Gut Bacteria Tied to Ankylosing Spondylitis Severity

Findings on α-diversity and bacteria levels in the gut microbiota of persons with ankylosing spondylitis, from a scientific review of the literature, show changes to both have correlations with changes in the chronic autoimmune connective-tissue condition, according to an investigation recently published in Frontiers in Cellular and Infection Microbiology.¹

Previous research also shows a potential relationship between gut microbiota and ankylosing spondylitis pathophysiology,^2-4 but much remains to be learned, the present study authors pointed out.¹ For the present analysis, the Chao1 index was used to evaluate bacteria species richness and the Shannon index and the Simpson index were used to evaluate bacteria species richness and evenness.

“The etiology of AS is multifactorial, with genetic, environmental, and immunological factors playing a role,” they wrote. “While the exact mechanisms by which the gut microbiota influences ankylosing spondylitis are not fully understood, studies have reported alterations in the composition and diversity of the gut microbiota in patients.”

Their comprehensive synthesis of the existing data had them search PubMed, Embase, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, China Science and Technology Journal Database, and China National Knowledge Internet for studies published from inception through July 30, 2023. Forty-seven studies—covering 2494 patients with ankylosing spondylitis and 1885 healthy controls—were ultimately included that investigated α-diversity, a common indicator of gut health,⁵ and bacteria gut levels.¹ The authors used a comprehensive list of search terms: gastrointestinal microbiome, microbiome, gastrointestinal tract, intestinal microbiome, bacteria, intestinal tract, microflora, gastrointestinal tract, ankylosing spondylitis, and axial spondyloarthritis, and their synonyms.

In a subanalysis within this study, of 582 patients, the gut microbiota was shown to be significantly decreased in the patients with active disease. | Image Credit: © Julien Tromeur-stock.adobe.com

Index Results

Comparing results between the patients with ankylosing spondylitis and the healthy controls, the authors saw that results for Chao1 were significantly reduced in patients with the condition (standardized mean difference [SMD], –0.44; 95% CI, –0.80 to –0.07; P < .001; I² = 80.3%), indicating lower microbial special count. Also seen were markedly lower results for the study patients according to the Shannon index (SMD, –0.27; 95% CI, –0.49 to –0.04; P < .001; I² = 85.6%) and the Simpson index (SMD, –0.30; 95% CI, –0.53 to –0.06; P < .001; I² = 76.2%), which “point toward an overall reduction in microbial diversity.”

Patients who were treatment naive also exhibited significant differences per their α-diversity compared with patients being treated with disease-modifying antirheumatic drugs or nonsteroidal anti-inflammatory drugs, according to drops in their Shannon index scores (SMD, –0.33; 95% CI, –0.64 to –0.02; P = .001). The authors believe this may indicate recovery of microbial diversity following treatment.

A subanalysis then classified of 582 patients as having active disease or inactive disease. The gut microbiota was shown to be significantly decreased in the patients with active disease, according to the indices (all P < .001):

• Chao1: SMD, –0.33 (95% CI, –0.74 to 0.08)
• Shannon: SMD, –0.33 (95% CI, –0.69 to 0.03)
• Simpson: SMD, –0.36 (95% CI, –0.68 to –0.05)

For specific bacteria, there were higher levels of Bacteroidetes and lower levels of Bifidobacterium. Both are bacteria shown to be beneficial to gut health,^6,7 but Bacteroides species can also be detrimental, depending on the disease state.⁷ The lower levels of Bifidobacterium (SMD, –0.42; 95% CI, –2.37 to 1.52; P < .001), therefore, likely indicate a drop in gut health, as do the rise in the Bacteroidetes (SMD, 0.42; 95% CI, –0.93 to 1.76; P < .001).¹

“The interplay between the gut fungal community and the host’s immune system is critical for maintaining homeostasis,” the authors emphasized. “In addition, our study found that some patients had gastrointestinal complications, which may be related to drug therapy.”

Speaking to the importance of their results, the authors note that their findings on reduced α-diversity and its correlation with disease activity align with growing evidence that says the same, “indicating a potential dysbiosis that may contribute to the disease’s inflammatory processes.”

Still, they emphasize that even in light of that agreement, they still speak to the need for greater understanding of the immunomodulatory effects of gut microbiota bacterial changes and their potential as therapeutic targets.

References

1. Su QY, Zhang Y, Qiao D, et al. Gut microbiota dysbiosis in ankylosing spondylitis: a systematic review and meta-analysis. Front Cell Infect Microbiol. 2024:14:1376525. doi:10.3389/fcimb.2024.1376525

2. Asquith M, Sternes PR, Costello ME, et al. HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome. Arthritis Rheumatol. 2019;71(10):1642-1650. doi:10.1002/art.40917

3. Chen Z, Zheng X, Wu X, et al. Adalimumab therapy restores the gut microbiota in patients with ankylosing spondylitis. Front Immunol. 2021:12:700570. doi:10.3389/fimmu.2021.700570

4. Min HK, Na HS, Jhun JY, et al. Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function. Front Immunol. 2023:14:1096565. doi:10.3389/fimmu.2023.1096565

5. Li Z, Zhou J, Liang H, et al. Differences in alpha diversity of gut microbiota in neurological diseases. Front Neurosci. 2022:16:879318. doi:10.3389/fnins.2022.879318

6. Why Bifidobacteria are so good for you. Healthline. Accessed October 25, 2024. https://www.healthline.com/nutrition/why-bifidobacteria-are-good

7. Wexler HM. Bacteroides: the good, the bad, and the nitty-gritty. Clin Microbiol Rev. 2007;20(4):593-621. doi:10.1128/CMR.00008-07