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Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke.

Abstract

Bacterial infection a leading cause of death among patients with stroke, with elderly patients often presenting with more debilitating outcomes. The findings from our retrospective study, supported by previous clinical reports, showed that increasing age is an early predictor for developing fatal infectious complications after stroke. However, exactly how and why older individuals are more susceptible to infection after stroke remains unclear. Using a mouse model of transient ischaemic stroke, we demonstrate that older mice (>12 months) present with greater spontaneous bacterial lung infections compared to their younger counterparts (7-10 weeks) after stroke. Importantly, we provide evidence that older poststroke mice exhibited elevated intestinal inflammation and disruption in gut barriers critical in maintaining colonic integrity following stroke, including reduced expression of mucin and tight junction proteins. In addition, our data support the notion that the localized pro-inflammatory microenvironment driven by increased tumour necrosis factor-α production in the colon of older mice facilitates the translocation and dissemination of orally inoculated bacteria to the lung following stroke onset. Therefore, findings of this study demonstrate that exacerbated dysfunction of the intestinal barrier in advanced age promotes translocation of gut-derived bacteria and contributes to the increased risk to poststroke bacterial infection.

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  • Authors+Show Affiliations

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia. Department of Medicine (Academic Unit), Peninsula Clinical School, Central Clinical School, Monash University, Frankston, Victoria, Australia.

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

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    Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

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    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

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    Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.

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    Monash Biomedical Imaging, Monash University, Clayton, Victoria, Australia.

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    Department of Medicine (Academic Unit), Peninsula Clinical School, Central Clinical School, Monash University, Frankston, Victoria, Australia.

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    Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.

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    Stroke and Ageing Research Group, Department of Medicine, School of Clinical Sciences, Monash Medical Centre, Monash University, Clayton, Victoria, Australia.

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    Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.

    Department of Medicine, Centre for Inflammatory Diseases, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.

    Source

    Aging cell : 2019 Jun 14 pg e12980

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31199577

    Citation

    Wen, Shu Wen, et al. "Advanced Age Promotes Colonic Dysfunction and Gut-derived Lung Infection After Stroke." Aging Cell, 2019, pp. e12980.
    Wen SW, Shim R, Ho L, et al. Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke. Aging Cell. 2019.
    Wen, S. W., Shim, R., Ho, L., Wanrooy, B. J., Srikhanta, Y. N., Prame Kumar, K., ... Wong, C. H. Y. (2019). Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke. Aging Cell, pp. e12980. doi:10.1111/acel.12980.
    Wen SW, et al. Advanced Age Promotes Colonic Dysfunction and Gut-derived Lung Infection After Stroke. Aging Cell. 2019 Jun 14;e12980. PubMed PMID: 31199577.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke. AU - Wen,Shu Wen, AU - Shim,Raymond, AU - Ho,Luke, AU - Wanrooy,Brooke J, AU - Srikhanta,Yogitha N, AU - Prame Kumar,Kathryn, AU - Nicholls,Alyce J, AU - Shen,S J, AU - Sepehrizadeh,Tara, AU - de Veer,Michael, AU - Srikanth,Velandai K, AU - Ma,Henry, AU - Phan,Thanh G, AU - Lyras,Dena, AU - Wong,Connie H Y, Y1 - 2019/06/14/ PY - 2019/02/06/received PY - 2019/04/16/revised PY - 2019/05/12/accepted PY - 2019/6/15/entrez KW - aging KW - bacteria KW - colon KW - infection KW - stroke SP - e12980 EP - e12980 JF - Aging cell JO - Aging Cell N2 - Bacterial infection a leading cause of death among patients with stroke, with elderly patients often presenting with more debilitating outcomes. The findings from our retrospective study, supported by previous clinical reports, showed that increasing age is an early predictor for developing fatal infectious complications after stroke. However, exactly how and why older individuals are more susceptible to infection after stroke remains unclear. Using a mouse model of transient ischaemic stroke, we demonstrate that older mice (>12 months) present with greater spontaneous bacterial lung infections compared to their younger counterparts (7-10 weeks) after stroke. Importantly, we provide evidence that older poststroke mice exhibited elevated intestinal inflammation and disruption in gut barriers critical in maintaining colonic integrity following stroke, including reduced expression of mucin and tight junction proteins. In addition, our data support the notion that the localized pro-inflammatory microenvironment driven by increased tumour necrosis factor-α production in the colon of older mice facilitates the translocation and dissemination of orally inoculated bacteria to the lung following stroke onset. Therefore, findings of this study demonstrate that exacerbated dysfunction of the intestinal barrier in advanced age promotes translocation of gut-derived bacteria and contributes to the increased risk to poststroke bacterial infection. SN - 1474-9726 UR - https://www.unboundmedicine.com/medline/citation/31199577/Advanced_age_promotes_colonic_dysfunction_and_gut-derived_lung_infection_after_stroke L2 - https://doi.org/10.1111/acel.12980 DB - PRIME DP - Unbound Medicine ER -