Bifidobacterium animalis subsp. lactis Bi-07 supports lactose digestion in vitro and in randomized, placebo- and lactase-controlled clinical trials

Pia Rasinkangas, Sofia D Forssten, Maija Marttinen, Alvin Ibarra, Gordana Bothe, Jouni Junnila, Ralf Uebelhack, Yves Donazzolo, Arthur C Ouwehand, Pia Rasinkangas, Sofia D Forssten, Maija Marttinen, Alvin Ibarra, Gordana Bothe, Jouni Junnila, Ralf Uebelhack, Yves Donazzolo, Arthur C Ouwehand

Abstract

Background: Probiotics may alleviate lactose maldigestion.

Objectives: The objective was to select a probiotic with high lactase activity and compare it with lactase and placebo in clinical trials.

Methods: Bacterial cultures were screened for lactase activity in a model of the upper gastrointestinal (GI) tract. Bifidobacterium animalis subsp. lactis Bi-07 (Bi-07) counts were adjusted in subsequent experiments to correspond to 4500 Food Chemicals Codex (FCC) units of lactase, the amount in the European Food Safety Authority (EFSA)-approved health claim. Two crossover clinical trials, Booster Alpha and Booster Omega, were performed in participants with lactose intolerance, where 2 × 1012 CFUs Bi-07, 4662 FCC lactase, or placebo was consumed simultaneously with a lactose challenge, with 1-wk washouts between challenges. The trial designs were identical except for the source of lactose. Breath hydrogen concentration (BHC) was measured to assess the effect of the investigational products on lactose digestion, for which incremental area under the curve (iAUC) was the primary outcome. Peak BHC, cumulative BHC, and GI symptoms were secondary outcomes.

Results: Bi-07 was superior to placebo in reducing BHC [iAUC, parts per million (ppm) ∙ h] in both trials (Booster Alpha: geometric least square mean ratio: 0.462; 95% CI: 0.249, 0.859; P = 0.016; Booster Omega: 0.227; 95% CI: 0.095, 0.543; P = 0.001). Lactase was superior to placebo in Booster Alpha (0.190; 95% CI: 0.102, 0.365; P < 0.001) but not Booster Omega (0.493; 95% CI: 0.210, 1.156; P = 0.102). Noninferiority of Bi-07 compared with lactase was observed in Booster Omega (0.460; 95% CI: 0.193, 1.096; P = 0.079; CI upper limit < 1.25 noninferiority margin). Odds of abdominal pain (compared with placebo: 0.32, P = 0.036) and flatulence (compared with placebo: 0.25, P = 0.007) were lower with lactase in Booster Alpha. Increased odds of nausea were seen with Bi-07 (compared with placebo: 4.0, P = 0.005) in Booster Omega.

Conclusions: Bi-07 has high lactase activity, and in 2 clinical trials, it supported lactose digestion in individuals with lactose intolerance.These trials were registered at clinicaltrials.gov as NCT03659747 (Booster Alpha) and NCT03814668 (Booster Omega).

Keywords: Bifidobacterium lactis Bi-07; breath hydrogen concentration; in vitro; lactase; lactose intolerance; lactose maldigestion; probiotic; randomized controlled trial.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Study design of the clinical trials, Booster Alpha and Booster Omega. BHC, breath hydrogen concentration; BHC eligibility, check-up of possible foods and actions affecting breath gas measurement; ConMed, concomitant medication; GI, gastrointestinal; I & E, inclusion and exclusion criteria review; w/ IP, with Investigational Product; w/o IP, without Investigational Product.
FIGURE 2
FIGURE 2
Lactase activity measurement of untreated milk (blank control), placebo (maltodextrin; negative control), lactase (commercial lactase), Bi-07, and 4500 U laboratory-grade β-galactosidase (positive control) in milk. Results are presented as mean ± SD from 3 separate experiments. (A) Amount of lactose monohydrate (g/100 mL) during the 6-h treatment for each of the studied samples. (B) Change in pH during the 6-h treatment in each of the studied samples. Bi-07, Bifidobacterium animalis subsp. lactis Bi-07.
FIGURE 3
FIGURE 3
CONSORT flow diagrams of the 2 clinical trials, Booster Alpha (A) and Booster Omega (B). Randomization completed: participant was withdrawn from the study after randomization; abnormal biology: screening assessments showed biologically relevant abnormal blood test values, and the participant was not included in the study; supplementary participant: any potential participant who was prescreened for the study but not randomly assigned, because the required number of randomly assigned participants was obtained before the randomization visit. Bi-07, Bifidobacterium animalis subsp. lactis Bi-07; PP, per-protocol.
FIGURE 4
FIGURE 4
Mean BHC by treatment in per-protocol population during the 6-h lactose challenge in both clinical trials. (A) Booster Alpha (n = 33 for each treatment) and (B) Booster Omega (n = 32 for Bi-07 and n = 34 for lactase and placebo). The SEM at each time point is shown as vertical line segments. BHC, breath hydrogen concentration; Bi-07, Bifidobacterium animalis subsp. lactis Bi-07.
FIGURE 5
FIGURE 5
Radar plots of the proportion (mean percentage) of participants in the per-protocol population (Booster Alpha: n = 33 for each treatment; Booster Omega: n = 32 for Bi-07 and n = 34 for lactase and placebo) with gastrointestinal symptoms in both clinical trials. (A) Participants having at least mild symptoms in Booster Alpha, (B) participants having at least moderate symptoms in Booster Alpha, (C) participants having at least mild symptoms in Booster Omega, and (D) participants having at least moderate symptoms in Booster Omega. Bi-07, Bifidobacterium animalis subsp. lactis Bi-07.

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