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

Laura Díaz-Marugan, Mattia Gallizioli, Leonardo Márquez-Kisinousky, Silvia Arboleya, Annalaura Mastrangelo, Francisca Ruiz-Jaén, Jordi Pedragosa, Climent Casals, Francisco Javier Morales, Sara Ramos-Romero, Sara Traserra, Carles Justicia, Miguel Gueimonde, Marcel Jiménez, Josep Lluís Torres, Xabier Urra, Ángel Chamorro, David Sancho, Clara G. De Los Reyes-Gavilán, Francesc Miró-MurAnna M. Planas*

*Autor corresponent d’aquest treball

Producció científica: Contribució a una revistaArticleRecercaAvaluat per experts

9 Cites (Scopus)

Resum

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.
Idioma originalEnglish
Pàgines (de-a)1875-1887
Nombre de pàgines13
RevistaStroke
Volum54
Número7
DOIs
Estat de la publicacióPublicada - de jul. 2023

Fingerprint

Navegar pels temes de recerca de 'Poststroke Lung Infection by Opportunistic Commensal Bacteria Is Not Mediated by Their Expansion in the Gut Microbiota'. Junts formen un fingerprint únic.

Com citar-ho