Ophiopogon japonicus Polysaccharides Promote Microbial Production Of Chenodeoxycholic Acid To Alleviate Ulcerative Colitis in Mice by Inhibiting the STING1-Related NF-κB Pathway

Ophiopogon japonicus polysaccharides (OJP) commonly used as functional food additives have been known to have various pharmacological activities. However, the exact roles of OJP in treating ulcerative colitis (UC) remain unknown. Here, we found that oral administration of OJP at different dosages effectively alleviated colonic injury and restored intestinal homeostasis in UC mice in a gut microbiota-dependent manner. Notably, the OJP treatment markedly improved the gut dysbiosis by enriching probiotics, especially Lactobacillus salivarius, and triggering the production of chenodeoxycholic acid (CDCA), a primary bile acid with controversial biological function. Supplementation with both CDCA and L. salivarius can significantly repair gut barrier dysfunction and alleviate intestinal inflammation in DSS-induced UC mice. Mechanistically, CDCA treatment strikingly inhibited the STING1-related NF-κB pathway in UC mice probably by binding to STING1, thus strongly suppressing colonic inflammatory status. These results suggest that OJP has potential preventive or therapeutic effects for inflammatory diseases.