Multi-ancestry GWAS of diarrhea during acute SARS-CoV2 infection identifies multiple novel loci and contrasting etiological roles of irritable bowel syndrome subtypes (preprint)

A substantial proportion of acute SARSCoV2 infection cases exhibit gastrointestinal symptoms, yet the genetic determinants of these extrapulmonary manifestations are poorly understood. Using survey data from 239,866 individuals who tested positively for SARSCoV2, we conducted a multi-ancestry GWAS of 80,289 cases of diarrhea occurring during acute COVID19 infection (33.5%). Six loci (CYP7A1, LZFTl1/CCR9, TEME182, NALCN, LFNG, GCKR) met genomewide significance in a trans-ancestral analysis. The top significant GWAS hit mapped to the CYP7A1 locus, which plays an etiologic role in bile acid metabolism and is in high LD (r2= 0.93) with the SDCBP gene, which was previously implicated in antigen processing and presentation in the COVID-19 context. Another association was observed with variants in the LZTFL1/CCR9 region, which is a known locus for COVID19 susceptibility and severity. PheWAS showed a shared association across three of the six SNPs with irritable bowel syndrome (IBS) and its subtypes. Mendelian randomization showed that genetic liability to IBS-diarrhea increased (OR=1.40,95%,CI[1.33,1.47]), and liability to IBS-constipation decreased (OR=0.86, 95%CI[0.79,0.94]) the relative odds of experiencing COVID19+ diarrhea. Our genetic findings provide etiological insights into the extrapulmonary manifestations of acute SARSCoV2 infection.

Meta-analysis: Post-COVID-19 functional dyspepsia and irritable bowel syndrome.

INTRODUCTION: The burden of post-COVID-19 functional dyspepsia (FD) and irritable bowel syndrome (IBS) remains unclear. The aim of this meta-analysis was to estimate the rate of post-COVID-19 FD and IBS. METHODS: MEDLINE, Scopus and Embase were searched through 17 December 2022. Studies reporting the incidence of FD and/or IBS in COVID-19 survivors and controls (without COVID-19), when available, according to the Rome criteria, were included. Estimated incidence with 95% confidence intervals (CI) was pooled. The odds ratio (OR) with 95% confidence intervals (CI) was pooled; heterogeneity was expressed as I2 . RESULTS: Ten studies met the inclusion criteria and were included in the analysis. Overall, four studies including 1199 COVID-19 patients were considered for FD. Post-COVID-19 FD was reported by 72 patients (4%, 95% CI: 3%-5% and I2 0%). The pooled OR for FD development (three studies) in post-COVID-19 patients compared to controls was 8.07 (95% CI: 0.84-77.87, p = 0.071 and I2 = 67.9%). Overall, 10 studies including 2763 COVID-19 patients were considered for IBS. Post-COVID-19 IBS was reported by 195 patients (12%, 95% CI: 8%-16%, I2 95.6% and Egger's p = 0.002 test). The pooled OR for IBS development (four studies) in COVID-19 patients compared to controls was 6.27 (95% CI: 0.88-44.76, p = 0.067 and I2 = 81.4%); considering only studies with a prospective COVID-19 cohort (three studies), the pooled OR was 12.92 (95% CI: 3.58-46.60, p < 0.001 and I2 = 0%). CONCLUSIONS: COVID-19 survivors were found to be at risk for IBS development compared to controls. No definitive data are available for FD.

Early symptoms preceding post-infectious irritable bowel syndrome following COVID-19: a retrospective observational study incorporating daily gastrointestinal symptoms.

BACKGROUND: Intestinal microinflammation with immune dysfunction due to severe acute respiratory syndrome coronavirus 2 reportedly precipitates post-infectious irritable bowel syndrome. This study aimed to elucidate potential risk factors for subsequent development of irritable bowel syndrome, hypothesizing that it is associated with specific symptoms or patient backgrounds. METHODS: This single-center retrospective observational study (2020-2021) included adults with confirmed coronavirus disease requiring hospital admission and was conducted using real-world data retrieved from a hospital information system. Patient characteristics and detailed gastrointestinal symptoms were obtained and compared between patients with and without coronavirus disease-induced irritable bowel syndrome. Multivariate logistic models were used to validate the risk of developing irritable bowel syndrome. Moreover, daily gastrointestinal symptoms during hospitalization were examined in patients with irritable bowel syndrome. RESULTS: Among the 571 eligible patients, 12 (2.1%) were diagnosed with irritable bowel syndrome following coronavirus disease. While nausea and diarrhea during hospitalization, elevated white blood cell count on admission, and intensive care unit admission were associated with the development of irritable bowel syndrome, nausea and diarrhea were identified as risk factors for its development following coronavirus disease, as revealed by the adjusted analyses (odds ratio, 4.00 [1.01-15.84] and 5.64 [1.21-26.31], respectively). Half of the patients with irritable bowel syndrome had both diarrhea and constipation until discharge, and constipation was frequently followed by diarrhea. CONCLUSIONS: While irritable bowel syndrome was rarely diagnosed following coronavirus disease, nausea and diarrhea during hospitalization precede the early signs of irritable bowel syndrome following coronavirus disease.

Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

Clinical outcomes associated with complementary and alternative medicine-related "immunity-boosting" practices in patients with cirrhosis during the COVID-19 pandemic - an observational study.

During the coronavirus disease 2019 pandemic, Ayurvedic herbal supplements and homeopathic immune boosters (IBs) were promoted as disease-preventive agents. The present study examined the clinical outcomes among patients with chronic liver disease who presented with complications of portal hypertension or liver dysfunction temporally associated with the use of IBs in the absence of other competing causes. This single-center retrospective observational cohort study included patients with chronic liver disease admitted for the evaluation and management of jaundice, ascites, or hepatic encephalopathy temporally associated with the consumption of IBs and followed up for 180 days. Chemical analysis was performed on the retrieved IBs. From April 2020 to May 2021, 1022 patients with cirrhosis were screened, and 178 (19.8%) were found to have consumed complementary and alternative medicines. Nineteen patients with cirrhosis (10.7%), jaundice, ascites, hepatic encephalopathy, or their combination related to IBs use were included. The patients were predominantly male (89.5%). At admission, 14 (73.75%) patients had jaundice, 9 (47.4%) had ascites, 2 (10.5%) presented with acute kidney injury, and 1 (5.3%) had overt encephalopathy. Eight patients (42.1%) died at the end of the follow up period. Hepatic necrosis and portal-based neutrophilic inflammation were the predominant features of liver biopsies. IB analysis revealed detectable levels of (heavy metals) As (40%), Pb (60%), Hg (60%), and various hepatotoxic phytochemicals. Ayurvedic and Homeopathic supplements sold as IBs potentially cause the worsening of preexisting liver disease. Responsible dissemination of scientifically validated, evidence-based medical health information from regulatory bodies and media may help ameliorate this modifiable liver health burden.

Анализ влияния коморбидной сердечно-сосудистой патологии на течение и Ð¸ÑÑ Ð¾Ð´Ñ‹ COVID-19 у Ð³Ð¾ÑÐ¿Ð¸Ñ‚Ð°Ð»Ð¸Ð·Ð¸Ñ€Ð¾Ð²Ð°Ð½Ð½Ñ‹Ñ Ð¿Ð°Ñ†Ð¸ÐµÐ½Ñ‚Ð¾Ð² в первую и вторую волну пандемии в Евразийском регионе.

Цель:  Ð˜Ð·ÑƒÑ‡ÐµÐ½Ð¸Ðµ особенностей клинического течения новой коронавирусной инфекции и  влияния сопутствующих заболеваний на исход заболевания у госпитализированных больных с инфекцией SARS-CoV-2 в первую и вторую волны пандемии.Методы и результаты.  Для оценки особенностей течения COVID-19 в Евразийском регионе были созданы международные регистры АКТИВ 1 и во время второй волны пандемии АКТИВ 2. Набор больных в регистр АКТИВ 1 проводили с 29.06.20 по 29.10.20, набрано 5 397 пациентов. Прием пациентов на учет в АКТИВ 2 проводили с 01.11.20 до 30.03.21, набрано 2 665 больных.Результаты. Госпитальная летальность снизилась в  Ð¿ÐµÑ€Ð¸Ð¾Ð´ второй волны пандемии и  ÑÐ¾ÑÑ‚Ð°Ð²Ð¸Ð»Ð° 4,8 % против 7,6 % в  Ð¿ÐµÑ€Ð¸Ð¾Ð´ первой волны. В  Ð¿ÐµÑ€Ð¸Ð¾Ð´ второй волны пациенты были старше, имели больше сопутствующих заболеваний и поступали в стационар в более тяжелом состоянии, пациенты имели более высокий уровень полиморбидности. В период второй волны пандемии увеличилась заболеваемость бактериальной пневмонией и сепсисом, но реже встречались тромбозы глубоких вен и «Ñ†Ð¸Ñ‚Ð¾ÐºÐ¸Ð½Ð¾Ð²Ñ‹Ð¹ шторм¼. Наиболее неблагоприятными для прогноза смертности, как в первую, так и во вторую волны эпидемии были сочетания сопутствующих заболеваний: артериальная гипертензия (АГ) + хроническая сердечная недостаточность (ХСН) + сахарный диабет (СД) + ожирение, АГ + ишемическая болезнь сердца (ИБС) + ХСН + СД, АГ + ИБС + ХСН + ожирение.Заключение. Ð£ пациентов во вторую волну пандемии наблюдалось более обширное поражение ткани легких, чаще возникала фебрильная лихорадка, были выше уровни С-реактивного белка и  Ñ‚Ñ€Ð¾Ð¿Ð¾Ð½Ð¸Ð½Ð°, ниже уровни гемоглобина и лимфоцитов. Это, вероятно, связано с различной тактикой госпитализации пациентов в первую и вторую волны пандемии в странах, принявших участие в формировании регистров АКТИВ 1 и АКТИВ 2.

Post-infection functional gastrointestinal disorders following coronavirus disease-19: A Prospective follow-up cohort study (preprint)

Background:Acute gastrointestinal infections can lead to post-infectious irritable bowel syndrome (PI-IBS). Moreover, coronavirus disease (COVID-19) is related to long-term gastrointestinal sequelae. In this study, the frequency, disease spectrum, and risk factors for post-infection functional gastrointestinal disease (PI-FGID) in COVID-19 patients and healthy controls were prospectively examined. Methods: Validated Rome III and Rome IV questionnaires were used to assess the incidence of PI-FGID in 190 COVID-19 patients, and 160 healthy controls prospectively followed for 1, 3, and 6 months. Results:Six（3.2%）, 1（0.5%）, 3（1.6%）, 5（2.6%）, 6（3.2%）COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at 1 month, respectively, while 4（2.1%）, 1（0.5%）, 4（2.1%）, 4（2.1%）, and 6（3.2%）COVID-19 patients had diarrhea, abdominal pain, constipation, dyspepsia and their overlap at three months, respectively. Furthermore, 2（1.3%）, 4（2.5%）, and 3（1.9%）healthy controls developed constipation, dyspepsia, and their overlap at one month, respectively (P=0.193), while 2（1.3%）, 4（2.5%), and 2（1.3%）healthy controls developed constipation, dyspepsia and their overlap at three months, respectively (P=0.286). FGIDs incidence was higher among COVID-19 patients（8.9%) than in healthy controls（3.1%) at 6-month follow-up (P=0.025). Moreover, 7 (3.7%), 5 (2.6%), 3 (1.6%), and 2 (1.1%) COVID-19 patients developed IBS, functional dyspepsia（FD）, functional diarrhea（FDr）, functional constipation（FC）at six months, respectively, while only 2 (1.3%) and 3 (1.9%) healthy controls developed IBS and FD at six months, respectively. Notably, gastrointestinal（GI）symptoms at onset were the independent risk factors for post-COVID-19 FGIDs at six months. Conclusions: COVID-19 increases new-onset PI-FGID at six months compared with healthy controls. GI symptom at the onset of COVID-19 is an independent risk factor for post-COVID-19 FGIDs.

An Updated Comparative Study on the Impact of COVID-19 Infection and Vaccination in Patients with Inflammatory Bowel Disease and Irritable Bowel Syndrome.

BACKGROUND AND AIMS: This study assessed the differences in swabbing rates, vaccine uptake, COVID-19 infection, hospitalization rates and outcomes in patients suffering from inflammatory bowel disease (IBD) on immunomodulation and patients diagnosed with irritable bowel syndrome (IBS). METHODS: A population consisting of 250 IBD and 250 IBS patients was randomly selected from the local database. Apart from demographic data, the following data was collected: number of COVID-19 swabs taken, vaccination rates, type of vaccine administered, infection secondary to COVID-19, hospitalization and outcomes. RESULTS: IBD patients performed significantly more swabs tests for SARS-CoV-2 detection compared with IBS patients in both phases of the study. Whilst the IBS cohort recorded a larger number of COVID-19 infection and less hospitalisations whilst infected, IBD patients had a better outcome whilst infected since hospitalisation reason in the latter was not related to COVID-19 infection. IBD patients had a larger uptake of COVID-19 vaccines. CONCLUSIONS: This study was the first of its nature locally and internationally as it compared two unrelated cohorts of patients followed up in gastroenterology. Vaccination rates in both cohorts were higher than those reported internationally. In concordance with international studies, IBD patients are not at an increased risk of worse outcomes from COVID-19 infection compared to non-IBD cohorts.

Patient satisfaction after remotely delivered gut-directed hypnotherapy for irritable bowel syndrome during the COVID-19 era: implications for future practice.

OBJECTIVE: Gut-directed hypnotherapy (GDH) is an evidence-based treatment for irritable bowel syndrome (IBS). Adoption of remote GDH has been accelerated by the COVID-19 pandemic. We aimed to evaluate patient experience and satisfaction following remote GDH. DESIGN: On completing 12 sessions of remote GDH via Skype using the Manchester protocol, patients with refractory IBS completed a feedback form on their experience. The proportion reporting positive outcomes (≥30% improvement in global IBS symptoms or abdominal pain, satisfaction, recommendation to family/friends) were compared by patient factors (age, gender, proximity, preferences). RESULTS: Of 52 patients completing the feedback form, 27 (52%) indicated that they would have opted for remote over face-to-face GDH, regardless of the pandemic situation. On a five-point scale (5=easy), patients rated the platform easy-to-use (mean 4.5±0.8) without impairment of communication (mean rating 4.6±0.8). Following remote GDH, 30/52 (58%) reported ≥30% global IBS symptom improvement, and 24/52 (46%) reported ≥30% pain reduction. 90% would recommend remote GDH to others. Only 39% felt they would have benefitted more from face to face. Those who would have chosen remote GDH regardless of the pandemic were more likely to be satisfied (p=0.01). Age, gender and proximity did not influence outcomes, satisfaction and likelihood of recommending remote GDH to others. Difficulties during remote sessions were infrequent in both those that were satisfied, and those that would have preferred face to face. CONCLUSION: These data support the need to continue developing remote GDH in the post-COVID era but suggest that there is still a role for face-to-face GDH, with patient choice being an important factor.

Mint and Menthol: A Review of Potential Health Benefits and wider Human effects (preprint)

Mint and to a lesser extent menthol have been used since antiquity for medicinal purposes. Key components of mint and menthol use such as composition and intake, safety and traditional uses are discussed prior to a review of clinical and human performance outcomes in the areas of digestive and respiratory health; antibacterial and anti-fungal properties, nocioception, migraine and headache and emerging evidence regarding COVID 19. Evidence suggests benefit for patients with irritable bowel syndrome and related digestive issues, with analgesic and respiratory effects also noted. Perceptual characteristics relating to thermal comfort and sensation, taste sensitivity and alertness are also considered; these effects are predominantly driven by stimulation of transient receptor potential melastatin 8 (TRPM8) activity resulting in sensations of cooling and freshness, with lesser influence on thirst. Finally, sport performance is considered as a domain that may further elucidate some of the aforementioned underpinning outcomes due to its systemic and dynamic nature, especially when performed in hot environmental conditions.

Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 infection (PASC) in a Large Academic Medical Center in the US (preprint)

Objective: The growing number of Coronavirus Disease-2019 (COVID-19) survivors who are affected by Post-Acute Sequelae of SARS CoV-2 infection (PACS) represent a worldwide public health challenge. Yet, the novelty of this condition and the resulting limited data on underlying pathomechanisms so far hampered the advancement of effective therapies. Using electronic health records (EHR) data, we aimed to characterize PASC-associated diagnoses and to develop risk prediction models. Methods: In our cohort of 63,675 COVID-19 positive patients seen at Michigan Medicine, 1,724 (2.7 %) had a recorded PASC diagnosis. We used a case control study design comparing PASC cases with 17,205 matched controls and performed phenome-wide association studies (PheWASs) to characterize enriched phenotypes of the post-COVID-19 period and potential PASC pre-disposing phenotypes of the pre-, and acute-COVID-19 periods. We also integrated PASC-associated phenotypes into Phenotype Risk Scores (PheRSs) and evaluated their predictive performance. Results: In the post-COVID-19 period, cases were significantly enriched for known PASC symptoms (e.g., shortness of breath, malaise/fatigue, and cardiac dysrhythmias) but also many musculoskeletal, infectious, and digestive disorders. We found seven phenotypes in the pre-COVID-19 period (irritable bowel syndrome, concussion, nausea/vomiting, shortness of breath, respiratory abnormalities, allergic reaction to food, and circulatory disease) and 69 phenotypes in the acute-COVID-19 period (predominantly respiratory, circulatory, neurological, digestive, and mental health phenotypes) that were significantly associated with PASC. The derived pre-COVID-19 PheRS and acute-COVID-19 PheRS had low accuracy to differentiate cases from controls; however, they stratified risk well, e.g., a combination of the two PheRSs identified a quarter of the COVID-19 positive cohort at a 3.5-fold increased risk for PASC compared to the bottom 50% of their distributions. Conclusions: Our agnostic screen of time stamped EHR data uncovered a plethora of PASC-associated diagnoses across many categories and highlighted a complex arrangement of presenting and likely pre-disposing features -- the latter with a potential for risk stratification approaches. Yet, considerably more work will need to be done to better characterize PASC and its subtypes, especially long-term consequences, and to consider more comprehensive risk models.

Irritable bowel syndrome following COVID-19: an underestimated consequence of SARS-CoV-2 infection.

INTRODUCTION: Gastrointestinal (GI) symptoms are a common manifestation of COVID­19. OBJECTIVES: We aimed to investigate whether GI symptoms persist in patients previously infected with SARS­CoV­2 in the form of post­infection irritable bowel syndrome (PI­IBS). PATIENTS AND METHODS: A prospective, single­center evaluation of questions regarding IBS was conducted using the Rome IV Adult Diagnostic Questionnaire among 257 patients previously hospitalized for COVID­19. RESULTS: GI symptoms (abdominal pain with diarrhea or constipation) were reported at the following time points: at discharge from the hospital, and after 3 and 6 months of follow­up. GI symptoms not meeting the full Rome IV diagnostic criteria for IBS due to too short symptom duration were reported by 28 individuals (10.6%) at hospital discharge, 58 (22.3%) after 3 months, and 70 (26.9%) after 6 months. The full Rome IV criteria for IBS were not met at discharge by any of the participants, but they were met after 3 and 6 months of follow­up in 14 (5.4%) and 15 individuals (5.8%), respectively. CONCLUSION: Persistent GI symptoms following COVID­19 are frequent and deserve significant and growing attention of gastroenterologists and other health care practitioners. The Rome IV criteria may be too strict to address the full spectrum of GI symptoms following COVID­19.

In drug-refractory IBS, group CBT with interoceptive exposure improved symptoms and QoL at 13 wk.

SOURCE CITATION: Kikuchi S, Oe Y, Ito Y, et al. Group cognitive-behavioral therapy with interoceptive exposure for drug-refractory irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol. 2022;117:668-77. 35103022.

Satisfaction With Telehealth Among Patients With Irritable Bowel Syndrome During COVID-19: Cross-Sectional Survey Findings.

INTRODUCTION: Coronavirus disease 2019 rapidly shifted health care toward telehealth. We assessed satisfaction with and preferences for telehealth among patients with irritable bowel syndrome (IBS). METHODS: We conducted a cross-sectional survey in an integrated healthcare system in Southern California with members aged 18-90 years with an International Classification of Diseases 9 and 10 codes for IBS from office-based encounters between June 1, 2018, and June 1, 2020. Eligible patients were emailed a survey assessing telehealth satisfaction overall and by patient-related factors, IBS characteristics, health and technologic literacy, utilization, and coronavirus disease 2019 perceptions. We identified perceived telehealth benefits and challenges. Multivariable logistic regression identified predictors of telehealth dissatisfaction. RESULTS: Of 44,789 surveys sent, 5,832 (13.0%) patients responded and 1,632 (3.6%) had Rome IV IBS. Among 1,314 (22.5%) patients with IBS and prior telehealth use (mean age 52.6 years [17.4]; 84.9% female; and 59.4% non-Hispanic White, 29.0% Hispanic, and 5.6% non-Hispanic Black), 898 (68.3%) were satisfied, 130 (9.9%) were dissatisfied, and 286 (21.8%) felt neutral. In addition, 78.6% would use telehealth again. Independent predictors of telehealth dissatisfaction include social media use of once a week or less (adjusted odds ratio [OR] = 2.1; 1.3-3.5), duration of IBS for <1 year (adjusted OR = 8.2; 1.9-35.8), and willingness to travel 60 plus minutes for face-to-face visits (adjusted OR = 2.6; 1.4-3.7). Patients' main concern with telehealth was a lack of physical examination. DISCUSSION: Most of the patients with IBS are satisfied with telehealth. Shorter duration of IBS diagnosis, comfort with technology, and increased willingness to travel were associated with telehealth dissatisfaction. These predictors may help identify a target population for a focused IBS-telehealth program.

Association between multiple sleep dimensions and functional bowel disorders among Chinese college freshmen.

BACKGROUND: Although sleep disorder is thought as a risk factor for functional bowel disorders, its impact role in adolescents remains unknown and the contribution of different sleep dimensions may deserve further attention. This study aimed to evaluate the relationship between multiple sleep dimensions and functional bowel disorders among Chinese college freshmen. METHODS: A cross-sectional survey was conducted in college freshmen from Huazhong University of Science and Technology in Wuhan, China in September 2019 with random cluster sampling method. All participants completed questionnaires about living habits, sleep and digestive symptoms. Diagnosis of irritable bowel syndrome and functional constipation were based on the Rome IV criteria. Univariate and multivariate logistic regression models were applied to assess the association of sleep dimensions with irritable bowel syndrome or functional constipation. RESULTS: Based on the 3335 individuals who completed the questionnaire, the overall prevalence of irritable bowel syndrome and functional constipation in college freshmen were 2.5% and 1.7%, respectively. Multivariate analysis revealed that compared with individuals reporting good sleep quality, those reporting poor (OR = 7.269, 95%CI: 2.876-18.370) were associated with increased risk of irritable bowel syndrome. Similarly, those reporting fair (OR = 2.068, 95%CI: 1.010-4.236) and poor (OR = 5.664, 95%CI: 1.864-17.205) were associated with increased risk of functional constipation. There was no statistically significant association between other sleep dimensions (sleep duration, sleep timing, or sleep latency) and irritable bowel syndrome or functional constipation. CONCLUSION: Self-reported poor sleep quality was a stronger independent predictor of functional bowel disorders than other sleep dimensions among Chinese college freshmen. Future intervention studies should consider the role of sleep quality for the prevention of FBDs in adolescents.

Protocol for faecal microbiota transplantation in irritable bowel syndrome: the MISCEAT study - a randomised, double-blind cross-over study using mixed microbiota from healthy donors.

INTRODUCTION: Several studies have demonstrated dysbiosis in irritable bowel syndrome (IBS). Therefore, faecal microbiota transplantation, whose effect and safety have been proven in Clostridioides difficile infections, may hold promise in other conditions, including IBS. Our study will examine the effectiveness of stool transfer with artificially increased microbial diversity in IBS treatment. METHODS AND ANALYSIS: A three-group, double-blind,randomised, cross-over, placebo-controlled study of two pairs of gut microbiota transfer will be conducted in 99 patients with diarrhoeal or mixed type of IBS. Patients aged 18-65 will be randomised into three equally sized groups: group A will first receive two enemas of study microbiota mixture (deep-frozen stored stool microbiota mixed from eight healthy donors); after 8 weeks, they will receive two enemas with placebo (autoclaved microbiota mixture), whereas group B will first receive placebo, then microbiota mixture. Finally, group C will receive placebos only. The IBS Severity Symptom Score (IBS-SSS) questionnaires will be collected at baseline and then at weeks 3, 5, 8, 11, 13, 32. Faecal bacteriome will be profiled before and regularly after interventions using 16S rDNA next-generation sequencing. Food records, dietary questionnaires, anthropometry, bioimpedance, biochemistry and haematology workup will be obtained at study visits during the follow-up period. The primary outcome is the change in the IBS-SSS between the baseline and 4 weeks after the intervention for each patient compared with placebo. Secondary outcomes are IBS-SSS at 2 weeks after the intervention and 32 weeks compared with placebo and changes in the number of loose stools, Bristol stool scale, abdominal pain and bloating, anthropometric parameters, psychological evaluation and the gut microbiome composition. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Thomayer University Hospital, Czechia (G-18-26); study results will be published in peer-reviewed journals and presented at international conferences and patient group meetings. TRIAL REGISTRATION NUMBER: NCT04899869.