Antibiotic use during pregnancy is linked to offspring gut microbial dysbiosis, barrier disruption, and altered immunity along the gut-lung axis.
Th17 cell
antibiotics
asthma
gut-lung axis
pregnancy
Journal
European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
16
05
2023
received:
13
01
2023
accepted:
21
06
2023
medline:
23
10
2023
pubmed:
11
7
2023
entrez:
11
7
2023
Statut:
ppublish
Résumé
Antibiotic use during pregnancy is associated with increased asthma risk in children. Since approximately 25% of women use antibiotics during pregnancy, it is important to identify the pathways involved in this phenomenon. We investigate how mother-to-offspring transfer of antibiotic-induced gut microbial dysbiosis influences immune system development along the gut-lung axis. Using a mouse model of maternal antibiotic exposure during pregnancy, we immunophenotyped offspring in early life and after asthma induction. In early life, prenatal-antibiotic exposed offspring exhibited gut microbial dysbiosis, intestinal inflammation (increased fecal lipocalin-2 and IgA), and dysregulated intestinal ILC3 subtypes. Intestinal barrier dysfunction in the offspring was indicated by a FITC-dextran intestinal permeability assay and circulating lipopolysaccharide. This was accompanied by increased T-helper (Th)17 cell percentages in the offspring's blood and lungs in both early life and after allergy induction. Lung tissue additionally showed increased percentages of RORγt T-regulatory (Treg) cells at both time points. Our investigation of the gut-lung axis identifies early-life gut dysbiosis, intestinal inflammation, and barrier dysfunction as a possible developmental programming event promoting increased expression of RORγt in blood and lung CD4
Identifiants
pubmed: 37431194
doi: 10.1002/eji.202350394
doi:
Substances chimiques
Anti-Bacterial Agents
0
Nuclear Receptor Subfamily 1, Group F, Member 3
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2350394Informations de copyright
© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.
Références
Cait, A., Wedel, A., Arntz, J. L., Duinkerken, J., Datye, S., Cait, J., Alhasan, M. M. et al., Prenatal antibiotic exposure, asthma, and the atopic march: A systematic review and meta-analysis. Allergy: Eur. J. Allerg. Clin. Immunol. 2022. 77: 3233-3248.
Arrieta, M.-C., Stiemsma, L.1 T., Dimitriu, P. A., Thorson, L., Russell, S., Yurist-Doutsch, S., Kuzeljevic, B. et al., Early infancy microbial and metabolic alterations affect risk of childhood asthma. Sci. Transl. Med. 2015. 7:307ra152.
Olin, A., Henckel, E., Chen, Y., Lakshmikanth, T., Pou, C., Mikes, J., Gustafsson, A. et al., Stereotypic immune system development in newborn children. Cell. 2018. 174: 1277-1292.e14.
Abrahamsson, T. R., Jakobsson, H. E., Andersson, A. F., Björkstén, B., Engstrand, L. and Jenmalm, M. C., Low gut microbiota diversity in early infancy precedes asthma at school age. Clin. Exp. Allergy. 2014. 44: 842-850.
Gensollen, T., Iyer, S. S., Kasper, D. L. and Blumberg, R. S., How colonization by microbiota in early life shapes the immune system. Science. 2016. 352: 539-544.
Zheng, D., Liwinski, T. and Elinav, E., Interaction between microbiota and immunity in health and disease. Cell. Res. 2020. 30: 492-506.
Kalbermatter, C., Fernandez Trigo, N., Christensen, S. and Ganal-Vonarburg, S. C., Maternal microbiota, early life colonization and breast milk drive immune development in the newborn. Front. Immunol. 2021. 12: 1768.
Martin, R., Nauta, A., Ben Amor, K., Knippels, L., Knol, J. and Garssen, J., Early life: Gut microbiota and immune development in infancy. Benef. Microbes. 2010. 1: 367-382.
Fujimura, K. E., Sitarik, A. R., Havstad, S., Lin, D. L., Levan, S., Fadrosh, D., Panzer, A. R. et al., Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat. Med. 2016. 22: 1187-1191.
Round, J. L. and Mazmanian, S. K., The gut microbiome shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 2009. 9: 313.
Herbst, T., Sichelstiel, A., Schär, C., Yadava, K., Bürki, K., Cahenzli, J., Mccoy, K. et al., Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respirat. Crit. Care Med. 2012. 184: 198-205.
Zhao, D., Su, H., Cheng, J., Wang, Xu, Xie, M., Li, K., Wen, L. et al., Prenatal antibiotic use and risk of childhood wheeze/asthma: A meta-analysis. Pediatr. Allergy Immunol. 2015. 26: 756-764.
Rantala, A. K., Tapia, G., Magnus, M. C., Stene, L. C., Jaakkola, J J.K., Størdal, K., Karlstad, Ø. et al., Maternal antibiotic use and infections during pregnancy and offspring asthma: The Norwegian Mother, Father and Child Cohort Study and a nationwide register cohort. Eur. J. Epidemiol. 2022. 37: 983-992.
Russell, S. L., Gold, M. J., Willing, B. P., Thorson, L., Mcnagny, K. M. and Finlay, B. B., Perinatal antibiotic treatment affects murine microbiota, immune responses and allergic asthma. Gut. Microbes. 2013. 4: 158-164.
Alhasan, M. M., Cait, A. M., Heimesaat, M. M., Blaut, M., Klopfleisch, R., Wedel, A., Conlon, T. M., Yildirim, A. O., Sodemann, E. B., Mohn, W. W., Bereswill, S. and Conrad, M. L., Antibiotic use during pregnancy increases offspring asthma severity in a dose-dependent manner. Allergy. 2020. 75: 1979-1990.
Bookstaver, P. B, Bland, C. M., Griffin, B., Stover, K. R., Eiland, L. S. and Mclaughlin, M., A review of antibiotic use in pregnancy. Pharmacother. J. Hum. Pharmacol. Drug Ther. 2015. 35: 1052-1062.
Momen, N. C. and Liu, X., Maternal antibiotic use during pregnancy and asthma in children: Population-based cohort study and sibling design. Eur. Respir. J. 2021. 57: 2000937.
Frati, F., Salvatori, C., Incorvaia, C., Bellucci, A., Di Cara, G., Marcucci, F. and Esposito, S., The role of the microbiome in asthma: The gut-lung axis. Int. J. Mol. Sci. 2018. 20: 123.
Sokolowska, M., Frei, R., Lunjani, N., Akdis, C. A. and O'Mahony, L. M, Microbiome and asthma. Asthma Res. Pract. 2018. 4: 1-9.
Chen, C. M., Chou, H. C. and Yang, Y. C. S. H., Maternal antibiotic treatment disrupts the intestinal microbiota and intestinal development in neonatal mice. Front. Microbiol. 2021.12: 1356.
Enaud, R., Prevel, R., Ciarlo, E., Beaufils, F., Wieërs, G., Guery, B. and Delhaes, L., The gut-lung axis in health and respiratory diseases: A place for inter-organ and inter-kingdom crosstalks. Front. Cell Infect Microbiol. 2020. 10: 9.
Budden, K. F., Gellatly, S. L., Wood, D. L. A., Cooper, M. A., Morrison, M., Hugenholtz, P. Hansbro, P. M. et al., Emerging pathogenic links between microbiota and the gut-lung axis. Nat. Rev. Microbiol. 2016. 15: 55-63.
Roduit, C., Frei, R., Ferstl, R., Loeliger, S., Westermann, P., Rhyner, C., Schiavi, E. et al., High levels of butyrate and propionate in early life are associated with protection against atopy. Allergy 2019. 74: 799-809.
Wu, W., Sun, M., Chen, F., Cao, A. T., Liu, H., Zhao, Y., Huang, X. et al., Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43. Mucosal. Immunol. 2016. 10: 946-956.
Ghosh, S. S., Wang, J., Yannie, P. J. and Ghosh, S., Intestinal barrier dysfunction, LPS translocation, and disease development. J. Endocr. Soc. 2020. 4: bvz039.
Dzidic, M., Abrahamsson, T. R., Artacho, A., Björkstén, B., Collado, M. C., Mira, A. and Jenmalm, M. C., Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development. J. Allergy Clin. Immunol. 2017. 139, 1017-1025.e14.
Wagner, C., Torow, N., Hornef, M. W. and Lelouard, H., Spatial and temporal key steps in early-life intestinal immune system development and education. FEBS J. 2022. 289: 4731-4757.
Huang, Y., Mao, K., Chen, Xi, Sun, M.-A., Kawabe, T., Li, W., Usher, N. et al., S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense. Science 2018. 359: 114-119.
Zeng, B., Shi, S., Ashworth, G., Dong, C., Liu, J. and Xing, F., ILC3 function as a double-edged sword in inflammatory bowel diseases. Cell. Death Dis. 2019. 10: 1-12.
Pu, Q., Lin, P., Gao, P., Wang, Z., Guo, K., Qin, S., Zhou, C. et al., Gut microbiota regulate gut-lung axis inflammatory responses by mediating ILC2 compartmental migration. J. Immunol. 2021. 207: 257-267.
Jarade, A., Garcia, Z., Marie, S., Demera, A., Prinz, I., Bousso, P., Di Santo, J. P. et al., Inflammation triggers ILC3 patrolling of the intestinal barrier. Nat. Immunol. 2022. 23: 1317-1323.
Hammond, K. A., Adaptation of the Maternal Intestine During Lactation. J. Mammary Gland Biol. Neoplasia 1997. 2: 243-252.
Poggi, A., Benelli, R., Venè, R., Costa, D., Ferrari, N., Tosetti, F. and Zocchi, M. R., Human gut-associated natural killer cells in health and disease. Front. Immunol. 2019. 10: 961.
Ganal-Vonarburg, S. C. and Duerr, C. U., The interaction of intestinal microbiota and innate lymphoid cells in health and disease throughout life. Immunology 2020. 159: 39-51.
Chang, Y., Kim, Ju W, Yang, S., Chung, D. H., Ko, J. S., Moon, J. S. and Kim, H. Y., Increased GM-CSF-producing NCR-ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease. Wiley. https://doi.org/10.1002/cti2.1311
Wang, L., Xiao, W., Zheng, Y., Xiao, R., Zhu, G., Wang, M., Li, Y. et al., High dose lipopolysaccharide triggers polarization of mouse thymic Th17 cells in vitro in the presence of mature dendritic cells. Cell. Immunol. 2012. 274: 98-108.
Chassaing, B., Srinivasan, G., Delgado, M. A., Young, A. N., Gewirtz, A. T. and Vijay-Kumar, M., Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation. PLoS One 2012. 7: e44328.
Huus, K. E., Petersen, C. and Finlay, B. B, Diversity and dynamism of IgA−microbiota interactions. Nat. Rev. Immunol. 21: 514-525.
Mirpuri, J., Raetz, M., Sturge, C. R., Wilhelm, C. L., Benson, A., Savani, R. C., Hooper, L. V. et al., Proteobacteria-specific IgA regulates maturation of the intestinal microbiota. Gut. Microbes. 2013. 5: 28-39.
Rogier, E. W., Frantz, A. L., Bruno, M. E. C., Wedlund, L., Cohen, D. A., Stromberg, A. J. and Kaetzel, C. S., Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. Proc. Natl. Acad. Sci. U. S. A. 2014. 111: 3074-3079.
Takeuchi, T., Miyauchi, E., Kanaya, T., Kato, T., Nakanishi, Y., Watanabe, T., Kitami, T. et al., Acetate differentially regulates IgA reactivity to commensal bacteria. Nat. 2021. 595: 560-564.
Kim, M., Qie, Y., Park, J. and Kim, C. H., Gut microbial metabolites fuel host antibody responses. Cell. Host Microbe. 2016. 20: 202-214.
Salguero, M. V., Al-Obaide, M. A. I., Singh, R., Siepmann, T. and Vasylyeva, T. L., Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp. Ther. Med. 2019. 18: 3461.
Phillippi, D. T., Daniel, S., Pusadkar, V., Youngblood, V. L., Nguyen, K. N., Azad, R. K., Mcfarlin, B. K. et al., Inhaled diesel exhaust particles result in microbiome-related systemic inflammation and altered cardiovascular disease biomarkers in C57Bl/6 male mice. Part. Fibre. Toxicol. 2022. 19: 1-29.
Zhou, S-Yi, Gillilland, M., Wu, X., Leelasinjaroen, P., Zhang, G., Zhou, H., Ye, Bo et al., FODMAP diet modulates visceral nociception by lipopolysaccharide-mediated intestinal inflammation and barrier dysfunction. J. Clin. Invest. 2018. 128: 267-280.
Park, J-H., Jeong, So-Y, Choi, Ah-J and Kim, S-J, Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1. Immunol. Lett. 2015. 165: 10-19.
Ohnmacht, C., Park, J-H., Cording, S., Wing, J. B., Atarashi, K., Obata, Y., Gaboriau-Routhiau, V. et al., The microbiota regulates type 2 immunity through RORγt+ T cells. Science 2015. 349: 989-993.
Luo, W., Hu, J., Xu, W. and Dong, J., Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma. Front. Immunol. 2022. 13: 4598.
Zhao, Y., Yang, J., Gao, Ya-D and Guo, W., Th17 immunity in patients with allergic asthma. Int. Arch. Allergy Immunol. 2010. 151: 297-307.
Na, H., Lim, H., Choi, G., Kim, B-K., Kim, S-H., Chang, Y-S., Nurieva, R. et al., Concomitant suppression of TH2 and TH17 cell responses in allergic asthma by targeting retinoic acid receptor-related orphan receptor γt. J. Allergy Clin. Immunol. 2018. 141: 2061-2073.e5.e5.
Conrad, M. L., Yildirim, A. Ö., Sonar, S. S., Kılıç, A., Sudowe, S., Lunow, M., Teich, R. et al., Comparison of adjuvant and adjuvant-free murine experimental asthma models. Clin. Exp. Allergy 2009. 39: 1246-1254.
Schloss, P. D., Westcott, S. L., Ryabin, T., Hall, J. R., Hartmann, M., Hollister, E. B., Lesniewski, R. A. et al., Introducing mothur: Open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl. Environ. Microbiol. 2009. 75: 7537-7541.
Pruesse, E., Quast, C., Knittel, K., Fuchs, B. M., Ludwig, W., Peplies, J. and Glockner, F. O., SILVA: A comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res. 2007. 35: 7188-7196.
Mcmurdie, P. J. and Holmes, S., An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One 2013. 8: e61217.
Gómez-Gallego, C., Jaakkola, U. M., Salminen, S., Periago, M. J., Ros, G., Frias, R. and Iio, A method to collect high volumes of milk from mice. An. Vet. Murcia. 2013. 29: 55-61.
Gronke, K., Kofoed-Nielsen, M. and Diefenbach, A., Isolation and flow cytometry analysis of innate lymphoid cells from the intestinal lamina propria. Methods Mol. Biol. 2017. 1559: 255-265.
Duerr, C. U. and Fritz, J. H., Isolation of group 2 innate lymphoid cells from mouse lungs. Methods Mol. Biol. 2017. 1656: 253-261.