Altered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis

Abstract

IntroductionPrior studies have established altered microbiota and immunologic reactivity to enteric commensal organisms in inflammatory bowel disease (IBD). Since intestinal inflammation is present in a subset of patients with both pediatric and adult spondyloarthritis (SpA), we hypothesized that SpA patients may also have altered microbiota and immune responsiveness to enteric organisms.MethodsStool and blood specimens were collected from children with enthesitis-related arthritis (ERA) and non-inflammatory controls. DNA purified from stool was subject to PCR amplification and sequencing of the variable IV region from the 16S rDNA gene. IgA and IgG Enzyme-linked Immunosorbent Assays (ELISAs) were performed on select species of bacteria in most subjects.ResultsTwenty-five children with ERA and 13 controls were included. The ERA patients had less Faecalibacterium prausnitzii (3.8% versus 10%, P = 0.008) and lachnospiraceae family (12 versus 7.0%, P = 0.020), a statistically significant increase in bifidobacterium (1.8% versus 0%, P = 0.032) and a non-statistically significant increase in Bacteroides (21% versus 11%, P = 0.150). Akkermansia muciniphila was abundant (>2%) in 7/27 ERA patients but none of the controls (P = 0.072.) Cluster analysis revealed two clusters of ERA patients: Cluster one (n = 8) was characterized by high levels of Bacteroides genus, while a second (n = 15) cluster had similar levels as the controls. Seven of 17 (41%) of the ERA subjects in Cluster 2 compared to 0/8 of the subjects in Cluster 1 had abundant Akkermansia muciniphila (P = 0.057). Serum IgA and IgG antibody levels against F. prausnitzii and B. fragilis were similar between patients and controls, whereas the two groups showed divergent responses when the fecal relative abundances of F. prausnitzii and Bacteroides were compared individually against IgA antibody levels recognizing F. prausnitzii and B. fragilis, respectively.ConclusionThe abundance of F. prausnitzii in the stool among patients with ERA is reduced compared to controls, and Bacteroides and A. muciniphila are identified as associative agents in subsets of ERA patients. Differences in the humoral responses to these bacteria may contribute to disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0486-0) contains supplementary material, which is available to authorized users.

Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case–Control Study

“…12,13 At least 1 category of JIA has been associated with distinct intestinal microbial populations. 14 Antibiotics can alter some subjects' intestinal microbiota for $6 months. [15][16][17] Correspondingly, anaerobic antibiotic use has been associated with incident pediatric IBD.…”

Histopathological features of gastrointestinal mucosal biopsies in children with juvenile idiopathic arthritis

“…Differences in the humoral responses to these bacteria may contribute to disease. So ERA patients may also have altered microbiota and immune responsiveness to enteric organisms which could influence gut inflammation (24), however, we do not have any data about microbiota to support this.…”

“…Stoll et al found a reduced abundance of Faecalibacterium in the stool of children with enthesitis-related JIA (24). Differences in the humoral responses to these bacteria may contribute to disease.…”

The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases

“…A similar gut microbiota profile was present in patients with inflammatory bowel disease [43]. In children with enthesitis-related arthritis (ERA) a different microbiome signature has been observed characterized by (i) less Faecalibacterium prausnitzii and lachnospiraceae family, (ii) a statistically significant increase in Bifidobacterium, and (iii) an abundance of Akkermansia muciniphila [44]. Cluster analysis revealed the presence of two clusters of ERA patients: in cluster one there were high levels of Bacteroides genus; in cluster 2 similar levels of Bacteroides genus, but abundant A. muciniphila were observed, indicating Bacteroides and A. muciniphila as associative agents in subsets of ERA patients.…”