Multistrain Probiotic Increases the Gut Microbiota Diversity in Obese Pregnant Women: Results from a Randomized, Double-Blind Placebo-Controlled Study

Sofie Ingdam Halkjær, Victoria Elizabeth de Knegt, Bobby Lo, Lisbeth Nilas, Dina Cortes, Anders Elm Pedersen, Hengameh Chloé Mirsepasi-Lauridsen, Lee O'Brien Andersen, Henrik Vedel Nielsen, Christen Rune Stensvold, Thor Bech Johannesen, Thomas Kallemose, Karen Angeliki Krogfelt, Andreas Munk Petersen, Sofie Ingdam Halkjær, Victoria Elizabeth de Knegt, Bobby Lo, Lisbeth Nilas, Dina Cortes, Anders Elm Pedersen, Hengameh Chloé Mirsepasi-Lauridsen, Lee O'Brien Andersen, Henrik Vedel Nielsen, Christen Rune Stensvold, Thor Bech Johannesen, Thomas Kallemose, Karen Angeliki Krogfelt, Andreas Munk Petersen

Abstract

Background: Maternal obesity is associated with adverse pregnancy outcomes. Probiotic supplementation during pregnancy may have positive effects on blood glucose, gestational weight gain (GWG), and the risk of gestational diabetes mellitus [GDM and glycated hemoglobin (HbA1c)].

Objectives: This feasibility study involved a daily probiotic intervention in obese pregnant women from the early second trimester until delivery. The primary aim was to investigate the effect on GWG and maternal glucose homeostasis (GDM and HbA1c). Secondary aims were the effect on infant birth weight, maternal gut microbiota, and other pregnancy outcomes.

Methods: We carried out a randomized double-blinded placebo-controlled study in 50 obese pregnant women. Participants were randomly allocated (1:1) to multistrain probiotic (4 capsules of Vivomixx®; total of 450 billion CFU/d) or placebo at 14-20 weeks of gestation until delivery. Participants were followed with 2 predelivery visits at gestational week 27-30 and 36-37 and with 1 postdelivery visit. All visits included blood and fecal sampling. An oral-glucose-tolerance test was performed at inclusion and gestational week 27-30.

Results: Forty-nine participants completed the study. Thirty-eight participants took >80% of the capsules (n = 21), placebo (n = 17). There was no significant difference in GWG, GDM, HbA1c concentrations, and infant birth weight between groups. Fecal microbiota analyses showed an overall increase in α-diversity over time in the probiotic group only (P = 0.016).

Conclusions: Administration of probiotics during pregnancy is feasible in obese women and the women were willing to participate in additional study visits and collection of fecal samples during pregnancy. Multistrain probiotic can modulate the gut microbiota in obese women during pregnancy. A larger study population is needed to uncover pregnancy effects after probiotic supplementation. This trial was registered at clincaltrials.gov as NCT02508844.

Keywords: gestational diabetes mellitus; gestational weight gain; microbiota; obesity; pregnancy; probiotics.

Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram of inclusion and study visits for participants randomly assigned to probiotic and placebo group. Forty-nine participants completed the study until delivery. Participants with missed visits due to preterm delivery or discontinued capsule intervention were not excluded from following study visits.
FIGURE 2
FIGURE 2
Gestational weight gain in probiotic and placebo group. GWG, gestational weight gain; ITT, intention-to-treat; PP, per protocol.
FIGURE 3
FIGURE 3
Change in α-diversity over time in the probiotic and placebo group. Blue = baseline sample, gestational week 14–20; green = gestational week 27–30; red = gestational week 36–37; orange= 2–3 d after birth. Central line is median, box range extend to 25th and 75th percentile, whiskers extend to the value present in the data set that is furthest from the mean but within 1.5 IQR of the 25th/75th percentile.
FIGURE 4
FIGURE 4
Relative abundance of Bifidobacterium (4a), Lactobacillus (4b) and Streptococcus(4c) salivarius (y-axis) in the probiotic and placebo group. x-axis: blue = probiotic/placebo baseline, gestational week 14–20; green = probiotic/placebo gestational week 27–30; red = probiotic/placebo gestational week 36–37; blue = probiotic/placebo 2–3 d after birth. y-axis: plotted values are log10(percent abundance +1).
FIGURE 4
FIGURE 4
Relative abundance of Bifidobacterium (4a), Lactobacillus (4b) and Streptococcus(4c) salivarius (y-axis) in the probiotic and placebo group. x-axis: blue = probiotic/placebo baseline, gestational week 14–20; green = probiotic/placebo gestational week 27–30; red = probiotic/placebo gestational week 36–37; blue = probiotic/placebo 2–3 d after birth. y-axis: plotted values are log10(percent abundance +1).
FIGURE 4
FIGURE 4
Relative abundance of Bifidobacterium (4a), Lactobacillus (4b) and Streptococcus(4c) salivarius (y-axis) in the probiotic and placebo group. x-axis: blue = probiotic/placebo baseline, gestational week 14–20; green = probiotic/placebo gestational week 27–30; red = probiotic/placebo gestational week 36–37; blue = probiotic/placebo 2–3 d after birth. y-axis: plotted values are log10(percent abundance +1).
FIGURE 5
FIGURE 5
Principal coordinate analysis on the prokaryotic microbiome in the probiotic and placebo group during the study. Blue = baseline, gestational week 14–20; green = gestational week 27–30; red = gestational week 36–37; orange = 2–3 d after birth.

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