Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures

Abstract

BACKGROUND The healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis. AIM To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients. METHODS We performed serological profiling of 100 Crohn’s disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery ( n = 150) and validation ( n = 150) sets. Statistical analysis was performed using R packages. RESULTS Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showing higher prevalence in CD patients relative to healthy controls. We also identified antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showing higher prevalence in healthy controls relative to UC patients. Using these novel antibodies, we built biomarker panels with area under the curve (AUC) of 0.81, 0.87, and 0.82 distinguishing CD vs control, UC vs control, and CD vs UC, respectively. Subgroup analysis revealed that penetrating CD behavior, colonic CD location, CD patients with a history of surgery, and extensive UC exhibited highest antibody prevalence among all patients. We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation. CONCLUSION We have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.

Syringic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota

“…Importantly, there is a complex interaction between the gut microbiota and pro-inflammatory factors in colitis, 54 and the pathogenesis of colitis can be alleviated by a balanced interaction between beneficial microorganisms, host genetic factors, and environmental triggers. 55 FMT alleviates IBD and chronic gastrointestinal disorders by improving the structure of the gut microbiota.…”

“…Importantly, there is a complex interaction between the gut microbiota and pro-inflammatory factors in colitis, and the pathogenesis of colitis can be alleviated by a balanced interaction between beneficial microorganisms, host genetic factors, and environmental triggers . FMT alleviates IBD and chronic gastrointestinal disorders by improving the structure of the gut microbiota. , Additionally, it reduces the expression of key cytokines in the colon, regulates gut microbiota function, inhibits activation of the nuclear factor kappa B signaling pathway, and alleviates colitis .…”

Biomarkers in IBD: What to Utilize for the Diagnosis?

“…Novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showed higher prevalence in CD patients relative to healthy controls, while antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showed higher prevalence in healthy controls relative to ulcerative colitis patients. Using these novel antibodies, a biomarker panel was built to distinguish between Crohn’s disease vs. control, ulcerative colitis vs. control, and Crohn’s disease vs. ulcerative colitis, respectively [ 34 ].…”

Leaky gut, circulating immune complexes, arthralgia, and arthritis in IBD: coincidence or inevitability?

“…Gut microbiota dysbiosis compromises intestinal barrier function, elevating permeability and facilitating the entry of microbes, viruses, and pathogenic antigens into visceral organs ( 5 ). Patients with IBD showed significantly higher food-specific IgG antibody levels than healthy controls ( 6 ); autoantibodies reactive to colonic proteins ( 7 ) and anti-microbial antibodies have also been identified ( 8 ). In individuals with IBD, serum complement component 3 (C3) concentrations were elevated compared with those in healthy volunteers ( 9 ).…”