Glycan-Based Shaping Of The Microbiota During Primate Evolution

Genes encoding certain glycosyltransferases are thought to be under relatively high selection pressure, due to the involvement of the glycans that they synthesize in host-microbe interactions. Here we used a mouse model to investigate whether the loss of α-1,3-galactosyltransferase (GGTA1) function and Galα1-3Galβ1-4GlcNAcβ1-R (αGal) expression during primate evolution might have affected host-microbiota interactions. We found thatGgta1deletion in mice shaped the composition of the gut microbiota in relation to the bacterial species present. This occurred via an immunoglobulin (Ig)-dependent mechanism, associated with IgA targeting of αGal-expressing bacteria. Systemic infection by the Ig-shaped microbiota elicited a less severe form of sepsis than infection with the non-Ig-shaped microbiota. This suggests that in the absence of host αGal, the microbiota is shaped towards lower pathogenicity, likely providing a fitness gain to the host. We infer that high selection pressure exerted by bacterial sepsis may have contributed to increase frequency ofGGTA1loss-of-function mutations in ancestral primates that gave rise to humans.