Faecal Microbiota Transplantation (FMT) in Patients With IBSmechanism(s) of Action
Faecal Microbiota Transplantation (FMT) in Patients With IBSmechanism(s) of Action
Two hundrad patients are randomized to either 90 g transplant, 90 g transplant twice with
 1week interval into the distal small intestine via working channel of a gastroscope, or to 90
 g transplant into the coecum of the colon via working channel of a colonoscope. The patients
 shall complete 5 questionnaires measuring symptoms, fatigue and quality of life and collect a
 feces sample at 0, 2 weeks, 1 month, and 3 months. Dysbiosis and fecal bacterial are
 determined by using 16S rRNA gene.
Patients Two hundrad patients who fulfil Rome IV criteria for irritable bowel syndrome (IBS)
 shall be included in the study. All the IBS subtypes shall be included.

 Donor Investigators are going to use the same super-donor they used in their previous
 randomised double-blind, placebo-controlled study. The donor is athletic Caucasian man aging
 36 years. He is non-smoker and is completely healthy without any medication and with a BMI of
 23.5. He is not relative to any of the patients in the trial. He was borne by vaginal
 delivery and breastfeed. He was treated 3 times with antibiotics during his life. He trains 5
 times weekly an hour each time. He took regularly dietary supplements rich in proteins,
 vitamins, fibres and minerals that made his diet richer than average in these substances. He
 was screened according to the guidelines for donors for FMT. Before he was accepted as a
 donor the microbiota was analysed in a faecal sample using GA-map Dysbiosis test. The
 analysis revealed a dysbiosis index (DI)= 1, indicating normobiosysis. In addition, he had
 excess of bacteria belonging to the Firmicutes. His faeces shall be tested every third moth
 during the trial.

 Protocol

 The patients are randomized to either 90 g transplant, 90 g transplant twice with 1week
 interval into the distal small intestine, or to 90 g transplant into the coecum of the colon.
 The patients shall complete 5 5 questionnaires and deliver fecal samples at the baseline, 2
 weeks, 1 month and 3 month after FMT.

 Faeces collection, preparation and administration Faeces from both the donor and patients
 shall be collected and stored at - 80•. Frozen faeces shall be thawed and each 30 g is
 dissolved in 30 mL of 0.9% sterile saline. The dissolved stool administrated to the patients,
 after overnight fast, through working channel of gastroduodeno-scope in pars descendent
 duodenum distal to the papilla of Vater or to the coecum through working channel of a
 colonoscope.

 Analysis Questionnaires

 1. IBS symptom severity Scale (IBS-SSS).

 2. Birmingham Symptom scale.

 3. IBS-quality of life (IBSQo) Questionnaire.

 4. Short form of Nepean Dyspepsia Index (SF-NDI).

 5. Fatigue Assessment Scale (FAS).

 Microbiome analysis Gut microbiota analysis is performed using the Genetic analysis-mapTM
 Dysbiosis test (Genetic Analysis AS, Oslo, Norway) by algorithmically assessing faecal
 bacterial abundance and profile (dysbiosis index, DI), and potential deviation in the
 microbiome from normobiosis. GA-map test is based on faecal homogenization, mechanical
 bacterial cell disruption and automated total bacterial genomic DNA extraction using magnetic
 beads. DI is based on 54 DNA probes targeting more than 300 bacterial strains based on their
 16S rRNA sequence in seven variable regions (V3-V9). Twenty-six bacteria probes are species
 specific, 19 detect bacteria on genus level, and 9 probes detect bacteria at higher taxonomic
 levels. Probe labelling is by single nucleotide extension and hybridization to complementary
 probes coupled to magnetic beads, and signal detection by using BioCode 1000A 128-Plex
 Analyser (Applied BioCode, Santa Fe Springs, CA, USA). A DI above 2 shows a microbiota
 profile that differs from that of the normobiotic reference collection (DI 1-2:
 non-dysbiosis, DI: moderate, DI 4-5: severe dysbiosis).
Inclusion Criteria:

 1. Patients who fulfil Rome IV criteria for the diagnosis of IBS.

 2. Patients were investigated to exclude other gastrointestinal organic cause(s).

 3. Moderate-to-severe IBS symptoms, as indicated by a score of ≥175 on the IBS Severity
 Scoring System (IBS-SSS).

 Exclusion Criteria:

 1. Pregnant or lactating women.

 2. The use of antibiotics or probiotics within 1 month prior to FMT.

 3. Immunocompromised patients defined as those treated by immune- suppressive
 medications.

 4. Patients with co-morbidity such as kidney failure or chronic heart disease.

 5. System disease such as diabetes.

 6. Patients with serious psychiatric disorders or drug abuse.