Effects of POPs-induced SIRT6 alteration on intestinal mucosal barrier function: A comprehensive review

Persistent organic pollutants (POPs) are pervasive organic chemicals with significant environmental and ecological ramifications, extending to adverse human health effects due to their toxicity and persistence. The intestinal mucosal barrier, a sophisticated defense mechanism comprising the epithelial layer, mucosal chemistry, and cellular immunity, shields the host from external threats and fosters a symbiotic relationship with intestinal bacteria. Sirtuin 6 (SIRT6), a sirtuin family member, is pivotal in genome and telomere stability, inflammation regulation, and metabolic processes. Result shows POPs have been implicated in the intestinal diseases, particularly in intestinal barrier dysfunction, through mechanisms such as cellular damage, epigenetic alterations, inflammation, microbiota changes, and metabolic disruptions. While the impact of SIRT6 expression changes on intestinal barrier functions has been reviewed, the mechanisms linking POPs to SIRT6 remain elusive. This review summarized the latest research results on the effects of POPs on intestinal barrier, discussed the role of SIRT6 from multiple mechanism perspectives, proposed new research directions on POPs, SIRT6 and intestinal health, and explored the therapeutic potential of SIRT6.