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

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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1473-1486
Number of pages14
JournalNature Immunology
Issue number9
Early online date14 Aug 2023
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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