短期饮食变化可导致粘膜和全身免疫功能低下

SCI

23 August 2023

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

（nature immunology, IF: 30.5）

Siracusa F, Schaltenberg N, Kumar Y, Lesker TR, Steglich B, Liwinski T, Cortesi F, Frommann L, Diercks BP, Bönisch F, Fischer AW, Scognamiglio P, Pauly MJ, Casar C, Cohen Y, Pelczar P, Agalioti T, Delfs F, Worthmann A, Wahib R, Jagemann B, Mittrücker HW, Kretz O, Guse AH, Izbicki JR, Lassen KG, Strowig T, Schweizer M, Villablanca EJ, Elinav E, Huber S, Heeren J, Gagliani N. 

CORRESPONDENCE TO: f.siracusa@uke.de; n.gagliani@uke.de

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. 

包括小鼠和人类在内的杂食性动物倾向于选择富含脂肪的高能量营养物质而非植物性饮食，尤其是在短时间内，但这种短期摄入高能量营养物质对健康的影响尚不清楚。本文展示了模仿人类社会饮食行为的短期重复性 "盛宴饮食 "会破坏肠道微生物群的潜在缓冲作用，并重组粘膜相关淋巴组织的免疫结构。第一次饮食转换足以诱发短暂的粘膜免疫抑制和全身免疫抑制，导致对伤寒沙门氏菌和李斯特菌感染的易感性增加。对模型抗原挑战的反应能力也受到损害。这些观察结果可以解释为，由于微生物提供的纤维代谢物减少，mTOR活性受损，导致CD4+ T细胞代谢能力和细胞因子产生减少。重新引入膳食纤维可重新恢复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转换对人类CD4+ T细胞功能的影响。因此，短期营养变化会造成粘膜和全身免疫力的短暂抑制，为病原体感染创造机会。

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