Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles

Jian Tan; Duan Ni; Jemma Taitz; Gabriela Veronica Pinget; Mark Read; Alistair Senior; Jibran Abdul Wali; Reem Elnour; Erin Shanahan; Huiling Wu; Steven J Chadban; Ralph Nanan; Nicholas Jonathan Cole King; Georges Emile Grau; Stephen J Simpson; Laurence Macia

doi:10.1038/s41467-022-31761-y

Dietary protein increases T-cell-independent sIgA production through changes in gut microbiota-derived extracellular vesicles

Nat Commun. 2022 Jul 27;13(1):4336. doi: 10.1038/s41467-022-31761-y.

Authors

Jian Tan^{1

2}, Duan Ni^{1

2}, Jemma Taitz^{1

2}, Gabriela Veronica Pinget^{1

2}, Mark Read^{1

3}, Alistair Senior^{1

4}, Jibran Abdul Wali^{1

4}, Reem Elnour^{1

4}, Erin Shanahan^{1

4}, Huiling Wu^{1

5

6}, Steven J Chadban^{1

5

6}, Ralph Nanan^{1

7}, Nicholas Jonathan Cole King^{1

2

8}, Georges Emile Grau^{2

9}, Stephen J Simpson^{1

4}, Laurence Macia^{10

11

12}

Affiliations

¹ Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
² School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³ School of Computer Science, Faculty of Engineering, University of Sydney, Sydney, NSW, Australia.
⁴ School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, NSW, Australia.
⁵ Kidney Node Laboratory, The Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia.
⁶ Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
⁷ Sydney Medical School Nepean, University of Sydney, Sydney, NSW, Australia.
⁸ Sydney Cytometry, The University of Sydney and The Centenary Institute, Sydney, NSW, Australia.
⁹ Vascular Immunology Unit, The University of Sydney, Sydney, NSW, Australia.
¹⁰ Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia. Laurence.macia@sydney.edu.au.
¹¹ School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia. Laurence.macia@sydney.edu.au.
¹² Sydney Cytometry, The University of Sydney and The Centenary Institute, Sydney, NSW, Australia. Laurence.macia@sydney.edu.au.

Abstract

Secretory IgA is a key mucosal component ensuring host-microbiota mutualism. Here we use nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, and identify dietary protein as the major driver of secretory IgA production. Protein-driven secretory IgA induction is not mediated by T-cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high protein fed mice produces significantly higher quantities of extracellular vesicles, compared to those of mice fed high-carbohydrate or high-fat diets. These extracellular vesicles activate Toll-like receptor 4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We show that succinate, produced in high concentrations by microbiota of high protein fed animals, increases generation of reactive oxygen species by bacteria, which in turn promotes extracellular vesicles production. Here we establish a link between dietary macronutrient composition, gut microbial extracellular vesicles release and host secretory IgA response.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dietary Proteins
Extracellular Vesicles* / metabolism
Gastrointestinal Microbiome*
Immunoglobulin A, Secretory / metabolism
Mice
T-Lymphocytes / metabolism

Substances

Dietary Proteins
Immunoglobulin A, Secretory