一项发表于《Nature Communications》的研究由约翰·克瑞安（John Cryan）与APC Microbiome Ireland（爱尔兰科克大学附设研究中心）团队执行，聚焦咖啡如何透过肠脑轴影响健康。研究比较31位规律饮用者与31位不饮者，欧盟食品安全局（EFSA）将每日3到5杯界定为一般安全且中等摄取量，实验设计还加入「停喝2周后再重启饮用」条件，且重启时分为含咖啡因与脱咖啡因两组，以区分咖啡因与其他化学成分的作用。作者指出结果显示咖啡效应远超越单一刺激作用，且可透过复合途径同时影响肠道微生物、代谢及情绪表征。
研究发现常规饮用者的肠道菌群组成显著改变，尤其是 Eggerthella 与 Cryptobacterium curtum 的比例上升；前者与胃肠酸分泌相关，后者参与胆汁酸合成，均被诠释为有助于清除有害肠道菌、降低感染风险的方向。行为层面上，规律饮咖啡者的冲动性与情绪反应性高于未饮者，但停喝2周后，这两项指标下降，并且与停滞初期常见的疲劳、头痛等症状同步减弱，呈现可逆趋势。
研究关键在于重建期的对照结果：含咖啡因与脱咖啡因均可降低自觉压力与部分忧郁指标；但含咖啡因更显著改善焦虑与部分注意力，脱咖啡因则对记忆、睡眠品质与体能活动度有较明显帮助。这些结果支持除咖啡因外，还有多酚等生物活性成分参与调节，且至少部分效应与微生物与代谢改变无关。免疫层面，饮用者在研究期内表现出较低发炎标记与较高抗发炎分子；在停喝2周时，发炎标记上升。皮质醇未见显著生理性差异，显示至少在一般条件下咖啡对客观压力反应影响有限，但主观压力感受会改变。
A study in Nature Communications led by John Cryan at APC Microbiome Ireland examined how coffee affects the gut-brain axis, metabolism, and mood beyond simple stimulation. It compared 31 regular coffee drinkers with 31 non-drinkers. EFSA defines moderate use as 3 to 5 cups per day for most adults. The design used a withdrawal and reintroduction phase: participants stopped drinking coffee for 2 weeks, then resumed with either caffeinated or decaffeinated coffee, allowing caffeine-specific effects to be separated from non-caffeine components.
The study found that regular coffee intake altered intestinal microbiome composition, including higher abundances of Eggerthella and Cryptobacterium curtum. These taxa are linked to gastric/intestinal acid processes and bile-acid synthesis, and were described as potentially helping remove harmful gut bacteria and reduce infection risk. Behaviorally, regular drinkers showed more impulsiveness and emotional reactivity than non-drinkers, yet these traits decreased after 2 weeks of abstinence. Withdrawal also reduced some early symptoms associated with regular use, such as fatigue and headache.
On reintroduction, both caffeinated and decaffeinated coffee reduced perceived stress and certain depression indicators. Caffeinated coffee was associated with improvements in anxiety and some attention measures, whereas decaffeinated coffee was linked to benefits in memory, sleep quality, and physical activity, supporting non-caffeine biological activity likely driven by compounds such as polyphenols. Coffee consumers had lower inflammatory markers and higher anti-inflammatory molecules, while some inflammatory markers rose during abstinence, suggesting a protective effect. No meaningful differences in cortisol were observed between consumers and non-consumers, implying limited physiological stress-response change under normal conditions despite changes in perceived stress. (Key numbers: 2)