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 the baseline, and at 3, 6 and 12 months after FMT. 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 questionnaires and deliver fecal samples at the baseline, and at 3 , 6 , and 12 months 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.