Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison

Abstract

While probiotics are a multi-billion dollar industry, there is little evidence to show that supplementing infants provides any health benefits. We conducted an observational study where 35 of 86 participating mothers self-administered probiotics during breastfeeding, as well as directly to their infants. The primary objective was to determine if probiotic exposure influenced the infants' fecal microbiome while the secondary objective assessed associated changes to the mothers' breast milk immunity and infant health. Analysis of infant fecal microbiome throughout the first 6 months of life revealed that probiotics were associated with higher abundances of Bifidobacterium at week 1 only. Short-chain fatty acid production and predicted metagenomic functions of the microbial communities were not altered. While probiotics did not alter breast milk immune markers, fecal sIgA responses were higher among probiotic supplemented infants. Surprisingly, this was not associated with better health outcomes, as the probiotic cohort had higher incidences of mucosal-associated illnesses as toddlers. This retrospective clinical comparison suggests that probiotic exposure during infancy has limited effects on gut microbial composition yet is associated with increased infection later in life. These correlative findings caution against probiotic supplementation during infancy until rigorous controlled follow-up studies determining their safety and efficacy have occurred.

Trial registration: ClinicalTrials.gov NCT03297801.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1

Flow of participants through the trial.

Figure 2

Alpha diversity measures of fecal microbiota over a 6-month period of probiotics and no probiotics exposed infants. The alpha diversity in the infants’ stool did not differ between the two groups at any time point (1 week to 6 months of age). While the two groups were not different from each other, Faith’s phylogenetic diversity in the no probiotics group significantly increased at months 4 and 5 when compared to the first week, whereas the probiotics group showed no significant increases. *Denotes P < 0.05.

Figure 3

Beta diversity assessment of microbial communities over a 6-month period of probiotics and no probiotics exposed infants. (A) PCoA plots based on the Bray-Curtis dissimilarity distance show no distinct clustering of microbial communities at any age except for at 1 week. (B) Table summary of PERMANOVA results ran on the Bray-Curtis dissimilarity, and weighted and unweighted UniFrac distances between the two groups. The values at the intersect of a blue cell (probiotics group) and an orange cell (no probiotics group) show the estimated P value of the corresponding time points.

Figure 4

Differences in the abundance of taxa between the groups were assessed using two complimentary approaches at each time-point. (A) Differences in the relative abundance of Bifidobacterium spp. in the probiotics group at one week of age was detected as significantly different using ANCOM (P < 0.05, F-statistic = 7.5). (B) LEfSe results showing significantly different taxa between fecal samples between probiotics and no probiotics infants at one week of age. The cladogram reports the taxa showing different abundance values according to LEfSe. Colors indicate the lineages that are encoded within corresponding samples. Higher taxa abundance in the probiotics group is colored blue whereas higher taxa abundance in the no probiotics group is colored orange. (C) Infants directly supplemented with BioGaia according to the manufacturers recommendations show similar results to (A and B). P < 0.05.

Figure 5

Abundances of fecal SCFAs acetic acid, butyric acid, and propionic acid between probiotics and no probiotics exposed infants at 5 months of age expressed as mass % (g SCFA/g dry weight stool).

Figure 6

Immune markers in breast milk of mothers with or without probiotic supplementation at 5 months. The scatter dot plot shows the mean and standard error mean.

Figure 7

Infant exposure to probiotics correlates with increased mucosal illness during the first 2 years of life and corresponding immune responses at 5 months of age. (A) Infants exposed to probiotics had significantly higher reported mucosal infections compared to the no probiotics group but were able to clear infections at similar rates. (B) Probiotic exposure during the first 6 months is associated with no changes in breast milk sIgA but modest increases in fecal sIgA. (C) There were no differences in either breast milk or infant stool IgE levels. *Denotes P < 0.05.