Effect of 4-thiazolidinone derivative and nimesulide on parietal intestinal microbiota of rats during induced inflammation process in vivo

Abstract

Nonsteroidal anti-inflammatory drugs, which are widely used in the treatment of diseases accompanied by pain and fever, can cause diseases of the gastrointestinal tract and are associated with disturbances of the intestinal microbiota. The search for new compounds that could affect the community of microorganisms, exhibiting antimicrobial and anti-inflammatory effects, is an important task of modern medicine and veterinary medicine. One of the promising molecules that have such effects are 4-thiazolidinone derivatives. The aim of this study was to analyze the effect of the newly synthesized compound Les6490 and drug nimesulide on the intestinal wall microbiota of rats in vivo under the conditions of Freund’s adjuvant-induced inflammatory process. The study of the effect of the above-mentioned drugs on the intestinal microbiota in vivo was carried out on a biomodel of rats, which were intragastrically administered with the test substances for two weeks. The study material was the parietal mucos of the small intestine, the microbiome of which was studied using 16S rRNA sequencing. Metagenomic analysis made it possible to analyze the types of microorganisms in experimental groups with induced inflammation (groups A and AL) and without it (groups K, L, N). It was established that the composition of the microbiome of the intestinal tract of rats changes under the conditions of induced inflammation and under the action of the compound Les6490 (groups A and L) in comparison with the control group (group K). The influence of Les6490 on the intestinal tract microbiome composition in rats is similar to that of nimesulide, but the effect is more pronounced. The compound Les6490 potentiates the growth of Helicobacter and has an effect against Stenotrophomonas in the group without induced inflammation (group L), but in the group of inflammation (group AL) no such effect is observed. The compound alone (not in inflammation models) leads to increased species diversity of the rat gut microbiome.