Increasing the Dose and/or Repeating Faecal Microbiota Transplantation (FMT) Increases the Response in Patients with Irritable Bowel Syndrome (IBS).
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SUBMITTER: El-Salhy M
PROVIDER: S-EPMC6628324 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Increasing the Dose and/or Repeating Faecal Microbiota Transplantation (FMT) Increases the Response in Patients with Irritable Bowel Syndrome (IBS).
El-Salhy Magdy M Hausken Trygve T Hatlebakk Jan Gunnar JG
Nutrients 20190624 6
<h4>Background</h4>Faecal microbiome transplantation (FMT) appears to be an effective method for treating irritable bowel syndrome (IBS) patients. However, it is not clear if a high transplant dose and/or repeating FMT are/is needed to ensure a response. The present study was undertaken to clarify this matter.<h4>Methods</h4>Ten IBS patients who did not respond to a 30-g transplant subsequently received a 60-g transplant into the duodenum via a gastroscope. The patients provided faecal samples b ...[more]
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Project description:BackgroundFaecal 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.AimTo 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.MethodsThe 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.ResultsThere 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.ConclusionThere 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.
| S-EPMC8117742 | biostudies-literature
Project description:Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with alterations in bowel function. Given the heterogeneity of the symptoms, multiple pathophysiologic factors are suspected to play a role. We classified women with IBS into four subgroups based on distinct symptom profiles. In-depth shotgun proteomic analysis was carried out to profile the urinary proteomes to identify possible proteins associated with these subgroups. First void urine samples with urine creatinine level?100 mg/dL were used after excluding samples that tested positive for blood. Urine from 10 subjects representing each symptom subgroup was pooled for proteomic analysis. The urine proteome was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a data-independent method known as Precursor Acquisition Independent From Ion Count (PAcIFIC) that allowed extended detectable dynamic range. Differences in protein quantities were determined by peptide spectral counting followed by validation of select proteins with ELISA or a targeted single reaction monitoring (LC-SRM/MS) approach. Four IBS symptom subgroups were selected: (1) Constipation, (2) Diarrhea+Low Pain, (3) Diarrhea+High Pain, and (4) High Pain+High Psychological Distress. A fifth group consisted of Healthy Control subjects. From comparisons of quantitative spectral counting data among the symptom subgroups and controls, a total of 18 proteins that showed quantitative differences in relative abundance and possible physiological relevance to IBS were selected for further investigation. Three of the 18 proteins were chosen for validation by either ELISA or SRM. An elevated expression of gelsolin (GSN) was associated with the high pain groups. Trefoil Factor 3 (TFF3) levels were higher in IBS groups compared to controls. In this study, the IBS patients subclassified by predominant symptoms showed differences in urine proteome levels. Proteins showing distinctive changes are involved in homeostasis of intestinal function and inflammatory response. These findings warrant future studies with larger, independent cohorts to enable more extensive assessment and validation of urinary protein markers as a diagnostic tool in adults with IBS.
| S-EPMC3631108 | biostudies-literature
Project description:Abnormal gut-brain interactions are common in irritable bowel syndrome (IBS), but the associations between neurophysiological measures and their relation to gastrointestinal (GI) symptoms are poorly understood. Our aim was to explore these relationships and define the most relevant neurophysiology measures for GI symptom severity in IBS. IBS patients underwent small intestinal motility (manometry; fasted and fed contraction frequency, phase III time) and secretion (transmural potential difference), rectal sensorimotor (barostat; sensory thresholds, tone response, compliance), autonomic nervous system (baroreceptor sensitivity and effectiveness), and colonic motor function (transit time) examinations. GI symptom severity (GSRS-IBS), and anxiety and depression (HAD) as a proxy measure of central nervous system (CNS) dysfunction, were assessed. In total 281 IBS patients (Rome II criteria) were included (74% females, median age 36 [interquartile range 28-50] years). Significant correlations between neurophysiology measures were stronger within, rather than between, different neurophysiological examinations. The strongest neurophysiology-symptom correlations occurred between a combination of CNS and visceral sensitivity parameters, and GSRS-IBS total score and pain domain (??=?0.40, p?<?0.001, and ??=?0.38, p?<?0.001). Associations between GI symptoms in IBS and individual and combinations of neurophysiological factors occurred, primarily in CNS and visceral sensitivity measures, providing new insights into the clinical presentation of IBS.
| S-EPMC7300023 | biostudies-literature
Project description:ObjectiveSome IBS patients possess detailed memories of the events surrounding their bowel symptom onset ("episodic memories"). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.MethodsReferral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories.Results14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories.ConclusionsIBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.
| S-EPMC9243497 | biostudies-literature
Project description:BackgroundAlthough irritable bowel syndrome (IBS) is more common in women, little is known about the role of hormonal changes and menopause in IBS. This study aimed to evaluate for differences in gastrointestinal (GI) and psychological symptoms between pre- and postmenopausal women with IBS compared to age-matched men with IBS.MethodsPatients with Rome-positive IBS were identified. Premenopausal women were <45 years of age with regular menses. Postmenopausal women were ≥45 years without menses for at least 1 year. Younger men were <45 years, and older men were ≥45 years. Questionnaires measured severity of IBS symptoms, somatic symptoms, health-related quality of life (HRQOL), and psychological symptoms. Multivariable linear or logistic regressions evaluating relationships between age and sex were performed.Key results190 premenopausal women (mean age 30.25 years), 52 postmenopausal women (mean age 54.38 years), 190 men <45 years (mean age 30.45 years), and 52 men ≥45 years (mean age 53.37 years) were included. Postmenopausal IBS women had greater severity of IBS symptoms (P = .003) and worse physical HRQOL (P = .048) compared to premenopausal women. No differences were observed between age-matched older and younger IBS men. Constipation increased with age for both sexes but was the principal IBS subtype in women only.Conclusions and inferencesPostmenopausal women with IBS have more severe IBS symptoms than premenopausal women, while no comparable age-related changes were seen in IBS men. The modulatory effect of female sex hormones on brain-gut interactions which affect visceral perception and GI function likely contributes to these findings.
| S-EPMC7529855 | biostudies-literature
Project description:BackgroundDiarrhea-predominant irritable bowel syndrome (IBS-d) significantly diminishes the health-related quality of life (HRQOL) of patients. Psychological and social impacts are common with many IBS-d patients reporting comorbid depression, anxiety, decreased intimacy, and lost working days. The Irritable Bowel Syndrome Quality of Life (IBS-QOL) questionnaire is a 34-item instrument developed and validated for measurement of HRQOL in non-subtyped IBS patients. The current paper assesses this previously-validated instrument employing data collected from 754 patients who participated in a randomized clinical trial of a novel treatment, eluxadoline, for IBS-d.MethodsPsychometric methods common to HRQOL research were employed to evaluate the IBS-QOL. Many of the historical analyses of the IBS-QOL validations were used. Other techniques that extended the original methods were applied where more appropriate for the current dataset. In IBS-d patients, we analyzed the items and substructure of the IBS-QOL via item reduction, factor structure, internal consistency, reproducibility, construct validity, and ability to detect change.ResultsThis study supports the IBS-QOL as a psychometrically valid measure. Factor analyses suggested that IBS-specific QOL as measured by the IBS-QOL is a unidimensional construct. Construct validity was further buttressed by significant correlations between IBS-QOL total scores and related measures of IBS-d severity including the historically-relevant Irritable Bowel Syndrome Adequate Relief (IBS-AR) item and the FDA's Clinical Responder definition. The IBS-QOL also showed a significant ability to detect change as evidenced by analysis of treatment effects. A minority of the items, unrelated to the IBS-d, performed less well by the standards set by the original authors.ConclusionsWe established that the IBS-QOL total score is a psychometrically valid measure of HRQOL in IBS-d patients enrolled in this study. Our analyses suggest that the IBS-QOL items demonstrate very good construct validity and ability to detect changes due to treatment effects. Furthermore, our analyses suggest that the IBS-QOL items measure a univariate construct and we believe further modeling of the IBS-QOL from an item response theory (IRT) approach under both non-treatment and treatment conditions would greatly further our understanding as item-based methods could be used to develop a short form.
| S-EPMC3895767 | biostudies-literature
Project description:BackgroundAnxiety and depression are complications in Irritable bowel syndrome (IBS) patients. In this study, we recruited 18 IBS patients with mild-modest anxiety and depression behaviors, and after the screening, we defined the FMT treatment group (n = 9) and the control group (n = 9). The IBS symptom severity scale (IBS-SSS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Irritable Bowel Syndrome Quality of Life (IBS-QOL) and Bristol stool scale (BSS) were evaluated one week before FMT (baseline), one-week-, one-month-, two-month-, and three-month-following FMT. Meanwhile, we determined the SCFAs in the patient's feces and serum and continued the metagenomic analysis of the microorganisms in the patient's feces.ResultsThe results showed that the patient's anxiety and depression behavior gradually improved with FMT treatment. Moreover, the illness and quality of life had also been relieved significantly. The content of isovaleric acid and valeric acid was significantly reduced in the FMT group compared to the Col group. Metagenomic analysis showed that FMT treatment decreased the abundance of Faecalibacterium, Eubacterium and Escherichia. From KEGG functional analysis, we confirmed that the top five abundant pathways were "bacterial chemotaxis, "flagellar assembly", "glycine, serine and threonine metabolism", "apoptosis", and "bacterial invasion of epithelial cells".ConclusionsFMT treatment can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score, indicating that FMT can improve patients' symptoms. The high throughput sequencing results show that Bifidobacterium and Escherichia play the most critical role in the formation and recovery of IBS-D patients. The GC/MS data indicated that faeces isovaleric acid and valeric acid might be more suitable as a metabolic indicator of IBS-D remission. Trial registration ChiCTR, ChiCTR1900024924, Registered 3 August 2019, https://www.chictr.org.cn/showproj.aspx?proj=41676 .
| S-EPMC8715582 | biostudies-literature
Project description:BACKGROUND:Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients. METHODS:Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR?+?IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins. RESULTS:The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR?+?IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR?+?IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor-? characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR?+?IBS, n = 9; IBS, n = 14). CONCLUSIONS:SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.
| S-EPMC7216771 | biostudies-literature
Project description:ObjectiveFaecal 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.DesignThis 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.ResultsResponses 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.ConclusionsFMT 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).
| S-EPMC7229896 | biostudies-literature
Project description:To determine rates of faecal biomarker results capable of suggesting potentially treatable causes of irritable bowel syndrome (IBS) symptomatology in a population of patients with symptoms of IBS who meet Rome III criteria for that condition.Descriptive, retrospective study in which faecal biomarker results (dichotomised into 'normal' and 'abnormal' values) were related to data from patient-completed questionnaire data identifying demographics, Rome III criteria for IBS and IBS phenotype (IBS-D, IBS-C, IBS-M and IBS-U).Commercial reference laboratory.Individuals whose physicians ordered faecal biomarker testing for evaluation of chronic abdominal symptoms consistent with IBS.None.Rates of occurrence of abnormal results on any of seven faecal biomarkers suggesting a treatable cause for IBS symptoms.Abdominal symptoms meeting Rome III criteria for IBS were present in 3553 records (the population), which were subjected to further analysis. Abnormal biomarker results (the outcomes) occurred in 94% of cases; 73% and 65% of records indicated growth of a bacterial potential pathogen and low growth of beneficial organisms, respectively. Abnormal results for all other faecal biomarkers occurred with frequencies from 5% to 13%. Frequency of abnormal results for elastase, calprotectin, eosinophil protein X, and beneficial organisms rose significantly with age, and differed significantly across IBS phenotypes.A large proportion of patients manifesting symptoms meeting Rome III IBS diagnostic criteria have faecal biomarker results indicating potential underlying, treatable causes of their symptoms. Faecal biomarker testing is an appropriate means of identifying potentially treatable causes of IBS symptoms.
| S-EPMC5036220 | biostudies-literature