The FIDGIT Study. Exploring the relationship between Fibromyalgia, Digestive Markers and the Gastrointestinal Tract in adult women.

Adult women with fibromyalgia and matched controls. Ideally, data will be gathered over a two-three week period for each participant. All participants will be required to: 1. Collect samples of faeces and saliva for microbiome testing. These sample will be collected at home, and before presenting for hydrogen-methane breath testing. Equipment for collection and detailed instructions are provided. Microbiome analysis conducted using 16S rRNA or metagenomic analysis. 2. Provide blood samples for RNA metatranscriptomics, determination of IgG antibodies, and for FORT/FORD testing (free radical and antioxidant defence measure) 3. Undergo hydrogen-methane breath testing on 3 separate occasions. Each is following either a diet low in fermentable compounds for two days, or a one-day low residue diet and 12 hour overnight (water-only) fast. The following substrates will be administered, on separate days, with a minimum of 2 days between each test: a. Glucose 50g (or 1g/kg if less than 50kg body weight): breath samples collected at 15 minute intervals for 120 minutes b. Lactulose 10g: breath samples collected at 15 minute intervals for 180 minutes c. Fructose 25g: breath samples collected at 15 minute intervals for 180 minutes Breath testing will be conducted by one of two methods: a. In-house. Whereby the participant attends the research centre, samples are collected and analysed by a research assistant. Baseline breath gases will be calculated from the average of three breath samples (collected over a maximum periodof 5 minutes). All participants with an average hydrogen or methane gas concentration of 10ppm or higher at baseline will be instructed to conduct a mouthwash. Three repeat breath samples are taken within 5 minutes after the mouthwash. Where a significant reduction (at least -10ppm or 25%) in breath gas or gases is recorded, participants will also be invited to contribute to the OMG Study (Trial No: 380620) b. Remotely, using the test kit provided by the manufacturer (Quintron). Guidance and support for correct collection is provided by a research assistant. A link to an explanatory video is provided to guide the collection process for at-home participants. All breath samples will be analysed on the same equipment (with test-tube extraction adaptor for remotely collected samples), by a research assistant trained in the use of the analyser. All symptoms reported during breath testing are also recorded. In-house participants may have oral samples collected during the first breath test (prior to ingestion of the test substrate). In-house participants will also have capillary blood samples collected for blood sugar monitoring during the glucose challenge 4. Collect 3 urine samples over a single 4-hour period, not to be collected during menstruation. Urine collections are done by the participant, at home, at least 48 hours before presenting for breath testing. At recruitment appointment, the procedure is explained by the study coordinator or research assistant. Detailed written instructions and all collection equipment is provided. Participants are advised to avoid the following foods for 24 hours prior to commencing collection of the urine samples: Celery, onions, pumpkin, mushrooms, snow peas, sweet potato, peaches, chocolate, any substance with artificial sweetener (e.g., cough drops, sweets, chewing gum), fermented foods and probiotics (including yoghurt) Day of testing: - Fast (no food, water intake as specified) from arising until 4 hours after starting the test. - Collect 1x 10mL samples from first morning urination (control sample). - Ingest 100 ml water with 10 g lactulose and 5 g mannitol - No water consumption for the following 2 hours - Continue collecting urine, with aliquoted samples at 2- and 4-hours post ingestion (to evaluate recovery of these saccharides in urine as a marker of intestinal hyperpermeability) - 250mL water at 2 hours and 3 hours post-ingestion - Remain without food until the 4-hour collection is complete. - Continue collecting urine until 4 hours after initial sample 5. Collect swabs from surfaces in their home and/or workplace for evaluation of mould exposure. 6. All participants complete a single, integrated online questionnaire (hosted in REDCap) which merges the following tools: • American College of Rheumatology fibromyalgia diagnostic criteria (ACR) 2016. (Wolfe et al. 2016) • Revised Fibromyalgia Impact Questionnaire (FIQR) (Bennett et al. 2009; Burckhardt, Clark, and Bennett 1991) • Rome IV (Drossman and Hasler 2016; Palsson et al. 2016) • Functional Bowel Disorder Severity Index (FBDSI) (Drossman et al. 1995; Sperber et al. 2000) • Headache Symptom Questionnaire (HSQ) (van der Meer et al. 2019; (IHS) 2013) • Medical Outcomes Study Sleep Scale (SSS) (Williams and Arnold 2011) • Short Form Survey -36 (SF36) (McHorney et al. 1994; Hays, Sherbourne, and Mazel 1995) • Oral Health Questionnaire (OHQ) (Petersen, Baez, and World Health 2013) To assess nutritional intake, the online photo-recognition assessment tool, DietID (R), is administered. The questionnaire is to be submitted before all testing is completed.