← Map/THREAD · GUT-IMMUNE-AXIS
Gut–Immune Axis
How gut bacteria, the gut barrier, and the immune cells lining the gut all influence inflammation in AS.
Why this is a thread
For a long time, gut and joints were treated as separate medical territories. They aren't. Most people with AS show measurable inflammation in their gut even when they don't notice it. The bacteria living there, the strength of the gut barrier, and the immune cells lining it all influence whether inflammation stays local or spreads to the spine. This thread tracks the research into that conversation, including newer work on microbiome-targeted treatments. Faecal transplants for ulcerative colitis, defined bacterial consortia for C. difficile, oral non-live preparations for psoriasis. None of these are AS treatments yet, but they are the closest the field has to a 'treat the gut, help the joints' approach.
16 papers on the board
HLA-B27-associated gut microbiota and amino acid perturbations promote ankylosing spondylitis through M1 macrophage activation
Gut Microbes
Shows that HLA-B27, the gene most strongly linked to AS, reshapes which bacteria live in the gut and how the body handles certain amino acids, which in turn activates the inflammatory immune cells driving the disease. Suggests targeting the gut and these metabolic changes could become a real treatment route.
Fruit and vegetable intake as a mediator in the association between ultra-processed food and disease activity in ankylosing spondylitis.
Clinical rheumatology
Among 104 people with ankylosing spondylitis in Türkiye, eating more ultra-processed food went with higher disease activity, partly because it displaced fruit and vegetables, which were independently linked to lower activity. It is a snapshot rather than a trial, so it cannot prove diet changes the disease, but it points the same way as the gut-microbiome research.
Experimental models of spondyloarthritis: Pathophysiological insights and translational challenges.
Journal of autoimmunity
This review takes stock of the mouse and rat models used to study spondyloarthritis and what each has taught us: the gut-joint connection, IL-23-driven inflammation where tendons meet bone, and the TNF pathways that became today's drugs. No single model captures the whole disease, which is one reason lab findings so often fail to translate, and the authors map what better models would need.
Comprehensive Phenotyping of Circulating T- and B-Cell Subsets in Patients with Ankylosing Spondylitis Associated with Crohn's Disease.
Cells
Comparing blood immune cells from people with ankylosing spondylitis plus Crohn's disease against those with either condition alone, the combined group had more regulatory T cells and a distinct pattern of memory T and B cells. It is a small pilot, but it suggests AS with gut disease is immunologically its own thing, not simply AS and Crohn's added together.
Refinement of the Pathogenic T Cell Receptor Motif Suggests Type 17 CD8+ T Cells Initiate HLA-B*27-associated Autoimmunity.
bioRxiv : the preprint server for biology
A specific family of killer T cells that recognise HLA-B27 was found in people with axial spondyloarthritis, uveitis and psoriatic arthritis but not healthy controls, and these cells appear to switch into an IL-17-producing mode in the gut. It is a direct line from the HLA-B27 gene, through the gut, to the inflammation that IL-17 drugs block, in one set of cells.
Arthritis in inflammatory bowel disease.
Rheumatology (Oxford, England)
This review covers joint disease in inflammatory bowel disease: spinal involvement in anywhere from 6 to 62 percent of IBD patients depending on how it is looked for, joint symptoms often appearing before the bowel diagnosis, and treatments that have to work for both the gut and the spine. Shared genetics, a leaky gut barrier and immune cells travelling between gut and joint are the proposed links.
Gut microbiota and ankylosing spondylitis: current insights and future challenges
Microbial Cell
Comprehensive review of how gut bacterial imbalance disrupts the IL-23/IL-17 inflammatory pathway and weakens the intestinal barrier in AS. Identifies the lack of standardised methodology and large cohorts as the bottleneck for translating this into treatments.
Dysbiosis of Gut Microbiota in Ankylosing Spondylitis Patients
Dove Medical Press
Confirms that intestinal dysfunction precedes or amplifies systemic inflammation in AS. Frames gut microbiota as the convergence point where genetic, immune, and microbial factors meet.
The role of gut microbiota in autoimmune disease progression and therapy: a comprehensive synthesis
Frontiers in Microbiomes
Review and meta-analysis of dysbiosis across rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. Identifies bidirectional gut-immune interactions via mucosal modulation and T-regulatory cell activity.
Gut microbiota in rheumatoid arthritis: mechanistic insights, clinical biomarkers, and translational perspectives
Autoimmunity Reviews
Review of the gut microbiota in rheumatoid arthritis, with diet as an upstream variable: Western diet → dysbiosis → inflammation; Mediterranean and plant-based diets → microbial diversity → immune tolerance. Same dysbiosis mechanism as the AS papers, with an environmental modifier layer the AS papers don't yet emphasise.
Gut microbiome and immune system crosstalk in chronic inflammatory diseases
Microorganisms
Review covering rheumatoid arthritis, IBD, psoriasis, lupus, asthma, and vasculitis, all sharing gut-immune disruption as a common mechanism. Synthesises FMT, dietary modification, and probiotic/prebiotic approaches.
Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized control trials
Techniques in Coloproctology
Meta-analysis of 14 randomised trials and 600 patients. FMT achieves combined clinical and endoscopic remission with an odds ratio of 2.25 vs placebo; oral delivery hits 3.15, multi-donor pooled 3.32. Maintenance at 12 months not statistically significant, durability is the open question.
Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection
Nature Medicine
Phase 2 trial of VE303, a defined consortium of 8 human commensal bacterial strains, for recurrent C. difficile infection. 80% reduction in recurrence vs placebo; primary endpoint met; Phase 3 planned.
Quantitative Alterations in Short-Chain Fatty Acids in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Biomolecules
Systematic review and meta-analysis of short-chain fatty acids (SCFA), particularly butyrate, across IBD subgroups. Butyrate is significantly reduced in patients vs controls and suppresses pro-inflammatory cytokines, but clinical trials remain inconsistent due to delivery, degradation, and unstandardised dosing.
A randomized, double-blinded, phase 2 trial of EDP1815, an oral immunomodulatory preparation of Prevotella histicola, in adults with mild-to-moderate plaque psoriasis
Frontiers in Medicine
Phase 2 trial of EDP1815, a non-live oral biotherapeutic derived from Prevotella histicola, for mild-to-moderate plaque psoriasis. Hits the same Th1/Th2/Th17 pathway central to AS. Clinical efficacy confirmed in psoriasis but discontinued in atopic dermatitis: same pathway, different microenvironment, different outcome.
Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Nutrients
Meta-analysis across 13 RCTs. CRP reduced significantly (mean difference −3.04 mg/L, p<0.001) but DAS28 disease activity score showed no consistent change after excluding high-risk-of-bias trials. Biochemical signal without clinical translation; strain-dependent, L. casei and L. acidophilus show the strongest individual signals.