Increasing the transplant dose and repeating faecal microbiota transplantation results in the responses of male patients with IBS reaching those of females.

BACKGROUND: Faecal microbiota transplantation (FMT) performed with a proper protocol is a safe treatment for IBS that has high efficacy and durable effects. Females have been reported to respond better than males to FMT. The present study aimed at determining whether increasing the transplant dose or repeating FMT improve the responses of males to FMT. METHODS: This study included 186 IBS patients (131 females and 55 males) who were randomized at a 1:1:1 ratio to receive 90 g of donor faeces once into the large intestine, once into the small intestine or twice into the small intestine. Patients completed five questionnaires that assessed their symptoms and quality of life, and provided faecal samples at baseline and at 3, 6 and 12 months after FMT. The faecal bacterial profile and dysbiosis index were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. RESULTS: The response rates to FMT at all observation times did not differ significantly between females and males regardless of the transplant administration route or whether it was repeated. Faecal Alistipes levels were higher in females than in males at baseline and increased in both females and males after FMT. In the repeated group, the Alistipes levels did not differ between females and males after FMT. CONCLUSIONS: Increasing the transplant dose and repeating FMT results in the responses of male IBS patients to FMT reaching those of females regardless of the administration route. Alistipes spp. levels appear to play a role in this improvement.www.clinicaltrials.gov (NCT04236843).

Factors Underlying the Difference in Response to Fecal Microbiota Transplantation Between IBS Patients with Severe and Moderate Symptoms.

BACKGROUND: Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS. AIMS: The present study aimed to determine the effects of the transplant dose, route of administering it and repeating FMT on this difference. METHODS: This study included 186 patients with IBS randomized 1:1:1 into groups with a 90-g transplant administered once to the colon (LI), once to the duodenum (SI), or twice to the distal duodenum twice (repeated SI). The patients provided a fecal sample and were asked to complete three questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and Dysbiosis index were analyzed using 16 S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9. RESULTS: There was no difference in the response rates between severe IBS and moderate IBS for SI and repeated SI at all observation intervals after FMT. In the LI group, the response rate at 3 months after FMT was higher for moderate IBS than for severe IBS. The levels of Dorea spp. were higher and those of Streptococcus salivarius subsp. Thermophilus, Alistipes spp., Bacteroides and Prevotella spp., Parabacteroides johnsoni and Parabacteroides spp. were lower in moderate IBS than in severe IBS. CONCLUSIONS: There was no difference in the response to FMT between severe and moderate IBS when a 90-g transplant was administered to the small intestine. The difference in the bacterial profile between severe and moderate IBS may explain the difference in symptoms between these patients. ( www. CLINICALTRIALS: gov : NCT04236843).

Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation.

BACKGROUND & AIMS: The long-term efficacy and possible adverse events of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS) are unknown. This study performed a 3-year follow-up of the patients in our previous clinical trial to clarify these aspects. METHODS: This study included 125 patients (104 females, and 21 males): 38 in a placebo group, 42 who received 30 g of donor feces, and 45 who received 60 g of donor feces. Feces was administered to the duodenum. The patients provided a fecal sample and completed 5 questionnaires at baseline and at 2 and 3 years after FMT. Fecal bacteria and dysbiosis index were analyzed using 16S ribosomal RNA gene polymerase chain reaction DNA amplification/probe hybridization covering the V3 to V9 regions. RESULTS: Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. The response rates were significantly higher in the 30-g and 60-g groups than in the placebo group. Patients in the 30-g and 60-g groups had significantly fewer IBS symptoms and fatigue, and a greater quality of life both at 2 and 3 years after FMT. The dysbiosis index decreased only in the active treatment groups at 2 and 3 years after FMT. Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups. No long-term adverse events were recorded. CONCLUSIONS: FMT performed according to our protocol resulted in high response rates and long-standing effects with only few mild self-limited adverse events. This study was registered at www. CLINICALTRIALS: gov (NCT03822299).

The fecal microbiota transplantation response differs between patients with severe and moderate irritable bowel symptoms.

OBJECTIVES: Fecal microbiota transplantation (FMT) is a promising intervention for patients with irritable bowel syndrome (IBS). The present study aimed to identify any differences in FMT response between patients with severe and moderate IBS symptoms. MATERIALS AND METHOD: The study included the 164 patients who participated in our previous study, of which 96 (58.5%) and 68 (41.5%) had severe (S-IBS-S) and moderate (Mo-IBS-S) IBS, respectively. The patients were randomly divided into a placebo group (own feces) and 30-g and 60-g (donor feces) FMT groups. Patients completed three questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT, and provided fecal samples before and 1 month after FMT. The fecal bacteria were analyzed using the 16S rRNA gene in PCR DNA amplification covering the V3-V9 variable genes. RESULTS: Response rates of the placebo group did not differ between S-IBS-S and Mo-IBS-S patients at 2 weeks, 1 month and 3 months after FMT. The response rates in the active treatment group were higher in S-IBS-S patients than in Mo-IBS-S patients at each observation time. FMT reduced abdominal symptoms and fatigue and improved the quality of life in patients with both severe and moderate IBS. Patients with S-IBS-S had higher levels of Eubacterium siraeum, and lower levels of Eubacterium rectale than Mo-IBS-S, after FMT. CONCLUSION: Patients with S-IBS-S have a higher response rate to FMT and a marked improvement in fatigue and in quality of life compared with those with Mo-IBS-S. The clinical trial registration number is NCT03822299 and is available at www.clinicaltrials.gov.

Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study.

OBJECTIVE: Faecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in two previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings. DESIGN: This randomised, double-blind, placebo-controlled study randomised 165 patients with IBS to placebo (own faeces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from one healthy, well-characterised donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analysed by 16S rRNA gene sequencing, at 1 month following FMT. RESULTS: Responses occurred in 23.6%, 76.9% (p<0.0001) and 89.1% (p<00.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms. CONCLUSIONS: FMT is an effective treatment for patients with IBS. Utilising a well-defined donor with a normal DI and favourable specific microbial signature is essential for successful FMT. The response to FMT increases with the dose. Trial registration www.clinicaltrials.gov (NCT03822299) and www.cristin.no (ID657402).

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.

Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome.

OBJECTIVE: Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients. METHODS: Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included. A standard colonoscopy was performed in both the patients and controls, and biopsy samples were taken from the colon and the rectum. The biopsy samples were stained with hematoxylin-eosin and immunostained for CgA. The density of CgA cells was determined by computerized image analysis. RESULTS: In the colon and rectum, the CgA cell densities were far higher in both IBS and healthy Thai subjects than in Norwegians. The colonic CgA cell density was lower in Norwegian IBS patients than in controls, but did not differ between Thai IBS patients and controls. In the rectum, the CgA cell densities in both Thai and Norwegian patients did not differ from those of controls. CONCLUSIONS: The higher densities of CgA cells in Thai subjects than Norwegians may be explained by a higher exposure to infections at childhood and the development of a broad immune tolerance, by differences in the intestinal microbiota, and/or differing diet habits. The normal CgA cell density in Thai IBS patients in contrast to that of Norwegians may be due to differences in pathophysiology.

Enteroendocrine, Musashi 1 and neurogenin 3 cells in the large intestine of Thai and Norwegian patients with irritable bowel syndrome.

OBJECTIVES: The prevalence, gender distribution and clinical presentation of IBS differ between Asian and Western countries. This study aimed at studying and comparing enteroendocrine, Musashi 1 (Msi 1) and neurogenin 3 (neurog 3) cells in Thai and Norwegian IBS patients. MATERIAL AND METHODS: Thirty Thai and 61 Norwegian IBS patients as well as 20 Thai and 24 Norwegian controls were included. Biopsy samples were taken from each of the sigmoid colon and the rectum during a standard colonoscopy. The samples were immunostained for serotonin, peptide YY, oxyntomodulin, pancreatic polypeptide, somatostatin, Msi 1 and neurog 3. The densities of immunoreactive cells were determined with computerized image analysis. RESULTS: The densities of several enteroendocrine cell types were altered in both the colon and rectum of both Thai and Norwegian IBS patients. Some of these changes were similar in Thai and Norwegian IBS patients, while others differed. CONCLUSIONS: The findings of abnormal densities of the enteroendocrine cells in Thai patients support the notion that enteroendocrine cells are involved in the pathophysiology of IBS. The present observations highlight that IBS differs in Asian and Western countries, and show that the changes in large-intestine enteroendocrine cells in Thai and Norwegian IBS patients might be caused by different mechanisms.

The relation between celiac disease, nonceliac gluten sensitivity and irritable bowel syndrome.

Wheat products make a substantial contribution to the dietary intake of many people worldwide. Despite the many beneficial aspects of consuming wheat products, it is also responsible for several diseases such as celiac disease (CD), wheat allergy, and nonceliac gluten sensitivity (NCGS). CD and irritable bowel syndrome (IBS) patients have similar gastrointestinal symptoms, which can result in CD patients being misdiagnosed as having IBS. Therefore, CD should be excluded in IBS patients. A considerable proportion of CD patients suffer from IBS symptoms despite adherence to a gluten-free diet (GFD). The inflammation caused by gluten intake may not completely subside in some CD patients. It is not clear that gluten triggers the symptoms in NCGS, but there is compelling evidence that carbohydrates (fructans and galactans) in wheat does. It is likely that NCGS patients are a group of self-diagnosed IBS patients who self-treat by adhering to a GFD.

Factors affecting the outcome of fecal microbiota transplantation for patients with irritable bowel syndrome.

BACKGROUND: A previous study that introduced a Fecal microbiota transplantation (FMT) protocol with a high efficacy applied a combination of favorable factors. AIMS: The present study aimed to evaluate some of these factors. METHODS: This study included 186 patients with IBS randomized 1:1:1 into transplant administered to the colon (single LI), to the duodenum (single SI), or to the duodenum twice with a 1-week interval (repeated SI). The patients provided a fecal sample and were asked to complete five questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and dysbiosis index (DI) were analyzed using 16S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9. RESULTS: The response rate was significantly higher in single SI than in single LI at 12 months after FMT. Symptoms and quality of life improved in all the treated groups at all time intervals after FMT. The abdominal symptoms were significantly reduced and the quality of life improved for repeated SI compared with for single SI. DI significantly decreased in all the treated groups at all observation times after FMT. The bacterial profiles changed in all groups at all observation intervals. However, these changes differed between single LI and single SI/repeated SI. CONCLUSION: Administrating transplant to the small intestine had a long-term higher response rate than that administrated to the large intestine, and led to long-term colonization of beneficial bacteria. Repeating FMT had more effect on symptoms and quality of life than a single FMT. (www. CLINICALTRIALS: gov: NCT04236843).

Factors underlying the long-term efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome.

The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures (www.clinicaltrials.gov: NCT04236843).

Diet, Food, and Nutritional Exposures and Inflammatory Bowel Disease or Progression of Disease: an Umbrella Review.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), contributes to substantial morbidity. Understanding the intricate interplay between dietary factors and the incidence and progression of IBD is essential for developing effective preventative and therapeutic strategies. This umbrella review comprehensively synthesizes evidence from systematic reviews and meta-analyses to evaluate these complex associations. Dietary factors associated with an increased incidence and/or progression of IBD include a high intake of red and processed meat, other processed foods, and refined sugars, together with a low intake of vegetables, fruits, and fiber. For most other food groups, the results are mixed or indicate no clear associations with IBD, CD, and UC. Some differences seem to exist between UC and CD and their risk factors, with increased intake of dietary fiber being inversely associated with CD incidence but not clearly associated with UC. Dietary fiber may contribute to maintaining the gut epithelial barrier and reduce inflammation, often through interactions with the gut microbiota. This seems to play an important role in inflammatory mechanisms in the gut and in IBD incidence and progression. Diets low in fermentable saccharides and polyols can alleviate symptom burden, but there are concerns regarding their impact on the gut microbiota and their nutritional adequacy. Mediterranean diets, vegetarian diets, and a diet low in grains, sugars, and lactose (specific carbohydrate diet) are also associated with lower incidence and/or progression of IBD. The associations of dietary patterns are mirrored by inflammatory biomarkers. IBD is typically treated pharmaceutically; however, many patients have a suboptimal response to medical treatments. The findings from this umbrella review could provide evidence for nutritional counseling and be a valuable addition to traditional treatment plans for IBD. This systematic review was registered at PROSPERO as CRD440252.

The outcome of primary per oral endoscopic myotomy (POEM) for treatment of achalasia: Norwegian single-center experience with long-term follow-up.

BACKGROUND AND AIMS: Per oral endoscopic myotomy (POEM) has become an established treatment for achalasia, but no Scandinavian studies with long-term follow-up exist. This study from a tertiary referral center in Norway investigates the short-, mid-, and long-term feasibility, safety, efficacy, and complications of POEM. METHODS: Prospective data from the first 84 patients who underwent POEM from 2014 to 2019 were analyzed. The median follow-up time was 44 months. Clinical success was defined as the Eckardt score (ES) ⩽3, and reflux as pathological if the acid exposure time (pH < 4) was more than 6%. ES was used for symptom evaluation before, and at 6, 12, and up to 64 months after POEM. RESULTS: A total of 50 males and 34 females were included. A total of 43 (51%) were treatment naïve, 24 (28.6%) had been previously treated with botulinum toxin, pneumatic balloon dilatation, or both, and 17 (20.2%) were previously treated with Heller's myotomy. The median post-POEM ES at 12 months was 1 (0-9), compared to pre-POEM 7 (4-12) (p < 0.01). At 12 months after POEM, clinical success persisted in 74 patients (88.1%). Clinical success was the highest for patients who were naïve to treatment, 41/43 (95%), and lower for those previously treated with Heller's myotomy 12/17 (70.6%). Long-term follow-up at 5-6 years of 42 patients showed a clinical success rate of 94%. We experienced adverse events in five patients (6%). Post-POEM pathological reflux was found in 46% (28/61). After 3-4 years, the median ES was 1, and after 5-6 years, it was 2. CONCLUSION: POEM was safe and relieved the symptoms of achalasia significantly and persistently. The procedure had a better outcome in treatment naïve than previously treated patients. However, POEM is associated with significantly increased esophageal acid exposure. TWITTER SUMMARY: Norwegian single-center study: POEM had a clinical success rate of 94% after 5-6 years since its introduction at the center in 2014, providing a safe and effective treatment for achalasia.

Irritable bowel syndrome patients who are not likely to respond to fecal microbiota transplantation.

BACKGROUND: Fecal microbiota transplantation (FMT) interventions have recently been advocated to not succeed in every irritable bowel syndrome (IBS) patient, since the outcome of FMT varies with the IBS subset. This study investigated the factors potentially affecting FMT response using the same patient cohort used in our previous study. METHODS: This study included 109 patients who received allogenic FMT. Patients completed five questionnaires that assessed their symptoms and quality of life at baseline and at 2 weeks, 1 month, and 3 months after FMT. Patients also provided fecal samples at baseline and 1 month after FMT. The fecal bacterial profile and dysbiosis index (DI) were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9. Response to FMT was defined as a decrease of ≥50 points in the total IBS-SSS score after FMT. RESULTS: An IBS patient's response or nonresponse to FMT was not determined by age, IBS duration, IBS subtype, IBS symptoms, fatigue, quality of life, or DI. There were more male nonresponders than responders, and the fluorescence signals of Alistipes were lower in nonresponders than in responders. CONCLUSIONS: We concluded that IBS patients who are male and/or have low fecal Alistipes levels are most likely to not respond to FMT treatment. Whether low fecal Alistipes levels could be used as a marker for predicting the outcome of FMT remains to be determined. www. CLINICALTRIALS: gov (NCT03822299).

The Effect of Anaerobically Cultivated Human Intestinal Microbiota Compared to Fecal Microbiota Transplantation on Gut Microbiota Profile and Symptoms of Irritable Bowel Syndrome, a Double-Blind Placebo-Controlled Study.

Fecal microbiota transplantation (FMT) from healthy donors has been shown to improve the symptoms of irritable bowel syndrome (IBS) and changes the profile of the gut microbiota for the recipients. Alternatively, anaerobically cultivated human intestinal microbiota (ACHIM) can be used to manipulate the gut microbiota. The aim of the current study was to compare the efficacy and safety of ACHIM suspension with donor-FMT and placebo (patient's own feces) to treat IBS. Out of the 62 originally included eligible patients with diarrhea-predominant IBS and their respective donors, only 43 patients completed the study by answering the questionnaires and delivering fecal samples before transplantation and after 1, 4, 12 and 24 weeks. The patients were randomized into three subgroups for receiving ACHIM suspension (n = 17), donor-FMT (n = 11), or placebo (n = 15), and were followed up for 24 weeks. Fecal samples were analyzed by sequencing 16S rRNA gene using the GA-map Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). IBS symptom questionnaires improved in all three subgroups. Bacterial strain signals in IBS patients were more significant for Actinobacteria spp. and Bifidobacteria spp. after receiving donor-FMT compared to placebo and for Alistipes onderdonkii before and after treatment in the subgroups of ACHIM and donor-FMT vs. placebo. These signals change after treatment with ACHIM suspension and donor FMT towards those measured for healthy controls, but not after placebo. IBS symptom questionnaires improved in all three forms of transplantation. Some bacterial strain signals were significantly different between ACHIM and donor-FMT vs. placebo. However, the placebo subgroup failed to change the gut microbiota towards signals measured for healthy controls. The safety and efficacy of ACHIM and donor-FMT seems similar in the current study, but further larger studies are needed.

Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome.

BACKGROUND: We recently found fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) patients to be an effective and safe treatment after 3 months. The present follow-up study investigated the efficacy and safety of FMT at 1 year after treatment. METHODS: This study included 77 of the 91 IBS patients who had responded to FMT in our previous study. Patients provided a fecal sample and completed five questionnaires to assess their symptoms and quality of life at 1 year after FMT. The dysbiosis index (DI) and fecal bacterial profile were analyzed using a 16S rRNA gene-based DNA probe hybridization. The levels of fecal short-chain fatty acids (SCFAs) were determined by gas chromatography. RESULTS: There was a persistent response to FMT at 1 year after treatment in 32 (86.5%) and 35 (87.5%) patients who received 30-g and 60-g FMT, respectively. In the 30-g FMT group, 12 (32.4%) and 8 (21.6%) patients showed complete remission at 1 year and 3 months, respectively; the corresponding numbers in the 60-g FMT group were 18 (45%) and 11 (27.5%), respectively. Abdominal symptoms and the quality of life were improved at 1 year compared with after 3 months. These findings were accompanied by comprehensive changes in the fecal bacterial profile and SCFAs. CONCLUSIONS: Most of the IBS patients maintained a response at 1 year after FMT. Moreover, the improvements in symptoms and quality of life increased over time. Changes in DI, fecal bacterial profile and SCFAs were more comprehensive at 1 year than after 3 months. www.clinicaltrials.gov (NCT03822299).

Current status of fecal microbiota transplantation for irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder. Although IBS is a benign condition, it reduces the quality of life considerably. While there is currently no effective treatment for this disorder, fecal microbiota transplantation (FMT) seems to be promising. PURPOSE: The aim of this review was to analysis possible factors affecting the success or failure of the randomized controlled trials (RCTs) of FMT for IBS and highlighting the gaps in our knowledge that need to be filled and of sketching a possible model for successful FMT in IBS patients. METHODS: A systematic search was conducted of literature published in English from January 2015 to December 2020 using the keywords: fecal microbiota transplantation, randomized trials, and IBS. KEY RESULTS: Seven randomized controlled trials (RCTs) on the efficacy of FMT for IBS were found in the literature. Four of the seven RCTs found various positive effects, while the other three did not find any effect. CONCLUSIONS AND INFERENCES: The efficacy of FMT for IBS appears to be donor-dependent. The effective (super) donor would need to have a favorable microbiota signature, and 11 clinical criteria that are known to be associated with a favorable microbiota have been suggested for selecting FMT donors for IBS. Comparing the microbiota of the effective donors with those of healthy subjects would reveal the favorable microbiota signature required for a super-donor. However, the studies reviewed were not designed to compare efficacy of different donor types. The dose of the fecal transplant is also an important factor influencing the outcome of FMT for IBS. However, further studies designed to test the effect of fecal transplant dose are needed to answer this question. Administering the fecal transplant to either the small or large intestine seems to be effective, but the optimal route of administration remains to be determined. Moreover, whether single or repeated FMT is more effective is also still unclear. A 1-year follow-up of IBS patients who received FMT showed that adverse events of abdominal pain, diarrhea, and constipation were both mild and self-limiting.

Responses to faecal microbiota transplantation in female and male patients with irritable bowel syndrome.

BACKGROUND: Faecal microbiota transplantation (FMT) seems to be a promising treatment for irritable bowel syndrome (IBS) patients. In Western countries (United States and Europe), there is a female predominance in IBS. A sex difference in the response to FMT has been reported recently in IBS patients. AIM: To investigate whether there was a sex difference in the response to FMT in the IBS patients who were included in our previous randomized controlled trial of the efficacy of FMT. METHODS: The study included 164 IBS patients who participated in our previous randomized controlled trial. These patients had moderate-to-severe IBS symptoms belonging to the IBS-D (diarrhoea-predominant), IBS-C (constipation-predominant) and IBS-M (mixed) subtypes, and had not responded to the National Institute for Health and Care Excellence (NICE)-modified diet. They belonged in three groups: placebo (own faeces), and active treated group (30-g or 60-g superdonor faeces). The patients completed the IBS severity scoring system (IBS-SSS), Fatigue Assessment Scale (FAS) and the IBS quality of life scale (IBS-QoL) questionnaires at the baseline and 2 wk, 1 mo and 3 mo after FMT. They also provided faecal samples at the baseline and 1 mo after FMT. The faecal bacteria profile and dysbiosis were determined using the 16S rRNA gene polymerase chain reaction DNA amplification covering V3-V9; probe labelling by single nucleotide extension and signal detection. The levels of short-chain fatty acids (SCFAs) were determined by gas chromatography and flame ionization. RESULTS: There was no sex difference in the response to FMT either in the placebo group or active treated group. There was no difference between females and males in either the placebo group or actively treated groups in the total score on the IBS-SSS, FAS or IBS-QoL, in dysbiosis, or in the faecal bacteria or SCFA level. However, the response rate was significantly higher in females with diarrhoea-predominant (IBS-D) than that of males at 1 mo, and 3 mo after FMT. Moreover, IBS-SSS total score was significantly lower in female patients with IBS-D than that of male patients both 1 mo and 3 mo after FMT. CONCLUSION: There was no sex difference in the response to FMT among IBS patients with moderate-to-severe symptoms who had previously not responded to NICE-modified diet. However, female patients with IBS-D respond better and have higher reduction of symptoms than males after FMT.

Ultrasound imaging for assessing functions of the GI tract.

OBJECTIVE: In the following review we outline how ultrasound can be used to measure physiological processes in the gastrointestinal tract. APPROACH: We have investigated the potential of ultrasound in assessing gastrointestinal physiology including original research regarding both basic methodology and clinical applications. MAIN RESULTS: Our main findings show the use of ultrasound to study esophageal motility, measure volume and contractility of the stomach, assess motility, wall thickness, and perfusion of the small bowel, and evaluate wall vascularization and diameters of the large bowel. SIGNIFICANCE: Ultrasound is a widely accessible technology that can be used for both scientific and clinical purposes. Being radiation-free and user friendly, the examination can be frequently repeated enabling longitudinal studies. Furthermore, it does not influence normal GI physiology, thus being useful to estimate motility and subtle changes in physiology. Accordingly, ultrasound scanning and physiological measurements may make a big difference for the scientist and the doctor; and for the patients who receive an efficient work-up.

Gastroparesis Symptoms Associated with Intestinal Hypomotility: An Explorative Study Using Wireless Motility Capsule.

OBJECTIVE: Gastric emptying measurements are mandatory in gastroparesis diagnostics, but the association between delayed emptying and symptoms is questionable. It is imperative to find biomarkers better correlated to symptom generation. Hence, we examined the association between symptom severity and gastrointestinal motility measured by wireless motility capsule. PATIENTS AND METHODS: In this prospective single-centre study, patients with gastroparesis symptoms were simultaneously investigated with gastric emptying scintigraphy and wireless motility capsule, measuring regional transit times and contractility parameters. Symptom severity was assessed with the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM), including the Gastroparesis Cardinal Symptom Index (GCSI). RESULTS: We included 107 patients (70% women). In the whole patient group, nausea correlated with the gastric (rs = -0.31, p = 0.007), small bowel (rs = -0.41, p < 0.001) and colonic (rs = -0.33, p = 0.012) motility indices. In patients with idiopathic etiology, nausea correlated with small bowel motility index (rs = -0.81, p < 0.001) and mean stomach pressure (rs = -0.64, p = 0.013). We also found negative correlations between total GCSI score and maximum pressure of the small bowel (rs = -0.77, p < 0.001) and colon (rs = -0.74, p = 0.002). In diabetes patients, total PAGI-SYM score correlated with colonic motility index (rs = -0.34, p = 0.012), and mean pressure of the colon correlated with upper abdominal pain (rs = -0.37, p = 0.007). We found no association between symptoms, gastric emptying nor any other transit times. CONCLUSION: In patients with gastroparesis symptoms, we found that symptom severity was associated with intestinal hypomotility. Based on these results, gastroparesis diagnostics should also include an evaluation of the small bowel and colon.