The Intestinal Microbiome in Spondyloarthritis

Tejpal Gill; Mark Asquith; James T. Rosenbaum; Robert A. Colbert

Disclosures

Curr Opin Rheumatol. 2015;27(4):319-325. 

In This Article

Ankylosing Spondylitis

A recent study[44] revealed distinct microbial colonization in the terminal ileum of a small number of patients with AS, using healthy individuals as controls. There was an increase in the abundance of Lachnospiraceae, Ruminococcaceae, and Prevotellaceae in AS patients. Interestingly, these bacterial species are also observed in the Dextran Sulphate Sodium (DSS) DSS-induced colitis model of mice.[45] Although the authors saw a decreased abundance of Streptococcus and Actinomyces in comparison to the control population, they did not see any differences in the bacteria normally associated with reactive arthritis or even Klebsiella species, which have been hypothesized to trigger AS.[46]

A study[47] comparing certain gut microbes in AS patients with age-matched controls revealed an increase in sulphate reducing Bacteriodes in patients. In a follow-up study[48] with AS patients and healthy controls, these authors reported that reduced levels of IL-10 production upon stimulation of their PBMCs with autologous Bacteroides. Previous studies in HLA-B27 transgenic rats[24] also reported that recolonization of the gut of germ-free animals with Bacteroides led to gut inflammation, whereas Lactobacillus and fusiform bacteria did not result in inflammatory lesions. Klebsiella pneumonia, long hypothesized to be involved in the pathogenesis of AS based in part on higher serum levels of Immunoglobulin A (IgA) IgA antibodies[49] could not be confirmed by others.[50]

Treatment of HLA-B27 transgenic rats with SpA using prebiotics (compounds that induce growth or activity of commensals) has shown some benefit for colitis,[13] raising hope for future therapies aimed at altering the gut microbiome. There are a number of mechanisms by which HLA-B27 might alter the microbiome. For example, human monocytic cells expressing HLA-B27 exhibit impaired handling of Salmonella,[51] and exhibit reduced proliferative capacity against Lipopolysaccharide (LPS) LPS, suggesting that intracellular effects of HLA-B27 might be involved in shaping the intestinal microbiome. One study[52] reported that of 104 patients with spondyloarthropathies that were tested, polymorphisms in nucleotide-binding oligomerization domain containing 2 (NOD2) NOD2 were frequent in SpA patients with chronic gut inflammation (comparable to Crohn's patients), whereas, in SpA patients with acute gut inflammation or without gut inflammation, NOD2 polymorphisms were similar to the control population. Studies with HLA-B27 transgenic animals that are resistant to SpA-associated gut inflammation might be helpful in resolving these scenarios.

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