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Article

Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the TLR4/NF-κB Signaling Pathway, Gut Microbiota Modulation, and Liver Protection

by
Jiali Tang
†,
Mengyao Zhang
†,
Jiaying Wang
†,
Haijing Zhang
,
Zhong Wang
,
Ziteng Lei
,
Chengtao Wang
* and
Wei Chen
*
Key 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
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Foods 2025, 14(7), 1270; https://doi.org/10.3390/foods14071270
Submission received: 11 February 2025 / Revised: 30 March 2025 / Accepted: 1 April 2025 / Published: 4 April 2025
(This article belongs to the Special Issue Microbiology, Biochemistry and Potential Human Health Benefits of Fermented Food Products)
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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.
Keywords: hydroxytyrosol; colitis; gut microbiota; liver injury; antioxidant activity; anti-inflammatory effect hydroxytyrosol; colitis; gut microbiota; liver injury; antioxidant activity; anti-inflammatory effect
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MDPI and ACS Style

Tang, J.; Zhang, M.; Wang, J.; Zhang, H.; Wang, Z.; Lei, Z.; Wang, C.; Chen, W. Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the TLR4/NF-κB Signaling Pathway, Gut Microbiota Modulation, and Liver Protection. Foods 2025, 14, 1270. https://doi.org/10.3390/foods14071270

AMA Style

Tang J, Zhang M, Wang J, Zhang H, Wang Z, Lei Z, Wang C, Chen W. Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the TLR4/NF-κB Signaling Pathway, Gut Microbiota Modulation, and Liver Protection. Foods. 2025; 14(7):1270. https://doi.org/10.3390/foods14071270

Chicago/Turabian Style

Tang, Jiali, Mengyao Zhang, Jiaying Wang, Haijing Zhang, Zhong Wang, Ziteng Lei, Chengtao Wang, and Wei Chen. 2025. "Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the TLR4/NF-κB Signaling Pathway, Gut Microbiota Modulation, and Liver Protection" Foods 14, no. 7: 1270. https://doi.org/10.3390/foods14071270

APA Style

Tang, J., Zhang, M., Wang, J., Zhang, H., Wang, Z., Lei, Z., Wang, C., & Chen, W. (2025). Hydroxytyrosol Ameliorates Colon Inflammation: Mechanistic Insights into Anti-Inflammatory Effects, Inhibition of the TLR4/NF-κB Signaling Pathway, Gut Microbiota Modulation, and Liver Protection. Foods, 14(7), 1270. https://doi.org/10.3390/foods14071270

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