Randomised Clinical Trial

Bifidobacterium Lactis NCC2818 Probiotic vs Placebo, and Impact on gut Transit Time, Symptoms, and gut Microbiology in Chronic Constipation

Eirini Dimidi; Ausra Zdanaviciene; Stephanos Christodoulides; Shiva Taheri; Petra Louis; Peter I. Duncan; Nashmil Emami; Rafael Crabbé; C. Antonio De Castro; Peter McLean; Gabriela E. Bergonzelli; Kevin Whelan; S. Mark Scott


Aliment Pharmacol Ther. 2019;49(3):251-264. 

In This Article

Abstract and Introduction


Background: Constipation is a prevalent gastrointestinal disorder. Patient dissatisfaction with prescribed medications is common, and there is need for alternative management strategies. Evidence shows that Bifidobacterium species may be beneficial in constipation.

Aim: To investigate changes in physiological and clinical measures of gut function in patients with chronic constipation following the consumption of Bifidobacterium lactis NCC2818, compared to placebo.

Methods: Participants were randomised to a 4-week supplementation with B. lactis NCC2818 (1.5 x 1010 CFU/d) or placebo. Gut transit time was measured using a radio-opaque marker, while symptoms and quality of life were assessed using validated questionnaires. Gut microbiota composition was assessed using quantitative polymerase chain reaction. Analysis of covariance was used for normally distributed variables, and Mann-Whitney test for non-normally distributed variables.

Results: Seventy-five participants were randomised. There was no significant difference between the probiotic and placebo groups in gut transit time change from baseline to week 2 (−11.7 hours, SD 33.0 hours vs −12.9 hours, SD 33.6 hours; P = 0.863) or to week 4 (−20.4 hours, SD 32.5 h vs −8.7 hours, SD 33.8 hours; P = 0.103). There were also no improvements in stool output, symptoms, or quality of life. No differences were found in Bifidobacterium concentrations between the probiotic and placebo groups at week 4 (9.5 log10/g dry faeces, SD 0.3 vs 9.4 log10/g, SD 1.0; P = 0.509).

Conclusions: Bifidobacterium lactis NCC2818 was not effective in the management of mild chronic constipation. This study highlights the importance of further studies and their publication to better understand the strain-specific effects of probiotics.


Constipation is a common burdensome functional bowel disorder in which symptoms of difficult, infrequent, or incomplete defaecation predominate.[1] Management remains challenging, with constipation representing a significant healthcare burden costing up to $7522 per year per patient.[2] Despite the range of treatments available including laxatives and fibre supplements, approximately half of patients are dissatisfied with current management strategies, with the main complaint relating to limited efficacy.[3] Hence, there is an unmet need for alternative treatments for the management of constipation-related symptoms.

Probiotics are "live microorganisms that, when administered in adequate amounts, confer a health benefit to the host".[4] In the past decade, research has focused on their effectiveness in chronic constipation, possibly mediated through an effect on regulating gut dysmotility by impacting the gut microbiota, with the subsequent release of metabolites, including short-chain fatty acids (SCFA) during fermentation,[5–7] that are known to interact with the enteric nervous system and the immune system.5

A systematic review and meta-analysis revealed 14 RCTs investigated the effect of probiotics in adults with chronic constipation;[8] this suggested that probiotics may improve whole gut transit time (WGTT), stool frequency, and stool consistency, with subgroup analysis based upon species indicating significant effects in favour of Bifidobacterium lactis .[8] However, despite favourable results reported, the clinical importance of probiotics in constipation remains uncertain, due to small study sample sizes, high heterogeneity in the study design of the individual studies, and limitations in study methodologies, including the use of nonvalidated assessment tools. Nevertheless, the promising findings of the meta-analysis, justify further research to identify B. lactis strains that may be effective in the management of chronic constipation.

Therefore, the aim of this study was to investigate changes in gut transit time and gastrointestinal symptoms following 4 weeks consumption of a probiotic strain in a randomised, double-blind, placebo-controlled manner, in adults with constipation.