斯坦福大学Christoph A. Thaiss小组的一项最新研究开发出了肠道内感受功能障碍驱动与年龄相关的认知衰退。这一研究成果发表在2026年3月11日出版的国际学术期刊《自然》上。

通过绘制小鼠整个生命周期中微生物组衰老及其功能后果的高分辨率图，研究人员确定了衰老过程中肠-脑信号抑制导致海马神经元激活受损和记忆编码丧失的机制。具体来说，产生中链脂肪酸的肠道细菌的积累，如金斯坦副杆菌，可以通过GPR84信号驱动外周髓细胞炎症。其结果是迷走神经传入神经元功能受损，大脑接收的内感受性信号减弱，海马功能下降。

研究人员利用这一途径来确定增强老年小鼠记忆的干预措施，如噬菌体靶向副杆菌，GPR84抑制和迷走神经活动的恢复。这些发现表明了脑衰老过程中内感受功能障碍的关键作用，并表明刺激肠-脑交流的内感受模拟疗法可能会抵消与年龄相关的认知能力下降。

据了解，衰老伴随着记忆功能的衰退，在人群中的表现极不均匀。影响认知衰退的脑外因素，如胃肠道信号，已成为外周干预的有吸引力的目标，但其潜在机制仍不清楚。

附：英文原文

Title: Intestinal interoceptive dysfunction drives age-associated cognitive decline

Author: Cox, Timothy O., Devason, Ashwarya S., de Araujo, Alan, Mason, Sydney, Subramanian, Madhav, Salvador, Andrea F. M., Descamps, Hlne C., Kim, Junwon, Zhu, Yixuan, Litichevskiy, Lev, Jung, Sunhee, Song, Won-Suk, Corts-Martn, Adrin, Henderson, Nathan T., Huang, Kuei-Pin, Nguyen, Thao, Sae-Lee, Wisath, Umana, Iboro C., Sacta, Maria, Rahman, Ryan J., Wisser, Stephen, Nelson, J. Andrew D., Golynker, Ilona, McSween, Alana M., Hohmann, Eric F., Patel, Shaan, Bub, Anna L., Soekler, Clara, Blank, Niklas, Hoxha, Kevther, Boccia, Lavinia, Wong, Andrea C., Bahnsen, Klaas, Kim, Jihee, Biderman, Natalie, Abbasian, Dina, Shoffler, Clarissa, Petucci, Christopher, McAllister, Fiona E., Alhadeff, Amber L., Fuccillo, Marc V., Hill, Colin, Jang, Cholsoon, Betley, J. Nicholas, de Lartigue, Guillaume, Lee, Virginia Y.-M., Levy, Maayan, Thaiss, Christoph A.

Issue&Volume: 2026-03-11

Abstract: Ageing is accompanied by declining memory function, with extremely heterogeneous manifestation in the human population1. Brain-extrinsic factors influencing cognitive decline, such as gastrointestinal signals, have emerged as attractive targets for peripheral interventions2,3,4,5,6, but the underlying mechanisms remain largely unclear. Here, by charting a high-resolution map of microbiome ageing and its functional consequences throughout the lifespan of mice, we identify a mechanism by which inhibition of gut–brain signalling during ageing results in impaired neuronal activation in the hippocampus and loss of memory encoding. Specifically, accumulation of gut bacteria that produce medium-chain fatty acids, such as Parabacteroides goldsteinii, can drive peripheral myeloid cell inflammation through GPR84 signalling. As a result, the function of vagal afferent neurons is impaired, the interoceptive signal received by the brain is weakened and hippocampal function declines. We leverage this pathway to define interventions that enhance memory in aged mice, such as phage targeting of Parabacteroides, GPR84 inhibition and restoration of vagal activity. These findings indicate a key role for interoceptive dysfunction in brain ageing and suggest that interoceptomimetics that stimulate gut–brain communication may counteract age-associated cognitive decline.

DOI: 10.1038/s41586-026-10191-6

Source: https://www.nature.com/articles/s41586-026-10191-6