Probiotic supplementation during pregnancy alters gut microbial networks of pregnant women and infants

Ting Huang, Zhe Li, Kian Deng Tye, Sze Ngai Chan, Xiaomei Tang, Huijuan Luo, Dongju Wang, Juan Zhou, Xia Duan, Xiaomin Xiao, Ting Huang, Zhe Li, Kian Deng Tye, Sze Ngai Chan, Xiaomei Tang, Huijuan Luo, Dongju Wang, Juan Zhou, Xia Duan, Xiaomin Xiao

Abstract

Background: Probiotic supplementation has been popular and widespread, yet we still lack a comprehensive understanding of how probiotic supplementation during pregnancy affects the gut microbial networks of pregnant women and infants. In this study, we firstly used network analysis to compare the gut microbiota of pregnant women with and without probiotic supplementation, as well as their infants.

Methods: Thirty-one pairs of healthy pregnant women and infants were recruited and randomly divided into the probiotic group (15 mother-infant pairs) and the control group (16 mother-infant pairs). Pregnant women in the probiotic group consumed combined probiotics from 32 weeks to delivery. Fecal samples were collected from pregnant women and infants at several time points. Gut microbiota was evaluated using 16S rRNA gene sequencing. Intestinal microbial network and topological properties were performed using the molecular ecological network analysis.

Results: No significant difference was found between the probiotic and control groups on the microbial alpha and beta diversity. As the gestational age increased, the total links, average degree, average clustering coefficient, robustness, and the proportion of positive correlations were increased in pregnant women with probiotics administration. In contrast, these indices were decreased in infants in the probiotic group.

Conclusion: Probiotic supplement does not change the microbial diversity of pregnant women and infants, but significantly alters the intestinal microbial network structure and properties. Although pregnant women have more complicated and stable networks after probiotic administration, their infants have less stable networks.

Keywords: 16S rRNA; community stability; gut microbiota; microbial network; pregnancy; probiotics.

Conflict of interest statement

The 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.

Copyright © 2022 Huang, Li, Tye, Chan, Tang, Luo, Wang, Zhou, Duan and Xiao.

Figures

FIGURE 1
FIGURE 1
Flow chart for screening participants.
FIGURE 2
FIGURE 2
Overview of the networks in pregnant women and infants. Each node represents one OTU, edges indicate significant correlations between OTUs. Different color represents different modules. PC1 and PP1 represent feces from pregnant women in the control group and the probiotic group at the first sampling time, respectively; PC2 and PP2 represent feces from pregnant women in the control group and the probiotic group at the second sampling time CD1, CD3, CD14, and CM6 represent feces from infants in the control group at day 1, 3, 14, and month 6 after birth, respectively; PD1, PD3, PD14, and PM6 represent feces from infants in the probiotic group at day 1, 3, 14, and month 6 after birth, respectively.
FIGURE 3
FIGURE 3
Topological properties of microbial networks, including total nodes (A), average path distance (B), total links (C), average degree (D), average clustering coefficient (E), and modularity (F). P1 = Fecal samples of pregnant women at the first time collection; P2 = Fecal samples of pregnant women at the second time collection; D1 = Infant fecal samples collected at day 1 after birth; D3 = Infant fecal samples collected at day 3 after birth; D14 = Infant fecal samples collected at day 14 after birth; M6 = Infant fecal samples collected at month 6 after birth.
FIGURE 4
FIGURE 4
Modules within gut microbial networks of pregnant women with or without probiotic supplementation. The colors of nodes represent different major phyla; pie charts exhibit the phylum level composition of modules with ≥ 5 nodes. Red edges indicate positive correlations between nodes, whereas green edges indicate negative correlations. The bar underneath each networks demonstrate the proportion of positive and negative correlations.
FIGURE 5
FIGURE 5
Modules within gut microbial networks of infants in the control group. The colors of nodes represent different major phyla; pie charts exhibit the phylum level composition of modules with ≥ 5 nodes. Red edges indicate positive correlations between nodes, whereas green edges indicate negative correlations. The bar underneath each networks demonstrate the proportion of positive and negative correlations.
FIGURE 6
FIGURE 6
Modules within gut microbial networks of infants in the probiotic group. The colors of nodes represent different major phyla; pie charts exhibit the phylum level composition of modules with ≥ 5 nodes. Red edges indicate positive correlations between nodes, whereas green edges indicate negative correlations. The bar underneath each networks demonstrate the proportion of positive and negative correlations.
FIGURE 7
FIGURE 7
Microbial network stability of pregnant women and infants. Robustness of pregnant women is measured as the proportion of the remaining taxa after (A) randomly removing 50% of nodes and (B) 50% of potential keystones taxa. Statistical significance was determined by the one-way ANOVA. *P < 0.05; ***P < 0.001. Panels (C,D) showed the robustness of infants. The calculation method is the same as panels (A,B), respectively. Different lowercase letters above the bars indicate differences with P < 0.05, whereas the same letter indicates no significant difference.

References

    1. Al Alam D., Danopoulos S., Grubbs B., Ali N. A. B. M., MacAogain M., Chotirmall S. H., et al. (2020). Human fetal lungs harbor a microbiome signature. Am. J. Respir. Crit. Care Med. 201 1002–1006. 10.1164/rccm.201911-2127LE
    1. Baldassano S. N., Bassett D. S. (2016). Topological distortion and reorganized modular structure of gut microbial co-occurrence networks in inflammatory bowel disease. Sci. Rep. 6:26087. 10.1038/srep26087
    1. Barabási A.-L. (2009). Scale-free networks: A decade and beyond. Science 325 412–413. 10.1126/science.1173299
    1. Chen Y., Li Z., Tye K. D., Luo H., Tang X., Liao Y., et al. (2019). Probiotic supplementation during human pregnancy affects the gut microbiota and immune status. Front. Cell. Infect. Microbiol. 9:254. 10.3389/fcimb.2019.00254
    1. Collado M. C., Rautava S., Aakko J., Isolauri E., Salminen S. (2016). Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci. Rep. 6:23129. 10.1038/srep23129
    1. Cong J., Zhu J., Zhang C., Li T., Liu K., Liu D., et al. (2019). Chemotherapy alters the phylogenetic molecular ecological networks of intestinal microbial communities. Front. Microbiol. 10:1008. 10.3389/fmicb.2019.01008
    1. Deng Y., Jiang Y.-H., Yang Y., He Z., Luo F., Zhou J. (2012). Molecular ecological network analyses. BMC Bioinform. 13:113. 10.1186/1471-2105-13-113
    1. Differding M. K., Mueller N. T. (2020). Human milk bacteria: Seeding the infant gut? Cell Host Microbe 28 151–153. 10.1016/j.chom.2020.07.017
    1. Dotterud C. K., Avershina E., Sekelja M., Simpson M. R., Rudi K., Storrø O., et al. (2015). Does maternal perinatal probiotic supplementation alter the intestinal microbiota of mother and child? J. Pediatr. Gastroenterol. Nutr. 61 200–207. 10.1097/MPG.0000000000000781
    1. Dunne J. A., Williams R. J., Martinez N. D. (2002). Food-web structure and network theory: The role of connectance and size. Proc. Natl. Acad. Sci. U.S.A. 99 12917–12922. 10.1073/pnas.192407699
    1. Faust K., Raes J. (2012). Microbial interactions: From networks to models. Nat. Rev. Microbiol. 10 538–550. 10.1038/nrmicro2832
    1. Ferretti P., Pasolli E., Tett A., Asnicar F., Gorfer V., Fedi S., et al. (2018). Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe 24 133.e–145.e. 10.1016/j.chom.2018.06.005
    1. Fuhrman J. A. (2009). Microbial community structure and its functional implications. Nature 459 193–199. 10.1038/nature08058
    1. Gomaa E. Z. (2020). Human gut microbiota/microbiome in health and diseases: A review. Antonie Van Leeuwenhoek 113 2019–2040. 10.1007/s10482-020-01474-7
    1. Guimerà R., Nunes Amaral L. A. (2005). Functional cartography of complex metabolic networks. Nature 433 895–900. 10.1038/nature03288
    1. Hasain Z., Mokhtar N. M., Kamaruddin N. A., Mohamed Ismail N. A., Razalli N. H., Gnanou J. V., et al. (2020). Gut microbiota and gestational diabetes mellitus: A review of host-gut microbiota interactions and their therapeutic potential. Front. Cell. Infect. Microbiol. 10:188. 10.3389/fcimb.2020.00188
    1. Hill C., Guarner F., Reid G., Gibson G. R., Merenstein D. J., Pot B., et al. (2014). Expert consensus document. The international scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 11 506–514. 10.1038/nrgastro.2014.66
    1. Ismail I. H., Oppedisano F., Joseph S. J., Boyle R. J., Robins-Browne R. M., Tang M. L. K. (2012). Prenatal administration of Lactobacillus rhamnosus has no effect on the diversity of the early infant gut microbiota. Pediatr. Allergy Immunol. 23 255–258. 10.1111/j.1399-3038.2011.01239.x
    1. Jain S., Krishna S. (2001). A model for the emergence of cooperation, interdependence, and structure in evolving networks. Proc. Natl. Acad. Sci. U.S.A. 98 543–547. 10.1073/pnas.98.2.543
    1. Kristensen N. B., Bryrup T., Allin K. H., Nielsen T., Hansen T. H., Pedersen O. (2016). Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: A systematic review of randomized controlled trials. Genome Med. 8:52. 10.1186/s13073-016-0300-5
    1. Liang X., Li Z., Tye K. D., Chen Y., Luo H., Xiao X. (2021). The effect of probiotic supplementation during pregnancy on the interaction network of vaginal microbiome. J. Obstet. Gynaecol. Res. 47 103–113. 10.1111/jog.14434
    1. Liu S., Yu H., Yu Y., Huang J., Zhou Z., Zeng J., et al. (2022). Ecological stability of microbial communities in Lake Donghu regulated by keystone taxa. Ecol. Indic. 136:108695. 10.1016/j.ecolind.2022.108695
    1. Ma Z. S. (2018). The P/N (Positive-to-Negative Links) ratio in complex networks-A promising in silico biomarker for detecting changes occurring in the human microbiome. Microb. Ecol. 75 1063–1073. 10.1007/s00248-017-1079-7
    1. Mishra A., Lai G. C., Yao L. J., Aung T. T., Shental N., Rotter-Maskowitz A., et al. (2021). Microbial exposure during early human development primes fetal immune cells. Cell 184 3394.e–3409.e. 10.1016/j.cell.2021.04.039
    1. Montesinos-Navarro A., Hiraldo F., Tella J. L., Blanco G. (2017). Network structure embracing mutualism–antagonism continuums increases community robustness. Nat. Ecol. Evol. 1 1661–1669. 10.1038/s41559-017-0320-6
    1. Murphy R., Morgan X. C., Wang X. Y., Wickens K., Purdie G., Fitzharris P., et al. (2019). Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: Sub-sample analysis from a RCT. Benef. Microbes 10 5–17. 10.3920/BM2017.0191
    1. Sanders M. E. (2008). Probiotics: Definition, sources, selection, and uses. Clin. Infect. Dis. 46 S58–S61. 10.1086/523341
    1. Shin D. Y., Park J., Yi D. Y. (2021). Comprehensive analysis of the effect of probiotic intake by the mother on human breast milk and infant fecal microbiota. J. Korean Med. Sci. 36:e58. 10.3346/jkms.2021.36.e58
    1. Singh A., Sarangi A. N., Goel A., Srivastava R., Bhargava R., Gaur P., et al. (2018). Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India: An open-label, single-arm pilot study. BMC Gastroenterol. 18:85. 10.1186/s12876-018-0819-6
    1. Walker R. W., Clemente J. C., Peter I., Loos R. J. (2017). The prenatal gut microbiome: Are we colonized with bacteria in utero? Pediatr Obes 12 3–17. 10.1111/ijpo.12217
    1. Wang J., Gu X., Yang J., Wei Y., Zhao Y. (2019). Gut microbiota dysbiosis and increased plasma LPS and TMAO levels in patients with preeclampsia. Front Cell Infect Microbiol 9:409. 10.3389/fcimb.2019.00409
    1. Xiao F., Zhu W., Yu Y., Huang J., Li J., He Z., et al. (2022). Interactions and stability of gut microbiota in zebrafish increase with host development. Microbiol. Spectr. 10:e0169621. 10.1128/spectrum.01696-21
    1. Yuan M. M. (2021). Climate warming enhances microbial network complexity and stability. Nat. Climate Change 11:18.
    1. Zhou J., Deng Y., Luo F., He Z., Tu Q., Zhi X. (2010). Functional molecular ecological networks. mBio 1 e169–10. 10.1128/mBio.00169-10

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