Axial spondyloarthritis patients have altered mucosal IgA response to oral and fecal microbiota.

Axial spondyloarthritis (axSpA) is an inflammatory arthritis involving the spine and the sacroiliac joint with extra-articular manifestations in the eye, gut, and skin. The intestinal microbiota has been implicated as a central environmental component in the pathogenesis of various types of spondyloarthritis including axSpA. Additionally, alterations in the oral microbiota have been shown in various rheumatological conditions, such as rheumatoid arthritis (RA).

Network-Based Differences in the Vaginal and Bladder Microbial Communities Between Women With and Without Urgency Urinary Incontinence.

Background: Little is known about the relationship of proximal urogenital microbiomes in the bladder and the vagina and how this contributes to bladder health. In this study, we use a microbial ecology and network framework to understand the dynamics of interactions/co-occurrences of bacteria in the bladder and vagina in women with and without urgency urinary incontinence (UUI).

Methods: We collected vaginal swabs and catheterized urine specimens from 20 women with UUI (cases) and 30 women without UUI (controls).

HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.

Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases.

Expression of Cytokines in Porcine Iris, Retina and Choroidal Tissues Stimulated by Microbe-associated Molecular Patterns.

Purpose: The innate immune system is strongly implicated in the pathogenesis of uveitis. This study was designed to clarify the responses of the innate immune system in uveal tissues.

Materials And Methods: We utilized quantitative, real-time RT-PCR to measure mRNA of innate immune system receptors from porcine iris, choroid, and retina tissues.

Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthritis.

Acarose is an anti-diabetic drug and exhibits anti-arthritic effects. We hypothesized that acarbose influences the gut microbiota to affect the course of arthritis and tested this hypothesis in a collagen-induced arthritis (CIA) murine model. Acarbose in drinking water was administered gastric gavage started prior to or at the time of CIA induction.

Preliminary Report on Interleukin-22, GM-CSF, and IL-17F in the Pathogenesis of Acute Anterior Uveitis.

Anterior uveitis is the most common anatomic subset of uveitis. We developed a novel multi-parametric flow cytometry panel to identify immune dysregulation signatures in HLA B27-associated acute anterior uveitis (AAU) and axial spondyloarthritis (AxSpA). We used fluorescence activated cell sorting to characterize T cell cytokine expression in stimulated T cell subsets from patients with AAU (n = 4) compared to healthy controls (n = 14) or subjects with AxSpA (n = 6).

Novel Inter-omic Analysis Reveals Relationships Between Diverse Gut Microbiota and Host Immune Dysregulation in HLA-B27-Induced Experimental Spondyloarthritis.

Objective: To define inflammation-related host-microbe interactions in experimental spondyloarthritis (SpA) using novel inter-omic approaches.

Methods: The relative frequency of gut microbes was determined by 16S ribosomal RNA (rRNA) gene sequencing, and gene expression using RNA-Seq of host tissue. HLA-B27/human β -microglobulin-transgenic (HLA-B27-transgenic) and wild-type rats from dark agouti, Lewis, and Fischer backgrounds were used.

Controlling for Contaminants in Low-Biomass 16S rRNA Gene Sequencing Experiments.

Microbial communities are commonly studied using culture-independent methods, such as 16S rRNA gene sequencing. However, one challenge in accurately characterizing microbial communities is exogenous bacterial DNA contamination, particularly in low-microbial-biomass niches. Computational approaches to identify contaminant sequences have been proposed, but their performance has not been independently evaluated.

HLA Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome.

Objective: HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype-disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and fecal microbiome signatures.

Performance of Microbiome Sequence Inference Methods in Environments with Varying Biomass.

Microbiome community composition plays an important role in human health, and while most research to date has focused on high-microbial-biomass communities, low-biomass communities are also important. However, contamination and technical noise make determining the true community signal difficult when biomass levels are low, and the influence of varying biomass on sequence processing methods has received little attention. Here, we benchmarked six methods that infer community composition from 16S rRNA sequence reads, using samples of varying biomass.

Disruption of Intestinal Homeostasis and Intestinal Microbiota During Experimental Autoimmune Uveitis.

Purpose: We determine the changes in intestinal microbiota and/or disruptions in intestinal homeostasis during uveitis.

Methods: Experimental autoimmune uveitis (EAU) was induced in B10.RIII mice with coadministration of interphotoreceptor retinoid-binding protein peptide (IRBP) and killed mycobacterial antigen (MTB) as an adjuvant.

Community profiling of the urinary microbiota: considerations for low-biomass samples.

Many studies have shown that the urinary tract harbours its own microbial community known as the urinary microbiota, which have been implicated in urinary tract disorders. This observation contradicts the long-held notion that urine is a sterile biofluid in the absence of acute infection of the urinary tract. In light of this new discovery, many basic questions that are crucial for understanding the role of the urinary microbiota in human health and disease remain unanswered.

The microbiome and HLA-B27-associated acute anterior uveitis.

Acute anterior uveitis (AAU) and the spondyloarthritis (SpA) subtypes ankylosing spondylitis, reactive arthritis and psoriatic arthritis are among the inflammatory diseases affected by the biology of the intestinal microbiome. In this Review, the relationship between AAU, SpA and the microbiome is discussed, with a focus on the major SpA risk gene HLA-B*27 and how it is associated with both intestinal tolerance and the loss of ocular immune privilege that can accompany AAU. We provide four potential mechanisms to account for how dysbiosis, barrier function and immune response contribute to the development of ocular inflammation and the pathogenesis of AAU.

Spondyloarthritis, Acute Anterior Uveitis, and Fungi: Updating the Catterall-King Hypothesis.

Spondyloarthritis is a common type of arthritis which affects mostly adults. It consists of idiopathic chronic inflammation of the spine, joints, eyes, skin, gut, and prostate. Inflammation is often asymptomatic, especially in the gut and prostate.

Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?

Purpose Of Review: The intestinal microbiome is thought to play a role in the pathogenesis of inflammatory bowel disease (IBD). There are many shared clinical manifestations between IBD and spondyloarthritis (SpA), of which the most common are peripheral arthritis and uveitis. Clinical overlap along with similar genetics between these diseases suggests a possible shared pathogenetic mechanism, which might center on the intestinal microbiota.

Effects of HLA-B27 on Gut Microbiota in Experimental Spondyloarthritis Implicate an Ecological Model of Dysbiosis.

Objective: To investigate whether HLA-B27-mediated experimental spondyloarthritis (SpA) is associated with a common gut microbial signature, in order to identify potential drivers of pathogenesis.

Methods: The effects of HLA-B27 on 3 genetic backgrounds, dark agouti (DA), Lewis, and Fischer, were compared, using wild-type littermates and HLA-B7-transgenic Lewis rats as controls. Cecum and colon tissue specimens or contents were collected from the rats at 2, 3-4, and 6-8 months of age, and histologic analysis was performed to assess inflammation, RNA sequencing was used to determine gene expression differences, and 16S ribosomal RNA gene sequencing was used to determine microbiota differences.

Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine.

Short chain fatty acids (SCFA) are metabolites of intestinal bacteria resulting from fermentation of dietary fiber. SCFA are protective in various animal models of inflammatory disease. We investigated the effects of exogenous administration of SFCAs, particularly propionate, on uveitis using an inducible model of experimental autoimmune uveitis (EAU).

Estrogen protection against EAE modulates the microbiota and mucosal-associated regulatory cells.

Sex hormones promote immunoregulatory effects on multiple sclerosis. In the current study we evaluated the composition of the gut microbiota and the mucosal-associated regulatory cells in estrogen or sham treated female mice before and after autoimmune encephalomyelitis (EAE) induction. Treatment with pregnancy levels of estrogen induces changes in the composition and diversity of gut microbiota.

Intestinal Metabolites Are Profoundly Altered in the Context of HLA-B27 Expression and Functionally Modulate Disease in a Rat Model of Spondyloarthritis.

Objective: HLA-B27-associated spondyloarthritides are associated with an altered intestinal microbiota and bowel inflammation. We undertook this study to identify HLA-B27-dependent changes in both host and microbial metabolites in the HLA-B27/β -microglobulin (β m)-transgenic rat and to determine whether microbiota-derived metabolites could impact disease in this major model of spondyloarthritis.

Methods: Cecal contents were collected from Fischer 344 33-3 HLA-B27/β m-transgenic rats and wild-type controls at 6 weeks (before disease) and 16 weeks (with active bowel inflammation).

The Microbiome: a Revolution in Treatment for Rheumatic Diseases?

Purpose Of Review: The microbiome is the term that describes the microbial ecosystem that cohabits an organism such as humans. The microbiome has been implicated in a long list of immune-mediated diseases which include rheumatoid arthritis, ankylosing spondylitis, and even gout. The mechanisms to account for this effect are multiple.

Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity?

Objectives: Traditionally, the urinary tract has been thought to be sterile in the absence of a clinically identifiable infection. However, recent evidence suggests that the urinary tract harbors a variety of bacterial species, known collectively as the urinary microbiome, even when clinical cultures are negative. Whether these bacteria promote urinary health or contribute to urinary tract disease remains unknown.

Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis.

Purpose: To investigate the contribution of the gut microbiota to the pathogenesis of uveitis.

Methods: Experimental autoimmune uveitis (EAU) in B10.RIII mice was induced using interphotoreceptor binding protein peptide.

The interaction between host genetics and the microbiome in the pathogenesis of spondyloarthropathies.

Purpose Of Review: The intestinal microbiome is increasingly implicated in the pathogenesis of ankylosing spondylitis, reactive arthritis, and other diseases collectively known as the spondyloarthropathies (SpAs). In common with other complex inflammatory diseases, SpAs have both a strong genetic and environmental component. Recent genetic studies have highlighted host pathways that may intersect the host-microbiota interaction and offer novel paradigms to understand the pathophysiology of these diseases.

Does the Microbiome Cause B27-related Acute Anterior Uveitis?

The microbiome is strongly implicated in a broad spectrum of immune-mediated diseases. Data support the concept that HLA molecules shape the microbiome. We provide hypotheses to reconcile how HLA-B27 might affect the microbiome and in turn predispose to acute anterior uveitis.

Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis.

Objective: The HLA-B27/β2 -microglobulin (β2 m)-transgenic (Tg) rat is a leading model of B27-associated spondyloarthritis (SpA), and the disease is dependent on the presence of intestinal bacteria. Previous studies have shown that adult HLA-B27/β2 m-Tg rats have an altered intestinal microbiota. This study sought to better define the age-dependent changes to both mucosal immune function and dysbiosis in this rat model of SpA.