Glycan-based shaping of the microbiota during primate evolution

Area of Science:

• Immunology
• Microbiology
• Evolutionary Biology
• Glycobiology

Background:

• Glycosyltransferase genes, like GGTA1, are under selection due to the role of synthesized glycans in host-microbe interactions.
• The alpha-1,3-galactosyltransferase gene (GGTA1) synthesizes the Galα1-3Galβ1-4GlcNAcβ1-R (αGal) glycan.

Purpose of the Study:

• To investigate the impact of GGTA1 gene loss and absent αGal glycan expression on host-microbiota interactions in a mouse model.
• To explore potential evolutionary implications for primate adaptation, specifically the loss of GGTA1 function.

Main Methods:

• Utilized a mouse model with GGTA1 gene deletion to study gut microbiota composition.
• Investigated the role of immunoglobulin (Ig)-dependent mechanisms, specifically IgA, in targeting αGal-expressing bacteria.
• Assessed sepsis severity following systemic infection with either Ig-shaped or non-Ig-shaped microbiota inoculums.

Main Results:

• GGTA1 deletion significantly altered the gut microbiota composition in mice.
• An immunoglobulin (Ig)-dependent mechanism was identified, where IgA targeted αGal-expressing bacteria.
• Mice infected with Ig-shaped microbiota exhibited less severe sepsis compared to those infected with non-Ig-shaped microbiota.

Conclusions:

• Absence of host αGal expression allows antibodies to shape the microbiota towards lower pathogenicity.
• Reduced microbiota pathogenicity following GGTA1 deletion in mice suggests a potential selective advantage.
• This finding supports the hypothesis that GGTA1 loss-of-function mutations may have been favored in ancestral primates due to reduced susceptibility to bacterial sepsis.