Connessione Microbiota-Microglia: i metaboliti derivanti dai Lactobacilli modulano la Neuroinfiammazione e lo stress ossidativo in cellule microgliali umane

Nowadays, diseases such as Multiple Sclerosis or Alzheimer's have as a common cause the inflammatory process at the brain level. Neuroinflammation is an inflammatory response of the central nervous system, characterized by the activation of immune cells such as microglia. It can be caused by infections, trauma, neurodegenerative diseases and other conditions. This inflammation can contribute to neuronal damage and cognitive dysfunction, playing a crucial role in neurodegenerative diseases. Associated with neuroinflammation is the alteration of the intestinal microbiota that can cause the development of the inflammatory process not only at the systemic level but can also influence the state of the blood-brain barrier. The latter can alter its permeability, causing the entry of molecules that can damage nerve cells and microglia in the brain, triggering aberrant mechanisms at the molecular and functional level of brain cells. This condition results in brain imbalances and dysfunctional states that lead to a deterioration of mental health and neurodegenerative disease. However, to counteract the adverse neuroinflammatory effects, the intestinal microbiota can intervene through metabolites (for example, short-chain fatty acids SCFA) produced by microorganisms beneficial to the health of the body known as probiotics. They, in particular Lactobacilli, introduced in the first section of this doctoral thesis, have been the subject of study throughout my doctoral course in Applied Neuroscience, as they have aroused considerable interest in me for their potential effects on the brain and in particular on microglial cells. The latter, resident macrophage cells of our central nervous system, are the main sentinels of inflammation in numerous neurodegenerative diseases such as multiple sclerosis. Through the use of these human cells, I have developed an experimental in vitro path focusing on the effects that Lactobacilli metabolites develop on inflamed microglia cells. By simulating the condition of neuroinflammation through the use of lipopolysaccharide (LPS), a product released by gram-negative bacteria, I observed the effects on microglia cells, analyzing a regulator that plays a crucial role in the cellular response to oxidative stress, Nrf2 (nuclear factor erythroid 2-related factor 2) and genes encoding antioxidant enzymes, such as superoxide dismutase type 1 (SOD1), regulated by it. Furthermore, I observed the effects that Lactobacilli metabolites develop on microglial production of inflammatory and anti-inflammatory cytokines such as TNFα and IL10. This study led to the publication of a first-name paper and led me to write and further publish a review in which I focused my attention on the intervention of probiotics in therapies against neurodegenerative diseases. In this document, the reader will be able to embark on a cultural journey in which he will explore the role that microglia cells have also through the reading of a book chapter that has seen its publication and that highlights the importance of the cerebral immune system, underlining the key functions of microglial cells, crucial to better understand the mechanisms that develop during the neurodegeneration process.