About this Research Topic
Autoimmune Diseases (ADs) are considered to be a significant cause of morbidity and mortality worldwide and their global incidence is increasing exponentially, especially in industrialized countries.
The etiopathogenesis of ADs is multifactorial, involving genetic predisposition and environmental factors. Among these factors, several studies have highlighted the role of gut inflammation in the pathogenesis of autoimmune diseases. The intestinal mucosa provides primary protection against external environmental triggers, moreover commensal intestinal microbiota plays a crucial role in the regulation of the mucosal immune system. The gut should then be considered a key regulator in the context of ADs and gut alterations may result in aberrant immune responses leading to an imbalance between pro-inflammatory and regulatory mediators (cells, cytokines, etc), which may contribute to autoimmune diseases.
Enteric viral infections have been associated with the onset of ADs, in particular Celiac Disease (CeD) and type 1 diabetes (T1D). Interestingly, specific viral infections have been shown to promote loss of tolerance to dietary antigens, suggesting that multiple triggers can influence gut immune homeostasis promoting autoimmune responses.
Growing evidence has shown that dietary interventions and exposure to enteric pathogens induce alterations in the intestinal microbiota (a condition known as “dysbiosis”) and in gut permeability, influencing the immune system, in particular, altering immune homeostasis towards self-antigens. Furthermore, intestinal dysbiosis can influences the expression level of Toll-like receptors (TLRs) on antigen presenting cells. Multiple human studies reported compositional and functional changes of mucosal microbiota (i.e. Firmicutes/ Bacteroidetes ratio) in patients with T1D, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA). Specific pathogen-free (SPF) and in germ-free (GF) mouse models have been widely used to validate the role of microbiota in ADs. Notably, GF mice have decreased intestinal plasma cells and secretory IgA, downregulated T helper 17 cells (Th17) and regulatory T cells (Treg) in the intestinal lamina propria. The role of probiotics and faecal microbiota transplantation (FMT) in ADs has also been object of multiple studies, however how the microbiota can be manipulated as a therapeutic intervention in the context of immune mediated disorders and ADs remains elusive.
This Research Topic aims at providing an overview on the relationship between the gut immune system and ADs by gathering state of the art papers covering the major aspects of intestinal inflammatory immune responses, human ADs and animal data that advance the understanding the role of the gut in the pathogenesis of ADs.
In this research topic, we encourage the submission of Original research articles, Mini-Reviews and Clinical studies that broadly match, but are not limited to, the following sub-topics:
- Pro-inflammatory intestinal environmental triggers in ADs (dietary antigens, viruses, bacteria, etc).
- Modulation of intestinal mucosal immunity by dietary interventions and enteric pathogens
- Anatomical and functional gut alteration in ADs: intestinal barrier dysfunction and dysbiosis
- Immunological impact of dysbiosis and its role in ADs pathogenesis
- Environment induced epigenetic modifications, their role in the intestinal immune system and ADs
- The putative modulatory role of probiotics and antibiotics in ADs
- Role of fecal microbiota transplantation in ADs
The etiopathogenesis of ADs is multifactorial, involving genetic predisposition and environmental factors. Among these factors, several studies have highlighted the role of gut inflammation in the pathogenesis of autoimmune diseases. The intestinal mucosa provides primary protection against external environmental triggers, moreover commensal intestinal microbiota plays a crucial role in the regulation of the mucosal immune system. The gut should then be considered a key regulator in the context of ADs and gut alterations may result in aberrant immune responses leading to an imbalance between pro-inflammatory and regulatory mediators (cells, cytokines, etc), which may contribute to autoimmune diseases.
Enteric viral infections have been associated with the onset of ADs, in particular Celiac Disease (CeD) and type 1 diabetes (T1D). Interestingly, specific viral infections have been shown to promote loss of tolerance to dietary antigens, suggesting that multiple triggers can influence gut immune homeostasis promoting autoimmune responses.
Growing evidence has shown that dietary interventions and exposure to enteric pathogens induce alterations in the intestinal microbiota (a condition known as “dysbiosis”) and in gut permeability, influencing the immune system, in particular, altering immune homeostasis towards self-antigens. Furthermore, intestinal dysbiosis can influences the expression level of Toll-like receptors (TLRs) on antigen presenting cells. Multiple human studies reported compositional and functional changes of mucosal microbiota (i.e. Firmicutes/ Bacteroidetes ratio) in patients with T1D, systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA). Specific pathogen-free (SPF) and in germ-free (GF) mouse models have been widely used to validate the role of microbiota in ADs. Notably, GF mice have decreased intestinal plasma cells and secretory IgA, downregulated T helper 17 cells (Th17) and regulatory T cells (Treg) in the intestinal lamina propria. The role of probiotics and faecal microbiota transplantation (FMT) in ADs has also been object of multiple studies, however how the microbiota can be manipulated as a therapeutic intervention in the context of immune mediated disorders and ADs remains elusive.
This Research Topic aims at providing an overview on the relationship between the gut immune system and ADs by gathering state of the art papers covering the major aspects of intestinal inflammatory immune responses, human ADs and animal data that advance the understanding the role of the gut in the pathogenesis of ADs.
In this research topic, we encourage the submission of Original research articles, Mini-Reviews and Clinical studies that broadly match, but are not limited to, the following sub-topics:
- Pro-inflammatory intestinal environmental triggers in ADs (dietary antigens, viruses, bacteria, etc).
- Modulation of intestinal mucosal immunity by dietary interventions and enteric pathogens
- Anatomical and functional gut alteration in ADs: intestinal barrier dysfunction and dysbiosis
- Immunological impact of dysbiosis and its role in ADs pathogenesis
- Environment induced epigenetic modifications, their role in the intestinal immune system and ADs
- The putative modulatory role of probiotics and antibiotics in ADs
- Role of fecal microbiota transplantation in ADs
Keywords: Autoimmunity, Gut
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