Metabolic modelling reveals increased autonomy and antagonism in type 2 diabetic gut microbiota

Type 2 diabetes (T2D) presents a global health concern, with evidence highlighting the role of the human gut microbiome in metabolic diseases. This study employs metabolic modelling to elucidate changes in host-microbiome interactions in T2D. Glucose levels, diet, 16S sequences and metadata were collected for 1866 individuals. In addition, microbial community models, and ecological interactions were simulated for the gut microbiomes. Our findings revealed a significant decrease in metabolic fluxes provided by the host's diet to the microbiome in T2D patients, accompanied by increased within-community exchanges. Moreover, the diabetic microbiomes shift towards increased exploitative ecological interactions at the expense of collaborative interactions. The reduced microbiome-to-host butyrate flux, along with decreased fluxes of amino acids (including tryptophan), nucleotides, and B vitamins from the host's diet, further highlight the dysregulation in microbial-host interactions in diabetes. In addition, microbiomes of T2D patients exhibit enrichment in energy metabolism, indicative of increased metabolic activity and antagonism. This study sheds light on the increased microbiome autonomy and antagonism accompanying diabetes, and provides candidate metabolic targets for intervention studies and experimental validation.