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Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the
Jiali Tang1, Mengyao Zhang1, Jiaying Wang1
1Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, School of Food and Health, Beijing Technology and Business University, No. 33 Fucheng Road, Beijing 100048, China.
Abstract:
Inflammatory bowel disease (IBD) is a chronic disease influenced by a complex interplay of factors, including genetics, environmental, and gut microbiota. This study aimed to explore the therapeutic potential of the natural polyphenolic compound hydroxytyrosol (HT) in modulating dextran sodium sulfate (DSS)-induced colitis in mice. The findings demonstrate that oral administration of HT significantly alleviated colitis symptoms, as evidenced by a reduction in the disease activity index and improvements in colonic pathology. HT was found to inhibit the release of pro-inflammatory cytokines, enhance antioxidant status, and mitigate oxidative stress. Furthermore, HT contributed to the restoration of the gut barrier by reinstating tight junction proteins, reducing the inflammatory marker lipopolysaccharide (LPS), and suppressing inflammation-related genes. This compound also modulated the NLRP3-Cas-1-GSDMD-IL-1β inflammatory pathway and inhibited the NF-κB (nuclear factor kappa B) pathway, thereby alleviating colitis. Gut microbial analysis revealed that HT enriched the abundance of Bacteroidota and altered the balance between Bacteroidota and Firmicutes in mice. Correlation analysis between bacterial microbiota and inflammatory factors suggested that HT may alleviate colitis by modulating the relative abundance of Alistipes, Bacteroides, and unclassified_f__Muribaculaceae. These findings underscore the potential of HT as a therapeutic agent in the treatment of colitis.
Insights
Hydroxytyrosol (HT) effectively treats colitis in mice by reducing inflammation and restoring gut barrier function. This natural compound also positively modulates gut microbiota, offering therapeutic potential for inflammatory bowel disease (IBD).
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Inflammatory bowel disease (IBD) is a chronic condition influenced by genetics, environment, and gut microbiota.
- Dextran sodium sulfate (DSS)-induced colitis is a common mouse model for studying IBD pathogenesis and potential therapies.
Purpose of the Study:
- To investigate the therapeutic effects of hydroxytyrosol (HT), a natural polyphenol, on DSS-induced colitis in mice.
- To elucidate the mechanisms underlying HT's anti-inflammatory and gut-protective actions.
Main Methods:
- Oral administration of hydroxytyrosol (HT) to mice with DSS-induced colitis.
- Assessment of clinical colitis symptoms, colonic pathology, pro-inflammatory cytokine levels, and oxidative stress markers.
- Analysis of gut barrier integrity markers (tight junction proteins, LPS), inflammatory pathways (NLRP3, NF-κB), and gut microbiota composition.
Main Results:
- HT significantly reduced colitis severity, improved colonic pathology, inhibited pro-inflammatory cytokines, and enhanced antioxidant status.
- HT restored gut barrier function by increasing tight junction proteins and reducing LPS levels.
- HT modulated the NLRP3 and NF-κB inflammatory pathways and favorably altered gut microbiota composition, enriching Bacteroidota.
Conclusions:
- Hydroxytyrosol (HT) demonstrates significant therapeutic potential for treating colitis.
- HT alleviates colitis through anti-inflammatory, antioxidant, gut barrier-protective, and microbiota-modulating mechanisms.
- HT's ability to target key inflammatory pathways and influence gut bacteria highlights its promise as a natural therapeutic agent for IBD.
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