Study investigates the connection between dysbiosis of the gut microbiome and uveitis.

A review of prior studies on the relationship between uveitis and gut dysbiosis was recently published in The American Journal of Pathology.

A rare eye disorder called uveitis can have serious morbid consequences. The disorder, which can induce blindness, has unknown origins and triggers.

Corticosteroids and immunomodulatory drugs are the main uveitis therapies. Despite recent therapeutic developments, such as biological medicines, disease recurrence is still common, and managing the disease can be difficult.

In order to identify new therapeutic targets, it is important to continue study into the pathophysiological processes that underlie uveitis.

Possible connections between the gut microbiome and autoimmune uveitis
The idea behind molecular mimicry When mimicker antigens are found in the gut microbiome, autoreactive T-cells can form in response, which can result in molecular mimicry against self-antigens.

When the immune system recognizes particular antigens as foreign, autoreactive T-cells begin to grow against host antigens. In a study conducted in vitro, intestinal contents transferred to lymph nodes associated with experimental autoimmune uveitis (EAU) activated T-cells.

When administered intraperitoneally to mice of the wild type, these T-cells can cause uveitis. This lends credence to the idea that antigens found in gut contents can activate ocular tissues.

The imbalance between effector and regulatory T-cells: Pathologic antigens are presented by antigen-presenting cells in the gut lymphatics, which activate Th1 and Th17 and cause an inflammatory response.

Together, the two cell types support immunological homeostasis. Dysbiosis can result in an imbalance that boosts pro-inflammatory T-cells, which can lead to inflammatory diseases outside the gastrointestinal tract including uveitis.

Increased intestinal permeability: If bacteria’s products move outside the intestines, they can aggravate autoimmune illnesses or cause inflammation.

Due to dysbiosis, the intestinal barrier may become permeable, allowing bacteria or their metabolites to move through the circulatory system.

Antigen exposure that mimics host cells has the potential to either exacerbate auto-sensitization or directly cause inflammation.

Production of microbial metabolites: Intestinal bacteria are thought to create short-chain fatty acids (SCFA), which are thought to have anti-inflammatory properties.

By balancing regulatory and effector T-cells, SCFAs also reduce the symptoms of inflammatory disorders. Through the inhibition of Th1/Th17 cells and the induction of regulatory T cells, SCFAs support immunological tolerance in the gut lymphatic tissues.

Microbiome’s Effect on autoimmune uveitis
As the two main mouse autoimmune uveitis models, the spontaneous and induced models of EAU have been used to study alterations in the gut microbiome connected to uveitis.

The inter-photoreceptor retinoid-binding protein (IRBP), a retinal protein, is actively immunized in the induced model to cause an autoimmune response against the host retina.

In the induced EAU model, mice treated with water experienced less severe uveitis than mice treated with oral broad-spectrum antibiotics given one week before vaccination. The study discovered that intraperitoneal antibiotic therapy had no effect on gut bacteria load or uveitis severity.

This shows that rather than an indirect anti-inflammatory effect of the antibiotics, alterations in the gut flora may be the condition’s root cause. Antibiotics like metronidazole and others have immunosuppressive effects.

After receiving antibiotics, intestinal regulatory T-cells rose after two weeks and extraintestinal regulatory T-cells grew at three and four weeks.

Similar outcomes have been obtained by other trials using a variety of antimicrobial therapies and vaccination in germ-free settings. To prevent microbial contamination, sterile settings are used to breed and grow germ-free mice.

Through a sterile cesarean section, fresh colonies and strains are created, which are subsequently transferred to a germ-free setting. Inflammation was reduced by treatment one week before the onset of the disease, not during it.

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According to the study, mice’s pre-existing gut microbiota plays a significant role in illness induction rather than acting as a different pathway for lowering inflammation brought on by antibiotic therapy.

Metronidazole and vancomycin both reduced uveitis in the induced model when given orally separately. Neomycin and ampicillin, however, did not have the same impact. When given independently, ampicillin and neomycin had different impacts on the generation of regulatory T-cells but did not lessen uveitis.

The gut microbiome was treated with vancomycin and metronidazole to reduce the numbers of Dorea, Coprococcus, Adlecreutzia, Clostridium, and Lactobacillus species, which are linked to the development of uveitis and may be sources of mimicker antigens.

According to the study’s findings, there is a direct link between gut flora and uveitis. Based on studies in humans, it is known that the gut microbiome changes in disease states, and studies in animals have demonstrated that dysbiosis causes autoimmunity rather than just being associated with it.

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To use this understanding in clinical settings, more study is required. The putative advantages of microbial metabolite supplementation, such as SCFAs, are not supported by clinical research. To prove their efficacy, further longitudinal patient studies will be required.

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