Mutation elevation and functional alterations in Escherichia coli are pertinent to the onset of gestational diabetes mellitus

In the gut microbiome, purifying selection clears deleterious mutations. However, it is unknown whether this selection pressure is modifiable or what its health implications are. Here, we studied metagenomic and metabolic changes linked to gestational diabetes mellitus (GDM), and observed an increase in Escherichia coli (E. coli) mutations during host pregnancy, linking these genetic changes to host physiology. Severe depletion of bacterial genes before GDM onset was mostly traced to E. coli despite its stable abundance-indicating that functional genetic signals outweigh taxonomic shifts. E. coli and related microbes displayed pregnancy-linked single nucleotide polymorphism elevation, enriched at GDM onset in loci encoding membrane and biofilm components. These pangenomic alterations correlated with handicapped intermicrobial interactions of E. coli and with host serum metabolic abnormalities. We propose that pregnancy relaxes purifying selection, permitting mutation elevation in certain gut bacteria. Resulting functional deficits, potentially through altered ecology and metabolism, may subsequently impact host glucose regulation.