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However, the interplay between host metabolites and gut microbes in IBS pathogenesis remains incompletely understood. Here, through integrated microbiome and metabolome profiling of faecal sample from seafarers before and after long\u2010term voyages, we identify a reciprocal interaction between the essential amino acid\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine and the gut bacterium\n                    <jats:italic>Holdemanella biformis<\/jats:italic>\n                    (\n                    <jats:italic>H. biformis<\/jats:italic>\n                    ).\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine was depleted in individuals with voyage\u2010induced IBS, whereas\n                    <jats:italic>H. biformis<\/jats:italic>\n                    abundance increased concurrently. In a mouse model of diarrhoea\u2010predominant IBS,\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine supplementation restored intestinal barrier integrity, reduced visceral hypersensitivity, and alleviated anxiety\u2010like behaviours through modulation of tryptophan metabolism. In contrast, oral administration of\n                    <jats:italic>H. biformis<\/jats:italic>\n                    improved tight junction protein expression but paradoxically worsened anxiety\u2010like phenotypes. In vitro, both\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine and\n                    <jats:italic>H. biformis<\/jats:italic>\n                    supernatant promoted epithelial wound healing and ZO\u20101 expression. Mechanistically,\n                    <jats:italic>H. biformis<\/jats:italic>\n                    degrades\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine via lysine degradation pathway, while\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine suppresses\n                    <jats:italic>H. biformis<\/jats:italic>\n                    growth possibly by downregulating pathways involved in carbohydrate and energy metabolism. These findings reveal a stress\u2010sensitive, bidirectional metabolic loop in between\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lysine and\n                    <jats:italic>H. biformis<\/jats:italic>\n                    , with complementary but opposing effects on gut and neurological function. Targeting this axis may offer new strategies for IBS and other gut\u2010brain axis disorders.\n                  <\/jats:p>","DOI":"10.1002\/imo2.70042","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T09:50:44Z","timestamp":1754473844000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A reciprocal interaction between L\u2010lysine and\n                    <i>Holdemanella biformis<\/i>\n                    modulates intestinal barrier function and anxiety in irritable bowel syndrome"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1237-585X","authenticated-orcid":false,"given":"Chun\u2010Hui","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-1960","authenticated-orcid":false,"given":"Xue","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Shen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7881-0156","authenticated-orcid":false,"given":"Wen\u2010Bin","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-8159","authenticated-orcid":false,"given":"Zhuan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Changhai Hospital; National Key Laboratory of Immunity and Inflammation Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)32115-2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-021-01123-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00925-21"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph16071153"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-044633"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01899-22"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45636-x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2436556100"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.12.3744"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/database\/baaa062"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.645951"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.14621"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.1039804"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-821324-7.00012-5"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-00988-y"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01068-x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0649-5"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.967644"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.022"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.135551"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.4c00086"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15051262"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2468-1253(16)30023-1"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00090"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12944"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-003-0358-4"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1116065"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-021-00843-1"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-022-00630-z"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10946"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14610"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.930626"},{"key":"e_1_2_11_34_1","unstructured":"Sanz Herranz Y. 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