Lactobacillus rhamnosus Strains Relieve Loperamide-Induced Constipation via Different Pathways Independent of Short-Chain Fatty Acids

Abstract

Increasing researches have confirmed the relationship between slow-transit constipation and gut microbiota dysbiosis. Many population and animal experiments have identified probiotics as effectors for the relief of constipation symptoms, but the specific mechanism remains unclear. In this intervention study, Lactobacillus rhamnosus strains isolated from five different sources were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators were evaluated. All five strains of L. rhamnosus were found to improve constipation to various degrees. However, contrary to previous studies, the abilities of L. rhamnosus strains to improve constipation symptoms were not associated with the levels of short-chain fatty acids (SCFAs) in the colon. The effects of different strains of L. rhamnosus on constipation relief were associated with different aspects of the GI tract, including gastrointestinal regulatory peptides, neurotransmitters, neurotrophic factors, and gut microbiota. The findings of this study demonstrate that L. rhamnosus strains can alleviate constipation-related symptoms via different pathways independent of SCFAs regulation. This study yields a new perspective for clinical use of probiotics to better improve constipation symptoms, by combining strains with different mechanisms for alleviation of constipation.

Prebiotics/Probiotics Mixture Induced Changes in Cecal Microbiome and Intestinal Morphology Alleviated the Loperamide-Induced Constipation in Rat

“…Intestinal microbiota at the phylum level involved Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia, and these phyla accounted for more than 98% of intestinal microbiota ( Guo et al, 2020 ). During loperamide-induced constipation, the relative abundance of Firmicutes decreases and that of Verrucomicrobia increases ( Wang et al, 2020 ). L. rhamnosus CCFM1068 administration has shown to decrease the abundance of the phylum Verrucomicrobia.…”

“…L. rhamnosus CCFM1068 administration has shown to decrease the abundance of the phylum Verrucomicrobia. The ability of L. rhamnosus CCFM1068 to alleviate constipation symptoms was associated with a decreased abundance of Verrucomicrobia ( Wang et al, 2020 ). We found that multi-strain probiotics and synbiotic co-administration significantly decreased the abundance of Verrucomicrobia compared to that of the Lop group, and constipation-relieving effect may be due to the reduction of the Verrucomicrobia phylum ( Fig.…”

“…The relative abundance of Oscillibacter was significantly increased in the Lop-Pro/Pre group. An increase in the abundance of Akkermansia has been observed in the feces of constipated mice ( Wang et al, 2020 ). An increase in Akkermansia abundance has also been observed in colon cancer patients, and Akkermansia may be related to the disease ( Hibberd et al, 2017 ).…”

“…Previous studies have shown that the abundance of specific species among intestinal bacteria differs in patients with constipation. People with symptoms of constipation reportedly have decreased abundance of Bifidobacteria and Lactobacillus and increased abundance of Bacteroidetes compared to the general population ( D’Onofrio et al, 2020 ; Wang et al, 2020 ). Such changes in the intestinal microbiota affect intestinal motility and intestinal environment ( Zhao and Yu, 2016 ).…”

Functional Constipation and the Gut Microbiome in Children: Preclinical and Clinical Evidence

“…Interestingly, a recent investigatory study (40) assessing the effects of Lactobacillus rhamnosus on treating loperamideinduced constipation showed variable degrees of symptomatic improvement which were bacterial strain-specific and independent of the previously reported SCFA effects (37,38). Specifically, L. rhamnosus increased serum peptide YY, colonic 5-HT, colonic brain-derived neurotrophic factor, and significantly increased α-diversity, with minor effects on improving β-diversity.…”