A groundbreaking study published in PLOS ONE has revealed a potential bidirectional link between gut microbiota and ankylosing spondylitis (AS), providing new insights into the role of gut health in this autoimmune disorder. Using genome-wide association study (GWAS) summary data, a group of Chinese researchers conducted two-sample Mendelian randomization analyses to uncover the genetic associations between 211 gut microbiota (GM) taxa and AS.
The results suggested that certain gut bacteria may either protect against or increase the risk of developing AS. Notably, a higher abundance of the Lactobacillaceae family, Rikenellaceae family, and Howardella genus was associated with a reduced risk of AS. Conversely, the presence of higher levels of Actinobacteria class and Ruminococcaceae_NK4A214_group genus correlated with an increased risk of the disease. IL23 and IFN-γ were identified as potential links between gut dysbiosis—particularly related to Actinobacteria—and the development of AS.
A study by Zhou et al. identified an enrichment of Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans, and Prevotella copri in patients with AS, while Enterococcus faecium strains E980 and TX0133a01 were found to be reduced. Similarly, Liu et al., using 16S rRNA sequencing, observed a significant increase in the abundance of the phyla Cyanobacteria, Deinococcota, Patescibacteria, Actinobacteriota, and Synergistota, alongside a relative decline in Acidobacteriota, Bdellovibrionota, Campylobacterota, Chloroflexi, Gemmatimonadota, Myxococcota, Nitrospirota, Proteobacteria, and Verrucomicrobiota in AS patients. Huang R et al. further reported an increase in Flavonifractor plautii, Oscillibacter, Parabacteroides distasonis, and Bacteroides nordii, along with a decrease in Collinsella aerofaciens in individuals with AS.
Dysbiosis of the gut microbiota (GM) is closely linked to the pathogenesis and susceptibility of AS through several mechanisms, such as increased intestinal permeability, activation of the gut immune system, interaction with genes like HLA-B27, and modulation of inflammatory cytokines and immune cell balance (e.g., Th17/Treg). Key inflammatory cytokines involved in AS include IL-23, IL-17, IFN-γ, and TNF-α, with the IL-23/IL-17 axis playing a critical role. Actinobacteria were found to promote IL-23 and IFN-γ secretion, suggesting these cytokines mediate GM dysbiosis in AS. While intestinal inflammation is linked to AS activity, GM dysbiosis appears crucial to the pathogenesis of both AS and inflammatory bowel disease (IBD), though IBD is not a direct mediator of GM effect on AS.
This study marks a significant step forward in understanding the connection between gut microbiota and autoimmune diseases. It points to Lactobacillaceae, Rikenellaceae, Howardella, Actinobacteria, and Ruminococcaceae as promising new therapeutic targets and monitoring indicators for AS. These findings highlight the potential for targeting gut microbiota in the treatment and management of AS, offering new avenues for personalized therapies.
References
- Du X, Li H, Zhao H, Cui S, Sun X, Tan X. Causal relationship between gut microbiota and ankylosing spondylitis and potential mediating role of inflammatory cytokines: A mendelian randomization study. PLoS One. 2024 Jul 31;19(7):e0306792.
- Zhou C, Zhao H, Xiao XY, Chen BD, Guo RJ, Wang Q, et al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis. J Autoimmun. 2020 Feb;107:102360.
- Liu B, Ding Z, Xiong J, Heng X, Wang H, Chu W. Gut Microbiota and Inflammatory Cytokine Changes in Patients with Ankylosing Spondylitis. Biomed Res Int. 2022 Aug 19;2022:1005111.
- Huang R, Li F, Zhou Y, Zeng Z, He X, Fang L, et al. Metagenome-wide association study of the alterations in the intestinal microbiome composition of ankylosing spondylitis patients and the effect of traditional and herbal treatment. J Med Microbiol. 2020 Jun;69(6):797-805.