Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo. Morphine-induced gut microbial dysbiosis exhibited distinct characteristic signatures, including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance and significant impairment in bile acids and morphine-3-glucuronide/morphine biotransformation in the gut.

Although it has been proposed that NNS do not affect glycemia (3), data from several recent studies suggest that NNS are not physiologically inert. First, it has been demonstrated that the gastrointestinal tract (4,5) and the pancreas (6,7) can detect sugars through taste receptors and transduction mechanisms that are similar to those indentified in taste cells in the mouth. Second, NNS-induced activation of gut sweet taste receptors in isolated duodenal L cells and pancreatic β-cells triggers the secretion of glucagon-like peptide 1 (GLP-1) (4,5) and insulin (6–9), respectively. Third, data from studies conducted in animal models demonstrate that NNS interact with sweet taste receptors expressed in enteroendocrine cells to increase both active and passive intestinal glucose absorption by upregulating the expression of sodium-dependent glucose transporter isoform 1 (5,10,11) and increasing the translocation of GLUT2 to the apical membrane of intestinal epithelia (12).

These variations were related to inflammation in the host