{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:32:09Z","timestamp":1786509129984,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cPioneer\u201d and \u201cLeading Goose\u201d R&amp;D Program of Zhejiang Province","award":["2025C01115"],"award-info":[{"award-number":["2025C01115"]}]},{"name":"Yangtze River Delta Science and Technology Innovation Community Joint Research Project","award":["2022CSJGG1000\/2023ZY1068"],"award-info":[{"award-number":["2022CSJGG1000\/2023ZY1068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Astilbin is a bioactive flavonoid with documented anti-inflammatory properties; however, its sustained interactions with the gut microbiota remain poorly understood. Fecal samples from three healthy donors were pooled and fermented with astilbin in an in vitro human colonic model over 7 days. This exploratory study aimed to characterize the temporal ecological shifts associated with prolonged astilbin exposure. Methods: Time-resolved 16S rRNA gene sequencing, PICRUSt2 functional prediction, BugBase phenotypic inference, and pseudo-targeted metabolomics were integrated to track microbial-metabolic dynamics. Results: Astilbin exposure was associated with a highly coordinated, three-stage microbial succession. Day 3 (D3) emerged as a putative inflection point, where the enrichment of pioneer degraders (Flavonifractor, Bacteroides) was temporally correlated with the appearance of polyphenol cleavage intermediates. This transition featured an early decrease in markers of proteolytic fermentation alongside a transient in vitro lipid-stress response. By D7, the community shifted toward a stable configuration enriched in butyrogenic taxa (Roseburia, Subdoligranulum, Megamonas), with progressive depletion of potentially opportunistic pathogens (Escherichia-Shigella). Multi-omics integration suggested that these structural successions were strongly associated with marked metabolic shifts. Inflammatory lipid markers (e.g., leukotriene B4) showed a characteristic \u201cD3-burst\/D7-clearance\u201d pattern, whereas potentially barrier-protective metabolites, particularly 3-indolepropionic acid (3-IPA, log2FC = 2.00) and urolithin B (log2FC = 1.18), accumulated substantially. Conclusions: This exploratory study provides valuable high-resolution insights into astilbin\u2019s potential as a dynamic ecological modulator. It outlines a temporal framework illustrating how the gut microbiota may shift from proteolytic fermentation toward 3-IPA-associated homeostasis. Although limited by a pooled fecal model and the absence of a vehicle control, these hypothesis-generating findings offer a solid foundation for future in vivo studies and mechanistic validations across diverse human cohorts.<\/jats:p>","DOI":"10.3390\/nu18162616","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:10:24Z","timestamp":1786374624000},"page":"2616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal Multi-Omics Reveals Microbial and Metabolic Succession Following Astilbin Treatment in a Human Colonic Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Tingwei","family":"Wang","sequence":"first","affiliation":[{"name":"College of Biological & Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Key Laboratory of Biomedical Intelligent Computing Technology, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3979-6357","authenticated-orcid":false,"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, International Joint Laboratory on Food Safety, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9405-1084","authenticated-orcid":false,"given":"Jian","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, International Joint Laboratory on Food Safety, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Instrumental Analysis and Laboratory Animal Center, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengfang","family":"Wu","sequence":"additional","affiliation":[{"name":"Instrumental Analysis and Laboratory Animal Center, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangen","family":"Xia","sequence":"additional","affiliation":[{"name":"Ningbo Xiabang New Pharmaceutical Technology Co., Ltd., Ningbo 315000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruowei","family":"Xia","sequence":"additional","affiliation":[{"name":"Ningbo Xiabang New Pharmaceutical Technology Co., Ltd., Ningbo 315000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Qu","sequence":"additional","affiliation":[{"name":"College of Biological & Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Key Laboratory of Biomedical Intelligent Computing Technology, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8990-3510","authenticated-orcid":false,"given":"Maiqiu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biological & Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Key Laboratory of Biomedical Intelligent Computing Technology, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Biological & Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China"},{"name":"Zhejiang Key Laboratory of Biomedical Intelligent Computing Technology, Hangzhou 310023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, International Joint Laboratory on Food Safety, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.chom.2023.03.016","article-title":"Cross-feeding in the gut microbiome: Ecology and mechanisms","volume":"31","author":"Culp","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1016\/j.cell.2024.03.034","article-title":"Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway","volume":"187","author":"Nie","year":"2024","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.tim.2021.02.001","article-title":"Microbial Regulation of Host Physiology by Short-chain Fatty Acids","volume":"29","author":"Wells","year":"2021","journal-title":"Trends Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"18792","DOI":"10.1021\/acs.jafc.3c06183","article-title":"Indole-3-Lactic Acid, a Tryptophan Metabolite of Lactiplantibacillus plantarum DPUL-S164, Improved Intestinal Barrier Damage by Activating AhR and Nrf2 Signaling Pathways","volume":"71","author":"Wang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2211501","DOI":"10.1080\/19490976.2023.2211501","article-title":"Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis","volume":"15","author":"Chen","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pivari, F., Mingione, A., Piazzini, G., Ceccarani, C., Ottaviano, E., Brasacchio, C., Cas, M.D., Vischi, M., Cozzolino, M.G., and Fogagnolo, P. (2022). Curcumin Supplementation (Meriva\u00ae) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease. Nutrients, 14.","DOI":"10.3390\/nu14010231"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.bcp.2017.04.033","article-title":"The gut microbiota: A key factor in the therapeutic effects of (poly)phenols","volume":"139","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ozdal, T., Sela, D.A., Xiao, J., Boyacioglu, D., Chen, F., and Capanoglu, E. (2016). The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility. Nutrients, 8.","DOI":"10.3390\/nu8020078"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Saad, A.M., Mohammed, D.M., Alkafaas, S.S., Ghosh, S., Negm, S.H., Salem, H.M., Fahmy, M.A., Semary, H.E., Ibrahim, E.H., and AbuQamar, S.F. (2025). Dietary polyphenols and human health: Sources, biological activities, nutritional and immunological aspects, and bioavailability\u2014A comprehensive review. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1653378"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7730","DOI":"10.1080\/10408398.2021.1917508","article-title":"Absorption, metabolism and bioavailability of flavonoids: A review","volume":"62","author":"Chen","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pan, L., Ye, H., Pi, X., Liu, W., Wang, Z., Zhang, Y., and Zheng, J. (2023). Effects of several flavonoids on human gut microbiota and its metabolism by in vitro simulated fermentation. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1092729"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155754","DOI":"10.1016\/j.phymed.2024.155754","article-title":"Astilbin inhibited neutrophil extracellular traps in gouty arthritis through suppression of purinergic P2Y6 receptor","volume":"130","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"104894","DOI":"10.1016\/j.phrs.2020.104894","article-title":"Astilbin: A promising unexplored compound with multidimensional medicinal and health benefits","volume":"158","author":"Sharma","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/jsfa.10669","article-title":"Astilbin lowers the effective caffeine dose for decreasing lipid accumulation via activating AMPK in high-fat diet-induced obese mice","volume":"101","author":"Yang","year":"2021","journal-title":"J. Sci. Food Agric."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5023","DOI":"10.1039\/D2FO00060A","article-title":"Astilbin from Smilax glabra Roxb. alleviates high-fat diet-induced metabolic dysfunction","volume":"13","author":"Wang","year":"2022","journal-title":"Food Funct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1002\/bmc.3111","article-title":"Identification of astilbin metabolites produced by human intestinal bacteria using UPLC-Q-TOF\/MS","volume":"28","author":"Zhao","year":"2014","journal-title":"Biomed. Chromatogr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110140","DOI":"10.1016\/j.jnutbio.2025.110140","article-title":"UPP1 as a potential target for astilbin in ameliorating high-fat diet-induced bone loss via MAPK signaling: A study incorporating gut microbiota and metabolomics","volume":"148","author":"Su","year":"2026","journal-title":"J. Nutr. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1038\/s41596-020-0341-5","article-title":"Development of a plasma pseudotargeted metabolomics method based on ultra-high-performance liquid chromatography-mass spectrometry","volume":"15","author":"Zheng","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xiong, H.-H., Lin, S.-Y., Chen, L.-L., Ouyang, K.-H., and Wang, W.-J. (2023). The interaction between flavonoids and intestinal microbes: A review. Foods, 12.","DOI":"10.3390\/foods12020320"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.1021\/jf902107d","article-title":"Interaction between phenolics and gut microbiota: Role in human health","volume":"57","author":"Selma","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Skonieczna-\u017bydecka, K., Jakubczyk, K., Maciejewska-Markiewicz, D., Janda, K., Ka\u017amierczak-Siedlecka, K., Kaczmarczyk, M., \u0141oniewski, I., and Marlicz, W. (2020). Gut Biofactory-Neurocompetent Metabolites within the Gastrointestinal Tract. A Scoping Review. Nutrients, 12.","DOI":"10.3390\/nu12113369"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shuvo, S.H., Kim, S., Jo, S., Rahim, A., Barman, I., Hossain, M.S., Yoon, Y., Tajdozian, H., Ahmed, I., and Atashi, A. (2025). Flavonifractor plautii as a Next-Generation Probiotic Enhancing the NGP F\/P Index in a Simulated Human Gut Microbiome Ecosystem. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17121603"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.1017\/gmb.2023.14","article-title":"The butyrate-producing and spore-forming bacterial genus Coprococcus as a potential biomarker for neurological disorders","volume":"4","author":"Notting","year":"2023","journal-title":"Gut Microbiome"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2649448","DOI":"10.1080\/19490976.2026.2649448","article-title":"From gut dysbiosis to eubiosis: Understanding microbiome recovery as an ecological process","volume":"18","author":"Kennedy","year":"2026","journal-title":"Gut Microbes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.2147\/JIR.S466777","article-title":"Pretreatment with indole-3-propionic acid attenuates lipopolysaccharide-induced cardiac dysfunction and inflammation through the AhR\/NF-\u03baB\/NLRP3 pathway","volume":"17","author":"Zhang","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Diether, N.E., and Willing, B.P. (2019). Microbial Fermentation of Dietary Protein: An Important Factor in Diet-Microbe-Host Interaction. Microorganisms, 7.","DOI":"10.3390\/microorganisms7010019"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1039\/D2FO03975C","article-title":"Bovine milk-derived extracellular vesicles prevent gut inflammation by regulating lipid and amino acid metabolism","volume":"14","author":"Du","year":"2023","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"159319","DOI":"10.1016\/j.bbalip.2023.159319","article-title":"Metabolic alterations of the gut-liver axis induced by cholic acid contribute to hepatic steatosis in rats","volume":"1868","author":"Liu","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, P., Guo, Z., Chen, F., Wu, Y., and Zhou, B. (2022). Recent Advances and Perspectives on the Health Benefits of Urolithin B, A Bioactive Natural Product Derived From Ellagitannins. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.917266"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8254","DOI":"10.1021\/acs.jafc.4c06689","article-title":"Curcumin Ameliorated Glucocorticoid-Induced Osteoporosis While Modulating the Gut Microbiota and Serum Metabolome","volume":"73","author":"Li","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s44316-024-00012-z","article-title":"Metabolic rewiring of microbial cell factories for improved production of succinic acid","volume":"1","author":"Das","year":"2024","journal-title":"Biotechnol. Sustain. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/s41467-021-20974-2","article-title":"Discovery of an ene-reductase for initiating flavone and flavonol catabolism in gut bacteria","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1017\/S0007114521003627","article-title":"Interactions between dietary flavonoids and the gut microbiome: A comprehensive review","volume":"128","author":"Baky","year":"2022","journal-title":"Br. J. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2616\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:25:30Z","timestamp":1786508730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":35,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["nu18162616"],"URL":"https:\/\/doi.org\/10.3390\/nu18162616","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}