{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:02:20Z","timestamp":1790179340988,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22408243"],"award-info":[{"award-number":["22408243"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["22402133"],"award-info":[{"award-number":["22402133"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acute alcohol\u2010induced liver injury (ALI) is an escalating global health concern driven by the absence of targeted therapies, difficulty in sustaining abstinence, and high mortality rate. Conventional treatments, such as corticosteroids and nutritional supplementation, remain suboptimal due to inconsistent efficacy, significant adverse effects, and limited understanding of the underlying pathogenic mechanisms. This work presents a living food\u2010grade microalgae\u2010laden hydrogel (FMH), fabricated from\n                    <jats:italic>Chlorella pyrenoidosa<\/jats:italic>\n                    (CP) and edible polysaccharides for the treatment of ALI. The natural polysaccharide scaffolds enable high\u2010efficiency in situ autotrophic growth of microalgae, exhibiting a 2.7\u2010time higher yield compared to conventional suspension culture. We validated the biosafety and nutritional functionality of the obtained FMH and confirmed its physiological and psychological contribution. The use of FMH as a dietary intervention alleviates ethanol\u2010induced hepatotoxicity for acute ALI by modulating oxidative stress, restoring immune equilibrium, and normalizing gut microbiota. This system not only holds translational potential as a dietary intervention for ALI management, but also establishes an oral platform for the delivery of living biotherapeutics in emerging biomedical applications.\n                  <\/jats:p>","DOI":"10.1002\/smll.202513746","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:10:31Z","timestamp":1790176231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Microalgae\u2010Laden Hydrogels Modulating the Intestinal Microbiota Metabolism for Acute Alcohol\u2010Induced Liver Injury Therapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7653-5754","authenticated-orcid":false,"given":"Zhixin","family":"Hu","sequence":"first","affiliation":[{"name":"College of Biomass Science and Engineering Key Laboratory of Leather Chemistry and Engineering of Ministry of Education National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8832-2825","authenticated-orcid":false,"given":"Hongtao","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Biomass Science and Engineering Key Laboratory of Leather Chemistry and Engineering of Ministry of Education National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5389-1474","authenticated-orcid":false,"given":"Xuanqi","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Biomass Science and Engineering Key Laboratory of Leather Chemistry and Engineering of Ministry of Education National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-5694","authenticated-orcid":false,"given":"Xinxu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases, Department of Prosthodontics West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-3457","authenticated-orcid":false,"given":"Linli","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5309-1979","authenticated-orcid":false,"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Clinical Research Center for Oral Diseases &amp; Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-3240","authenticated-orcid":false,"given":"Xiaojie","family":"Li","sequence":"additional","affiliation":[{"name":"College of Biomass Science and Engineering Key Laboratory of Leather Chemistry and Engineering of Ministry of Education National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3989-1843","authenticated-orcid":false,"given":"Yawen","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Biomass Science and Engineering Key Laboratory of Leather Chemistry and Engineering of Ministry of Education National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzheng","family":"Gao","sequence":"additional","affiliation":[{"name":"Bezos Centre for Sustainable Protein at the National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7901-2738","authenticated-orcid":false,"given":"Kui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5203-4737","authenticated-orcid":false,"given":"Jiajing","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Biomass Science and Engineering Key Laboratory of Leather Chemistry and Engineering of Ministry of Education National Engineering Laboratory for Clean Technology of Leather Manufacture Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jhep.2018.12.008","article-title":"Acute\u2010On\u2010Chronic liver failure in patients With alcohol\u2010Related liver disease","volume":"70","author":"Gustot T.","year":"2019","journal-title":"Journal of Hepatology"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41575-018-0099-1","article-title":"Alcohol, liver disease and the gut microbiota","volume":"16","author":"Bajaj J. S.","year":"2019","journal-title":"Nature Reviews Gastroenterology & Hepatology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2024.140460","article-title":"Hepatoprotective potential of four fruit extracts rich in different structural flavonoids Against alcohol\u2010Induced liver injury via gut microbiota\u2010Liver axis","volume":"460","author":"Chen Y.","year":"2024","journal-title":"Food Chemistry"},{"key":"e_1_2_8_5_1","doi-asserted-by":"crossref","DOI":"10.1038\/srep30119","article-title":"Evaluation of liver function and electroacupuncture efficacy of animals with alcoholic liver injury by the novel imaging methods","volume":"6","author":"Zhang D.","year":"2016","journal-title":"Scientific Reports"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.gande.2025.01.003","article-title":"Alcohol\u2010Associated liver disease: A review","volume":"3","author":"Nagarjuna D.","year":"2025","journal-title":"Gastroenterology & Endoscopy"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.3390\/antiox14101196","article-title":"Alcohol\u2010Induced Oxidative Stress and Gut\u2013Liver\u2013Brain Crosstalk: Expanding the Paradigm From ALD to MetALD","volume":"14","author":"Lee J. Y.","year":"2025","journal-title":"Antioxidants"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jhep.2017.06.013","article-title":"Sepsis in alcohol\u2010Related liver disease","volume":"67","author":"Gustot T.","year":"2017","journal-title":"Journal of Hepatology"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.crfs.2023.100621","article-title":"Extraction, functionality, and applications of Chlorella pyrenoidosa protein\/peptide","volume":"7","author":"Wu Q.","year":"2023","journal-title":"Current Research in Food Science"},{"key":"e_1_2_8_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.algal.2022.102696","article-title":"Key challenges for the commercial expansion of ingredients From algae Into human food products","volume":"64","author":"Hosseinkhani N.","year":"2022","journal-title":"Algal Research"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40643-016-0094-8","article-title":"Concentration and characterization of microalgae proteins From Chlorella pyrenoidosa","volume":"3","author":"Waghmare A. G.","year":"2016","journal-title":"Bioresources and Bioprocessing"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.algal.2023.103263","article-title":"Preparation and bioavailability of Chlorella pyrenoidosa protein hydrolysates\u2010Calcium chelate","volume":"75","author":"Yang J.","year":"2023","journal-title":"Algal Research"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.fufo.2025.100564","article-title":"Enhancing microalgal proteins for nutraceutical and functional food applications","volume":"11","author":"Kaur M.","year":"2025","journal-title":"Future Foods"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cej.2025.160429","article-title":"Carbon dots alleviate photoinhibition and enhance photosynthesis in Chlorella pyrenoidosa","volume":"507","author":"Chen F.","year":"2025","journal-title":"Chemical Engineering Journal"},{"key":"e_1_2_8_15_1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1007\/s43450-025-00650-y","article-title":"Optimal Phenolic Production from Microalgae Chlorella: A Review","volume":"35","author":"Madja A. R. A.","year":"2025","journal-title":"Revista Brasileira de Farmacognosia"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biortech.2023.128661","article-title":"Biological active metabolites From microalgae for healthcare and pharmaceutical industries: A comprehensive review","volume":"372","author":"Ibrahim T. N. B. T.","year":"2023","journal-title":"Bioresource Technology"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-022-00724-0","article-title":"Immunomodulatory functional foods and their molecular mechanisms","volume":"54","author":"Kim J. H.","year":"2022","journal-title":"Experimental & Molecular Medicine"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.3390\/molecules26082330","article-title":"An In Vitro Pilot Fermentation Study on the Impact of Chlorella pyrenoidosa on Gut Microbiome Composition and Metabolites in Healthy and Coeliac Subjects","volume":"26","author":"Linde C.","year":"2021","journal-title":"Molecules"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3390\/foods11050725","article-title":"Chlorella pyrenoidosa Polysaccharides as a Prebiotic to Modulate Gut Microbiota: Physicochemical Properties and Fermentation Characteristics In Vitro","volume":"11","author":"Lv K.","year":"2022","journal-title":"Foods"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1517\/17425247.2014.902047","article-title":"Therapeutic applications of hydrogels in oral drug delivery","volume":"11","author":"Sharpe L. A.","year":"2014","journal-title":"Expert Opinion on Drug Delivery"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1080\/10717544.2017.1279238","article-title":"pH\u2010Responsive carriers for oral drug delivery: Challenges and opportunities of current platforms","volume":"24","author":"Liu L.","year":"2017","journal-title":"Drug Delivery"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1002\/adfm.201600084","article-title":"Chitosan\u2013Alginate Microcapsules Provide Gastric Protection and Intestinal Release of ICAM\u20101\u2010Targeting Nanocarriers, Enabling GI Targeting In Vivo","volume":"26","author":"Ghaffarian R.","year":"2016","journal-title":"Advanced Functional Materials"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41467-017-00144-z","article-title":"Triggerable tough hydrogels for gastric resident dosage forms","volume":"8","author":"Liu J.","year":"2017","journal-title":"Nature Communications"},{"key":"e_1_2_8_24_1","doi-asserted-by":"crossref","first-page":"8075","DOI":"10.1080\/10408398.2025.2491646","article-title":"Chlorella sp. as a promising protein source: Insight to novel extraction techniques, nutritional and techno\u2010Functional attributes of derived proteins","volume":"65","author":"Bakshi S.","year":"2025","journal-title":"Critical Reviews in Food Science and Nutrition"},{"key":"e_1_2_8_25_1","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2020.565996","article-title":"Biochemical and Nutritional Evaluation of Chlorella and Auxenochlorella Biomasses Relevant for Food Application","volume":"7","author":"Canelli G.","year":"2020","journal-title":"Frontiers in Nutrition"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.3390\/nu15071645","article-title":"Impact of Regular Intake of Microalgae on Nutrient Supply and Cardiovascular Risk Factors: Results From the NovAL Intervention Study","volume":"15","author":"Sandgruber F.","year":"2023","journal-title":"Nutrients"},{"key":"e_1_2_8_27_1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.3390\/nu10080965","article-title":"Bioavailability and Safety of Nutrients From the Microalgae Chlorella vulgaris, Nannochloropsis oceanica and Phaeodactylum tricornutum in C57BL\/6 Mice","volume":"10","author":"Neumann U.","year":"2018","journal-title":"Nutrients"},{"key":"e_1_2_8_28_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodres.2025.116508","article-title":"Potential benefits of orally deliverable silymarin\u2010Loaded spirulina platensis in mitigating alcoholic liver disease","volume":"212","author":"Hao S.","year":"2025","journal-title":"Food Research International"},{"key":"e_1_2_8_29_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2020.113432","article-title":"Protective effects of n\u2010Butanol extract and iridoid glycosides of Veronica ciliata Fisch. Against ANIT\u2010Induced cholestatic liver injury in mice","volume":"266","author":"Hua W.","year":"2021","journal-title":"Journal of Ethnopharmacology"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2025.107906","article-title":"\u03b2\u2010Resorcylic acid prevents MASLD in ob\/ob mice by modulating lipid metabolism and inflammation in the liver","volume":"219","author":"L\u00f3pez\u2010Herrador S.","year":"2025","journal-title":"Pharmacological Research"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.2147\/DDDT.S521740","article-title":"Mechanisms of Total Glucosides of Paeony in Alleviating Methotrexate\u2010Induced Liver Injury","volume":"19","author":"Chen G.","year":"2025","journal-title":"Drug Design, Development and Therapy"},{"key":"e_1_2_8_32_1","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.3748\/wjg.v20.i25.8082","article-title":"Oxidative stress as a crucial factor in liver diseases","volume":"20","author":"Cicho\u017c\u2010Lach H.","year":"2014","journal-title":"World Journal of Gastroenterology"},{"key":"e_1_2_8_33_1","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/4234061","article-title":"Insights Into the Role and Interdependence of Oxidative Stress and Inflammation in Liver Diseases","volume":"2016","author":"Li S.","year":"2016","journal-title":"Oxidative Medicine and Cellular Longevity"},{"key":"e_1_2_8_34_1","doi-asserted-by":"crossref","DOI":"10.1093\/burnst\/tkad056","article-title":"The impact of gut microbiota changes on the intestinal mucus barrier in burned mice: A study using 16S rRNA and metagenomic sequencing","volume":"11","author":"Zha X.","year":"2023","journal-title":"Burns & Trauma"},{"key":"e_1_2_8_35_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.micres.2025.128317","article-title":"Akkermansia muciniphila: A key player in gut microbiota\u2010Based disease modulation","volume":"301","author":"Shaheen N.","year":"2025","journal-title":"Microbiological Research"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3390\/foods13060895","article-title":"Understanding Ligilactobacillus salivarius from Probiotic Properties to Omics Technology: A Review","volume":"13","author":"Yang Y.","year":"2024","journal-title":"Foods"},{"key":"e_1_2_8_37_1","doi-asserted-by":"crossref","DOI":"10.1080\/19490976.2021.1987783","article-title":"Oscillospira\u2014a candidate for the next\u2010Generation probiotics","volume":"13","author":"Yang J.","year":"2021","journal-title":"Gut Microbes"},{"key":"e_1_2_8_38_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.crfs.2025.101111","article-title":"Lacticaseibacillus rhamnosus HF01 postbiotics reprogram gut microbial tryptophan metabolism to coordinate enterohepatic barrier\u2010Insulin signaling axis","volume":"11","author":"Sun Y.","year":"2025","journal-title":"Current Research in Food Science"},{"key":"e_1_2_8_39_1","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.3390\/ijms26125486","article-title":"Gut Microbiota\u2010Targeted Therapeutics for Metabolic Disorders: Mechanistic Insights Into the Synergy of Probiotic\u2010Fermented Herbal Bioactives","volume":"26","author":"Fan Y.","year":"2025","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_8_40_1","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202401172","article-title":"Space\u2010Efficient 3D Microalgae Farming With Optimized Resource Utilization for Regenerative Food","volume":"36","author":"Liu H.","year":"2024","journal-title":"Advanced Materials"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202513746","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.202513746","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202513746","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:10:37Z","timestamp":1790176237000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202513746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":39,"alternative-id":["10.1002\/smll.202513746"],"URL":"https:\/\/doi.org\/10.1002\/smll.202513746","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"assertion":[{"value":"2025-11-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13746"}}