Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.
Faecal metabolite deficit, gut inflammation and diet in Parkinson's disease: Integrative analysis indicates inflammatory response syndrome.
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DOI：
10.1002/ctm2.1152
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发表时间：
2023-01
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
肠-脑轴在帕金森病（PD）的病理生理学中广泛涉及。我们采用一种综合方法，将肠道视为疾病修饰干预的靶点，对疾病的各个方面进行持续测量，而不考虑诊断界限。
我们通过饮食/外源性物质摄入、粪便代谢组、肠道炎症、血清细胞因子/趋化因子以及包括结肠转运时间在内的临床表型，对77名确诊为帕金森病的参与者和113名未患病者进行了特征描述。对可区分帕金森病状态的代谢物进行了完全连锁层次聚类分析。
在帕金森病患者之外，较长的结肠转运时间与粪便短链脂肪酸的缺乏有关，总体上与一个“含色氨酸的代谢物簇”有关。表型聚类分析将结肠转运与运动迟缓/运动减少、震颤、睡眠障碍和嗅觉障碍归为一类，每一种都单独与色氨酸簇缺乏有关。总体而言，脉搏较快与一个包括苯甲酸和一种咪唑环化合物（抗真菌药）以及维生素B3（抗炎药）的代谢物簇缺乏有关，并且与较高的血清CCL20（对淋巴细胞/树突状细胞向黏膜上皮的趋化作用）有关。帕金森病患者脉搏较快与体位性低血压无关。苯甲酸簇缺乏与（公认的）较低的咖啡因和酒精摄入量有关，色氨酸簇缺乏与较高的麦芽糖摄入量有关。帕金森病患者的游离糖摄入量增加，麦芽糖摄入量高出63%（p = 0.001）。帕金森病患者的粪便钙卫蛋白高出44%（95%置信区间为5%，98%）[p = 0.001，经质子泵抑制剂调整后（p = 0.001）]，16%的帕金森病先证者超过了与炎症性肠病相符的具有临床意义的炎症临界值。较高的麦芽糖摄入量与超过该钙卫蛋白临界值有关。
逐渐呈现的情况是：（i）临床表型由对肠道健康至关重要的微生物代谢物缺乏来描述；（ii）肠道炎症；（iii）全身炎症反应综合征。
帕金森病患者肠道炎症的一个标志物高出44%，16%的患者超过了炎症性肠病的临界值。它与较高的麦芽糖和蔗糖摄入量有关。逐渐呈现的情况是肠道炎症导致的全身炎症反应，临床表型由对肠道健康至关重要的粪便代谢物缺乏来描述。
Gut‐brain axis is widely implicated in the pathophysiology of Parkinson's disease (PD). We take an integrated approach to considering the gut as a target for disease‐modifying intervention, using continuous measurements of disease facets irrespective of diagnostic divide. We characterised 77 participants with diagnosed‐PD, 113 without, by dietary/exogenous substance intake, faecal metabolome, intestinal inflammation, serum cytokines/chemokines, clinical phenotype including colonic transit time. Complete‐linkage hierarchical cluster analysis of metabolites discriminant for PD‐status was performed. Longer colonic transit was linked to deficits in faecal short‐chain‐fatty acids outside PD, to a ‘tryptophan‐containing metabolite cluster’ overall. Phenotypic cluster analysis aggregated colonic transit with brady/hypokinesia, tremor, sleep disorder and dysosmia, each individually associated with tryptophan‐cluster deficit. Overall, a faster pulse was associated with deficits in a metabolite cluster including benzoic acid and an imidazole‐ring compound (anti‐fungals) and vitamin B3 (anti‐inflammatory) and with higher serum CCL20 (chemotactic for lymphocytes/dendritic cells towards mucosal epithelium). The faster pulse in PD was irrespective of postural hypotension. The benzoic acid‐cluster deficit was linked to (well‐recognised) lower caffeine and alcohol intakes, tryptophan‐cluster deficit to higher maltose intake. Free‐sugar intake was increased in PD, maltose intake being 63% higher (p = .001). Faecal calprotectin was 44% (95% CI 5%, 98%) greater in PD [p = .001, adjusted for proton‐pump inhibitors (p = .001)], with 16% of PD‐probands exceeding a cut‐point for clinically significant inflammation compatible with inflammatory bowel disease. Higher maltose intake was associated with exceeding this calprotectin cut‐point. Emerging picture is of (i) clinical phenotype being described by deficits in microbial metabolites essential to gut health; (ii) intestinal inflammation; (iii) a systemic inflammatory response syndrome. A marker of intestinal inflammation was 44% greater in Parkinson's disease, exceeding a cut‐point for inflammatory bowel disease in 16%. It was associated with a higher maltose and sucrose intake. The emerging picture is of systemic inflammatory response consequent on intestinal inflammation, clinical phenotype being described by deficits in faecal metabolites essential to gut health.
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影响因子：
4.4
作者：
Dobbs, Sylvia M.;Charlett, Andre;Bjarnason, Ingvar
通讯作者：
Bjarnason, Ingvar
DOI：
10.1042/cs0560089
发表时间：
1979-01-01
期刊：
CLINICAL SCIENCE AND MOLECULAR MEDICINE
影响因子：
--
作者：
BENDER, DA;EARL, CJ;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
15.1
作者：
Aho VTE;Houser MC;Pereira PAB;Chang J;Rudi K;Paulin L;Hertzberg V;Auvinen P;Tansey MG;Scheperjans F
通讯作者：
Scheperjans F
DOI：
10.1152/ajpregu.00442.2002
发表时间：
2003-05-01
影响因子：
2.8
作者：
Fukumoto, S;Tatewaki, M;Takahashi, T
通讯作者：
Takahashi, T
影响因子：
3.2
作者：
Dobbs SM;Dobbs RJ;Weller C;Charlett A;Augustin A;Taylor D;Ibrahim MA;Bjarnason I
通讯作者：
Bjarnason I