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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00342

The formation of glycan-specific natural antibodies repertoire in GalT-KO mice is determined by gut microbiota

  • 1Biomedical Research Institute of Bellvitge, Spain
  • 2Institut Pasteur de Lille, France
  • 3Stanford University, United States
  • 4Institute of Bioorganic Chemistry (RAS), Russia
  • 5Hospital Universitario de Bellvitge, Spain

Gut commensal bacteria are known to have a significant role in regulating the innate and adaptive immune homeostasis. Alterations in the intestinal microbial composition have been associated with several disease states, including autoimmune and inflammatory conditions. However, it is not entirely clear how commensal gut microbiota modulate and contribute to the systemic immunity, and whether circulating elements of the host immune system could regulate the microbiome. Thus, we have studied the diversity and abundance of specific taxons in the gut microbiota of inbred GalT-KO mice during seven months of animal life by metagenetic high-throughput sequencing (16S rRNA gene, variable regions V3-V5). The repertoire of glycan-specific natural antibodies, obtained by printed glycan array technology, was then associated with the microbial diversity for each animal by metagenome-wide association studies. Our data show that the orders clostridiales (most abundant), bacteriodales, lactobacillales and deferribacterales may be associated with the development of the final repertoire of natural anti-glycan antibodies in GalT-KO mice. The main changes in microbiota diversity (month-2 and month-3) were related to important changes in levels and repertoire of natural anti-glycan antibodies in these mice. Additionally, significant positive and negative associations were found between the gut microbiota and the pattern of specific anti-glycan antibodies. Regarding individual features, the gut microbiota and the corresponding repertoire of natural anti-glycan antibodies showed differences among the examined animals. We also found redundancy in different taxa associated with the development of specific anti-glycan antibodies. Differences in microbial diversity did not, therefore, necessarily influence the overall functional output of the gut microbiome of GalT-KO mice. In summary, the repertoire of natural anti-carbohydrate antibodies may be partially determined by the continuous antigenic stimulation produced by the gut bacterial population of each GalT-KO mouse. Small differences in gut microbiota diversity could determine different repertoire and levels of natural anti-glycan antibodies and consequently might induce different immune responses to pathogens or other potential threats.

Keywords: GalT-KO mice, Gut Microbiota, Metagenetic high-throughput sequencing, 16S rRNA gene, natural anti-glycan antibodies, Printed glycan array, Metagenome-wide association studies

Received: 09 Nov 2018; Accepted: 11 Feb 2019.

Edited by:

Daniel M. Altmann, Imperial College London, United Kingdom

Reviewed by:

Gabriela D. Perdigon, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
Maryam Dadar, Razi Vaccine and Serum Research Institute, Iran  

Copyright: © 2019 Bello-Gil, Audebert, Olivera-Ardid, Pérez Cruz, Even, Khasbiullina, Gantois, Shilova, Merlin, Costa, Bovin and Manez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Daniel Bello-Gil, Biomedical Research Institute of Bellvitge, Barcelona, Spain, dbello@idibell.cat