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Yet, butyrate has limited potential for clinical use due to its challenging handling in practice. We performed mouse experiments and translational analyses to determine whether butyrate-producing gut commensals,\n                      <jats:italic>Faecalibacterium prausnitzii<\/jats:italic>\n                      and\n                      <jats:italic>Anaerobutyricum soehngenii<\/jats:italic>\n                      , could provide protection against bacterial pneumonia and serve as next-generation probiotics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We pre-treated C57BL\/6J mice with butyrate,\n                      <jats:italic>F. prausnitzii<\/jats:italic>\n                      (recently reclassified as\n                      <jats:italic>F. duncaniae<\/jats:italic>\n                      ) or\n                      <jats:italic>A. soehngenii<\/jats:italic>\n                      , and subsequently infected them intranasally with\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      . To assess the relevance in humans, we assessed associations between rectal levels of\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      , immune responses and clinical outcomes in 115 patients with community-acquired pneumonia (CAP) and in a separate validation cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pre-treatment with\n                      <jats:italic>F. prausnitzii<\/jats:italic>\n                      , but not\n                      <jats:italic>A. soehngenii<\/jats:italic>\n                      , protected mice against bacterial pneumonia, as reflected by reduced bacterial growth and dissemination, lessened organ damage, and dampened inflammation. Similar to butyrate pre-treatment,\n                      <jats:italic>F. prausnitzii<\/jats:italic>\n                      resulted in reduced pulmonary interleukin (IL)-6 and CXCL1. In humans, gut\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      was decreased during CAP compared to matched controls. CAP patients with higher gut\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      levels had lower IL-6-producing capacity and downregulated inflammatory gene expression. Higher intestinal\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      levels were associated with better clinical outcomes in independent cohorts of CAP and critically ill patients, which remained significant when controlled for potential confounders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This is the first study showing that the gut commensal\n                      <jats:italic>F. prausnitzii<\/jats:italic>\n                      provides protection against bacterial pneumonia and has translational potential. This motivates future studies investigating the clinical potential of\n                      <jats:italic>F. prausnitzii<\/jats:italic>\n                      as a novel probiotic for pneumonia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.02208-2024","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T15:50:20Z","timestamp":1754581820000},"page":"2402208","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Butyrate-producing gut bacterium\n                    <i>Faecalibacterium prausnitzii<\/i>\n                    protects against bacterial pneumonia"],"prefix":"10.1183","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-9887","authenticated-orcid":false,"given":"Robert F.J.","family":"Kullberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine C.A.","family":"van Linge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex F.","family":"de Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xanthe","family":"Brands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Phuong Nam","family":"Bui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6781-6408","authenticated-orcid":false,"given":"Joe M.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00ebl R.","family":"Faber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aswin","family":"Verhoeven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 M.","family":"van den Wijngaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter J.","family":"de Jonge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan W.","family":"Haak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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