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Understanding the horizontal transfer of BGCs can reveal insights into microbial adaptation, resource utilization, and evolutionary mechanisms, thereby advancing biotechnological applications. Despite its importance, horizontal transfer of BGCs within the gut microbiota remains poorly understood. In this study, we introduce a novel tool, the Horizontally Transferred Biosynthetic Gene Clusters Finder (HTBGC\u2010Finder), designed to systematically identify potential horizontally transferred BGCs (HTBGCs) within the extensive human gut microbiota. Using HTBGC\u2010Finder, we identified 81 potential HTBGCs, underscoring the prevalence and significance of horizontal gene transfer in shaping the genetic landscape of the gut microbiome. Remarkably, ribosomally synthesized and post\u2010translationally modified peptides (RiPPs) constituted the majority of these HTBGCs (76 out of 81, 93.83%), exhibiting a significantly higher transfer rate compared to non\u2010RiPPs (Chi\u2010squared test,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Upon detailed examination of BGCs, cyclic\u2010lactone\u2010autoinducer (CLA) and RiPP recognition element (RRE)\u2010containing BGCs were predominant, representing nearly three\u2010quarters of the total (45, or 55.56%, and 14, or 17.28%, respectively). Notably, CLA BGCs also demonstrated a higher transfer rate than non\u2010CLA BGCs (Chi\u2010squared test,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Taxonomy profiling revealed that horizontal BGC transfer occurred exclusively in the phyla Bacteroidota (synonym Bacteroidetes) and Bacillota (synonym Firmicutes), with 50 and 31 instances, respectively. Furthermore, cross\u2010phylum transfer events were observed, highlighting the complex interactions between the gut microbiota and host health. These findings offer valuable insights into the horizontal transfer dynamics of BGCs within the gut microbiome and their potential implications for host\u2010microbiota interactions.\n                  <\/jats:p>","DOI":"10.1002\/imo2.62","type":"journal-article","created":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T01:09:01Z","timestamp":1738458541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Systematic characterization of horizontally transferred biosynthetic gene clusters in the human gut microbiota using HTBGC\u2010Finder"],"prefix":"10.1002","volume":"2","author":[{"given":"Jiacheng","family":"Wu","sequence":"first","affiliation":[{"name":"Microbiome\u2010X, School of Public Health, Cheeloo College of Medicine Shandong University Jinan China"},{"name":"CAS Key Laboratory of Computational Biology, Bio\u2010Med Big Data Center, Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Microbiome\u2010X, School of Public Health, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Microbiome\u2010X, School of Public Health, Cheeloo College of Medicine Shandong University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Li","sequence":"additional","affiliation":[{"name":"Microbiome\u2010X, School of Public Health, Cheeloo College of Medicine Shandong University Jinan China"},{"name":"State Key Laboratory of Microbial Technology Shandong University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Microbiome\u2010X, School of Public Health, Cheeloo College of Medicine Shandong University Jinan China"},{"name":"CAS Key Laboratory of Computational Biology, Bio\u2010Med Big Data Center, Shanghai Institute of Nutrition and Health Chinese Academy of Sciences Shanghai China"},{"name":"State Key Laboratory of Microbial Technology Shandong University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4284-2604","authenticated-orcid":false,"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Microbiome\u2010X, School of Public Health, Cheeloo College of Medicine Shandong University Jinan China"},{"name":"State Key Laboratory of Microbial Technology Shandong University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0965-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz882"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.2c00700"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-019-0107-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1657"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/tpj.15490"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609073103"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b01055"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/82_2016_499"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof9020171"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/b515619j"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01110-2"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/md13084754"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.1.5.409"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.632230"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2022.2036099"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01801"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/c6np00017g"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/md20060341"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5353.996"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2005.pto960401.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.07.004"},{"key":"e_1_2_11_25_1","doi-asserted-by":"crossref","unstructured":"Fischbach Michael A. 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