Mucosal Immunity and the Gut-Microbiota-Brain-Axis in Neuroimmune Disease

Abstract

Recent advances in next-generation sequencing (NGS) technologies have opened the door to a wellspring of information regarding the composition of the gut microbiota. Leveraging NGS technology, early metagenomic studies revealed that several diseases, such as Alzheimer’s disease, Parkinson’s disease, autism, and myalgic encephalomyelitis, are characterized by alterations in the diversity of gut-associated microbes. More recently, interest has shifted toward understanding how these microbes impact their host, with a special emphasis on their interactions with the brain. Such interactions typically occur either systemically, through the production of small molecules in the gut that are released into circulation, or through signaling via the vagus nerves which directly connect the enteric nervous system to the central nervous system. Collectively, this system of communication is now commonly referred to as the gut-microbiota-brain axis. While equally important, little attention has focused on the causes of the alterations in the composition of gut microbiota. Although several factors can contribute, mucosal immunity plays a significant role in shaping the microbiota in both healthy individuals and in association with several diseases. The purpose of this review is to provide a brief overview of the components of mucosal immunity that impact the gut microbiota and then discuss how altered immunological conditions may shape the gut microbiota and consequently affect neuroimmune diseases, using a select group of common neuroimmune diseases as examples.

Immune cell signatures and causal association with irritable bowel syndrome: A mendelian randomization study

“…The Fc receptor CD16a (FcγRIIIa), a feature of CD56Dim NK cells, interacts with the constant region of Immunoglobulin G (IgG) antibodies. This interaction triggers Antibody-Dependent Cell-Mediated Cytotoxicity, a process that is crucial for the NK cells' ability to eliminate target cells[ 50 ]. In the gastrointestinal tract, NK cells may exert a more pronounced influence on gut homeostasis compared to their circulating counterparts, owing to their localized cytokine production.…”

Potential diagnostic markers and therapeutic targets for periodontitis and Alzheimer's disease based on bioinformatics analysis

“…10,11 The gut microbiota and its metabolites play a crucial role in the metabolism of neurotransmitters, which are key participants in neuroimmunity. 12 Imbalance between excitatory and inhibitory neurotransmitters in the nervous system is associated with the development and progression of neurological diseases. 13 In recent years, there has been increasing interest in exploring the potential effects of periodontitis outside the oral cavity, particularly its impact on the nervous system.…”

“…Some studies have shown that the gut microbiota communicates bidirectionally with the nervous system through regulating neurologic and immune‐related signaling pathways, participating in the development and progression of various neurological diseases 10,11 . The gut microbiota and its metabolites play a crucial role in the metabolism of neurotransmitters, which are key participants in neuroimmunity 12 . Imbalance between excitatory and inhibitory neurotransmitters in the nervous system is associated with the development and progression of neurological diseases 13 …”

Impact and Advances in the Role of Bacterial Extracellular Vesicles in Neurodegenerative Disease and Its Therapeutics

“…Among the NDs, a research study has shown that in AD brain, microglial activation contributes to amyloid-beta deposition and neuronal damage [41]. In addition, in PD few research studies have shown that in the brain T cells infiltrate the substantia nigra and promote neuroinflammation [42,43]. Moreover, in multiple sclerosis, few studies have shown that dysbiosis and gut-derived molecules contribute to neuroinflammation and disease progression [44][45][46].…”

“…This neuroimmune system helps keep the homeostasis in balance. If this balance is distraught, it can lead to chronic inflammation, damage to neurons, and eventually NDs [41,42]. In terms of NDs, the neuroimmune system is made up of immune cells like microglia and astrocytes that become active when there is neuroinflammation [43].…”