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 language | English |
|---|---|
| Article number | e12980 |
| Number of pages | 13 |
| Journal | Aging Cell |
| Volume | 18 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1 Oct 2019 |
Keywords
- aging
- bacteria
- colon
- infection
- stroke
Cite this
}
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, Vol. 18, No. 5, e12980, 01.10.2019.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke
AU - Wen, Shu Wen
AU - Shim, Ray
AU - Ho, Luke
AU - Wanrooy, Brooke John
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
PY - 2019/10/1
Y1 - 2019/10/1
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.
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.
KW - aging
KW - bacteria
KW - colon
KW - infection
KW - stroke
UR - http://www.scopus.com/inward/record.url?scp=85071665661&partnerID=8YFLogxK
U2 - 10.1111/acel.12980
DO - 10.1111/acel.12980
M3 - Article
C2 - 31199577
AN - SCOPUS:85071665661
VL - 18
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 5
M1 - e12980
ER -