{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:17:28Z","timestamp":1785284248389,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key R&D Program of Shandong Province","award":["2024CXPT048"],"award-info":[{"award-number":["2024CXPT048"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32471335"],"award-info":[{"award-number":["32471335"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Ejiao, a macromolecular protein complex derived from donkey hide, is a traditional Chinese medicine with clinically demonstrated efficacy against ulcerative colitis (UC). Due to its large molecular size and poor absorbability, its therapeutic effects are presumed to depend on gut microbiota. We hypothesized that specific gut bacteria capable of degrading Ejiao might also mediate its biological functions. Methods: To test this hypothesis, a systematic investigation was conducted by integrating culturomics, proteomics, metabolomics, 16S rRNA gene amplicon high-throughput sequencing, and animal disease models. Results: A total of 134 human gut bacterial strains capable of utilizing Ejiao as a nutrient source were isolated. Among them, Ligilactobacillus salivarius D3-8 exhibited the strongest growth in Ejiao-based medium. Genomic analysis identified 63 protease\/peptidase genes, and peptidomic profiling confirmed its degradation activity, which released 50 novel peptides. Notably, administration of L. salivarius D3-8 alone significantly alleviated dextran sodium sulfate (DSS)-induced colitis, concurrently increasing the abundance of beneficial bacterium Dubosiella newyorkensis and elevating the anti-inflammatory metabolite indole-3-carbinol via upregulated tryptophan metabolism. Conclusions: Our findings identify L. salivarius D3-8 as both a dedicated Ejiao-degrader and a protective probiotic against colitis. This work provides direct evidence that gut bacteria can utilize Ejiao and proposes a potential novel mechanistic framework in which the biological effects of Ejiao may be mediated through its interaction with specific, functionally potent degraders such as L. salivarius D3-8.<\/jats:p>","DOI":"10.3390\/nu18060947","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:03:27Z","timestamp":1773756207000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Macromolecule to Microbe: Identification of Ligilactobacillus salivarius D3-8 as a Key Degrader of Ejiao and a Novel Therapeutic Probiotic for Ulcerative Colitis"],"prefix":"10.3390","volume":"18","author":[{"given":"Wei","family":"Dai","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"},{"name":"Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"},{"name":"Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Feng","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Gelatine Medicines Research and Development, Dong\u2019e Ejiao Co., Ltd., Liaocheng 252201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Duan","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Gelatine Medicines Research and Development, Dong\u2019e Ejiao Co., Ltd., Liaocheng 252201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Gelatine Medicines Research and Development, Dong\u2019e Ejiao Co., Ltd., Liaocheng 252201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Gelatine Medicines Research and Development, Dong\u2019e Ejiao Co., Ltd., Liaocheng 252201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Gelatine Medicines Research and Development, Dong\u2019e Ejiao Co., Ltd., Liaocheng 252201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6782-3437","authenticated-orcid":false,"given":"Qingsen","family":"Shang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"},{"name":"Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Honap","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1001\/jama.2020.11583","article-title":"Ulcerative colitis in adults","volume":"324","author":"Glick","year":"2020","journal-title":"J. Am. Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115084","DOI":"10.1016\/j.jep.2022.115084","article-title":"Potential activity of traditional Chinese medicine against ulcerative colitis: A review","volume":"289","author":"Liu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1142\/S0192415X22500756","article-title":"Chinese medicine in the treatment of ulcerative colitis: The mechanisms of signaling pathway regulations","volume":"50","author":"Zheng","year":"2022","journal-title":"Am. J. Chin. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"116879","DOI":"10.1016\/j.jep.2023.116879","article-title":"Traditional Chinese medicine: A promising strategy to regulate the imbalance of bacterial flora, impaired intestinal barrier and immune function attributed to ulcerative colitis through intestinal microecology","volume":"318","author":"Wang","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106678","DOI":"10.1016\/j.jff.2025.106678","article-title":"Asini Corii Colla (Ejiao) as a health-care food and traditional Chinese medicine: A review of its chemical composition, pharmacological activity, quality control, modern applications","volume":"125","author":"Yu","year":"2025","journal-title":"J. Funct. Foods"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, L., Xu, Z.J., Jiang, T., Zhang, J.L., Huang, P.X., Tan, J.Q., Chen, G., Yuan, M., Li, Z., and Liu, H.B. (2021). Efficacy and safety of Ejiao (Asini Corii Colla) in women with blood deficient symptoms: A randomized, double-blind, and placebo-controlled clinical trial. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.718154"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"129423","DOI":"10.1016\/j.ijbiomac.2024.129423","article-title":"Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management","volume":"260","author":"Jia","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","first-page":"603","article-title":"Rectal administration of Panax notoginseng and Colla Corii Asini suppositories in ulcerative colitis: Clinical effect and influence on immune function","volume":"14","author":"Zeng","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2147\/DDDT.S468608","article-title":"Huanglian Ejiao Decoction alleviates ulcerative colitis in mice through regulating the gut microbiota and inhibiting the ratio of Th1 and Th2 cells","volume":"19","author":"Tang","year":"2025","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_12","first-page":"2464","article-title":"Herbalogical study of Colla Corii Asini (Ejiao)","volume":"45","author":"Zhang","year":"2020","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10887","DOI":"10.1039\/D1FO01802G","article-title":"Effects of Ejiao peptide\u2013iron chelates on intestinal inflammation and gut microbiota in iron deficiency anemic mice","volume":"12","author":"Cheng","year":"2021","journal-title":"Food Funct."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3934877","DOI":"10.1155\/2022\/3934877","article-title":"Effect of Ejiao (Asini Corii Colla) and turtle carapace glue on gut microbiota in nude mice with uterine fibroids based on high-throughput sequencing of 16SrRNA gene","volume":"2022","author":"Qiu","year":"2022","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s13238-020-00784-w","article-title":"Role of gut microbiota in identification of novel TCM-derived active metabolites","volume":"12","author":"Lin","year":"2021","journal-title":"Protein Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.eng.2018.11.013","article-title":"Enhancing clinical efficacy through the gut microbiota: A new field of traditional Chinese medicine","volume":"5","author":"Lu","year":"2018","journal-title":"Engineering"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Xia, W., Liu, B., Tang, S., Yasir, M., and Khan, I. (2022). The science behind TCM and Gut microbiota interaction-their combinatorial approach holds promising therapeutic applications. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.875513"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1002\/ptr.7607","article-title":"Crosstalk between traditional Chinese medicine-derived polysaccharides and the gut microbiota: A new perspective to understand traditional Chinese medicine","volume":"36","author":"Yue","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"147694","DOI":"10.1016\/j.ijbiomac.2025.147694","article-title":"How proinflammatory oligosaccharides are produced from carrageenan in mammalian gut? Key roles of Bacteroides xylanisolvens, Bacteroides zhangwenhongii, and Bacteroides difficilis","volume":"328","author":"Zhong","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40168-024-01768-2","article-title":"Bacteroides salyersiae is a potent chondroitin sulfate-degrading species in the human gut microbiota","volume":"12","author":"Wang","year":"2024","journal-title":"Microbiome"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"006421","DOI":"10.1099\/ijsem.0.006421","article-title":"EzBioCloud: A genome-driven database and platform for microbiome identification and discovery","volume":"74","author":"Chalita","year":"2024","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1002\/imt2.12","article-title":"Majorbio Cloud: A one-stop, comprehensive bioinformatic platform for multiomics analyses","volume":"1","author":"Ren","year":"2022","journal-title":"iMeta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125932","DOI":"10.1016\/j.ijbiomac.2023.125932","article-title":"Purification and characterization of a novel low-molecular-weight antimicrobial peptide produced by Lactiplantibacillus plantarum NMGL2","volume":"248","author":"Ren","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"128592","DOI":"10.1016\/j.ijbiomac.2023.128592","article-title":"Polyguluronate alleviates ulcerative colitis by targeting the gut commensal Lactobacillus murinus and its anti-inflammatory metabolites","volume":"257","author":"Pan","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41579-025-01183-w","article-title":"Gut microbiota-derived short-chain fatty acids and their role in human health and disease","volume":"23","author":"Mukhopadhya","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1016\/j.foodhyd.2011.02.007","article-title":"Functional and bioactive properties of collagen and gelatin from alternative sources: A review","volume":"25","author":"Montero","year":"2011","journal-title":"Food Hydrocoll."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ijbiomac.2017.05.151","article-title":"Fish collagen peptide inhibits the adipogenic differentiation of preadipocytes and ameliorates obesity in high fat diet-fed mice","volume":"104","author":"Lee","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pessione, E., and Cirrincione, S. (2016). Bioactive molecules released in food by lactic acid bacteria: Encrypted peptides and biogenic amines. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00876"},{"key":"ref_31","first-page":"314","article-title":"Composition and its antioxidant activity of Colla Corii Asini oligopeptides","volume":"41","author":"Fan","year":"2020","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1038\/s41467-024-45636-x","article-title":"Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway","volume":"15","author":"Zhang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41522-025-00645-6","article-title":"Hypertension inhibition by Dubosiella newyorkensis via reducing pentosidine synthesis","volume":"11","author":"Liu","year":"2025","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"123570","DOI":"10.1016\/j.carbpol.2025.123570","article-title":"Hawthorn pectin mitigates high-fat diet induced hyperlipidemia in mice through promoting Dubosiella newyorkensis","volume":"359","author":"Zhao","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e127551","DOI":"10.1172\/jci.insight.127551","article-title":"Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22-dependent manner","volume":"5","author":"Busbee","year":"2020","journal-title":"JCI Insight"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/10520295.2025.2561682","article-title":"Investigation of ameliorative effects of indole-3 carbinol on TNBS-induced ulcerative colitis in rats","volume":"100","author":"Epikmen","year":"2025","journal-title":"Biotech. Histochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/08830185.2021.1954638","article-title":"Tryptophan metabolites modulate inflammatory bowel disease and colorectal cancer by affecting immune system","volume":"41","author":"Ala","year":"2022","journal-title":"Int. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/s41467-025-55845-7","article-title":"Selective utilization of medicinal polysaccharides by human gut Bacteroides and Parabacteroides species","volume":"16","author":"Qu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Liu, N., Li, M., Yuan, X., Fu, T., Lv, Y., and Shang, Q. (2025). Selective utilization of polyguluronate by the human gut Bacteroides species. Mar. Drugs, 23.","DOI":"10.3390\/md23090348"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1142\/S0192415X24500885","article-title":"Research progress in ulcerative colitis: The role of traditional chinese medicine on gut microbiota and signaling pathways","volume":"52","author":"Zhang","year":"2024","journal-title":"Am. J. Chin. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tursi, A., D\u2019Avino, A., Brandimarte, G., Mocci, G., Pellegrino, R., Savarino, E.V., Gravina, A.G., and the HERICIUM-UC Study Group (2024). Enhancing oral 5-ASA effectiveness in mild-to-moderate ulcerative colitis through an H. erinaceus-based nutraceutical add-on multi-compound: The \u201cHERICIUM-UC\u201d two-arm multicentre retrospective study. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16091133"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/6\/947\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:08:44Z","timestamp":1773756524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/6\/947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["nu18060947"],"URL":"https:\/\/doi.org\/10.3390\/nu18060947","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]}}}