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Research Article | Open Access

Protein hydrolysates from animal source food earthworm protect against dextran sulfate sodium (DSS)-induced intestinal barrier injury

Jie Pana,bHui Zhaoa( )Liming JiacJinghua JiacJingning JiacYuhui LidQi TangaFeiya JiangaLiang BaiaMeiyan WangaYufeng Lid( )Zheng Wangb( )
Tianjin Key Laboratory of Food and Biotechnology, State Experimental and Training Centre of Food and Drug, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
Department of Pi-Wei Disease, Xuanwu Traditional Chinese Medical Hospital, Beijing 100050, China
Dilongli Bioengineering (Tianjin) Co., Ltd., Tianjin 301500, China
Department of Neurosurgery, Hebei Key Laboratory of Molecular Oncology, Tangshan Key Laboratory of Cancer prevention and Therapy, The Cancer Institute, Tangshan People’s Hospital, Tangshan 063001, China

Peer review under responsibility of Beijing Academy of Food Sciences.

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Highlights

• The earthworm is easily found in moist soil in every part of the earth and plays significant role in soil structure and organic matters. In addition to its attribute of animal source food, earthworm has been well recognized for its medicinal benefits because it is a plentiful supply of proteins, peptides, enzymes, and bioactive compounds.

• In this study, we hydrolyzed the crude earthworm protein extract and identified that almost all the peptides (earthworm protein hydrolysates, EWPH) generated by hydrolysis have their molecular weight less than 3000 Dalton. prediction in terms of network pharmacology and bioinformatics analysis suggested that the EWPH have the potential of anti-inflammation and anti-oxidation.

• On the basis of the above data, we explored whether EWPH effectively alleviate DSS-induced inflammatory bowel disease, a disease characterized by intestinal inflammation and excessive oxidative stress. Interestingly, treatment with EWPH led to predominant recovery of epithelial TJ protein production, downregulation of pro-inflammatory cytokines and oxidative stress. More importantly, the in vivo tests confirmed the predicted targets responsible for EWPH administration on inflamed intestine, such as SRC, STAT3, Caspase-3, and MMP9. Therefore, this study highlights a clear clue that EWPH safeguard intestinal barrier hemostasis. More importantly, given that the earthworms are easily founded and are sustainable on earth, our findings broaden the application of earthworm serving as a donor of protectant on intestinal barrier hemostasis and provide a clue to the development of earthworm-based nutraceuticals processing.

Abstract

The intestinal barrier is crucial for homeostasis. This study aimed to investigate the protective effects of earthworm protein hydrolysates (EWPH) on the intestinal mucosal barrier and elucidate the underlying mechanisms. We first hydrolyzed earthworm protein using alcalase and identified the primary peptide components of EWPH through Nano LC-MS/MS analysis. Network pharmacology and bioinformatics approaches were employed to predict potential targets associated with the intestinal mucosal barrier. Experimentally, we demonstrated that EWPH effectively protects against dextran sulfate sodium (DSS)-induced intestinal barrier damage in mice. The protective mechanisms involve not only the inhibition of the Toll-like receptor 4 (TLR4)-nuclear factor-κ (NF-κ)/mitogen-activated protein kinases (MAPK) signaling pathway in the intestinal epithelium but also the suppression of other key molecules implicated in intestinal mucosal barrier damage, including phosphorylated-SRC proto-oncogene (p-SRC), phosphorylated-signal transducer and activator of transcription 3 (p-STAT3), Caspase-3, and matrix metalloproteinase-9 (MMP9), thereby mitigating intestinal inflammation and mucosal barrier injury. This study provides evidence that EWPH have the potential to safeguard the intestinal barrier hemostasis.

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Food Science and Human Wellness
Article number: 9250618

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Cite this article:
Pan J, Zhao H, Jia L, et al. Protein hydrolysates from animal source food earthworm protect against dextran sulfate sodium (DSS)-induced intestinal barrier injury. Food Science and Human Wellness, 2025, 14(12): 9250618. https://doi.org/10.26599/FSHW.2025.9250618

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Received: 20 December 2024
Revised: 15 February 2025
Accepted: 11 April 2025
Published: 18 December 2025
© 2025 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).