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

Tan, J.; Ni, D.; Taitz, J.; Pinget, G.; Read, M.; Senior, A.; Wali, J.; Nanan, R.; King, N.; Grau, G.; Simpson, S.; Macia, L.

doi:10.1101/2020.11.30.405217

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bioRxiv · 10.1101/2020.11.30.405217

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

Tan, J.·Ni, D.·Taitz, J.·Pinget, G.·Read, M.·Senior, A.·Wali, J.·Nanan, R.·King, N.·Grau, G.·Simpson, S.·Macia, L.

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Abstract

Secretory IgA (sIgA) is a key mucosal component ensuring host-microbiota mutualism. Using nutritional geometry modelling in mice fed 10 different macronutrient-defined, isocaloric diets, we identified dietary protein as the major driver of sIgA production. Protein-driven sIgA induction was not mediated by T cell-dependent pathways or changes in gut microbiota composition. Instead, the microbiota of high-protein fed mice produced significantly higher quantities of extracellular vesicles (EV), compared to those of mice fed high-carbohydrate or high-fat diets. These EV activated TLR4 to increase the epithelial expression of IgA-inducing cytokine, APRIL, B cell chemokine, CCL28, and the IgA transporter, PIGR. We showed that succinate, produced in high concentrations by microbiota of high-protein fed animals, increased the generation of reactive oxygen species by bacteria, which in turn promoted EV production. This is the first report establishing a causal link between dietary macronutrient composition, gut microbial EV release and host sIgA response.

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Tan, J., Ni, D., Taitz, J., Pinget, G., Read, M., Senior, A., Wali, J., Nanan, R., King, N., Grau, G., Simpson, S., Macia, L.. 2020-12-02. Dietary protein increases T cell independent sIgA production through changes in gut microbiota-derived extracellular vesicles. https://doi.org/10.1101/2020.11.30.405217

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