Metabolites and microbial composition of stool of women with fecal incontinence: Study design and methods.
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ABSTRACT:
SUBMITTER: Arya LA
PROVIDER: S-EPMC5794661 | biostudies-literature | 2018 Feb
REPOSITORIES: biostudies-literature
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Metabolites and microbial composition of stool of women with fecal incontinence: Study design and methods.
Arya Lily A LA Richter Holly E HE Jelovsek Eric E Gantz Marie M Cichowski Sara S Zyczynski Halina H Dyer Keisha K Siddiqui Nazema N Carberry Cassandra C Broeckling Corey C Morrow Casey C Kashyap Purna P Meikle Susie S
Neurourology and urodynamics 20170801 2
<h4>Aims</h4>This paper aims to report the rationale, design, and the specific methodology of an ongoing nested observational study that will determine the association of the metabolite and microbial composition of stool with fecal incontinence (FI).<h4>Methods</h4>Eligible cases are participants with FI enrolled in the Controlling Anal Incontinence in women by Performing Anal Exercises with Biofeedback or Loperamide (CAPABLe) trial, a Pelvic Floor Disorders Network trial across eight clinical c ...[more]
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Project description:BACKGROUND: High systemic estrogen levels contribute to breast cancer risk for postmenopausal women, whereas low levels contribute to osteoporosis risk. Except for obesity, determinants of non-ovarian systemic estrogen levels are undefined. We sought to identify members and functions of the intestinal microbial community associated with estrogen levels via enterohepatic recirculation. METHODS: Fifty-one epidemiologists at the National Institutes of Health, including 25 men, 7 postmenopausal women, and 19 premenopausal women, provided urine and aliquots of feces, using methods proven to yield accurate and reproducible results. Estradiol, estrone, 13 estrogen metabolites (EM), and their sum (total estrogens) were quantified in urine and feces by liquid chromatography/tandem mass spectrometry. In feces, ?-glucuronidase and ?-glucosidase activities were determined by realtime kinetics, and microbiome diversity and taxonomy were estimated by pyrosequencing 16S rRNA amplicons. Pearson correlations were computed for each loge estrogen level, loge enzymatic activity level, and microbiome alpha diversity estimate. For the 55 taxa with mean relative abundance of at least 0.1%, ordinal levels were created [zero, low (below median of detected sequences), high] and compared to loge estrogens, ?-glucuronidase and ?-glucosidase enzymatic activity levels by linear regression. Significance was based on two-sided tests with ?=0.05. RESULTS: In men and postmenopausal women, levels of total urinary estrogens (as well as most individual EM) were very strongly and directly associated with all measures of fecal microbiome richness and alpha diversity (R?0.50, P?0.003). These non-ovarian systemic estrogens also were strongly and significantly associated with fecal Clostridia taxa, including non-Clostridiales and three genera in the Ruminococcaceae family (R=0.57-0.70, P=0.03-0.002). Estrone, but not other EM, in urine correlated significantly with functional activity of fecal ?-glucuronidase (R=0.36, P=0.04). In contrast, fecal ?-glucuronidase correlated inversely with fecal total estrogens, both conjugated and deconjugated (R?-0.47, P?0.01). Premenopausal female estrogen levels, which were collected across menstrual cycles and thus highly variable, were completely unrelated to fecal microbiome and enzyme parameters (P?0.6). CONCLUSIONS: Intestinal microbial richness and functions, including but not limited to ?-glucuronidase, influence levels of non-ovarian estrogens via enterohepatic circulation. Thus, the gut microbial community likely affects the risk for estrogen-related conditions in older adults. Understanding how Clostridia taxa relate to systemic estrogens may identify targets for interventions.
| S-EPMC3552825 | biostudies-other
Project description:Introduction and hypothesisTo evaluate change in fecal incontinence symptom severity after 8 weeks of darifenacin therapy in patients with double incontinence-urgency urinary incontinence (UUI) and fecal incontinence. Important secondary outcomes included fecal incontinence symptom distress and impact on quality of life, fecal incontinence episodes, global impression of improvement and overactive bladder symptom distress and impact.MethodsProspective open-label cohort study of women presenting primarily with UUI, diagnosed with double incontinence and electing antimuscarinic therapy for UUI. Women ≥ 18 years with moderate or greater bothersome UUI and fecal incontinence of liquid/solid stool with St. Marks (Vaizey) score ≥ 12 were included. Subjects were treated with darifenacin 15 mg daily for 8 weeks. The primary outcome was change in fecal incontinence symptom severity using the St. Marks (Vaizey) score after 8 weeks. Sample size was based on the minimally important difference of the St. Marks, -5, and standard deviation, ± 8.5; 30 subjects provided 80% power and type I error of 0.05, including a 15% attrition rate.ResultsThirty-two women were consented with mean baseline St. Marks (Vaizey) score of 18.0 ± 3.0. Mean age was 66.5 ± 10.3 years. Twenty-eight subjects (29/32, 87.5%) completed assessments. St. Marks (Vaizey) score significantly improved from 18.0 to 11.0 [mean difference - 7.0, 95% confidence interval (CI): -8.7, -5.3], and 19 subjects (19/32,67.9%) met the minimally important difference. Statistically significant improvements were also noted in fecal incontinence frequency, quality of life, and overactive bladder symptom bother and quality of life (all p < 0.01).ConclusionsDarifenacin can be considered a highly effective early intervention in women suffering from double incontinence.Clinical trial registrationBladder Antimuscarinic Medication and Accidental Bowel Leakage (BAMA), https://clinicaltrials.gov/ct2/show/NCT03543566 , NCT03543566.
| S-EPMC7736065 | biostudies-literature
Project description:PurposeUrinary incontinence and fecal incontinence are common disorders in women that negatively impact quality of life. In addition to known health and lifestyle risk factors, genetics may have a role in continence. Identification of genetic variants associated with urinary incontinence and fecal incontinence could result in a better understanding of etiologic pathways, and new interventions and treatments.Materials and methodsWe previously generated genome-wide single nucleotide polymorphism data from Nurses' Health Studies participants. The participants provided longitudinal urinary incontinence and fecal incontinence information via questionnaires. Cases of urinary incontinence (6,120) had at least weekly urinary incontinence reported on a majority of questionnaires (3 or 4 across 12 to 16 years) while controls (4,811) consistently had little to no urinary incontinence reported. We classified cases of urinary incontinence in women into stress (1,809), urgency (1,942) and mixed (2,036) subtypes. Cases of fecal incontinence (4,247) had at least monthly fecal incontinence reported on a majority of questionnaires while controls (11,634) consistently had no fecal incontinence reported. We performed a genome-wide association study for each incontinence outcome.ResultsWe identified 8 single nucleotide polymorphisms significantly associated (p <5×10-8) with urinary incontinence located in 2 loci, chromosomes 8q23.3 and 1p32.2. There were no genome-wide significant findings for the urinary incontinence subtype analyses. However, the significant associations for overall urinary incontinence were stronger for the urgency and mixed subtypes than for stress. While no single nucleotide polymorphism reached genome-wide significance for fecal incontinence, 4 single nucleotide polymorphisms had p <10-6.ConclusionsFew studies have collected genetic data and detailed urinary incontinence and fecal incontinence information. This genome-wide association study provides initial evidence of genetic associations for urinary incontinence and merits further research to replicate our findings and identify additional risk variants.
| S-EPMC7659982 | biostudies-literature
Project description:Background & aimsSome women with urge-predominant fecal incontinence (FI) have diarrhea-predominant irritable bowel syndrome and a stiffer and hypersensitive rectum. We evaluated the effects of the α2-adrenergic agonist clonidine on symptoms and anorectal functions in women with FI in a prospective, placebo-controlled trial.MethodsWe assessed bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) in 43 women (age, 58 ± 2 y) with urge-predominant FI, randomly assigned to groups given oral clonidine (0.1 mg, twice daily) or placebo for 4 weeks. Before and after administration of the medication, anal pressures were evaluated by manometry, and rectal compliance and sensation were measured using a barostat. Anal sphincter injury was evaluated by endoanal magnetic resonance imaging. Bowel symptoms were recorded in daily and weekly diaries. The primary end point was the FI and Constipation Assessment symptom severity score.ResultsFI scores decreased from 9.1 ± 0.3 to 7.6 ± 0.5 among subjects given placebo and from 8.1 ± 0.4 to 6.5 ± 0.6 among patients given clonidine. Clonidine did not affect FI symptom severity, bowel symptoms (stool consistency or frequency), anal pressures, rectal compliance, or sensation compared with placebo. However, when baseline data were used to categorize subjects as those with or without diarrhea, clonidine reduced the proportion of loose stools in patients with diarrhea only (P = .018). Clonidine also reduced the proportion of days with FI in patients with diarrhea (P = .0825).ConclusionsOverall, clonidine did not affect bowel symptoms, fecal continence, or anorectal functions, compared with placebo, in women with urge-predominant FI. Among patients with diarrhea, clonidine increased stool consistency, with a borderline significant improvement in fecal continence. ClinicalTrials.gov, Number NCT00884832.
| S-EPMC3900592 | biostudies-literature
Project description:ObjectivesFecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks.MethodsTo help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year.ResultsIn 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month.ConclusionsFurther knowledge sharing should help inform refinements of stool banking guidelines and best practices.
| S-EPMC8082449 | biostudies-literature
Project description:INTRODUCTION AND HYPOTHESIS:To compare fecal incontinence (FI) and urinary incontinence (UI) disclosure in women with dual incontinence (DI), and to assess UI disclosure in DI subjects compared with women with UI alone. We hypothesized that women with DI would be less likely to disclose FI in comparison to UI and as likely to disclose UI as women with UI alone. METHODS:We performed a retrospective chart review of new patient visits to an academic urogynecology clinic from 2007 to 2011. Clinical records were reviewed; demographic data and responses to the Incontinence Severity Index (ISI) and Wexner scales were recorded. Patients' written responses to the ISI and Wexner were compared with the diagnoses obtained from the oral history by the physician. RESULTS:Of 1,899 women in the database, 557 women were diagnosed with DI and 447 women were diagnosed with UI alone. Women with DI were less likely to orally disclose FI than UI (135 out of 557 [23 %], vs 485 out of 557 [87 %], p?<?0.001), but were as likely as women with UI alone to disclose UI (385 out of 447 [86 %] vs 485 out of 557 [87 %], p?=?0.66). In the multivariate analysis, DI subjects had greater odds of disclosing FI to their physicians if they had private insurance (OR 1.9, 95 %CI 1.2, 3.0) or Wexner score >7 (OR 9.0, 95 % CI 5.4,14.8) and lower ISI score (OR 1.5, CI 1.4, 1.6). CONCLUSIONS:Women with DI were less likely to report FI in comparison to UI. Patients were more likely to orally report FI when the symptoms were severe.
| S-EPMC4573595 | biostudies-literature
Project description:Dysbiotic configurations of the human gut microbiota have been linked with colorectal cancer (CRC). Human small non-coding RNAs are also implicated in CRC and recent findings suggest that their release in the gut lumen contributes to shape the gut microbiota. Bacterial small RNAs (bsRNAs) may also play a role in carcinogenesis but their role is less explored. Here, we performed small RNA and shotgun sequencing on 80 stool specimens of patients with CRC, or adenomas, and healthy subjects collected in a cross-sectional study to evaluate their combined use as a predictive tool for disease detection. We reported a considerable overlap and correlation between metagenomic and bsRNA quantitative taxonomic profiles obtained from the two approaches. Furthermore, we identified a combined predictive signature composed by 32 features from human and microbial small RNAs and DNA-based microbiome able to accurately classify CRC from healthy and adenoma samples (AUC= 0.87). In summary we reported evidence that host-microbiome dysbiosis in CRC can be observed also by altered small RNA stool profiles. Integrated analyses of the microbiome and small RNAs in the human stool may provide insights for designing more accurate tools for diagnostic purposes.
2019-08-30 | GSE132236 | GEO
Project description:BackgroundFecal incontinence (FI) is defined as the recurrent involuntary excretion of feces in inappropriate places or at inappropriate times. It is a major and highly embarrassing health care problem which affects about 2 to 24% of the adult population. The prevalence increases with age in both men and women. Physiotherapy interventions are often considered a first-line approach due to its safe and non-invasive nature when dietary and pharmaceutical treatment fails or in addition to this treatment regime. Two physiotherapy interventions, rectal balloon training (RBT) and pelvic floor muscle training (PFMT) are widely used in the management of FI. However, their effectiveness remains uncertain since well-designed trials on the effectiveness of RBT and PFMT versus PFMT alone in FI have never been published.Methods/designA two-armed randomized controlled clinical trial will be conducted. One hundred and six patients are randomized to receive either PFMT combined with RBT or PFMT alone. Physicians in the University Hospital Maastricht include eligible participants. Inclusion criteria are (1) adults (aged > or = 18 years), (2) with fecal incontinence complaints due to different etiologies persisting for at least six months, (3) having a Vaizey incontinence score of at least 12, (4) and failure of conservative treatment (including dietary adaptations and pharmacological agents). Baseline measurements consist of the Vaizey incontinence score, medical history, physical examination, medication use, anorectal manometry, rectal capacity measurement, anorectal sensation, anal endosonography, defecography, symptom diary, Fecal Incontinence Quality of Life scale (FIQL) and the PREFAB-score. Follow-up measurements are scheduled at three, six and 12 months after inclusion. Skilled and registered physiotherapists experienced in women's health perform physiotherapy treatment. Twelve sessions are administered during three months according to a standardized protocol.DiscussionThis section discusses the decision to publish a trial protocol, the actions taken to minimize bias and confounding in the design, explains the choice for two treatment groups, discusses the secondary goals of this study and indicates the impact of this trial on clinical practice.Trial registrationThe Netherlands Trial Register ISRCTN78640169.
| S-EPMC2234416 | biostudies-literature
Project description:Fecal incontinence is a highly prevalent and distressing condition that has a negative impact on quality of life. The etiology is often multifactorial, and the evaluation and treatment of this condition can be hindered by a lack of understanding of the mechanisms and currently available treatment options. This article reviews the evidence-based update for the management of fecal incontinence.
| S-EPMC4758704 | biostudies-literature
Project description:AimsThere is limited data addressing the value of vaginal biofeedback (VBF) on fecal incontinence (FI) symptoms. The objective of this pilot study was to evaluate whether use of a motion-based VBF device and app was effective for at-home treatment of women with FI. We hypothesized that VBF would result in improvement in FI symptoms.MethodsA single-arm 10-week prospective pilot trial in women with FI was conducted using the VBF device. The primary outcome was change in St. Mark's score from baseline to week 10. Secondary outcomes included change in 2-week bowel diary and FI quality of life (FIQoL). Statistical analysis included paired t test and Wilcoxon's signed-rank test.ResultsOf 29 enrolled women, 27 had data available for analysis. Mean (±SD) age was 60.9 (±14.4). 63% (17) subjects were White, 33% (9) were Black. Mean St. Mark's score was 14.6 (±4.4) at baseline and 11.6 (±5.1) at 10-weeks (p = 0.005). Changes in the total FIQol, and three of four subsets of the FIQoL scores were also significantly improved (p < 0.001). Bowel diary showed decrease in FI episodes, baseline 8.4 (±8.73) to 10 weeks 4.8 (±3.79), (p = 0.052).ConclusionsIn this pilot study, there was significant improvement in FI symptom-specific severity and quality of life using a vaginal, motion-based device for biofeedback. A larger study is needed to better understand the value of this device, which may be useful for women who prefer a vaginal device, which can be utilized at home compared with standard anal biofeedback for treatment of FI in the clinical setting.
| S-EPMC9300000 | biostudies-literature