The main findings of our study are as follows: (i) obesity and T2D increased circulating levels of markers of intestinal integrity damage and inflammation being associated with insulin resistance and lipid metabolism, (ii) expression levels of NLRP6 and IL18 were decreased in the jejunum from patients with obesity and T2D together with an upregulation of inflammatory markers and (iii) we further revealed that NLRP6 regulation is likely context-dependent, with taurine increasing and parthenolide decreasing its expression levels in human CCL-241 enterocytes. The gene discussed is IL18; the disease is obesity due to melanocortin 4 receptor deficiency.