{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:49:26Z","timestamp":1793386166336,"version":"4.5.0"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"787","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,2,26]]},"abstract":"<jats:p>\n                    The composition of the gut microbiota in patients with bronchiectasis has been proven to be distinct from that of healthy individuals, and this disrupted gut microbiota can exacerbate lung infections. However, the responsible microbes and mechanisms in the \u201cgut-lung\u201d axis in bronchiectasis remain unknown. Here, we report that\n                    <jats:italic>Eggerthella lenta<\/jats:italic>\n                    was enriched in the gut, and taurine ursodeoxycholic acid (TUDCA) was enriched in both the guts and sera of patients with bronchiectasis, with both being associated with disease severity. Fecal microbiota transfer from patients with bronchiectasis as well as administration of\n                    <jats:italic>E. lenta<\/jats:italic>\n                    independently exacerbated pulmonary\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infections in murine models.\n                    <jats:italic>E. lenta<\/jats:italic>\n                    \u2013associated TUDCA bound adenosine monophosphate\u2013activated protein kinase (AMPK) within neutrophils and interfered with the interaction between liver kinase B1 and AMPK, with a consequential decrease in AMPK phosphorylation. This ultimately reduced ATP production in neutrophils, inhibited their function, and compromised\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    elimination from the lung, aggravating tissue injury. Metformin treatment improved disease severity and outcome in the mouse models. In sum, the gut bacterium\n                    <jats:italic>E. lenta<\/jats:italic>\n                    raises the stakes of bacterial lung infection because it causes dysfunction of neutrophils circulated from serum to lung via the metabolite TUDCA. Interventions targeting\n                    <jats:italic>E. lenta<\/jats:italic>\n                    or AMPK phosphorylation may serve as adjunctive strategies to complement existing approaches for managing chronic pulmonary infection in bronchiectasis and other chronic respiratory disease states.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adq4409","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T13:59:56Z","timestamp":1740578396000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":31,"title":["A gut\n                    <i>Eggerthella lenta<\/i>\n                    \u2013derived metabolite impairs neutrophil function to aggravate bacterial lung infection"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7414-1766","authenticated-orcid":true,"given":"Le-Le","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2559-0772","authenticated-orcid":true,"given":"Xiyue","family":"Shen","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7625-0768","authenticated-orcid":true,"given":"Yingzhou","family":"Xie","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4435-8229","authenticated-orcid":true,"given":"Ai","family":"Ge","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Gu","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxin","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-9048","authenticated-orcid":true,"given":"Jayanth Kumar","family":"Narayana","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2254-6664","authenticated-orcid":true,"given":"Jochen","family":"Mattner","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universit\u00e4tsklinikum Erlangen and Friedrich-Alexander-Universit\u00e4t (FAU) Erlangen-N\u00fcrnberg, Erlangen 91054, Germany."},{"name":"FAU Profile Center Immunomedicine (FAU I-MED), FAU Erlangen-N\u00fcrnberg, Erlangen 91054, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-7607","authenticated-orcid":true,"given":"Sanjay H.","family":"Chotirmall","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore."},{"name":"Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore 308433, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8039-8973","authenticated-orcid":true,"given":"Jin-Fu","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai 200433, People\u2019s Republic of China."},{"name":"Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai 200040, People\u2019s Republic of China."},{"name":"Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650032, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2202819"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0049-2024"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.07.010"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31767-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2020.04.007"},{"key":"e_1_3_2_7_2","first-page":"1602","article-title":"A comprehensive analysis of the impact of Pseudomonas aeruginosa colonization on prognosis in adult bronchiectasis","volume":"12","author":"Finch S.","year":"2015","unstructured":"S. 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