Microbial composition is altered in a pharmacological model of slowed GI transit in aged rats

Background/Aims: Gastrointestinal(GI) motility is an integral part of digestive function. The enteric nervous system(ENS) is the primary controller of GI motility. Dysfunction of the ENS can cause impaired GI motility as seen in the case of constipation. Animal models mimicking symptoms of constipation have been developed by way of pharmacological manipulations. We have previously shown that loperamide, an opioid agonist that works by inhibiting enteric neuronal activity, reduces propulsion and delays GI transit, inducing constipation in aged rats. Previous studies have reported an association between altered GI motility and gut microbial population. Little is known about the changes in gut microbiota profile resulting from pharmacologically induced constipation in rats. The aim of this study was to examine how constipation induced by a pharmacological drug loperamide, affects the gut microbiota composition.

Methods: Caecal digesta samples were collected from adult male Sprague Dawley rats that were administered with 1 mg/kg/day loperamide(in 100%DMSO) or DMSO vehicle only(Control) for seven days via a subcutaneous 2 mL capacity slow release osmotic mini pump. Caecal microbial composition was determined by 16S rRNA gene amplicon sequencing.

Results: Significant differences in caecal microbial communities were observed between loperamide treated and control groups. At the phylum level Proteobacteria and Bacteroidetes were relatively more abundant in loperamide treated vs control(P<0.05). Comparison of community compositions using weighted UniFrac distances, a phylogenetic distance-based analysis showed a clear separation between loperamide and control communities. Permutation multivariate analysis of variance (PERMANOVA) confirmed that the overall differences in communities were significant(P=0.008). Alpha diversity also differed between groups, with loperamide treated rats showing significantly lower numbers of observed species compared to control rats(P=0.018).

Conclusion: Constipation induced by loperamide affects the diversity and abundance of gut microbiota. Identifying bacterial species that are associated with slowed GI transit may help in developing prebiotic and probiotic treatments for the management of constipation.