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

Wen, SW; Shim, R; Ho, L; Wanrooy, BJ; Srikhanta, YN; Prame Kumar, K; Nicholls, AJ; Shen, SJ; Sepehrizadeh, T; de Veer, M; Srikanth, VK; Ma, H; Phan, TG; Lyras, D; Wong, CHY

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

Wen, SW Shim, R Ho, L Wanrooy, BJ Srikhanta, YN Prame Kumar, K Nicholls, AJ Shen, SJ

Sepehrizadeh, T de Veer, M Srikanth, VK Ma, H Phan, TG Lyras, D Wong, CHY

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Publication Type:: Journal Article
Citation:: Aging Cell, 2019, 18 (5)
Issue Date:: 2019-10-01

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Field	Value	Language
dc.contributor.author	Wen, SW	en_US
dc.contributor.author	Shim, R	en_US
dc.contributor.author	Ho, L	en_US
dc.contributor.author	Wanrooy, BJ	en_US
dc.contributor.author	Srikhanta, YN	en_US
dc.contributor.author	Prame Kumar, K	en_US
dc.contributor.author	Nicholls, AJ	en_US
dc.contributor.author	Shen, SJ https://orcid.org/0000-0002-1004-1936	en_US
dc.contributor.author	Sepehrizadeh, T	en_US
dc.contributor.author	de Veer, M	en_US
dc.contributor.author	Srikanth, VK	en_US
dc.contributor.author	Ma, H	en_US
dc.contributor.author	Phan, TG	en_US
dc.contributor.author	Lyras, D	en_US
dc.contributor.author	Wong, CHY	en_US
dc.date.available	2019-05-12	en_US
dc.date.issued	2019-10-01	en_US
dc.identifier.citation	Aging Cell, 2019, 18 (5)	en_US
dc.identifier.issn	1474-9718	en_US
dc.identifier.uri	http://hdl.handle.net/10453/136357
dc.description.abstract	© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. 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.	en_US
dc.relation.ispartof	Aging Cell	en_US
dc.relation.isbasedon	10.1111/acel.12980	en_US
dc.subject.classification	Developmental Biology	en_US
dc.title	Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.citation.volume	18	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	5	en_US
pubs.publication-status	Published	en_US
pubs.volume	18	en_US

Abstract:

© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. 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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http://hdl.handle.net/10453/136357