Poststroke Lung Infection by Opportunistic Commensal Bacteria Is Not Mediated by Their Expansion in the Gut Microbiota.

Autor:	Díaz-Marugan L; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.).; Departament de Medicina, Facultat de Medicina (L.D.-M.), Universitat de Barcelona, Spain., Gallizioli M; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.)., Márquez-Kisinousky L; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain., Arboleya S; Instituto de Productos Lácteos de Asturias (IPLA-CSIC), CSIC, Villaviciosa, Spain (S.A., M. Gueimonde, C.G.d.l.R.-G.).; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011, Oviedo, Spain (S.A., M. Gueimonde, C.G.d.l.R.-G.)., Mastrangelo A; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.M., D.S.)., Ruiz-Jaén F; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.)., Pedragosa J; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.)., Casals C; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.).; Servei de Microbiología, Hospital Clínic, Barcelona, Spain (C.C., F.J.M.)., Morales FJ; Servei de Microbiología, Hospital Clínic, Barcelona, Spain (C.C., F.J.M.)., Ramos-Romero S; Institut de Química Avançada de Catalunya (IQAC) (S.R.-R., J.L.T.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Now with Facultat de Biologia (S.R.-R.), Universitat de Barcelona, Spain., Traserra S; Departament de Biologia Cel.lular, Fisiologia i Inmunologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain (S.T., M.J.)., Justicia C; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.)., Gueimonde M; Instituto de Productos Lácteos de Asturias (IPLA-CSIC), CSIC, Villaviciosa, Spain (S.A., M. Gueimonde, C.G.d.l.R.-G.).; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011, Oviedo, Spain (S.A., M. Gueimonde, C.G.d.l.R.-G.)., Jiménez M; Departament de Biologia Cel.lular, Fisiologia i Inmunologia, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Spain (S.T., M.J.)., Torres JL; Institut de Química Avançada de Catalunya (IQAC) (S.R.-R., J.L.T.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain., Urra X; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.).; Unitat Funcional de Patología Vascular Cerebral, Hospital Clínic, Barcelona, Spain (X.U., A.C.)., Chamorro Á; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.).; Unitat Funcional de Patología Vascular Cerebral, Hospital Clínic, Barcelona, Spain (X.U., A.C.)., Sancho D; Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (A.M., D.S.)., de Los Reyes-Gavilán CG; Instituto de Productos Lácteos de Asturias (IPLA-CSIC), CSIC, Villaviciosa, Spain (S.A., M. Gueimonde, C.G.d.l.R.-G.).; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011, Oviedo, Spain (S.A., M. Gueimonde, C.G.d.l.R.-G.)., Miró-Mur F; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.).; Now with Vall d'Hebron Institut de Recerca, Barcelona, Spain (F.M.-M.)., Planas AM; Instituto de Investigaciones Biomédicas de Barcelona (IIBB) (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.J., A.M.P.), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (L.D.-M., M. Gallizioli, L.M.-K., F.R.-J., J.P., C.C., C.J., X.U., A.C., F.M.-M., A.M.P.).
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2023 Jul; Vol. 54 (7), pp. 1875-1887. Date of Electronic Publication: 2023 May 25.
DOI:	10.1161/STROKEAHA.123.042755
Abstrakt:	Background: Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection. Methods: Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments. Results: Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae. Conclusions: Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection. Competing Interests: Disclosures None.
Databáze:	MEDLINE
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