Study on the relationship between autoimmune and inflammatory diseases and intestinal microbes

Autoimmune diseases and chronic inflammatory diseases are characterized by dysregulation of the immune response, leading to excessive and uncontrolled tissue inflammation
.

A variety of factors including genetic variation, environmental irritation and infection are considered to be the factors that cause persistent inflammation and pathology

Immunity dysregulation, leading to excessive and uncontrolled tissue inflammation, genetic variation, environmental irritation, and infection.

Heterologous promote nutrition and metabolism, enhance the barrier function, inhibiting disease original body and adjust Festival immunity

Understanding the regulation of intestinal microbes or microbial physiology on the host helps to better understand many diseases
.

HLA-DR mutations, toll like receptors (toll like receptors, TLRs) , inflammasomes and autophagy components are associated with a variety of diseases, which lead to immune response disorders and increased inflammation

HLA-DR mutations, toll like receptors (TLRs) , inflammasomes and autophagy components

Inflammatory bowel disease

Inflammatory bowel disease

IBD is characterized by an unregulated immune response to the microbiota, leading to chronic inflammation of the gastrointestinal tract (GI) .
The main forms of IBD are ulcerative colitis (UC) , and Crohn's disease (CD) , which can affect the entire gastrointestinal tract .
In IBD patients, potential anti-inflammatory microorganisms such as Bacteroides, Lachnospirace, and prausnitzii faecalibacterium prausnitzii are reduced, while potential inflammatory microorganisms such as Proteobacteria and gnavus rumen cocci are increased .
In addition, the increase in mucosal-associated bacteria leads to more contact between gut microbes and the immune system, and leads to antibacterial immunity related to the pathogenesis of IBD .

Imbalance of the immune response to the microbiota, leading to chronic inflammation of the gastrointestinal tract (GI) , ulcerative colitis (UC) , and Crohn’s disease (CD)

In humans, more than 240 genetic loci are associated with the risk of IBD
.

Gene mutations in pathways related to microflora interactions highlight common mechanisms of disease development

In addition, diet and dietary metabolites are key factors in the pathogenesis of IBD
.

In patients with IBD, specific bacteria, such as butyric acid-producing Prvobacterium and Rhodotorula hominis, are reduced

As there is evidence to support the potential of microflora in maintaining the stability of the intestinal environment and preventing inflammation, there has been great interest in using microbes to treat patients with IBD
.

The administration of probiotics has therapeutic effects in animal models and some patients, but clear and meaningful studies have not yet been found

In summary, the IBD research has demonstrated a variety of ways in which the microflora interacts with the host to regulate local inflammation, and suggests some microflora-related ways to treat this disease
.

Understanding the pathways affected in IBD will also help to improve the understanding of how microbes affect other inflammatory and autoimmune diseases, and will contribute to a broader understanding of how the microbiota can be used to improve patient prognosis

 

Systemic lupus erythematosus

Systemic lupus erythematosus systemic lupus erythematosus

Patients with systemic lupus erythematosus produce autoantibodies and pro-inflammatory cytokines, which cause diseases in multiple organs such as skin, blood, and kidneys, and are affected by many environments, including the intestinal microflora
.

Patients with systemic lupus erythematosus show dysbiosis of the gut and oral cavity

Decreased bacterial diversity is related to disease activity

In addition, the antibodies and T cells of patients with systemic lupus erythematosus recognize bacterial antigens from the oral, intestinal, and skin microflora, including Propionibacterium propionicum and Bacteroides
.

Molecular simulation is a possible link between microflora and systemic lupus erythematosus
.
One of the most common autoantibodies associated with systemic lupus erythematosus is directed against the widely expressed RNA binding protein Ro60
.
Antibodies against Ro60 are usually found before the development of SLE symptoms
.
Some human symbionts produce proteins similar to human Ro60.
Although these bacteria have been found in healthy people and lupus patients, only lupus patients have antibodies and T cells that react with the homologous genes of human Ro60 and microbial Ro60 .
In addition, in patients with systemic lupus erythematosus, the severity of the disease is related to the increase in Grignard bacteria .
Gnarfs condensed .
The IgG antibodies of patients with severely diseased systemic lupus erythematosus can recognize cell wall lipopolysaccharides from a subgroup of Gram bacteria .
Importantly, the auto-DNA antibodies of patients with systemic lupus erythematosus with lupus nephritis cross-react with Gram bacillus lipopolysaccharide .

One of the most common autoantibodies associated with systemic lupus erythematosus is directed against the widely expressed RNA binding protein Ro60
.
But only patients with lupus have antibodies and T cells that react with human Ro60 and microbial Ro60 homologous genes

     A variety of spontaneous and inducible murine lupus models have provided a good method for how microflora changes can regulate pathology
.
The cross between the mouse strain NZW and BXSB resulted in spontaneous lupus-related antiphospholipid syndrome and liver damage, mainly in male mice, due to the extra copy of the TLR7 gene
.
In these mice, Enterococcus gallisepticum migrated to the liver and triggered an autoimmune response
.
Removal of this pathogen with vancomycin can inhibit bacterial translocation, autoreactive T cells and autoantibodies
.
The intestinal permeability of sterile mice infected with Escherichia gallisepticum increased, and plasmacytoid dendritic cells (PDC) and Th17 cells in the lamina propria and mesenteric lymph nodes increased, which aggravated disease and mortality
.

Enterococcus gallisepticum migrates to the liver and triggers an autoimmune response
.

     Bacterial metabolites can also regulate systemic lupus erythematosus, just like Lactobacillus, as mentioned above, it can regulate intestinal inflammation by producing AhR activating ligands
.
In mouse models, compared with IBD, a high-protein diet with high tryptophan content is associated with an increase in pathology by promoting the production of anti-double-stranded DNA autoantibodies and an increase in T follicular helper cells (TFH)
.
The feces of lupus susceptible mice homozygous for NZM2410 lupus susceptibility quantitative trait loci (Sle1, Sle2 and Sle3) were screened for metabolism, and it was found that the metabolites of intestinal tryptophan-derived bacteria were increased and the fecal lactic acid bacteria were abundant
.

     In contrast, similar to IBD, a high-fiber diet is associated with improved outcomes in a murine lupus model
.
In the TLR7-dependent model, Lactobacillus reesei grows and then metastasizes to the mesenteric lymph nodes, spleen, and liver
.
Translocation leads to an increase in type I interferon (IFN-I) produced by PDC, which exacerbates the pathogenesis and mortality of the disease
.
This example shows the direct and indirect effects of gut symbiosis on disease progression
.
In summary, these results indicate that the intestinal microflora can regulate the pathogenesis of lupus through molecular simulation, changes in bacterial translocation, metabolites, or microbe-microbe competition
.
Each of these can lead to disorders of the immune response of tissues, including Th17 cells and PDC recruiting and activating the IFN-I pathway, which together aggravate the disease
.

      In summary, understanding the regulation of intestinal microbes or microbial physiology on the host helps to better understand many diseases, so as to better find new treatments for related diseases and better improve the prognosis
.

   

Some references:

Some references:

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