简单的饮食调整可帮助保护你的大脑免受痴呆症的影响

诸平

A nitrate-rich diet includes foods high in natural nitrates, such as leafy greens (spinach, arugula), beets, and certain fruits, which the body converts into nitric oxide, supporting blood flow and vascular health. According to new research, this diet promotes nitrate-reducing bacteria in the mouth, which may enhance cognitive function by aiding nitric oxide production—key for synaptic plasticity and long-term brain health.

昨天介绍了“胆固醇水平的波动与老年痴呆症风险增加60%有关”今天再来介绍PNAS Nexus2025年1月30日提供的有关消息,简单的饮食调整可帮助保护你的大脑免受痴呆症的影响(This Simple Diet Tweak Could Help Protect Your Brain Against Dementia)。

口腔中的细菌可能在大脑健康中发挥着令人惊讶的作用，可能会影响你随着年龄的增长认知能力的下降。一项新的研究表明，在绿叶蔬菜和地中海饮食中发现的富含硝酸盐的饮食可以支持有益的口腔细菌，这些细菌与提高记忆力和降低痴呆风险有关。(The bacteria in your mouth may play a surprising role in brain health, potentially influencing cognitive decline as you age. A new study suggests that a diet rich in nitrates—found in leafy greens and the Mediterranean diet—could support beneficial oral bacteria linked to better memory and lower dementia risk.)

一项研究表明，随着年龄的增长，我们口腔中的微生物生态系统可能会影响我们的认知功能。像益生元(prebiotics)这样的干预措施，包括饮食中的硝酸盐，可以帮助减缓认知能力的下降。相关研究于2025年1月28日已经在PNAS Nexus杂志网站发表——Joanna E L’Heureux, Anne Corbett, Clive Ballard, David Vauzour, Byron Creese, Paul G Winyard, Andrew M Jones, Anni Vanhatalo. Oral microbiome and nitric oxide biomarkers in older people with mild cognitive impairment and APOE4 genotype. PNAS Nexus, 2025 Jan 28; 4(1): pgae543. DOI: 10.1093/pnasnexus/pgae543. https://pmc.ncbi.nlm.nih.gov/articles/PMC11773611/

参与此项研究的有来自英国埃克塞特大学（Faculty of Health and Life Sciences, University of Exeter Medical School, University of Exeter, St Luke's campus, Exeter EX1 2LU, United Kingdom）、英国东安格利亚大学诺里奇医学院（Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, United Kingdom）、英国布鲁内尔大学（Department of Life Sciences, University of Brunel, London UB8 3PH, United Kingdom）的研究人员。

大约15%的老年人患有轻度认知障碍（mild cognitive impairment简称MCI），这是患痴呆症或阿尔茨海默病（Alzheimer’s disease）的最大危险因素。先前的研究已经建立了牙周炎（periodontitis）——牙龈疾病（gum disease）和认知功能恶化（worsening cognitive function）之间的联系。科学家们已经确定了两种将口腔健康与大脑健康联系起来的潜在途径：

1）口腔致病菌可能进入血液并进入大脑。

2）这些有害细菌可能会胜过硝酸还原细菌（nitrate-reducing bacteria），后者在产生一氧化氮（一种对大脑突触可塑性和长期增强至关重要的化合物）方面发挥关键作用。

口腔微生物组与认知健康的研究（Study on the Oral Microbiome and Cognitive Health）

安妮·瓦哈塔洛（Anni Vanhatalo）及其同事，对115名参与者的口腔微生物群组（oral microbiome）进行了分析，其中55人有轻度认知障碍。一些参与者有载脂蛋白E4 （apolipoprotein E4简称APOE4）等位基因｛apolipoprotein E4 (APOE4) allele｝，这增加了认知能力下降和阿尔茨海默病的风险。在轻度认知障碍组中，奈瑟菌属（genus Neisseria）细菌的相对丰度较高与更好的执行功能和视觉注意力有关。在健康的参与者中，奈瑟菌与工作记忆相关。

卟啉单胞菌属（genus Porphyromonas）细菌的高流行率预测轻度认知障碍状态，而中间普雷沃氏菌（Prevotella）预测APOE4携带者状态（APOE4-carrier status）。根据作者的说法，饮食可以影响口腔微生物群组，而富含硝酸盐的饮食——如地中海饮食（Mediterranean diet）和停止高血压饮食的饮食方法（‘Dietary Approaches to Stop Hypertension’ diet）——有利于与良好认知结果相关的细菌。

本研究是由英国国家卫生和保健研究所（National Institute for Health and Care Research）部分资助的独立研究，作为埃克塞特生物医学研究中心（英国）的一部分｛Exeter Biomedical Research Centre (United Kingdom) (Grant Ref: NIHR203320)｝。它还得到了联合王国西南半岛应用卫生研究和护理领导国家卫生和护理研究合作研究所（National Institute of Health and Care Research Collaboration for Leadership in Applied Health Research and Care South-West Peninsula, United Kingdom）、埃克塞特大学卡洛塔·帕尔默奖学金（University of Exeter Carlotta Palmer studentship）、部分资金来自英国医学研究理事会（Medical Research Council）的“接近发现：行业参与基金”[外部合作、创新和创业精神：埃克塞特的转化医学2 (EXCITEME2)｛Medical Research Council through the Proximity to Discovery: Industry Engagement Fund [External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter 2 (EXCITEME2), ref. MC_PC_17189]｝的支持。本项目使用的设备由惠康信托机构战略支持基金｛Wellcome Trust Institutional Strategic Support Fund (WT097835MF)｝、惠康信托多用户设备奖｛Wellcome Trust Multi User Equipment Award (WT101650MA)｝和生物技术和生物科学研究理事会LOLA奖｛Biotechnology and Biological Sciences Research Council LOLA award (BB/K003240/1)｝资助。

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Abstract

Apolipoprotein E4 (APOE4) genotype and nitric oxide (NO) deficiency are risk factors for age-associated cognitive decline. The oral microbiome plays a critical role in maintaining NO bioavailability during aging. The aim of this study was to assess interactions between the oral microbiome, NO biomarkers, and cognitive function in 60 participants with mild cognitive impairment (MCI) and 60 healthy controls using weighted gene co-occurrence network analysis and to compare the oral microbiomes between APOE4 carriers and noncarriers in a subgroup of 35 MCI participants. Within the MCI group, a high relative abundance of Neisseria was associated with better indices of cognition relating to executive function (Switching Stroop, r_s = 0.33, P = 0.03) and visual attention (Trail Making, r_s = −0.30, P = 0.05), and in the healthy group, Neisseria correlated with working memory (Digit Span, r_s = 0.26, P = 0.04). High abundances of Haemophilus (r_s = 0.38, P = 0.01) and Haemophilus parainfluenzae (r_s = 0.32, P = 0.03), that co-occurred with Neisseria correlated with better scores on executive function (Switching Stroop) in the MCI group. There were no differences in oral nitrate (P = 0.48) or nitrite concentrations (P = 0.84) between the MCI and healthy groups. Linear discriminant analysis Effect Size identified Porphyromonas as a predictor for MCI and Prevotella intermedia as a predictor of APOE4-carrier status. The principal findings of this study were that a greater prevalence of oral P. intermedia is linked to elevated genetic risk for dementia (APOE4 genotype) in individuals with MCI prior to dementia diagnosis and that interventions that promote the oral Neisseria–Haemophilus and suppress Prevotella-dominated modules have potential for delaying cognitive decline.

Significance Statement

Cognition typically declines during aging and mild cognitive impairment (MCI) may progress to the development of Alzheimer's disease (AD). Periodontal disease-causing bacteria have been linked to worsened cognitive function during aging and the development of AD, which may involve dysfunction of the nitrate–nitrite–nitric oxide pathway. We found that the oral Porphyromonas genus was associated with MCI and that the abundance of Prevotella intermedia was a predictor of apolipoprotein E4–carrier status. The balance between two metabolic pathways for oral nitrate reduction, denitrification, and dissimilatory nitrate reduction to ammonia (DNRA) was skewed toward DNRA in MCI. These findings have significant implications for understanding preclinical cognitive risk states and how cognitive decline could be delayed or prevented using prebiotic interventions.