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Published on: July 27, 2022
Maslinic acid alleviates ulcerative colitis by inhibiting the colitis-aggravating pathogen Clostridium perfringens
Bailu Geng1, Congmin Zhu2, Zilu Cui1
1State Key Laboratory of Digestive Health, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory of Early Gastrointestinal Cancer Medicine and Medical Devices, Beijing, 100050, China.
Background:
Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease, continues to pose therapeutic challenges due to the limitations of conventional drugs and their inability to prevent relapse. Emerging evidence highlights the crucial role of gut microbiota dysbiosis in UC pathogenesis, yet our understanding of specific harmful microbes and their contributions to disease development remains limited.
Purpose:
This study aims to (1) investigate the therapeutic potential of maslinic acid (MA), a food-derived natural compound, in colitis mice models; (2) elucidate the previously underestimated pathogenic role of Clostridium perfringens in UC development; and (3) reveal the molecular mechanisms underlying both C. perfringens pathogenesis and MA-mediated protection.
Methods:
We examined the therapeutic effect of MA using DSS-induced colitis model and performing metagenomic sequencing; elucidated the pathogenic role of C. perfringens using GMrepo database, clinical stool samples, and in vivo infection models. Additionally, we revealed its mechanism using inhibitors and markers of various cell death and inflammation pathways. The bactericidal effect of MA on C. perfringens was studied through in vitro experiments and two in vivo colitis models.
Results:
MA alleviates DSS-induced colitis and restores gut microbiota. C. perfringens is enriched following DSS administration while significantly decreased after treatment with MA. C. perfringens contributes to the development of colitis and induces ZBP1-mediated PANoptosis in intestinal epithelial cells, while stimulates inflammation through NOD2 activation. MA has direct bactericidal activity against C. perfringens through ROS induction. It can almost completely rescue the exacerbation of colitis-related pathological and physiological phenotypes caused by C. perfringens in two mice colitis models.
Conclusions:
Our study reveals that MA effectively mitigates DSS-induced colitis by inhibiting the colitis-aggravating pathogen C. perfringens and modulating gut microbiota. Furthermore, it elucidates the previously underestimated role and mechanism of C. perfringens in the development of UC. It also highlights the therapeutic potential of MA in preventing and treating UC, particularly in patients who are C. perfringens positive.
Insights
Maslinic acid (MA) treats colitis by reducing the harmful bacterium Clostridium perfringens, a key driver of ulcerative colitis (UC) inflammation. This study reveals MA
Area of Science:
- Gastroenterology and Gut Microbiome Research
- Immunology and Inflammatory Diseases
- Natural Product Therapeutics
Background:
- Ulcerative colitis (UC) presents significant therapeutic challenges due to conventional drug limitations and disease relapse.
- Gut microbiota dysbiosis is implicated in UC pathogenesis, but specific microbial contributions remain unclear.
Purpose of the Study:
- To evaluate maslinic acid (MA) as a potential therapeutic agent for colitis.
- To investigate the pathogenic role of Clostridium perfringens in UC development.
- To elucidate the molecular mechanisms of C. perfringens pathogenesis and MA's protective effects.
Main Methods:
- Therapeutic efficacy of MA assessed in DSS-induced colitis models.
- Metagenomic sequencing and GMrepo database used to analyze gut microbiota and C. perfringens.
- In vivo and in vitro experiments employed to determine C. perfringens pathogenicity and MA's bactericidal activity.
Main Results:
- MA alleviated DSS-induced colitis and restored gut microbiota balance.
- Clostridium perfringens was identified as a colitis-aggravating pathogen, inducing ZBP1-mediated PANoptosis and NOD2 activation.
- MA demonstrated direct bactericidal effects against C. perfringens via ROS induction, significantly mitigating colitis phenotypes.
Conclusions:
- Maslinic acid effectively treats colitis by targeting C. perfringens and modulating the gut microbiota.
- This study elucidates C. perfringens' pathogenic role and mechanism in UC development.
- MA shows therapeutic potential for UC, especially in C. perfringens-positive patients.
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