Short-term dietary changes can result in mucosal and systemic immune depression
Open accessAbstract
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.
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The effects of the short-term dietary switch are associated with a rapid reduction of SCFAs, impaired mTOR activity, and mitochondrial function of CD4+ T cells.
“These effects are associated with a rapid reduction of SCFAs, impaired mTOR activity, and mitochondrial function of CD4+ T cells.709”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [709]
A short-term dietary switch from a fiber-rich diet to a low-fiber feast diet induces a transient depression of mucosal and systemic immunity by impairing the metabolic fitness of both mucosal and peripheral CD4+ T cells.
“A recent study found that a short-term dietary switch from a fiber-rich diet to a low-fiber feast diet induced a transient depression of mucosal and systemic immunity by impairing the metabolic fitness of both mucosal and peripheral CD4+ T cells.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [709]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
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- Authors
- Siracusa, F., Schaltenberg, N., Kumar, Y., Lesker, T. R., Steglich, B., Liwinski, T., Cortesi, F., Frommann, L., Diercks, B.-P., Bönisch, F., Fischer, A. W., Scognamiglio, P., Pauly, M. J., Casar, C., Cohen, Y., Pelczar, P., Agalioti, T., Delfs, F., Worthmann, A., Wahib, R., Jagemann, B., Mittrücker, H.-W., Kretz, O., Guse, A. H., Izbicki, J. R., Lassen, K. G., Strowig, T., Schweizer, M., Villablanca, E. J., Elinav, E., Huber, S., Heeren, J., & Gagliani, N.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Helmholtz Centre for Infection Research (DE)
- University of Basel (CH)
- Weizmann Institute of Science (IL)
- F. Hoffmann-La Roche AG (CH)
- Medizinische Hochschule Hannover (DE)
- Karolinska University Hospital (SE)
- German Cancer Research Center (DE)
- Corresponding author
- Siracusa, Francesco
- Gagliani, Nicola
- ORCID
- Siracusa, Francesco
- Lesker, Till R.
- Steglich, Babett
- Liwinski, Timur
- Cortesi, Filippo
- Diercks, Björn-Phillip
- Fischer, Alexander W.
- Scognamiglio, Pasquale
- Casar, Christian
- Cohen, Yotam
- Pelczar, Penelope
- Agalioti, Theodora
- Worthmann, Anna
- Wahib, Ramez
- Mittrücker, Hans-Willi
- Kretz, Oliver
- Guse, Andreas H.
- Izbicki, Jakob R.
- Lassen, Kara G.
- Strowig, Till
- Schweizer, Michaela
- Villablanca, Eduardo J.
- Elinav, Eran
- Huber, Samuel
- Gagliani, Nicola
- Venue
- Nature Immunology
- Published
- 2023-08-14
- Volume
- 24
- Issue
- 9
- Pages
- 1473-1486
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC10457203
- OpenAlex
- W4385812566
- Cited by
- 64
- References
- 50
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 16 · 2023: 6
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- European Commission (800924)
- Deutsche Forschungsgemeinschaft (SFB1328, TRR333, 390874280, EXC2155, 450149205)
- Volkswagen Foundation (76251-99)
- Karolinska Institutet
- Associazione Italiana per la Ricerca sul Cancro (800924)
- Medizinischen Hochschule Hannover
- Universitätsklinikum Hamburg-Eppendorf
- H2020 European Research Council (715271)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- energy-dense diet, systemic immunity, gut microbiota, mucosa-associated lymphoid tissue, mTOR signaling, Salmonella typhimurium infection, Listeria monocytogenes infection, infection susceptibility, antigen response
- MeSH terms
- Animals, Humans, Mucous Membrane, Salmonella typhimurium, T-Lymphocytes, Immunity, Mucosal, Mice
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