Lactobacillus casei Strain Shirota Alleviates Constipation in Adults by Increasing the Pipecolinic Acid Level in the Gut.

Yangwenshan Ou,Liang Zhao,Ming Zhang,Shaoyang Ge,Shanbin Chen,Fazheng Ren,Hao Zhang,Huiyuan Guo

doi:10.3389/fmicb.2019.00324

Abstract

The benefits of probiotics for constipation are widely accepted, but the mechanisms involving gut metabolites are unclear. In this study, we investigated the effects of Lactobacillus casei strain Shirota (LcS) on constipated patients and revealed that a metabolite mediator is involved in the LcS-induced constipation alleviation. Sixteen constipated patients and 22 non-constipated participants were recruited. The subjects consumed 100 mL of an LcS beverage (108 CFU/mL) per day for 28 days. The fecal non-volatile metabolites were determined by GC/MS, and the targeted metabolites were further verified in a constipated mouse model. In constipated patients, LcS intervention significantly improved defecation frequency (from 4.81 to 7.81 times per week, p < 0.05), stool consistency (from 2.52 to 3.68, p < 0.05) and constipation-related symptoms. A total of 14 non-volatile fecal metabolites were obtained as potential constipation-related metabolites that were regulated by LcS. Among these metabolites, pipecolinic acid (PIPA) had a significant positive correlation with defecation frequency in constipated patients. PIPA significantly promoted the small intestinal propulsive rate (from 25.45 to 39.68%) and increased the number of fecal pellets (from 30.38 to 57.38 pellets) in constipated mice (p < 0.05). The 5-hydroxytryptamine (5-HT) and acetylcholine (ACh) in colonic tissue may be partly involved in PIPA-mediated constipation alleviation. In conclusion, PIPA was a metabolic mediator in the gut that participated in LcS-induced constipation alleviation.

Highlights

Constipation is defined as a difficulty in evacuating, which is characterized by a reduced defecation frequency (Bharucha, 2007)
Different probiotic strains or mixed formulas reduced the symptoms of constipation and alleviated constipationrelated diseases, such as irritable bowel syndrome (IBS) and depressive behaviors (Xu et al, 2018)
The results clearly showed that the high dose of pipecolinic acid (PIPA) could improve the intestinal movement and alleviate constipation symptoms in ADinduced constipation mice

Summary

Introduction

Constipation is defined as a difficulty in evacuating, which is characterized by a reduced defecation frequency (Bharucha, 2007). Different probiotic strains or mixed formulas reduced the symptoms of constipation and alleviated constipationrelated diseases, such as irritable bowel syndrome (IBS) and depressive behaviors (Xu et al, 2018). Koebnick et al (2003) found that 2 weeks of consecutive ingestion of 65 mL/day of beverages containing 6.5 × 109 CFU/mL Lactobacillus casei strain Shirota (LcS) led to a significant decline in the occurrence of hard and lumpy stool in constipated adults. Bifidobacterium lactis DN-173 010 at a dose of 1.25 × 1010 CFU for consecutive 4 weeks significantly reduced the colonic transit time by an average 12.2 h in constipated women (Agrawal et al, 2009). Lactobacillus reuteri DSM 17938 at a dose of 1.0 × 108 CFU noticeably improved bowel movements by 2.6 per week in constipated adults after 4 weeks of treatment (Ojetti et al, 2014), and it led to a significant alleviation of abdominal discomfort, pain and bloating in constipated adults after 105 days of administration (Riezzo et al, 2018)

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Discussion

Conclusion