Researchers identified consistent associations between gut Proteobacteria and reduced insulin sensitivity through a comprehensive multiomics analysis.
In the study, published in Gut, investigators examined the data from six independent studies, which included 1,046 participants across multiple cohorts.
The investigators found that several genera and species from the Proteobacteria phylum, particularly from the Enterobacteriaceae family (such as Escherichia and Shigella), showed negative associations with insulin sensitivity in the jejunum, ileum, colon, and visceral adipose tissue.
Analysis revealed that deoxycholic acid (DCA), a microbial-derived secondary bile acid, demonstrated negative associations with insulin sensitivity. DCA levels correlated positively with proinflammatory bacterial species and were also linked to gut permeability disruption and intestinal inflammation. The findings aligned with associations between DCA and western dietary patterns.
The investigators observed that T-cell–related signatures in the intestine were positively associated with insulin sensitivity, while in adipose tissue, T-cell signatures showed the opposite association. This suggested a potentially protective immune response in the intestine against insulin resistance, whereas a similar response in adipose tissue may indicate inflammation associated with insulin resistance.
Using Drosophila melanogaster models, both a high-fat diet and Enterobacter cloacae colonization induced transcriptional changes related to insulin resistance, supporting the human findings in an experimental setting.
The study, which used hyperinsulinemic-euglycemic clamp measurements as a gold-standard assessment of insulin sensitivity, highlighted the importance of large-scale, longitudinal research to further strengthen the findings. Led by researchers from multiple institutions, including the Girona Biomedical Research Institute, the work offered new insights into the complex interplay between gut microbiota, intestinal immune responses, and metabolic health.
Conflict of interest disclosures can be found in the study.
