Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study

Gut Microbes. 2015;6(1):66-77. doi: 10.1080/19490976.2015.1005484.


Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

Keywords: BB-12, Bifidobacterium animalis subsp lactis strain BB-12; CBER, Center for Biologics Evaluation and Research; FDA, Food and Drug Administration; IND, investigational new drug; NCCAM, National Center for Complementary and Alternative Medicine; NIH, National Institutes of Health; antibiotics; clinical trial; gut microbiota; probiotics; safety.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Bacterial Load
  • Bifidobacterium / growth & development*
  • Biomarkers / blood
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / adverse effects
  • Feces / microbiology
  • Female
  • Healthy Volunteers
  • Humans
  • Leukocytes / immunology
  • Male
  • Middle Aged
  • Pilot Projects
  • Probiotics / administration & dosage*
  • Probiotics / adverse effects*
  • Random Allocation
  • United States
  • Yogurt / microbiology*
  • Young Adult


  • Anti-Bacterial Agents
  • Biomarkers
  • Drugs, Investigational