Eight-Week Supplementation With Bifidobacterium lactis HN019 and Functional Constipation: A Randomized Clinical Trial

Abstract

Importance: Probiotic supplementation may improve bowel movements. However, large, properly designed studies are lacking.

Objective: To evaluate the potential benefit of Bifidobacterium animalis subsp lactis HN019 on constipation, expressed as complete spontaneous bowel movements (CSBMs).

Design, setting, and participants: This randomized triple-blind placebo-controlled clinical trial with 2 weeks of run-in and 8 weeks of intervention was conducted from December 25, 2020, to February 28, 2022, at 5 hospitals in Shanghai, China. Participants included healthy volunteers with functional constipation according to Rome III criteria, 18 to 70 years of age, and a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of less than 30.0. Eligibility after the run-in phase required the randomized participants to have 3 or fewer CSBMs/wk. Data were analyzed from September 29, 2022, to March 23, 2023, and reported as intention to treat.

Intervention: Participants were randomized to receive probiotic (B lactis HN019, 7.0 × 109 colony forming units (CFU)/d in maltodextrin at the start of the study and 4.69 × 109 CFU/d at the end of the study or maltodextrin placebo once a day for 8 weeks.

Main outcomes and measures: Primary outcome was change in CSBMs. Secondary outcomes included use of rescue medication, stool consistency, degree of straining for each bowel movement, abdominal pain, and bloating. Further, dietary habits and physical activity were recorded. Fecal samples were analyzed for moisture content, short-chain fatty acids, branched-chain fatty acids, microbiota composition, and calprotectin.

Results: Of the 283 individuals assessed for eligibility, 229 were randomized to either the placebo (n = 117) or the HN019 (n = 112) group. One participant in the placebo group discontinued due to COVID-19 restrictions. The 229 participants (194 [84.7% female) had a median age of 45 (38-52) years, mean (SD) BMI of 22.8 (2.5), and a mean (SD) of 0.77 (1.0) CSBM/wk. There was no difference in the change of weekly CSBMs from baseline to the end of study between the HN019 (least-square mean change, 0.80 [95% CI, 0.54-1.05]) and placebo (least-square mean change, 0.66 [95% CI, 0.41-0.90]) groups.

Conclusions and relevance: Although probiotics have been reported to improve bowel function, this large, well-conducted randomized clinical trial did not confirm such results. Daily consumption of B lactis HN019 at the tested dose of 4.69 × 109 CFU did not outperform placebo to increase CSBMs.

Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000029215.

Figure 1.. The CONSORT Participant Flow Diagram

B lactis HN019 indicates Bifidobacterium animalis subsp lactis HN019; ITT, intention to treat; and PP, per protocol.

Figure 2.. Study Outcomes

A, Mean change in complete spontaneous bowel movements (CSBMs). B, Mean log10 genomes of Bifidobacterium animalis subsp lactis HN019 in feces at baseline (visit 3) and at the end of the study (visit 5). Error bars indicate SD. C, Fecal microbiota alpha diversity measured by Faith phylogenetic diversity (PD) index (range, 4.51-19.20, with higher values indicating greater diversity). Horizontal bars indicate the median, first and third quartiles; boxes, the interquartile range; and error bars, the minimum and maximum values. D, Fecal microbiota alpha diversity measured by Shannon index (range, 3.39-6.77, with higher values indicating greater diversity). Horizontal bars indicate the median, first and third quartiles; boxes, the interquartile range; error bars, the minimum and maximum values; and data points, outliers. E, Taxonomic composition of fecal microbiota at phylum level. F, Taxonomic composition of fecal microbiota at genus level.