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

Area of Science:

• Neuroscience
• Immunology
• Gastroenterology

Background:

• Bacterial infections are a major cause of death in stroke patients, with older individuals experiencing worse outcomes.
• Increasing age is a known predictor of fatal infectious complications following stroke.
• The precise mechanisms underlying increased infection susceptibility in older post-stroke patients remain largely unknown.

Purpose of the Study:

• To investigate the mechanisms contributing to increased susceptibility to bacterial infections in older individuals after stroke.
• To explore the role of intestinal inflammation and gut barrier integrity in post-stroke infections.

Main Methods:

• Utilized a mouse model of transient ischemic stroke.
• Compared bacterial lung infections in older (>12 months) versus younger (7-10 weeks) mice post-stroke.
• Assessed intestinal inflammation, gut barrier integrity (mucin and tight junction proteins), and tumor necrosis factor-alpha (TNF-α) levels in the colon.

Main Results:

• Older mice exhibited significantly higher rates of spontaneous bacterial lung infections after stroke compared to younger mice.
• Older post-stroke mice displayed increased intestinal inflammation and compromised gut barrier function, evidenced by reduced mucin and tight junction protein expression.
• Elevated TNF-α production in the colon of older mice correlated with bacterial translocation from the gut to the lungs.

Conclusions:

• Advanced age exacerbates intestinal barrier dysfunction following stroke.
• This dysfunction promotes the translocation of gut-derived bacteria, increasing the risk of severe bacterial infections in older post-stroke patients.
• Targeting gut inflammation and barrier integrity may offer therapeutic strategies to reduce infectious complications in elderly stroke survivors.