Vinegar-processed frankincense ameliorates ulcerative colitis by targeting BSH-active bacteria preference-mediated GDCA hydrolysis

Ethnopharmacological relevance: Frankincense, is extensively used in both traditional Chinese medicine (TCM) and Indian practices for the treatment of ulcerative colitis (UC). In TCM, it is typically subjected to process with vinegar, which is believed to enhance its therapeutic efficacy. However, the underlying mechanism has yet to be elucidated. Aim of the study: To elucidate the underlying mechanism of frankincense vinegar processing from the perspective of bile salt hydrolase (BSH)-active bacteria preference and glycodeoxycholic acid (GDCA) hydrolysis. Materials and methods: Dextran sodium sulfate (DSS)-induced UC model was used to elucidate the superior improving effects of vinegar-processed frankincense (PF). 16S rRNA and metagenomic sequencing along with ultra-high performance liquid chromatography-triple quadrupole mass spectroscopy (UHPLC-TQ-MS) were employed to reveal the differential bacteria and its related disturbance of GDCA. The effects of PF and GDCA on BSH-active bacteria were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and in vitro experiments. Finally, the pro-inflammatory effects of GDCA and the mechanisms by which PF ameliorates UC were verified by establishing a UC pseudo-sterile mice model with GDCA intervention. Results: PF exhibited remarkable mitigating effects on UC (P < 0.05 or P < 0.01). Specifically, PF enhanced the BSH activity of Bifidobacterium longum and Lactobacillus acidophilus (P < 0.01), thereby promoting their dissociation efficiency toward glycine-conjugated bile acids (G-CBAs), particularly GDCA (P < 0.01). Furthermore, PF reduced GDCA levels by regulating the dissociation efficiency of Bifidobacterium longum and Lactobacillus acidophilus toward GDCA, thereby alleviating GDCA-induced exacerbation of UC. Conclusion: PF exhibits its superior amelioration effects on UC by enhancing the dissociation efficiency of Bifidobacteruum longum and Lactobacillus acidophilus towards G-CBAs, particularly GDCA.