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

Shu Wen Wen, Ray Shim, Luke Ho, Brooke John Wanrooy, Yogi Srikhanta, Kathryn Prame Kumar, Alyce J Nicholls, Sj Shen, Tara Sepehrizadeh, Michael De Veer, Velandai Srikanth, Henry Ma, Thanh Phan, Dena Lyras, Connie Wong

Research output: Contribution to journalArticleResearchpeer-review

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
Original languageEnglish
Number of pages13
JournalAging Cell
DOIs
Publication statusAccepted/In press - Jul 2019

Cite this

Wen, Shu Wen ; Shim, Ray ; Ho, Luke ; Wanrooy, Brooke John ; Srikhanta, Yogi ; Prame Kumar, Kathryn ; Nicholls, Alyce J ; Shen, Sj ; Sepehrizadeh, Tara ; De Veer, Michael ; Srikanth, Velandai ; Ma, Henry ; Phan, Thanh ; Lyras, Dena ; Wong, Connie. / Advanced age promotes colonic dysfunction and gut‐derived lung infection after stroke. In: Aging Cell. 2019.
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title = "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",
author = "Wen, {Shu Wen} and Ray Shim and Luke Ho and Wanrooy, {Brooke John} and Yogi Srikhanta and {Prame Kumar}, Kathryn and Nicholls, {Alyce J} and Sj Shen and Tara Sepehrizadeh and {De Veer}, Michael and Velandai Srikanth and Henry Ma and Thanh Phan and Dena Lyras and Connie Wong",
year = "2019",
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issn = "1474-9718",
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Advanced age promotes colonic dysfunction and gut‐derived lung infection after stroke. / Wen, Shu Wen; Shim, Ray; Ho, Luke; Wanrooy, Brooke John; Srikhanta, Yogi; Prame Kumar, Kathryn; Nicholls, Alyce J; Shen, Sj; Sepehrizadeh, Tara; De Veer, Michael; Srikanth, Velandai; Ma, Henry; Phan, Thanh; Lyras, Dena; Wong, Connie.

In: Aging Cell, 07.2019.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wen, Shu Wen

AU - Shim, Ray

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AU - Srikhanta, Yogi

AU - Prame Kumar, Kathryn

AU - Nicholls, Alyce J

AU - Shen, Sj

AU - Sepehrizadeh, Tara

AU - De Veer, Michael

AU - Srikanth, Velandai

AU - Ma, Henry

AU - Phan, Thanh

AU - Lyras, Dena

AU - Wong, Connie

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AB - 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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