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).

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).

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).

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).

Intestinal bacteria associated with irritable bowel syndrome and chronic fatigue.

The etiology of irritable bowel syndrome (IBS) is unknown. Abnormal intestinal bacterial profiles and low bacterial diversity appear to play important roles in the pathophysiology of IBS. This narrative review was designed to present recent observations made relating to fecal microbiota transplantation (FMT), which implicate possible roles of 11 intestinal bacteria in the pathophysiology of IBS. The intestinal abundances of nine of these bacteria increased after FMT in patients with IBS, and these increases were inversely correlated with IBS symptoms and fatigue severity. These bacteria were Alistipes spp., Faecalibacterium prausnitzii, Eubacterium biforme, Holdemanella biformis, Prevotella spp., Bacteroides stercoris, Parabacteroides johnsonii, Bacteroides zoogleoformans, and Lactobacillus spp. The intestinal abundances of two bacteria were decreased in patients with IBS after FMT and were correlated with the severity of IBS symptoms and fatigue (Streptococcus thermophilus and Coprobacillus cateniformis). Ten of these bacteria are anaerobic and one (Streptococcus thermophilus) is facultative anaerobic. Several of these bacteria produce short-chain fatty acids, especially butyrate, which is used as an energy source by large intestine epithelial cells. Moreover, it modulates the immune response and hypersensitivity of the large intestine and decreases intestinal cell permeability and intestinal motility. These bacteria could be used as probiotics to improve these conditions. Protein-rich diets could increase the intestinal abundance of Alistipes, and plant-rich diet could increase the intestinal abundance of Prevotella spp., and consequently improve IBS and fatigue.

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.

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).

Changes in colonic enteroendocrine cells of patients with irritable bowel syndrome following fecal microbiota transplantation.

OBJECTIVES: The aim was to investigate the effect of fecal microbiota transplantation (FMT) on colonic enteroendocrine cells densities in patients with irritable bowel syndrome (IBS). MATERIALS AND METHODS: This study is connected to the REFIT study, a double-blinded placebo-controlled trial to investigate using FMT for IBS treatment. Eighty-three subjects received either donor-FMT or placebo FMT (own feces) by colonoscope to cecum. Biopsies were obtained from sigmoid colon. Ten responders and ten non-responders consented to new biopsy one-year after FMT. Sixteen patients received donor-FMT and four received placebo FMT. Biopsies were immunostained for all of the colonic enteroendocrine cells and were quantified using computerized image analysis.Allocation sequence was revealed after obtaining re-biopsies and cells quantification. RESULTS: Scores for IBS-SSS (mean ± SEM) of responders (eight of 10 patients who received donor FMT) and non-responders changed from baseline to one year after FMT (297 ± 11 and 81 ± 16, p < .0001, and 270 ± 17 and 291 ± 16, p = .15, respectively). Using paired t-test to compare enteroendocrine cells densities one-year after FMT to baseline showed significant increase only in somatostatin immunoreactive cells density in the total IBS responders group (p = .023) and who received donor-FMT (p = .038). The densities of peptide YY and enteroglucagon immunoreactive cells increased significantly (p = .04 and .035, respectively) in donor-FMT recipients. No significant changes were noted in placebo FMT or nonresponders subgroups. CONCLUSION: This study shows that colonic enteroendocrine cells densities significantly change in responders group that received donor-FMT. The mechanisms for the cross talks between gut microbiota and colonic enteroendocrine cells remain to be investigated.

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).

Inhibition of Cellular and Animal Inflammatory Disease Models by NF-κB Inhibitor DHMEQ.

General inflammatory diseases include skin inflammation, rheumatoid arthritis, inflammatory bowel diseases, sepsis, arteriosclerosis, and asthma. Although these diseases have been extensively studied, most of them are still difficult to treat. Meanwhile, NF-κB is a transcription factor promoting the expression of many inflammatory mediators. NF-κB is likely to be involved in the mechanism of most inflammatory diseases. We discovered a specific NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), about 20 years ago by molecular design from a natural product. It directly binds to and inactivates NF-κB components. It has been widely used to suppress cellular and animal inflammatory disease models and was shown to be potent in vivo anti-inflammatory activity without any toxicity. We have prepared ointment of DHMEQ for the treatment of severe skin inflammation. It inhibited inflammatory cytokine expressions and lowered the clinical score in mouse models of atopic dermatitis. Intraperitoneal (IP) administration of DHMEQ ameliorated various disease models of inflammation, such as rheumatoid arthritis, sepsis, and also graft rejection. It has been suggested that inflammatory cells in the peritoneal cavity would be important for most peripheral inflammation. In the present review, we describe the synthesis, mechanism of action, and cellular and in vivo anti-inflammatory activities and discuss the clinical use of DHMEQ for inflammatory diseases.

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.

Fecal microbiota transplantation for irritable bowel syndrome: An intervention for the 21st century.

Irritable bowel syndrome (IBS) affects about 12% of the global population. Although IBS does not develop into a serious disease or increase mortality, it results in a considerable reduction in the quality of life. The etiology of IBS is not known, but the intestinal microbiota appears to play a pivotal role in its pathophysiology. There is no effective treatment for IBS, and so the applied treatments clinically focus on symptom relief. Fecal microbiota transplantation (FMT), an old Chinese treatment, has been applied to IBS patients in seven randomized controlled trials (RCTs). Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs, while there was no effect in the remaining three. Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients, the transplant dose, the route of administration, and the methods used to measure how the patients responded to FMT. The present frontier discusses these differences and proposes: (1) criteria for selecting an effective donor (superdonor); (2) selection criteria for patients that are suitable for FMT; (3) the optimal FMT dose; and (4) the route of transplant administration. FMT appears to be safe, with only mild, self-limiting side effects of abdominal pain, cramping, tenderness, diarrhea, and constipation. Although it is early to speculate about the mechanisms underlying the effects of FMT, the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products (specifically short-chain fatty acids) play an important role in improving the IBS symptoms seen after FMT. FMT appears to be a promising treatment for IBS, but further studies are needed before it can be applied in everyday clinical practice.

The Effects of Fecal Microbiota Transplantation on the Symptoms and the Duodenal Neurogenin 3, Musashi 1, and Enteroendocrine Cells in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.

Introduction: Interactions between the gut microbiota and enteroendocrine cells play important role in irritable bowel syndrome (IBS). Reduced stem cell densities and their differentiation into enteroendocrine cells may cause abnormal densities of the duodenal enteroendocrine cells in IBS patients. Materials and Methods: We aimed to investigate the effects of fecal microbiota transplantation (FMT) on stem cell differentiation into enteroendocrine cells as detected by neurogenin 3, stem cells as detected by Musashi 1, and the enteroendocrine cells in the duodenum of IBS patients. The study included 16 IBS patients according to Rome III criteria. Four patients were excluded. The remaining patients (n = 12, four females and eight males) were divided according to the cause of IBS into post-infectious (n = 6) and idiopathic (n = 6) IBS. They completed the following questionnaires before and 3 weeks after FMT: IBS-Symptom Severity Scoring system (IBS-SSS) and IBS-Symptom Questionnaire (IBS-SQ). Feces donated by healthy relatives of the patients were transplanted via gastroscope. Biopsies were taken from the descending part of the duodenum at baseline and 3 weeks after FMT. They were immunostained for neurogenin 3, Musashi 1, and all types of duodenal enteroendocrine cells and quantified by computerized image analysis. Microbiota analyses of feces collected just before and 3 weeks after FMT were performed using GA-map™ Dysbiosis test (Genetic Analysis AS, Oslo, Norway). Results: The total scores for IBS-SSS and IBS-SQ were significantly improved 3 weeks after receiving FMT, P = 0.0009 and <0.0001, respectively. The stem cell densities of neurogenin 3 increased significantly following FMT (P = 0.0006) but not for Musashi 1 (P = 0.42). The cell densities of chromogranin A, cholecystokinin, gastric inhibitory peptide, serotonin, and somatostatin, but not for secretin, have significantly changed in both IBS groups after 3 weeks from receiving FMT. Conclusion: More than two-thirds of IBS patients experienced improvement in their symptoms parallel to changes in the enteroendocrine cells densities 3 weeks after FMT. The changes in the enteroendocrine cell densities do not appear to be caused by changes in the stem cells or their early progenitors rather by changes in the differentiation progeny as detected by neurogenin 3. The study was retrospectively registered at ClinicalTrials.gov (ID: NCT03333291). Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03333291.

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.

The role of diet in the pathophysiology and management of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder that reportedly affects 5% to 20% of the world population. The etiology of IBS is not completely understood, but diet appears to play an important role in its pathophysiology. Asian diets differ considerably from those in Western countries, which might explain differences in the prevalence, sex, and clinical presentation seen between patients with IBS in Asian and Western countries. Dietary regimes such as a low-fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet and the modified National Institute for Health and Care Excellence (NICE) diet improve both symptoms and the quality of life in a considerable proportion of IBS patients. It has been speculated that diet is a prebiotic for the intestinal microbiota and favors the growth of certain bacteria. These bacteria ferment the dietary components, and the products of fermentation act upon intestinal stem cells to influence their differentiation into enteroendocrine cells. The resulting low density of enteroendocrine cells accompanied by low levels of certain hormones gives rise to intestinal dysmotility, visceral hypersensitivity, and abnormal secretion. This hypothesis is supported by the finding that changing to a low-FODMAP diet restores the density of GI cells to the levels in healthy subjects. These changes in gut endocrine cells caused by low-FODMAP diet are also accompanied by improvements in symptoms and the quality of life.

Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.

BACKGROUND: Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT. METHODS: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography. KEY RESULTS: The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P ≤ 0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P = 0.001, r = -0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT. CONCLUSION AND INFERENCES: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).