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Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice

Nature volume 534, pages 263266 (09 June 2016) | Download Citation


Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function1,2,3. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways4,5, plus glycans present on the antibody’s secretory component6. 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 mice7,8. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA9,10,11. 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.

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European Nucleotide Archive


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We thank D. O’Donnell, M. Karlsson, J. Serugo, and S. Wagoner for help with gnotobiotic husbandry; S. Deng, J. Guruge, J. Hoisington-Lopez and M. Meier for technical assistance; G. Dantas for help with maintaining our archive of de-identified human samples; and N. Griffin for comments about facets of the data analysis. This work was supported by grants from the National Institutes of Health (DK30292, DK052574), the Children’s Discovery Institute, the Bill & Melinda Gates Foundation, and the Crohn’s and Colitis Foundation of America. J.D.P. is a member of the Washington University Medical Scientist Training Program (National Institutes of Health GM007200).

Author information


  1. Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA

    • Joseph D. Planer
    • , Yangqing Peng
    • , Andrew L. Kau
    • , Laura V. Blanton
    •  & Jeffrey I. Gordon
  2. Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA

    • Joseph D. Planer
    • , Yangqing Peng
    • , Andrew L. Kau
    • , Laura V. Blanton
    •  & Jeffrey I. Gordon
  3. Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA

    • I. Malick Ndao
    • , Phillip I. Tarr
    •  & Barbara B. Warner


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B.B.W., P.I.T., M.I. and G.D. designed, enrolled and collected specimens from participants in the twin study. J.D.P. performed BugFACS and 16S rRNA analyses on human faecal samples. J.D.P. and J.I.G. designed the gnotobiotic mouse experiments; J.D.P. and Y.P. performed these experiments. J.D.P., A.L.K., L.V.B., Y.P., and J.I.G. analysed the data. J.D.P. and J.I.G. wrote the paper.

Competing interests

J.I.G. is co-founder of Matatu, Inc., a company characterizing the role of diet-by-microbiota interactions in animal health. The other authors declare that they have no competing interests.

Corresponding author

Correspondence to Jeffrey I. Gordon.

16S rRNA sequences in raw format before post-processing and data analysis have been deposited at the European Nucleotide Archive under project PRJEB11697.

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