Insulin Resistance-Associated Bifidobacterium longum Ameliorates Prediabetes via the 6-ketoLCA/TGR5/GLP-1 axis

Background Prediabetes, a global health concern characterized by insulin resistance (IR) and closely linked to obesity, was investigated in this study to identify key gut microbiota characteristics. The development of insulin resistance is associated with gut microbiota. Therefore, identifying key bacterial species linked to the progression of insulin resistance and modulating the gut microbiota to intervene in this process represent a strategy for mitigating prediabetes.
Results Using machine learning and other bioinformatics methods, we compared obese participants with normal glucose tolerance (NGT, n=28), prediabetes (preDM, n=41), and type 2 diabetes (T2D, n=35). Results revealed that Bifidobacterium longum (B. longum) and Streptococcus salivarius (S. salivarius) were the key species distinguishing among obese populations with varying degrees of glucose intolerance. The efficacy of B. longum and S. salivarius in alleviating prediabetes was subsequently validated in mice. Supplementation with B. longum restored IR and regulated bile acid metabolism in prediabetic mice. Further treatment with the bile acid derivative 6-ketoLCA demonstrated its role in activating the TGR5/GLP-1 signaling pathway to ameliorate prediabetes.
Conclusion These findings highlight that B. longum plays a critical role in the onset of T2D, and intervention with B. longum and 6-ketoLCA can prevent prediabetes from progressing to type 2 diabetes.