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. 2022 Sep 21:13:986340.
doi: 10.3389/fimmu.2022.986340. eCollection 2022.

Maternal gut microbiota during pregnancy and the composition of immune cells in infancy

Yuan Gao  1   2   3 , Martin O'Hely  1   4 , Thomas P Quinn  5 , Anne-Louise Ponsonby  4   6 , Leonard C Harrison  7   8 , Hanne Frøkiær  3 , Mimi L K Tang  4   9 , Susanne Brix  10 , Karsten Kristiansen  11 , Dave Burgner  4 , Richard Saffery  4   9 , Sarath Ranganathan  4   9 , Fiona Collier  1 , Peter Vuillermin  1   2
Affiliations

Maternal gut microbiota during pregnancy and the composition of immune cells in infancy

Yuan Gao et al. Front Immunol. .

Abstract

Background: Preclinical studies have shown that maternal gut microbiota during pregnancy play a key role in prenatal immune development but the relevance of these findings to humans is unknown. The aim of this prebirth cohort study was to investigate the association between the maternal gut microbiota in pregnancy and the composition of the infant's cord and peripheral blood immune cells over the first year of life.

Methods: The Barwon Infant Study cohort (n=1074 infants) was recruited using an unselected sampling frame. Maternal fecal samples were collected at 36 weeks of pregnancy and flow cytometry was conducted on cord/peripheral blood collected at birth, 6 and 12 months of age. Among a randomly selected sub-cohort with available samples (n=293), maternal gut microbiota was characterized by sequencing the 16S rRNA V4 region. Operational taxonomic units (OTUs) were clustered based on their abundance. Associations between maternal fecal microbiota clusters and infant granulocyte, monocyte and lymphocyte subsets were explored using compositional data analysis. Partial least squares (PLS) and regression models were used to investigate the relationships/associations between environmental, maternal and infant factors, and OTU clusters.

Results: We identified six clusters of co-occurring OTUs. The first two components in the PLS regression explained 39% and 33% of the covariance between the maternal prenatal OTU clusters and immune cell populations in offspring at birth. A cluster in which Dialister, Escherichia, and Ruminococcus were predominant was associated with a lower proportion of granulocytes (p=0.002), and higher proportions of both central naïve CD4+ T cells (CD4+/CD45RA+/CD31-) (p<0.001) and naïve regulatory T cells (Treg) (CD4+/CD45RA+/FoxP3low) (p=0.02) in cord blood. The association with central naïve CD4+ T cells persisted to 12 months of age.

Conclusion: This birth cohort study provides evidence consistent with past preclinical models that the maternal gut microbiota during pregnancy plays a role in shaping the composition of innate and adaptive elements of the infant's immune system following birth.

Keywords: birth cohort; fetal immunity; gut microbiota; maternal microbiota; neonatal T cells.

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Conflict of interest statement

The findings described in this paper are the subject of a provisional patent, licensed to Prevatex Pty Ltd, in which the following authors have a financial interest: PV, MOH, SR, ALP. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Participants and samples included in the study. Fecal samples from 284 mothers were collected at 36 weeks of gestation and the microbiome was analyzed by 16S rRNA gene amplicon sequencing. Cord blood samples from 216 neonates at birth, and peripheral blood samples from 181 infants at 6 months of age and 219 infants at 12 months were analyzed by flow cytometry.
Figure 2
Figure 2
Analysis workflow. All analyses were performed on maternal OTU clusters and/or infant immune profile at birth, 6 and 12 months of age.
Figure 3
Figure 3
Overall description of six OTU clusters in maternal gut during late pregnancy. (A) Each column shows the OTU composition of each cluster. Within each column, OTUs are ordered according to the percentage of their relative abundance in each cluster. The identifications of OTUs on species/genus level are listed in the box below; ‘Others’ are in Table S3 . (B) The partial least squares biplot shows the associations between OTU clusters (blue) and covariates (orange). The longer the arrow the stronger the association with other variables. An acute angle between arrows represents positive association, an obtuse angle represents negative association and orthogonal arrows represent no association.
Figure 4
Figure 4
Associations between maternal OTU clusters and immune cell profile in cord blood (n=216). (A) The partial least squares biplot shows the associations between OTU clusters (blue) and immune populations (orange). The acute angle between arrows to Cluster 1 and central naïve CD4+ T cells indicates a positive association, whereas the obtuse angle between Cluster 1 and granulocytes indicates a negative association. (B) Increases (with 95% confidence intervals) in log-transformed immune populations per unit change in automated balances for OTU Cluster 1 and 6 abundances.
Figure 5
Figure 5
Associations between maternal OTU clusters and CD4+ subpopulations at birth. (A) The partial least squares biplot shows the associations between OTU clusters (blue) and immune populations (orange)(n=216). The acute angles between Cluster 1 and central naïve CD4+ T cells suggest a positive association. (B) Increases (with 95% confidence intervals) in log-transformed immune populations (CD4+ T cells, and naïve and memory CD4+ T cells) per unit change in automated balances for Cluster 1 abundance. (C) The partial least squares biplot shows the associations between OTU clusters (blue) and immune populations (orange), The acute angle between arrows to Cluster 1 and naïve Tregs indicates a positive association (n=107). (D) Increases (with 95% confidence intervals) in log-transformed immune populations (CD4+ T cells, Tregs, and Foxp3 T cells) per unit change in automated balances for Cluster 1 abundance.
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References

    1. Gomez de Aguero M, Ganal-Vonarburg SC, Fuhrer T, Rupp S, Uchimura Y, Li H, et al. . The maternal microbiota drives early postnatal innate immune development. Science (2016) 351(6279):1296–302. doi: 10.1126/science.aad2571 - DOI - PubMed
    1. Hu M, Eviston D, Hsu P, Mariño E, Chidgey A, Santner-Nanan B, et al. . Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia. Nat Commun (2019) 10(1):1–13. doi: 10.1038/s41467-019-10703-1 - DOI - PMC - PubMed
    1. Gao Y, Nanan R, Macia L, Tan J, Sominsky L, Quinn TP, et al. . The maternal gut microbiome during pregnancy and offspring allergy and asthma. J Allergy Clin Immunol (2021) 148(3):669–78. doi: 10.1016/j.jaci.2021.07.011 - DOI - PubMed
    1. Schaub B, Liu J, Höppler S, Schleich I, Huehn J, Olek S, et al. . Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol (2009) 123(4):774–82.e5. doi: 10.1016/j.jaci.2009.01.056 - DOI - PubMed
    1. Roduit C, Wohlgensinger J, Frei R, Bitter S, Bieli C, Loeliger S, et al. . Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis. J Allergy Clin Immunol (2011) 127(1):179–85.e1. doi: 10.1016/j.jaci.2010.10.010 - DOI - PubMed

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