Short-term dietary changes can result in mucosal and systemic immune depression
Standard
Short-term dietary changes can result in mucosal and systemic immune depression. / Siracusa, Francesco; Schaltenberg, Nicola; Kumar, Yogesh; Lesker, Till R; Steglich, Babett; Liwinski, Timur; Cortesi, Filippo; Frommann, Laura; Diercks, Björn-Phillip; Bönisch, 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; 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; Heeren, Joerg; Gagliani, Nicola.
In: NAT IMMUNOL, Vol. 24, No. 9, 09.2023, p. 1473-1486.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Short-term dietary changes can result in mucosal and systemic immune depression
AU - Siracusa, Francesco
AU - Schaltenberg, Nicola
AU - Kumar, Yogesh
AU - Lesker, Till R
AU - Steglich, Babett
AU - Liwinski, Timur
AU - Cortesi, Filippo
AU - Frommann, Laura
AU - Diercks, Björn-Phillip
AU - Bönisch, Friedericke
AU - Fischer, Alexander W
AU - Scognamiglio, Pasquale
AU - Pauly, Mira J
AU - Casar, Christian
AU - Cohen, Yotam
AU - Pelczar, Penelope
AU - Agalioti, Theodora
AU - Delfs, Flemming
AU - Worthmann, Anna
AU - Wahib, Ramez
AU - Jagemann, Bettina
AU - Mittrücker, Hans-Willi
AU - Kretz, Oliver
AU - Guse, Andreas H
AU - Izbicki, Jakob R
AU - Lassen, Kara G
AU - Strowig, Till
AU - Schweizer, Michaela
AU - Villablanca, Eduardo J
AU - Elinav, Eran
AU - Huber, Samuel
AU - Heeren, Joerg
AU - Gagliani, Nicola
N1 - © 2023. The Author(s).
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - Humans
KW - Mice
KW - Animals
KW - Mucous Membrane
KW - Salmonella typhimurium
KW - T-Lymphocytes
KW - Immunity, Mucosal
U2 - 10.1038/s41590-023-01587-x
DO - 10.1038/s41590-023-01587-x
M3 - SCORING: Journal article
C2 - 37580603
VL - 24
SP - 1473
EP - 1486
JO - NAT IMMUNOL
JF - NAT IMMUNOL
SN - 1529-2908
IS - 9
ER -