Administration of two probiotic strains during early childhood does not affect the endogenous gut microbiota composition despite probiotic proliferation

Abstract

Background: Probiotics are increasingly applied to prevent and treat a range of infectious, immune related and gastrointestinal diseases. Despite this, the mechanisms behind the putative effects of probiotics are poorly understood. One of the suggested modes of probiotic action is modulation of the endogenous gut microbiota, however probiotic intervention studies in adults have failed to show significant effects on gut microbiota composition. The gut microbiota of young children is known to be unstable and more responsive to external factors than that of adults. Therefore, potential effects of probiotic intervention on gut microbiota may be easier detectable in early life. We thus investigated the effects of a 6 month placebo-controlled probiotic intervention with Bifidobacterium animalis subsp. lactis (BB-12®) and Lactobacillus rhamnosus (LGG®) on gut microbiota composition and diversity in more than 200 Danish infants (N = 290 enrolled; N = 201 all samples analyzed), as assessed by 16S rRNA amplicon sequencing. Further, we evaluated probiotic presence and proliferation by use of specific quantitative polymerase chain reaction (qPCR).

Results: Probiotic administration did not significantly alter gut microbiota community structure or diversity as compared to placebo. The probiotic strains were detected in 91.3% of the fecal samples from children receiving probiotics and in 1% of the placebo treated children. Baseline gut microbiota was not found to predict the ability of probiotics to establish in the gut after the 6 month intervention. Within the probiotics group, proliferation of the strains LGG® and BB-12® in the gut was detected in 44.7% and 83.5% of the participants, respectively. A sub-analysis of the gut microbiota including only individuals with detected growth of the probiotics LGG® or BB-12® and comparing these to placebo revealed no differences in community structure or diversity.

Conclusion: Six months of probiotic administration during early life did not change gut microbiota community structure or diversity, despite active proliferation of the administered probiotic strains. Therefore, alteration of the healthy infant gut microbiota is not likely to be a prominent mechanism by which these specific probiotics works to exert beneficial effects on host health.

Trial registration: NCT02180581 . Registered 30 June 2014.

Keywords: BB-12®; Early life; Gut microbiota; LGG®; Probiotic intervention.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Committees on Biomedical Research Ethics for the Capital Region of Denmark (H-4-2014-032), and the study was registered at clinicaltrials.org (NCT02180581) at June 30, 2014. The first participant was enrolled August 22, 2014. All parents signed a consent form.

Consent for publication

Not applicable.

Competing interests

Chr. Hansen A/S provided additional funding for the project, but had no influence on the interpretation of the data.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Administration of probiotics does not alter diversity and composition of the infant gut microbiota. a PCoA plots of weighted and unweighted UniFrac distances of the gut microbiota, b boxplots of gut microbial alpha diversity measures, and c boxplots of relative abundance of gut microbial families after probiotic (orange) or placebo (blue) intervention

Fig. 2

Sub-analyses of selected samples with active probiotic growth does not reveal impact on gut microbiota community structure. a-b Estimates of in situ growth of a BB-12® and b LGG® expressed as the ratio of excreted CFUs/day (excretion) to ingested CFUs/day (input) for all samples within the probiotics group. Means and medians are represented by dashed lines. c-d PCoA plots of weighted UniFrac distances of the gut microbiota in samples with detected growth of c BB-12® and d LGG® (orange) as compared to placebo (blue) intervention