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Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice.
Nature 2016; 534(7606):263-6Nat

Abstract

Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways, plus glycans present on the antibody's secretory component. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity.

Authors+Show Affiliations

Center for Genome Sciences &Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Center for Genome Sciences &Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Center for Genome Sciences &Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Center for Genome Sciences &Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.Center for Genome Sciences &Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study

Language

eng

PubMed ID

27279225

Citation

Planer, Joseph D., et al. "Development of the Gut Microbiota and Mucosal IgA Responses in Twins and Gnotobiotic Mice." Nature, vol. 534, no. 7606, 2016, pp. 263-6.
Planer JD, Peng Y, Kau AL, et al. Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. Nature. 2016;534(7606):263-6.
Planer, J. D., Peng, Y., Kau, A. L., Blanton, L. V., Ndao, I. M., Tarr, P. I., ... Gordon, J. I. (2016). Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. Nature, 534(7606), pp. 263-6. doi:10.1038/nature17940.
Planer JD, et al. Development of the Gut Microbiota and Mucosal IgA Responses in Twins and Gnotobiotic Mice. Nature. 2016 06 9;534(7606):263-6. PubMed PMID: 27279225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. AU - Planer,Joseph D, AU - Peng,Yangqing, AU - Kau,Andrew L, AU - Blanton,Laura V, AU - Ndao,I Malick, AU - Tarr,Phillip I, AU - Warner,Barbara B, AU - Gordon,Jeffrey I, Y1 - 2016/05/25/ PY - 2015/11/05/received PY - 2016/03/21/accepted PY - 2016/6/10/entrez PY - 2016/6/10/pubmed PY - 2016/7/7/medline SP - 263 EP - 6 JF - Nature JO - Nature VL - 534 IS - 7606 N2 - Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways, plus glycans present on the antibody's secretory component. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/27279225/Development_of_the_gut_microbiota_and_mucosal_IgA_responses_in_twins_and_gnotobiotic_mice_ L2 - https://doi.org/10.1038/nature17940 DB - PRIME DP - Unbound Medicine ER -