Discussion
T2D
Our study suggests that non-nutritive stevia pre-loads influence the entero-endocrine response following a mixed-meal tolerance test, and that this effect is different in participants with and without T2D. This study is the first to explore associations between the microbiome and the entero-endocrine response following a mixed-meal tolerance test combined with a non-nutritive pre-load. We found limited evidence for associations between the α-diversity of the oral microbiome composition and the entero-endocrine response, and no evidence for associations between gut microbiome composition and the entero-endocrine response.This study showed that downstream glucose response levels following a mixed-meal tolerance test were not affected by mouth rinsing with a non-nutritive sweetener pre-load. Among participants with pre-T2D, but not among those with T2D, glucose levels decreased after swallowing the non-nutritive pre-load. This is in line with other studies, which reported either glucose levels not to be affected or to be somewhat lower after a swallowed pre-load with a non-nutritive sweetener [GIP and GLP-1 increase after nutrient sensing, and stimulate secretion of insulin [Our explorative study found no evidence for the gut microbiome composition to be associated with the entero-endocrine response. Other studies, however, suggest that the gut microbiome may impact the entero-endocrine response, for instance via production of short-chain fatty acids, which can activate G-protein-coupled receptors such as GPR41 and GPR43 expressed in colon epithelial cells where they stimulate the secretion of gut hormones such as GLP-1 and PYY [Our study is not exempt from limitations. First, sample size was based on previous studies, since formal power calculations with regard to the gut and oral microbiome composition are difficult to perform due to variability and previous poor clinical trials [