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

Abstract

BackgroundProbiotics 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).ResultsProbiotic 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.ConclusionSix 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-1090-7) contains supplementary material, which is available to authorized users.

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“…Fecal samples from baseline and follow‐up were obtained from 201 children, and their gut microbiota composition has recently been described in detail elsewhere . To summarize, LGG and BB‐12 were detected in 91% and 95%, respectively, of the fecal samples from the probiotic group, and in 2% and 31%, respectively, of the fecal samples from the placebo group at follow‐up.…”

“…To summarize, LGG and BB‐12 were detected in 91% and 95%, respectively, of the fecal samples from the probiotic group, and in 2% and 31%, respectively, of the fecal samples from the placebo group at follow‐up. Noteworthy, the BB‐12 primer was subspecies specific, as opposed to strain specific …”

“…However, BB‐12 was also detected in 31% of the placebo group fecal samples at follow‐up. This could be due to the BB‐12 primer being subspecies and not strain specific, suggesting detection of endogenous Bifidobacterium animalis subsp lactis or due to prior ingestion of related strains through infant formula . From baseline to an age of 12.8 months (SD 1.4), 91 children in the placebo group used infant formulas, and of these, 26 had used formulas containing probiotics .…”

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“…However, no significant difference was noticed between the fecal specimens collected before and after probiotic intake, considering diversity and abundances of various bacterial taxa at all levels. The authors discussed this negative result as in line with comprehensive analyses that reveal a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults and children …”

“…The authors discussed this negative result as in line with comprehensive analyses that reveal a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults 86 and children. 87 A recent study attempted to clarify the association of alteration of Bacteroides and reduction in Firmicutes, in particular of Faecalibacterium prausnitzii in a cohort of adult and pediatric patients with spondyloarthritis and JIA-ERA. This cohort was composed of 11 adult and 30 pediatric patients, compared with, respectively, 10 and 19 age-matched controls.…”