{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:57:25Z","timestamp":1789437445296,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T00:00:00Z","timestamp":1741392000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    3\u2010hydroxybutyrate (3\u2010HB), an essential endogenous metabolite, shows significant therapeutic potential in several disease contexts. However, its clinical application has been hampered by limitations, such as adverse effects on the gut microbiota. This study introduces a genetically engineered strain of\n                    <jats:italic>Lactobacillus rhamnosus<\/jats:italic>\n                    GG (LGGK) that integrates the benefits of 3\u2010HB production with the probiotic properties of LGG. Using a murine colon cancer cachexia (CAC) model, LGGK supplementation significantly improved survival, reduced tumor progression, and alleviated muscle wasting. LGGK restored gut microbial diversity, increased the abundance of beneficial bacteria, and increased the production of short\u2010chain fatty acids while reducing harmful microbial populations. In addition, LGGK supplementation demonstrated anti\u2010inflammatory effects, effectively reducing elevated pro\u2010inflammatory cytokines in serum and skeletal muscle. These findings highlight LGGK as a dual\u2010action therapeutic approach that utilizes the metabolic benefits of 3\u2010HB and the gut\u2010modulating properties of LGG. This innovation offers a promising strategy for the treatment of CAC and potentially other metabolic and inflammatory disorders, and highlights the potential of engineered probiotics in advanced therapeutic applications.\n                  <\/jats:p>","DOI":"10.1002\/bit.28972","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:42:21Z","timestamp":1741714941000},"page":"1574-1589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Engineered\n                    <i>Lactobacillus rhamnosus<\/i>\n                    Producing 3\u2010Hydroxybutyrate: A Dual\u2010Action Therapeutic Strategy for Colon Cancer Cachexia"],"prefix":"10.1002","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-5514","authenticated-orcid":false,"given":"Xu","family":"Qiu","sequence":"first","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province College of Chemistry and Chemical Engineering, Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyun","family":"Zou","sequence":"additional","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province College of Chemistry and Chemical Engineering, Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taijie","family":"Lin","sequence":"additional","affiliation":[{"name":"Shanghai Diglean Health Technology Development Co. Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-1047","authenticated-orcid":false,"given":"Chenyun","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province College of Chemistry and Chemical Engineering, Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-2033","authenticated-orcid":false,"given":"Donghai","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory for Chemical Biology of Fujian Province College of Chemistry and Chemical Engineering, Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu085"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.027"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1039\/d3fo01307c"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474-4422(17)30408-8"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00624-w"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.105"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.03.011"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R036012"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-022-00826-2"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11091373"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13093202"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.702802"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04649-6"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-011-1006-9"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-018-1369-3"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-023-10117-y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0188-7"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056876"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12721"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.07.001"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1178638820980490"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.10104"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101667"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biodatasci-080917-013328"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.11.027"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127019"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11020381"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.4103\/2008-7802.207035"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2852"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12136"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00106.2021"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.041"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12784"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25190-5"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200700141"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-01014-8"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12010184"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11030402"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064916"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-022-09972-y"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-50972-x"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082247"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-10426-0"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-823733-5.00021-0"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-021-02317-3"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73384-x"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2020.109682"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0089-z"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7163\/aa66d3"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1335975"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04036-3"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227166"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01948-5"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500213200"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121829"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqy170"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312729"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2021.11.034"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11552"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16619"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.5191"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00760-2"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-021-11482-w"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105807"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3804"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-022-12265-7"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01415-6"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:01:06Z","timestamp":1760054466000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.28972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,8]]},"references-count":67,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/bit.28972"],"URL":"https:\/\/doi.org\/10.1002\/bit.28972","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,8]]},"assertion":[{"value":"2024-12-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}