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Gut dysbiosis and systemic inflammation in elderly hypertensive patients with amnestic mild cognitive impairment
Zongxin Ling1, Yiwen Cheng1, Xiaocui Xu2
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Introduction:
Gut microbial dysbiosis has been linked to both high blood pressure and neurodegeneration, but its involvement in hypertensive patients with amnestic mild cognitive impairment (aMCI) has not been well characterized in this specific population.
Methods:
In this cross-sectional investigation, we enrolled 205 older Chinese adults: 52 healthy controls, 83 hypertensive individuals with normal cognition (HTN-CN), and 70 hypertensive subjects with aMCI (HTN-aMCI). Gut microbiota composition was profiled by 16S rRNA sequencing, and serum levels of 27 inflammatory mediators were quantified by multiplex immunoassay.
Results:
Compared to the HTN-CN and control groups, the HTN-aMCI group showed not only a greater richness of gut microbes but also a markedly segregated microbial community structure. The HTN-aMCI microbiota was characterized by significant depletion of short-chain fatty acid (SCFA)-producing genera (Roseburia, Blautia, Faecalibacterium) and enrichment of opportunistic pathogens (Streptococcus, Clostridium_sensu_stricto_1, Enterococcus). Co-occurrence network analysis revealed disrupted microbial interactions in HTN-aMCI, and functional prediction showed enhanced lipopolysaccharide biosynthesis and reduced SCFA metabolism. HTN-aMCI patients had elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, IP-10, RANTES). Notably, after FDR correction, Blautia abundance correlated negatively with inflammatory markers and positively with cognitive scores, whereas pathobionts showed opposite patterns (all q < 0.05).
Discussion:
These findings indicate that hypertensive individuals with aMCI harbor a specific gut microbial dysbiosis marked by loss of SCFA producers, expansion of pathobionts, and disrupted microbial networks, which together associate with systemic inflammation and cognitive decline. Our results support the notion that targeting gut microbiota might represent a potential therapeutic avenue for hypertension-related cognitive impairment.
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