Browsing by Author "James-Stevenson, Toyia"

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    Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome
    (Wolters Kluwer, 2023-01-01) Waseem, Mohammed Ray; Shin, Andrea; Siwiec, Robert; James-Stevenson, Toyia; Bohm, Matthew; Rogers, Nicholas; Wo, John; Waseem, Lina; Gupta, Anita; Jarrett, Megan; Kadariya, Jhalka; Xu, Huiping; Medicine, School of Medicine
    Introduction: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. Methods: We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. Results: Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [-0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). Discussion: Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.
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    Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome
    (Wolters Kluwer, 2022) Calderon, Gerardo; Patel, Chirag; Camilleri, Michael; James-Stevenson, Toyia; Bohm, Matthew; Siwiec, Robert; Rogers, Nicholas; Wo, John; Lockett, Carolyn; Gupta, Anita; Xu, Huiping; Shin, Andrea; Medicine, School of Medicine
    Background goals: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). Study: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. Results: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. Conclusions: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.
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    Early Adverse Life Events and Post-Traumatic Stress Disorder in Patients with Constipation and Suspected Disordered Defecation
    (Wiley, 2022) Hendrix, Justin; Ranginani, Dheeksha; Montero, Anne Mary; Lockett, Carolyn; Xu, Huiping; James-Stevenson, Toyia; Shin, Andrea; Medicine, School of Medicine
    Background: Early adverse life events (EALs) and post-traumatic stress disorder (PTSD) are associated with irritable bowel syndrome (IBS). Disordered defecation (DD) presents with symptoms of IBS or functional constipation (FC) and is associated with psychological distress. However, the role of trauma and stress in chronic constipation is poorly defined. We aimed to examine EALS, PTSD, and psychological symptoms in patients with constipation and suspected DD. Methods: We conducted a survey study among adults with constipation who completed anorectal manometry (ARM) and balloon expulsion testing (BET). Data were collected on socio-demographics, EALs, PTSD, bowel symptoms, quality of life, and anxiety and depression. We performed comparisons between individuals with normal versus abnormal ARM or BET, subgroup analysis by detailed ARM and BET findings, and latent class analysis using individual EAL domains. Key results: Among 712 eligible patients, 69 completed the study. EALs and provisional PTSD were present in 75.4% and 27.5%, respectively; rates did not differ between those with normal versus abnormal ARM or BET. Normal testing was associated with higher rates of specific EAL domains (emotional abuse and mental illness), higher depression scores, and poorer mental component scores in both primary and subgroup comparisons (all p < 0.05). Normal testing was associated with a lower likelihood of high-EAL latent class (p = 0.01) membership. Presence of IBS or FC did not influence associations. Conclusions & inferences: Early adverse life events and PTSD are prevalent in patients with constipation and suspected DD. Those with normal ARM and BET have higher rates of prior emotional abuse and poorer mental health.
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    Evaluation of timed barium esophagram after per-oral endoscopic myotomy to predict clinical response
    (Thieme, 2021-11-12) DeWitt, John M.; Siwiec, Robert M.; Perkins, Anthony; Baik, Daniel; Kessler, William R.; Nowak, Thomas V.; Wo, John M.; James-Stevenson, Toyia; Mendez, Martha; Dickson, Destenee; Stainko, Sarah; Akisik, Fatih; Lappas, John; Al-Haddad, Mohammad A.; Medicine, School of Medicine
    Background and study aims: The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods: This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 (< 10 %), 2 (10 %-49 %), 3 (50 %-89 %) or 4 (> 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm 2 /mm Hg, and integrated relaxation pressure (IRP) < 15 mm Hg and incidence of gastroesophageal reflux disease (GERD) were compared by transit time. Results: Of 181 patients (58 % male, mean 53 ± 17 yr), TBE-PP was classified as Grade 1 in 122 (67.4 %), Grade 2 in 41 (22.7 %), Grade 3 in 14 (7.7 %) and Grade 4 in 4 (2.2 %). At 6 months, overall clinical response by ES (91.7 %), IRP (86.6 %), EGJ-DI (95.7 %) and the diagnosis of GERD (68.6 %) was similar between Grade 1 and Grade 2-4 TBE-PP. At 24 months, Grade 1 had a higher frequency of a normal IRP compared to Grades 2-4 (95.7 % vs. 60 %, P = 0.021) but overall response by ES (91.2 %), EGJ-DI (92.3 %) and the diagnosis of GERD (74.3 %) were similar. Conclusions: Contrast emptying rate by esophagram after POEM has limited utility to predict clinical response or risk of post-procedure GERD.
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    Fecal bile acids, fecal short-chain fatty acids, and the intestinal microbiota in patients with irritable bowel syndrome (IBS) and control volunteers
    (Cambridge University Press, 2018-06) Shin, Andrea; Nelson, David; Wo, John; Camilleri, Michael; James-Stevenson, Toyia; Siwiec, Robert; Bohm, Matthew; Gupta, Anita; Medicine, School of Medicine
    OBJECTIVES/SPECIFIC AIMS: Objectives and goals of this study will be to: (1) compare fecal microbiota and fecal organic acids in irritable bowel syndrome (IBS) patients and controls and (2) investigate the association between colonic transit and fecal microbiota in IBS patients and controls. METHODS/STUDY POPULATION: We propose an investigation of fecal organic acids, colonic transit and fecal microbiota in 36 IBS patients and 18 healthy controls. The target population will be adults ages 18–65 years meeting Rome IV criteria for IBS (both diarrhea- and constipation-predominant, IBS-D and IBS-C) and asymptomatic controls. Exclusion criteria are: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, visceral cancer, chronic infectious disease, immunodeficiency, uncontrolled thyroid disease, liver disease, or elevated AST/ALT>2.0× the upper limit of normal, (b) prior radiation therapy of the abdomen or abdominal surgeries with the exception of appendectomy or cholecystectomy >6 months before study initiation, (c) ingestion of prescription, over the counter, or herbal medications affecting gastrointestinal transit or study interpretation within 6 months of study initiation for controls or within 2 days before study initiation for IBS patients, (d) pregnant females, (e) antibiotic usage within 3 months before study participation, (f) prebiotic or probiotic usage within the 2 weeks before study initiation, (g) tobacco users. Primary outcomes will be fecal bile acid excretion and profile, short-chain fatty acid excretion and profile, colonic transit, and fecal microbiota. Secondary outcomes will be stool characteristics based on responses to validated bowel diaries. Stool samples will be collected from participants during the last 2 days of a 4-day 100 g fat diet and split into 3 samples for fecal microbiota, SCFA, and bile acid analysis and frozen. Frozen aliquots will be shipped to the Metabolite Profiling Facility at Purdue University and the Mayo Clinic Department of Laboratory Medicine and Pathology for SCFA and bile acid measurements, respectively. Analysis of fecal microbiota will be performed in the research laboratory of Dr David Nelson in collaboration with bioinformatics expertise affiliated with the Nelson lab. Colonic transit time will be measured with the previously validated method using radio-opaque markers. Generalized linear models will be used as the analysis framework for comparing study endpoints among groups. RESULTS/ANTICIPATED RESULTS: This study seeks to examine the innovative concept that specific microbial signatures are associated with increased fecal excretion of organic acids to provide unique insights on a potential mechanistic link between altered intraluminal organic acids and fecal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: Results may lead to development of targets for novel therapies and diagnostic biomarkers for IBS, emphasizing the role of the fecal metabolome.
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    Systematic review and meta-analysis: Efficacy of patented probiotic, VSL#3, in irritable bowel syndrome
    (Wiley, 2018-12) Connell, Mary; Shin, Andrea; James-Stevenson, Toyia; Xu, Huiping; Imperiale, Thomas F.; Herron, Jennifer; Medicine, School of Medicine
    Background: VSL#3 is a patented probiotic for which several clinical trials suggest benefits on motor function, bloating and symptoms of irritable bowel syndrome (IBS). Objectives: To quantify effects of VSL#3 on abdominal pain, stool consistency, overall response, abdominal bloating, and quality of life (QOL) in IBS through meta-analysis. Methods: MEDLINE (OvidSP and PubMed), EMBASE, Web of Science, and Scopus were searched up to May 2017. Using a fixed effects model, we pooled data from intention-to-treat analyses of randomized trials (RCTs) comparing VSL#3 to placebo in IBS. Data were reported as relative risk (RR), overall mean difference (MD) or standardized MD (SMD) with 95% confidence intervals (CI). Quality of evidence was rated using the GRADE approach. Key Results: Among 236 citations, five RCTs (243 patients) were included. No significant differences were observed for abdominal pain (SMD = −0.03; 95% CI −0.29–0.22), bloating (SMD = −0.15; 95% CI −0.40–0.11), proportion of bowel movements with normal consistency (overall MD = 0; 95% CI −0.09–0.08), or IBS-QOL (SMD = 0.08; 95% CI −0.22–0.39). VSL#3 was associated with a nearly statistically significant increase in overall response (RR=1.39; 95% CI 0.99–1.98). Conclusions & Inferences: In this systematic review and meta-analysis, there was a trend towards improvement in overall response with VSL#3, but no clear evidence effectiveness for IBS. However, the number and sample sizes of the trials are small and the overall quality of evidence for three of the five outcomes was low. Larger trials evaluating validated endpoints in well-defined IBS patients are warranted.
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    Use of Sacral Nerve Stimulation for the Treatment of Overlapping Constipation and Fecal Incontinence
    (International Scientific Information, 2017-03-07) Sreepati, Gouri; James-Stevenson, Toyia; Department of Medicine, IU School of Medicine
    BACKGROUND Fecal incontinence and constipation are common gastrointestinal complaints, but rarely occur concurrently. Management of these seemingly paradoxical processes is challenging, as treatment of one symptom may exacerbate the other. CASE REPORT A 51-year-old female with lifelong neurogenic bladder secondary to spina bifida occulta presented with progressive symptoms of daily urge fecal incontinence as well as hard bowel movements associated with straining and a sensation of incomplete evacuation requiring manual disimpaction. Pelvic floor testing showed poor ability to squeeze the anal sphincter, which indicated sphincter weakness as a major contributor to her fecal incontinence symptoms. Additionally, on defecography she was unable to widen her posterior anorectal angle or relax the anal sphincter during defecation consistent with dyssynergic defecation. A sacral nerve stimulator was placed for management of her fecal incontinence. Interestingly, her constipation also dramatically improved with sacral neuromodulation. CONCLUSIONS This unique case highlights the emerging role of sacral nerve stimulation in the treatment of complex pelvic floor dysfunction with improvement in symptoms beyond fecal incontinence in a patient with dyssynergic-type constipation.
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    The Virtual Gastroenterology Clinic
    (Elsevier, 2020) James-Stevenson, Toyia; Medicine, School of Medicine