Exploring the effects of time-restricted feeding on the immune function of obese individuals: a multi-omic approach

与营养处理不平衡有关的病理状况，如肥胖，与适应不良的免疫反应有关，从而增加了对病原性感染的易感性。肥胖受试者的免疫系统未能对病原体做出充分反应的确切机制尚不清楚，但伴随肥胖状况而来的低度脂肪慢性炎症似乎起到了相关作用。值得注意的是，基于严格热量限制的饮食干预已被证明对健康产生了有益的影响，包括改善免疫功能。然而，基于慢性卡路里限制的干预措施通常由于依从性差而失败，这突显了需要更吸引患者但在健康益处方面同样有效的替代营养干预措施。尽管有证据支持限时喂养(TRF)饮食对肥胖者代谢健康的有效性，但它们对免疫功能的影响仍未被探讨。鉴于肥胖、营养和免疫功能之间的相互作用概述了宿主对病原体的反应，OBESIMM项目的主要目标是准确定义TRF对人类肥胖者免疫功能的影响，以及它如何影响他们的免疫活性。为此，我们将在将接受TRF饮食的肥胖者中进行一项干预性研究，并探索这种干预如何重新编程他们的免疫系统，以增强他们防御感染病原体的能力。我们将使用结合细胞学、转录组学、代谢组学、元基因组学和系统生物学的多学科方法，以揭示TRF调节免疫和改善脂肪化炎的潜在机制。我们在人类中的研究将与临床前肥胖模型的使用相补充，以直接评估TRF对宿主对内毒素的反应的影响。此外，随着营养食品作为改善健康习惯和增强免疫系统的补充策略的出现，肥胖的临床前模型也将被用于研究一种基于三种具有免疫调节特性的生物活性化合物(蕨二烯、B-谷甾醇和泛喹酚)的高可溶性和生物可用共晶体的多种成分对宿主反应的影响。

Pathological conditions associated with unbalanced nutrient handling, such as obesity, are associated with maladapted immune responses that lead to increased susceptibility to pathogenic infections. The precise mechanisms by which the immune system of obese subjects fails to adequately respond to pathogens remain unclear, but the adipose low-grade chronic inflammation that accompanies the obese condition seems to play a relevant role. Remarkably, dietary interventions based on severe caloric restriction have proven to exert beneficial effects on health, including the improvement of the immune function. However, chronic calorie restriction-based interventions usually fail due to poor adherence, highlighting the need for alternative nutritional interventions more appealing to patients but equally effective in terms of health benefits. Despite evidence supporting the effectiveness of time-restricted feeding (TRF) diets on the metabolic fitness of obese individuals, their impact on the immune function remains unexplored. On the view of the interplay observed between obesity, nutrition and immune function that outlines the host response to pathogens, the main goal of the OBESIMM project is to precisely define the effect that TRF exerts on the immune function of human obese individuals and how it impacts their immunocompetence. For this, we will conduct an interventional study in obese human individuals who will be subjected to a TRF diet and explore how this intervention reprograms their immune system to enhance their capacity to defend from infectious pathogens. We will use a multidisciplinary approach that combines cytomics, transcriptomics, metabolomics, metagenomics and systems biology, in order to unravel potential mechanisms involved in the modulation of immunity and theimprovement of adipose meta-inflammation by TRF. Our study in humans will be complemented with the use of preclinical models of obesity to directly assess the impact that TRF has on host's response to lipopolysaccharide. In addition, in line with the emerging use of nutraceuticals as complementary strategies to improve healthy habits and boost immune system, the preclinical model of obesity will be used also to study the effects of a multi-ingredient based on high soluble and bioavailable co-crystals ofthree bioactive compounds with immunomodulatory properties (pterostilbene, B-sitosterol and ubiquinol) on the host's response.