{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:18:25Z","timestamp":1772979505673,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANPCyT\u2013FONCyT","award":["PICT-2016-0410"],"award-info":[{"award-number":["PICT-2016-0410"]}]},{"name":"ANPCyT\u2013FONCyT","award":["PICT 2021-I-A-00705"],"award-info":[{"award-number":["PICT 2021-I-A-00705"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["23H00354"],"award-info":[{"award-number":["23H00354"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["23K18072"],"award-info":[{"award-number":["23K18072"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["25K22412"],"award-info":[{"award-number":["25K22412"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007173","name":"Bio-oriented Technology Research Advancement Institution","doi-asserted-by":"crossref","award":["JPJ007097"],"award-info":[{"award-number":["JPJ007097"]}],"id":[{"id":"10.13039\/501100007173","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"crossref","award":["JP21zf0127001"],"award-info":[{"award-number":["JP21zf0127001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Background: Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut\u2013lung axis and improve respiratory innate immunity in a mouse model of Streptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) were orally administered to Swiss mice prior to pneumococcal challenge. The resistance to the infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads, prevented bacteremia, and attenuated lung injury. This protective effect was associated with selective modulation of respiratory immunity, characterized by reduced neutrophilic inflammation, increased lymphocyte recruitment, and enhanced activation of alveolar macrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-\u03b2, IFN-\u03b3, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages from LAFF998-treated mice exhibited a primed phenotype with heightened cytokine responses to pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to confer protection or significantly modulate respiratory immune responses. Conclusions: These findings demonstrate a strict strain-dependent effect among porcine L. salivarius isolates and identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innate immunity through the gut\u2013lung axis. This work supports further studies of LAFF998 as an immunobiotic strategy for the prevention of respiratory infections in pigs.<\/jats:p>","DOI":"10.3390\/ani16050825","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T13:00:02Z","timestamp":1772802002000},"page":"825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae"],"prefix":"10.3390","volume":"16","author":[{"given":"Kohtaro","family":"Fukuyama","sequence":"first","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solange","family":"Cisterna-Vergara","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Laboratory of Respiratory Immunology (LaRI), Division of Animal Immunology and Omics, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3862-4586","authenticated-orcid":false,"given":"Ayelen Antonella","family":"Baillo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman T4000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Lorenzo Pisarello","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman T4000, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weichen","family":"Gong","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-4960","authenticated-orcid":false,"given":"Julio","family":"Villena","sequence":"additional","affiliation":[{"name":"Laboratory of Respiratory Immunology (LaRI), Division of Animal Immunology and Omics, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4586-5553","authenticated-orcid":false,"given":"Haruki","family":"Kitazawa","sequence":"additional","affiliation":[{"name":"Food and Feed Immunology Group, Laboratory of Animal Food Function, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"},{"name":"Livestock Immunology Unit, International Education and Research Centre for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"V\u00f6tsch, D., Willenborg, M., Weldearegay, Y.B., and Valentin-Weigand, P. 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