Next, inactivation of IL-22 (and IL-23) signaling in mice deteriorates intestinal barrier, microbial alterations and expansion of pathogenic bacteria causing systemic increase in LPS and Trimethylamine N-oxide (TMAO), showing direct connection of those particular cytokines, the gut microbiota and obesity related comorbidities such as atherosclerosis (246). The gene discussed is IL22; the disease is obesity due to melanocortin 4 receptor deficiency.