H2020Individual fellowship2021–2023

MicroILCs · Deciphering how the gut Microbiota influences Innate Lymphoid Cells in obesity""""

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2021-01-01 → 2023-04-22
EU contribution
€160,932
Participants
1
Scheme
MSCA-IF

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Results in brief

MicroILCs: Deciphering how the gut Microbiota influences Innate Lymphoid Cells in obesity"

Obesity is a severe public health challenge globally and a significant determinant of disability and death. According to WHO, overweight and obesity have reached epidemic proportions in the European region, affecting almost 60% of adults and one in three school-aged children. Obesity substantially reduces health and well-being and, consequently, accounts for considerable costs that place a strain on national healthcare systems, economic productivity, and social resources. Besides, people with obesity often suffer from weight stigma that damages mental health and causes discrimination. Accordingly, addressing obesity is a priority for achieving the Sustainable Development Goals. In this sense, several policy frameworks and action plans to halt the rise in obesity have been set out; however, there have been consistent increases in the prevalence of overweight and obesity in the European Region, and no Member State is on track to reach the target of halting the rise in obesity by 2025. There is thus an urgent need to better understand the interplay between environmental obesity drivers (e.g., unhealthy diets) and individual response to such drivers (e.g., the response mediated by gut microbiota), to develop more effective interventions to combat obesity at population and individual levels. To overcome the pandemic worldwide evolution of obesity and cardiometabolic diseases, research has increasingly focused its attention on interventions targeting the gut microbiota. These strategies arise from the increasing evidence demonstrating that alterations in the microbiota influence adiposity, insulin resistance, and other hallmarks of obesity and metabolic syndrome. Nonetheless, the key bacteria relevant for obesity and the precise mechanisms by which they contribute to define metabolic phenotypes are unknown. Growing evidence points to the intestinal immune system as an important contributor to systemic inflammation associated with obesity. The intestine is the largest immune organ of the body, and is inhabited by trillions of bacteria that, in turn, influence immune function. It is also the first to be exposed to the effects of dietary patterns, which can modulate the gut microbiota. Thus, the gut microbiota could be essential to moderate or aggravate the response of the intestinal immune system to diet, influencing metabolic homeostasis at both intestinal and peripheral levels. The aim of the EU-funded MicroILCs project was to identify the key determinants of the gut ecosystem for the immune responses of the innate lymphoid cells (ILCs) in particular. Specifically, we have assessed the role of the microbiota in regulating ILCs as a possible driver of gut microbiota-mediated effects on obesity and metabolic dysfunction and, thereby, identified effective microbiota-based interventions to combat obesity.

Data: CORDIS, © European Union

Project objective

Obesity reaches epidemic proportions and currently represents a significant public health challenge. Curbing the prevalence of obesity is one health policy priority, whose achievement requires more effective preventive measures. A high-caloric diet and sedentary lifestyle are key determinants of obesity. The diet shapes gut microbiota composition, which may partly explain why microbiota alterations are associated with an obese phenotype in humans. These microbial alternations have been proven to contribute to energy metabolism and fat storage. This evidence has represented an unprecedented shift in the way we envision obesity management. However, translating this knowledge into microbiota modulation strategies that can be applied in the clinical setting needs a better understanding of the active players within the gut ecosystem, as well as, of the mechanisms underlying their dialog with the host. Preclinical studies show that the microbiota shapes immune responses beyond the intestine with consequences for metabolic health. This proposal aims to decipher the regulatory role of indigenous intestinal bacteria on the recently discovered innate lymphoid cells (ILCs). To achieve this goal, we will use the collection of intestinal human bacteria created in the context of the EUproject MyNewGut by the host institution, first, to identify those with ILCs stimulatory properties and second, to perform mechanistic studies in wild-type and mutant murine models of diet-induced obesity coupled to in vitro experiments with primary cell cultures. Overall, the objective of the MicroILCs proposal is to move forward in the understanding of the mechanisms whereby the gut microbiota controls the immune response to high-energy diets and affects the metabolic phenotype.

Original text from CORDIS.

Participants

  • AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MadridCoordinatorSpain

Links

Data: CORDIS, © European Union