lp 1518), or water, for 7 and 5 days, respectively, received two indomethacin injections in the last two days of probiotic supplementation

Summary

Introduction

Damage to the small intestine caused by non-steroidal anti-inflammatory drugs (NSAIDs) occurs more frequently than in the upper gastrointestinal tract, is more difficult to diagnose and no effective treatments exist. We conclude that oral probiotic supplementation in NSAID-induced inflammation increases intestinal antimicrobial activity and reinforces the intestinal epithelial barrier in order to avoid pathogens and commensal invasion and maintain intestinal homeostasis. Paneth cells, located at the bottom of the intestinal crypts, are responsible for the secretion of a diverse arsenal of antimicrobial peptides (AMPs) such as lysozymes, secretory phospholipase A2, defensins, defensin-like peptides and cathelicidins, which have high antimicrobial activity. This array of AMPs limits the invasion and adherence of pathogenic and commensal bacteria by disrupting the integrity of the bacterial cell membrane or wall[3]. Inflammatory bowel disease (IBD) is the collective name for a group of chronic inflammatory gastrointestinal disorders, including ulcerative colitis, Crohn’s disease (which constitutes the vast majority of the cases), and other less frequent conditions that share features of both disorders (non-classifiable inflammatory bowel disease and indeterminate colitis)

Methods

Results

Conclusion