Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study

Teng Ma; Ni Yang; Yong Xie; Yingmeng Li; Qiuping Xiao; Qiong Li; Hao Jin; Longjin Zheng; Zhihong Sun; Kexuan Zuo; Lai-Yu Kwok; Heping Zhang; Nonghua Lu; Wenjun Liu

doi:10.1016/j.phrs.2023.106755

Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study

Pharmacol Res. 2023 May:191:106755. doi: 10.1016/j.phrs.2023.106755. Epub 2023 Apr 3.

Authors

Teng Ma¹, Ni Yang², Yong Xie³, Yingmeng Li⁴, Qiuping Xiao², Qiong Li⁵, Hao Jin¹, Longjin Zheng², Zhihong Sun¹, Kexuan Zuo², Lai-Yu Kwok¹, Heping Zhang⁶, Nonghua Lu⁷, Wenjun Liu⁸

Affiliations

¹ Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
² Jiangzhong Pharmaceutical Co., Ltd., No.1899 Meiling Road, Nanchang 330103, China.
³ Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
⁴ Jiangzhong Pharmaceutical Co., Ltd., No.1899 Meiling Road, Nanchang 330103, China; Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
⁵ Jiangxi University of Chinese Medicine, No. 818 Yunwan Road, Nanchang 330002, China.
⁶ Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China; Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China. Electronic address: hepingdd@vip.sina.com.
⁷ Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China. Electronic address: lunonghua@ncu.edu.cn.
⁸ Jiangzhong Pharmaceutical Co., Ltd., No.1899 Meiling Road, Nanchang 330103, China. Electronic address: liuwenjun@crjz.com.

PMID: 37019193
DOI: 10.1016/j.phrs.2023.106755

Abstract

Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×10¹¹ CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.

Keywords: Chronic constipation; Fecal metabolome; Lactiplantibacillus plantarum P9; Metagenomics; Multi-omics.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Constipation / drug therapy
Constipation / microbiology
Double-Blind Method
Feces / microbiology
Gastrointestinal Diseases*
Humans
Lactobacillales*
Probiotics* / therapeutic use
Quality of Life
Treatment Outcome