Gut-lung axis: contribution of diet and intestinal microbiota to the regulation of lung mucosa-associated immune system

• Grant number: 19/12691-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2020
• Status: Discontinued
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Marina Caçador Ayupe
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis, AP.JP
• Associated scholarship(s): 21/15168-0 - Mechanisms involved in neutrophils recruitment to the lung post-treatment with a ketogenic diet, BE.EP.DR

Abstract

The barrier tissues, such as the gut, lung and skin, are highly complex environments. The gut, in particular, is the largest organ of the body exposed to antigens, including: infectious agents, microbiota and dietary components, which influence tissue homeostasis. Therefore, the intestinal mucosa-associated immune system, is endowed with a complex cellular network and highly regulated mechanisms, in order to maintain the local homeostasis. In this context, the dietary nutrients are essential for the correct functioning of intestinal mucosa-associated immune system and influence both: the composition of intestinal microbiota and immune cells. For instance, a high-fat/low-fiber food ingestion, promotes dysbiosis and increased intestinal permeability. On the other hand, the high-fiber diet intake promotes the anti-inflammatory effects, including increased infiltration of regulatory T cells (Tregs) in the gut. Currently, the high incidence of usage of unbalanced diets, such as malnourished and ketogenic diets, has raised several questions regarding the immunological safety of such nutritional changes. In general, unbalanced diets can promote dysbiosis and impairment of gut function, and their impact on the intestinal-associated immune system is unknown. In parallel and of interest for this project, studies have sought to understand how the breakdown of intestinal homeostasis influences other mucosal tissues, such as the lungs. It has been suggested the existence of an intense communication between the gut and lungs, through components present in the diet, microbiota and immune system. For instance, Short Chain Fatty Acids (SCFA) produced in the intestinal mucosa can reach the lungs and exert a protective effect against asthma development. We hypothesized that changes in diet that compromise intestinal mucosa-associated immune system may also interfere in the function of the pulmonary mucosa. We believe that this effect may be mediated by changes in the intestinal microbiota or by the cell trafficking between the two mucosal tissues. In this study, we will evaluate the effects of changes in diet on the regulation and function of the lung -associated immune system. For that, mice will be treated with a malnourished or a ketogenic diet followed by the induction of lung inflammation. We will analyze the changes in gut-associated immune cells and intestinal microbiota and how these alterations reflect on the pulmonary mucosa. Finally, we believe that the results obtained in this project can open perspectives not only for the study of mechanisms of cellular and molecular communication in the gut-lung axis, but also to emphasize the importance of nutritional monitoring policies in areas of malnutrition. (AU)