From fast food to healthy diet: Addressing the dynamic molecular mechanism of sequential diet switch-induced T cell plasticity for the purpose of developing new treatments for immuno-mediated diseases

Información del proyecto

Diet-namic

Identificador del acuerdo de subvención: 715271

DOI

10.3030/715271

Proyecto cerrado

Fecha de la firma de la CE 16 Noviembre 2016

Fecha de inicio 1 Diciembre 2016

Fecha de finalización 30 Noviembre 2022

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 1 499 695,00

Aportación de la UE

€ 1 499 695,00

Coordinado por

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
Germany

Periodic Reporting for period 4 - Diet-namic (From fast food to healthy diet: Addressing the dynamic molecular mechanism of sequential diet switch-induced T cell plasticity for the purpose of developing new treatments for immuno-mediated diseases)

Período documentado: 2021-06-01 hasta 2022-11-30

Resumen del contexto y de los objetivos generales del proyecto

We usually say that “we are what we eat”. However, it was not clear to what extent short-term dietary interventions can impact our health by modulating the immune system.

In short, we found that our immune system rapidly responds to changes in the diet, ranging from developing a status of immune depression or hyperactivation, to the extent of promoting cell death which licenses the efficacy of chemotherapy.

All in all, these results show the deep and rapid impact of the diet on our health. This project might provoke the idea that we can change the trajectory of many immune-related diseases, including cancer, by simply modulating what we do every day – eating. Finally, Diet-namic has provided a series of cellular and molecular mechanisms that can be targeted once simple dietary changes are no longer sufficient.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

We started by testing the effect of an unhealthy diet, named here as Feast Diet (FD) on T cells and consequently on intestinal homeostasis in mouse models. We found that after a short consumption of FD, the intestinal microbiota and the T cell composition in the intestine and mucosal-associated lymphoid tissues (MALTs) were drastically impacted and consequently the intestinal homeostasis was compromised. This effect could be reverted by a switched to a “healthy” diet. This data show how rapid the capacity of the T cells to adapt to environmental changes is and consequently how they mediate the effect of the diet on our health.
In parallel, we studied the molecular mechanisms of T cell adaptability and found one key signaling pathway, namely TGFβR/SMADs, which regulates this mechanism. In essence, we have made one initial step toward the development of future immune therapies that could “force” the anti-inflammatory fate of Th17 cells by targeting these specific molecular mechanisms, and thereby possibly reset the homeostasis in inflamed tissues of patients affected by Th17 cell-mediated immune-mediated inflammatory diseases.
Finally, we found that short-term consumption of a diet rich in tryptophan led to an increased concentration of the microbiota-derived metabolite indole-3-acetic acid (3-IAA) in the circulation of mice. The combination of 3-IAA and chemotherapy, licensed by neutrophil-derived myeloperoxidase, increases oxidative stress, reduces autophagic activity and ultimately halts colon and pancreatic cancer cell proliferation. Translating these findings back to humans, we found a strong correlation between the concentration of 3-IAA and the response to chemotherapy in two independent cohorts of pancreatic cancer patients.

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

Our results have the potential to change how society perceives the effect a basic daily decision, i.e. what type of diet we consume, can have. Our results might help people become fully aware of the real risks and benefits of the different types of diets we have available to us every day. Our data identify the specific components of the diet that can have such an impact, and can therefore pave the way to design a dietary intervention to maintain or restore health.

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