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

Pharmacological research. 2023;191:106755

Plain language summary

Chronic constipation (CC) is a common gastroenterological problem encountered in clinical practice, and it negatively impacts patients’ quality of life. Growing evidence indicates that the occurrence of CC is closely linked to gut dysbiosis. Several main probiotics have been used to relieve constipation. The main aim of this study was to systematically evaluate the beneficial effects of Lactiplantibacillus plantarum P9 (P9) administration on alleviating CC and impact on the host gut microbiota and its metabolites. This study was a 42-day longitudinal double-blind randomised controlled trial which enrolled a total of 181 patients with CC. Subjects were randomly assigned to the probiotic or placebo group. Subjects in P9 group received one sachet of P9 powder per day after meal. Results show that P9 administration significantly improved patients’ defecation frequency. In fact, P9 administration effectively alleviated constipation, and the symptom relief effects were linked to desired changes and interactions with different types of host microbes. Authors conclude that administering P9 could effectively relieve chronic constipation in adults and improve some aspects of their quality of life.

Expert Review


Conflicts of interest: None

Take Home Message:
  • This study suggested that P9-associated constipation symptom relief was not attributed to macroscopic changes in the host gut bacteriome and phageome
  • However, results supported that taking P9 could alleviate constipation, with the symptom relief effects linked to desired changes and interactions with different types of host microbes, including the gut commensal bacteria (L. plantarum, Ruminococcus_B gnavus, Oscillospiraceae sp., Lachnospiraceae sp.) and the bacteriophage family, Herelleviridae.

Evidence Category:
  • X A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
  • B: Systematic reviews including RCTs of limited number
  • C: Non-randomized trials, observational studies, narrative reviews
  • D: Case-reports, evidence-based clinical findings
  • E: Opinion piece, other

Summary Review:
Introduction

This study investigated the effect of a specific probiotic strain in alleviating Chronic Constipation (CC).

Methods

  • The study employed a 42-day randomised control trial (RTC) double-blind, placebo-controlled design, with 163 patients, (mean age =22.68 ±5.66 years for the probiotic group and 21.59 ±4.59 years for the placebo group), diagnosed with CC (Rome IV criteria)
  • The male to female ratio was 15–63 and 17–68 in probiotic and placebo groups respectively
  • Groups were standardised with no differences observed in baseline age, gender ratio, drug treatment, high-fibre diet and smoking between the two groups (P >0.18)
  • Participants were randomly assigned to the probiotic Lactiplantibacillis plantarum P9 (n=78; 2 g per sachet, 1 ×1011 CFU/day) or the placebo (n =85; maltodextrin powder) groups.

Results

Primary outcomes: weekly mean complete spontaneous bowel movements (CSBMs):

  • At 28-days CSBM was 28% higher in the P9 group (P=0.039) compared with the placebo group
  • At 42-days CSBM remained significantly higher in the P9 group (P=0.026) compared with the placebo group, and increased 2-fold compared with baseline (P <0.05)
  • Authors noted that the CSBM benefits were maintained even after 14 days of not taking the supplement.

Secondary outcomes: The effects of P9 supplementation on constipation-related parameters, including the weekly mean frequency of spontaneous bowel movements (SBMs) demonstrated:

  • After 28-days of P9 supplementation, SBMs were 12% higher than the placebo group (P=0.039)
  • No differences were observed in the weekly mean stool consistency and straining scores between groups (P>0.05).

Patients’ quality of life and psychological state, using a PAC-QOL questionnaire related to: worries and concerns (WO), physical discomfort, psychosocial discomfort, and satisfaction and found:

  • At day 14 WO in the P9 group was 1.22-fold lower than those in the placebo group (P <0.05)
  • No differences in the other 3 items between P9 and placebo groups (P >0.05) were observed
  • Supplementation resulted in a significant change in relative abundance of the P9 genome (≥0.01%)
  • However, no differences were observed in alpha diversity after P9 consumption compared with placebo.

Conclusion

  • The results indicated that P9 administration alleviated patients’ constipation symptoms and improved their quality of life but did not impact on gut bacteria or phageome
  • Lactiplantibacillis plantarum P9 supplementation impacted several beneficial bacteria species (e.g. (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), and reduced levels of other bacteria and phage taxa (e.g. Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae) which may be implicated in constipation relief mechanisms.

Clinical practice applications:
  • In this study, the use of P9 administration significantly improved patients’ defecation frequency which could have beneficial implications for patients suffering from chronic constipation
  • Probiotic effects are known to be strain- and host-specific, and based on this study P9 administration for relief of constipation needs to be taken for at least two weeks to improve aspects of patients’ quality of life and 4 weeks for improvements in constipation.

Considerations for future research:
  • Future trials should include factors that impact gut motility and constipation symptoms, such as: a detailed daily diet (dietary composition, fibre content, and water intake) and physical activity scale (intensity and duration), and longer term use of P9 or comparison across strains
  • The relatively small study size and short duration of this study, as well as the younger age groups included may be pertinent when considering future research.

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.

Lifestyle medicine

Fundamental Clinical Imbalances : Digestive, absorptive and microbiological
Patient Centred Factors : Mediators/Chronic constipation
Environmental Inputs : Diet ; Nutrients ; Microorganisms
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Stool
Bioactive Substances : Probiotics

Methodological quality

Jadad score : 4
Allocation concealment : Yes

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