Randomized open-label pilot study of the influence of probiotics and the gut microbiome on toxic metal levels in Tanzanian pregnant women and school children

Abstract

Exposure to environmental toxins is a 21st century global health problem that is often the result of dietary intake. Although efforts are made to reduce dietary toxin levels, they are often unsuccessful, warranting research into novel methods to reduce host exposure. Food-grade microbes that can be delivered to the gastrointestinal tract and that are capable of sequestering toxins present a safe and cost-effective intervention. We sought to investigate the potential for probiotic-supplemented yogurt to lower heavy metal levels in at-risk populations of pregnant women and in children in Mwanza, Tanzania, and to examine the microbiome in relation to toxin levels. Two populations suspected to have high toxic metal exposures were studied. A group of 44 school-aged children was followed over 25 days, and 60 pregnant women were followed over their last two trimesters until birth. A yogurt containing 10(10) CFU Lactobacillus rhamnosus GR-1 per 250 g was administered, while control groups received either whole milk or no intervention. Changes in blood metal levels were assessed, and the gut microbiomes of the children were profiled by analyzing 16S rRNA sequencing via the Ion Torrent platform. The children and pregnant women in the study were found to have elevated blood levels of lead and mercury compared to age- and sex-matched Canadians. Consumption of probiotic yogurt had a protective effect against further increases in mercury (3.2 nmol/liter; P = 0.035) and arsenic (2.3 nmol/liter; P = 0.011) blood levels in the pregnant women, but this trend was not statistically significant in the children. Elevated blood lead was associated with increases in Succinivibrionaceae and Gammaproteobacteria relative abundance levels in stool. Importance: Probiotic food produced locally represents a nutritious and affordable means for people in some developing countries to counter exposures to toxic metals. Further research and field trials are warranted to explore this approach in countries where communities are located near mining sites and agricultural areas, two types of areas where toxins are likely to be elevated.

Trial registration: ClinicalTrials.gov NCT01904513 NCT02021799.

FIG 1

Consort flow diagram, detailing participant enrollment, allocation, follow-up, and analysis.

FIG 2

Heat map representation of the gut microbiomes of SAC at the beginning and endpoint of the study. Data were summarized to the family level and plotted in terms of percent abundance. Across nearly all participants, Prevotellaceae were the most dominant family observed, while an unclassified Succinivibrionaceae was also of variably high abundance across many participants.

FIG 3

Association of OTU_1 (Succinivibrionaceae) (A) and OTU_215 (Gammaproteobacteria) (B) with elevated blood lead levels in a comparison of upper and lower quartiles of all samples (FDR, <0.05).