PhD Scientific Days 2024

Theoretical and Translational Medicine III.

Expanding the Immune System's Functionality: the Role of Microbiota

Text of the abstract

Introduction: From an evolutionary standpoint the immune systems may have been selected for their capacity to detect abrupt change of structural/micro-environment in the host. This detection saves resources that would have been spent on detecting continuously each pathogen's structural features. In line with the Discontinuity Theory of Immunity (DTI), both the innate and adaptive immune systems recognize sudden antigens variation in the microenvironment and respond by launching an inflammatory response. But the same systems are also quick to adjust to prolonged, gradual antigens exposure, which results in the development of immune tolerance. Immunity is built through a dynamic interaction between host-derived and non-host-derived factors. Aims: We’ll discuss how host-derived DTI assertions may be extended to non-host-derived ones and determine immunity during sudden or slow/chronic environmental change, as follows. 1) containment: is a strategy of the local resident microbiota to prevent exogenous factors moving from the gut lumen to other body parts and infecting the mucosal surface; 2) colonization resistance: is exerted by the resident microbiota against threatening MOs through a variety of mechanisms such as niche competition and antagonism, and quorum sensing to inform bacterial population on non resident microbial presence and virulence; 3) disease tolerance: is mediated by resident microbiota, to limit tissue damage caused by the presence of pathogenic MOs. Microbiota is also able to neutralize exogenous toxins. Methods: Given the theoretical aim of this study, our methodology will be based on a critical review of the relevant literature but also on a rigorous discussion of data obtained from our lab such as CRC and ALS patients serum levels of SCFA and cytokines, and microbiome characterization in its entirety (such as virome and mycobiota beyond bacterial strains). Results: As a result we expect this theoretical perspective to offer positive insights and to cast a new light on inflammatory response and immune tolerance mechanisms. Conclusions: We claim that non-host-derived factors referred to as the microbiome should be included in a new, legitimate and inclusive DTI. Future findings could have an impact on how research is conducted and perhaps lead to re-thinking lab and clinical protocols. Funding: no fund has been employed for this research.