Another potential immunomodulatory effect involves microbial diversity in two studies (20, 21): Low gut microbial diversity is associated with metabolic disease (42), and high diversity may be due to the high expression of SIRT1 and high levels of HDL (20) and improve body immune system, such as liver function mentioned in the study by Li et al. Emerging evidence showed that SIRT1 could promote gut microbial population shifts by influence inflammation and circadian rhythm (43). Here, SIRT1 is linked to metabolic disease.