Faecal Calprotectin as a Potential Non-invasive Inflammatory Marker in Pregnancy and Inflammatory Bowel Disease
Condition: Inflammatory Bowel Disease (IBD); Crohn's Disease (CD); Ulcerative Colitis (UC); Pregnancy
MeSH terms: Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases
Study type: Observational

Summary: 
      When women with rheumatoid arthritis become pregnant 75% of them will go into remission,
      despite stopping medication. This phenomenon is not well understood and is not seen in other
      inflammatory conditions. Once they give birth they often relapse. Bacteria in the stool and
      inside the gut have the ability to effect the immune system and some beneficial bacteria are
      known to down regulate inflammatory components of the immune system. Gut bacteria are also
      known to alter significantly during pregnancy and in other inflammatory conditions there are
      low levels of beneficial bacteria associated with diseases like ulcerative colitis. There is
      significant crossover between rheumatoid arthritis and inflammatory bowel disease with
      similar arthritic symptoms and mechanisms of inflammation. There is very limited
      investigation of gut bacteria and rheumatoid arthritis, but some animal work has shown that
      treatment with probiotics and prebiotics can improve the condition. The aim of this study is
      to examine the bacteria in the stool of women who are pregnant with rheumatoid arthritis and
      identify any significant bacteria changes that might be used to direct future research.
    

Detailed description: 
      Pregnancy has an interesting and different impact on inflammatory conditions that have much
      in common immunologically. In inflammatory bowel disease 33% will deteriorate, 33% will
      remain stable and 33% will improve. In rheumatoid arthritis 75% of women will improve. Gut
      microbiota alters significantly in pregnancy as do predominant immunological pathways and
      relapse post-partum is swift. Research on intestinal microbiota in women with inflammatory
      conditions is scant. The high remission rate in pregnancy gives us a unique opportunity to
      study the microbiota for changing patterns that could be identified in the future as
      potential therapeutic targets.

      The study aims to identify any bacterial changes from pre-conception through pregnancy to
      post-partum and comparing women who relapse with rheumatoid arthritis to those who remain in
      remission.

      Clinical condition will be assessed and stool and serum samples will be obtained from women
      during each trimester during pregnancy for analysis of serum and fecal biomarkers and for
      microbiota 16S rRNA (ribosomal ribonucleic acid) techniques. Group-specific 16S rRNA-targeted
      oligonucleotide probes labeled with the fluorescent dye Cy3 will be used for enumerating
      bacteria. The probes used will determine bifidobacteria, bacteroides, clostridia (Clostridium
      perfringens/histolyticum sub. Grp.), eubacterium recale-C histolyticum sub gp., agrobacterium
      rimae - Collinsella-Eggerthella lenta sub. Gp., Lactobacillus/Enterococcus spp.,
      desulfovibrio spp., Faecalibacterium prausnitzii and Escherichia coli, interferon-gamma and
      Interleukin 10 (IL-10). Total bacteria will be enumerated using flow cytometry techniques.

      The outcomes of this project would help identify microbiota patterns and bacteria species
      that are beneficial in rheumatoid arthritis and could be targets for potential gut
      immunomodulation therapy in the future to prolong periods of remissions.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant women are the basis of this study, both with and without IBD to be able to meet
        the primary objective. As a feasibility study, there is no data on what levels are to be
        expected in pregnant women and if those results may vary at different stage of pregnancy.
        The investigators have chosen a small population size that reflects their anticipated
        recruitment levels of pregnant IBD patients over 2 years in the West Midlands. The
        investigators would expect to see 2-3 pregnant IBD patients per annum. Across 7 identified
        collaborating sites to take part the investigators anticipate there to be between 30-42
        patients eligible over a 2 year period.
      
Biospecimen description: 
      Faecal calprotectin, faecal S100A12, serum S100 and serum calprotectin
    
Keywords: Inflammatory Bowel Disease; Pregnancy; Stool markers; Calprotectin; Faecal S100A12 (f-SA12); Faecal calprotectin (f-Cp)