Bordeaux Population Health Research Center, University of Bordeaux, INSERMUMR 1219, F-33000 Bordeaux, France.
Nutrition, Food Science and Gastronomy Department, Food Innovation Network (XIA), Institute of Nutrition and Food Safety (INSA-UB), Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain.
Nutrients. 2022 Nov 5;14(21):4688. doi: 10.3390/nu14214688.
The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut−brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case−control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r > 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.
肠道微生物群参与营养代谢，并产生代谢物，这些代谢物通过肠-脑轴向大脑发出信号，影响认知。人类研究迄今为止在识别与认知衰老相关的早期代谢变化方面取得的成功有限，这可能是由于代谢物覆盖范围或随访的限制。本研究纳入了来自三城人群为基础的队列中的老年人，他们在采血时尚未被诊断为痴呆症，并在随后的 12 年内重复进行认知测量。在一项针对认知衰退的病例对照研究中，我们使用靶向代谢组学平台在队列中鉴定了 72 种循环肠道衍生代谢物（发现组 n = 418；验证组 n = 420）。短链脂肪酸丙酸的血清水平较高与认知能力下降的几率增加相关（发现组中 1SD 的 OR = 1.40（95%CI 1.11, 1.75），验证组中为 1.26（1.02, 1.55））。进一步的分析表明，这种关联可能是通过高胆固醇血症和糖尿病来介导的。丙酸与血糖（r = 0.79）和肉类及奶酪的摄入量（r > 0.15）强烈相关，但与膳食纤维（r = 0.04）相关性较低，这表明益生菌食品本身的作用较小，但与加工食品可能存在关联，因为丙酸是一种常见的防腐剂。丙酸对代谢和认知的不利影响值得进一步研究。
