{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:27:20Z","timestamp":1791592040433,"version":"4.3.4"},"reference-count":113,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Butyrate\u2010producing bacteria have emerged as keystone species whose metabolic activity orchestrates host\u2010microbial homeostasis in the human gut. This review synthesizes current understanding of how these anaerobic Firmicutes, including\n                    <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                    ,\n                    <jats:italic>Roseburia spp<\/jats:italic>\n                    ., and\n                    <jats:italic>Eubacterium rectale<\/jats:italic>\n                    , function as key contributors to intestinal health through convergent mechanisms: serving as the primary energy source for colonocytes, enforcing mucosal hypoxia that excludes facultative pathogens, and modulating immunity via histone deacetylase inhibition and G\u2010protein\u2010coupled receptor signaling. We critically examine the translational trajectory of butyrogenic therapies across inflammatory bowel disease, colorectal cancer, and emerging applications in radiation injury, infection, and graft\u2010versus\u2010host disease. Despite compelling mechanistic rationale and consistent clinical associations linking butyrate\u2010producer depletion with disease activity, therapeutic translation faces formidable bottlenecks: extreme oxygen sensitivity complicates manufacturing; cross\u2010feeding networks necessitate ecological rather than monostrain approaches; and host context determines whether butyrate exerts protective or permissive effects. We evaluate cutting\u2010edge strategies to overcome these barriers, including rationally designed consortia, precision prebiotics, phage\u2010mediated niche engineering, synthetic biology approaches, and AI\u2010guided personalization. By integrating mechanistic insight with translational pragmatism, this review outlines a path toward evidence\u2010based butyrogenic therapies that may complement existing strategies for intestinal disease.\n                  <\/jats:p>","DOI":"10.1002\/biot.70260","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:50:51Z","timestamp":1781697051000},"source":"Crossref","is-referenced-by-count":2,"title":["Butyrate\u2010Producing Bacteria in Intestinal Disease Therapy: Potential and Challenges"],"prefix":"10.1002","volume":"21","author":[{"given":"Fenfen","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Clinical Medicine Gansu Medical College  Pingliang Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Gansu Medical College  Pingliang Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Gansu Medical College  Pingliang Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Gansu Medical College  Pingliang Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6912-6213","authenticated-orcid":false,"given":"Xiaolun","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Gansu Medical College  Pingliang Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.2c00431"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2106516"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205037"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2016.176"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1103836"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci193969"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106968.2009.01514.x"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1907272"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.02.018"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat9076"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12721"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00277"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102020\u2010321106"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101237\u20109"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201008812\u2010y"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.757718"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.07.003"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00889\u201014"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02307\u201016"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/2049\u20102618\u20101\u20108"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03115"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01945"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnv176"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2016.02.004"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.847439"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.12938\/bmfh.18\u2010029"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.106312"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010022\u201008967\u2010x"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12726"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201018259\u20100"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2021.1938380"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.44"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071775"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmx009"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01036"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22063061"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111436"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3400"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12672\u2010025\u201002686\u2010x"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804812105"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2025.108434"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S518155"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522\u2010025\u201000830\u20107"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400969RR"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.14744\/ejmo.2024.65019"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16040529"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2024.5632"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr254"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114512001948"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100328"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2023.108557"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2249143"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(00)02787\u20102"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.577236"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02236937"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164\u2010023\u201000410\u20105"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/aem.72.1.946\u2010949.2006"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4114"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2025.07.019"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2026.106526"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.12659\/msm.948912"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9123941"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2249143"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15102275"},{"key":"e_1_2_15_66_1","doi-asserted-by":"publisher","DOI":"10.1017\/s0954422410000247"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14163283"},{"key":"e_1_2_15_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2010.06.003"},{"key":"e_1_2_15_69_1","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000250014.92242.f3"},{"key":"e_1_2_15_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006378\u2010w"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096097"},{"key":"e_1_2_15_72_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070241"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2021.11.034"},{"key":"e_1_2_15_74_1","doi-asserted-by":"publisher","DOI":"10.1097\/hc9.0000000000000650"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.03.016"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001964\u20103"},{"key":"e_1_2_15_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2020.101608"},{"key":"e_1_2_15_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44320\u2010024\u201000067\u20100"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10482\u2010017\u20100836\u20104"},{"key":"e_1_2_15_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.03.016"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.047"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.757372"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu9091021"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.07.048"},{"key":"e_1_2_15_85_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11091234"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2023.09.008"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.111.017228"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751\u20107915.70080"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201065498\u20101"},{"key":"e_1_2_15_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1285169"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/cdn\/nzab107"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030666"},{"key":"e_1_2_15_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010023\u201012912\u20107"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15102416"},{"key":"e_1_2_15_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202417283"},{"key":"e_1_2_15_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.07.028"},{"key":"e_1_2_15_97_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15071566"},{"key":"e_1_2_15_98_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13036\u2010021\u201000259\u20104"},{"key":"e_1_2_15_99_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2316575"},{"key":"e_1_2_15_100_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13036\u2010019\u20100189\u20109"},{"key":"e_1_2_15_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.001"},{"key":"e_1_2_15_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056829\u20103"},{"key":"e_1_2_15_103_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.19296"},{"key":"e_1_2_15_104_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113816128411269250707073647"},{"key":"e_1_2_15_105_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12866\u2010024\u201003344\u2010y"},{"key":"e_1_2_15_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.04.005"},{"key":"e_1_2_15_107_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02685"},{"key":"e_1_2_15_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201028163\u20105"},{"key":"e_1_2_15_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.synbio.2024.12.005"},{"key":"e_1_2_15_110_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103615"},{"key":"e_1_2_15_111_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.20167416"},{"key":"e_1_2_15_112_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.2c00182"},{"key":"e_1_2_15_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3879"},{"key":"e_1_2_15_114_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13036\u2010025\u201000479\u2010y"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70260","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biot.70260","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.70260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:24:59Z","timestamp":1784550299000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.70260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":113,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/biot.70260"],"URL":"https:\/\/doi.org\/10.1002\/biot.70260","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"article-number":"e70260"}}