德国汉堡-埃彭多夫大学Nicola Gagliani研究组发现短期饮食变化会导致粘膜和系统性免疫功能下降。相关论文于2023年8月14日发表在《自然—免疫学》杂志上。

他们表明短期反复切换到“盛宴饮食”，模仿人类社会饮食行为，破坏了肠道微生物群的潜在缓冲作用，重组了粘膜相关淋巴组织的免疫结构。第一次饮食转换足以诱导短暂的粘膜免疫抑制和全身免疫抑制，导致对肠沙门氏菌、血清型鼠伤寒沙门氏菌和单核增生李斯特菌感染的易感性增加。用模型抗原应答抗原挑战的能力也受损。

这些观察结果可以解释为，由于纤维代谢物的微生物供应减少，mTOR活性受损，导致CD4+ T细胞代谢适应度和细胞因子产生减少。重新引入膳食纤维可以重新连接T细胞代谢，恢复粘膜和全身CD4+ T细胞功能和免疫力。最后，对人类志愿者的饮食干预证实了短期饮食改变对人类CD4+ T细胞功能的影响。因此，短期的营养变化会引起黏膜和全身免疫的短暂抑制，为致病性感染创造机会。

据介绍，杂食性动物，包括老鼠和人类，倾向于更喜欢富含脂肪的能量密集营养素，而不是植物性饮食，特别是在短期内，但这种短期消耗能量密集营养素的健康预后尚不清楚。

附：英文原文

Title: Short-term dietary changes can result in mucosal and systemic immune depression

Author: Siracusa, Francesco, Schaltenberg, Nicola, Kumar, Yogesh, Lesker, Till R., Steglich, Babett, Liwinski, Timur, Cortesi, Filippo, Frommann, Laura, Diercks, Bjrn-Phillip, Bnisch, Friedericke, Fischer, Alexander W., Scognamiglio, Pasquale, Pauly, Mira J., Casar, Christian, Cohen, Yotam, Pelczar, Penelope, Agalioti, Theodora, Delfs, Flemming, Worthmann, Anna, Wahib, Ramez, Jagemann, Bettina, Mittrcker, Hans-Willi, Kretz, Oliver, Guse, Andreas H., Izbicki, Jakob R., Lassen, Kara G., Strowig, Till, Schweizer, Michaela, Villablanca, Eduardo J., Elinav, Eran, Huber, Samuel, Heeren, Joerg, Gagliani, Nicola

Issue&Volume: 2023-08-14

Abstract: Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to ‘feast diets’, mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4+ T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.

DOI: 10.1038/s41590-023-01587-x

Source: https://www.nature.com/articles/s41590-023-01587-x