Glycan-based shaping of the microbiota during primate evolution

eLife

Patricia Bastos-Amador¹  Sumnima Singh¹  Silvia Cardoso¹  Bahtiyar Yilmaz¹  Jessica Ann Thompson¹  Daniel Sobral¹  Mauro Truglio¹  Miguel P Soares¹ 

[1] Instituto Gulbenkian de Ciência, Oeiras, Portugal;

关键词: immunology;    Alpha-gal;    primate evolution;    microbiota;    sepsis;    Mouse;   

DOI  :  10.7554/eLife.67450

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Genes encoding glycosyltransferases can be under relatively high selection pressure, likely due to the involvement of the glycans synthesized in host-microbe interactions. Here, we used mice as an experimental model system to investigate whether loss of α−1,3-galactosyltransferase gene (GGTA1) function and Galα1-3Galβ1-4GlcNAcβ1-R (αGal) glycan expression affects host-microbiota interactions, as might have occurred during primate evolution. We found that Ggta1 deletion shaped the composition of the gut microbiota. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with targeting of αGal-expressing bacteria by IgA. Systemic infection with an Ig-shaped microbiota inoculum elicited a less severe form of sepsis compared to infection with non-Ig-shaped microbiota. This suggests that in the absence of host αGal, antibodies can shape the microbiota towards lower pathogenicity. Given the fitness cost imposed by bacterial sepsis, we infer that the observed reduction in microbiota pathogenicity upon Ggta1 deletion in mice may have contributed to increase the frequency of GGTA1 loss-of-function mutations in ancestral primates that gave rise to humans.

【 授权许可】

CC BY