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.

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.

Inclusion Criteria:

• Healthy pregnant women (i.e. no-IBD and no significant comorbidities). pregnant IBD and rheumatoid women with any class of disease activity, non-pregnant IBD women and Rheumatoid arthritis women aged between 18 and 40.

Exclusion Criteria:

• Coeliac disease
• Familial adenomatous polyposis and hereditary nonpolyposis
• Rheumatoid arthritis (in healthy group or IBD groups)
• Irritable bowel syndrome (ROME III criteria)
• Lactose intolerance
• Other connective tissue inflammatory diseases
• Active infection
• NSAID, aspirin or anticoagulant us,
• Recipients of antibiotics in under 4 weeks of initial trial participation
• Women on the oral contraceptive pill

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.