Gulf War Illness Is Associated with Host Gut Microbiome Dysbiosis and Is Linked to Altered Species Abundance in Veterans from the BBRAIN Cohort.

Gulf War Illness (GWI) is a debilitating condition marked by chronic fatigue, cognitive problems, pain, and gastrointestinal (GI) complaints in veterans who were deployed to the 1990-1991 Gulf War. Fatigue, GI complaints, and other chronic symptoms continue to persist more than 30 years post-deployment. Several potential mechanisms for the persistent illness have been identified and our prior pilot study linked an altered gut microbiome with the disorder. This study further validates and builds on our prior preliminary findings of host gut microbiome dysbiosis in veterans with GWI. Using stool samples and Multidimensional Fatigue Inventory (MFI) data from 89 GW veteran participants (63 GWI cases and 26 controls) from the Boston biorepository, recruitment, and integrative network (BBRAIN) for Gulf War Illness, we found that the host gut bacterial signature of veterans with GWI showed significantly different Bray-Curtis beta diversity than control veterans. Specifically, a higher Firmicutes to Bacteroidetes ratio, decrease in Akkermansia sp., Bacteroides thetaiotamicron, Bacteroides fragilis, and Lachnospiraceae genera and increase in Blautia, Streptococcus, Klebsiella, and Clostridium genera, that are associated with gut, immune, and brain health, were shown. Further, using MaAsLin and Boruta algorithms, Coprococcus and Eisenbergiella were identified as important predictors of GWI with an area under the curve ROC predictive value of 74.8%. Higher self-reported MFI scores in veterans with GWI were also significantly associated with an altered gut bacterial diversity and species abundance of Lachnospiraceae and Blautia. These results suggest potential therapeutic targets for veterans with GWI that target the gut microbiome and specific symptoms of the illness.

Randomized double-blind placebo-controlled study to evaluate the effect of long-acting mesalamine on postinfectious irritable bowel syndrome with diarrhea.

BACKGROUND: A subset of patients with irritable bowel syndrome (IBS) develop their symptoms after gastroenteritis, referred to as postinfectious IBS (PI-IBS). PI-IBS is associated with low-grade intestinal inflammation. Previous studies have evaluated mesalamine, an anti-inflammatory drug, in patients with IBS. We evaluated the efficacy of long-acting mesalamine in patients with PI-IBS. METHODS: Sixty-one patients who developed diarrhea-predominant IBS (IBS-D) after gastroenteritis were randomized to receive either 2.4 g of long-acting mesalamine or placebo daily for 8-weeks. The symptoms assessed were abdominal pain, bloating, stool frequency, stool consistency, severity of diarrhea and constipation, satisfaction with bowel habits, and IBS affecting or interfering with life. Quality-of-life (QOL) was assessed using the IBS-QOL questionnaire. The prespecified primary outcome variable was the overall bowel symptom score (BSS) after 8-weeks of treatment. Effect sizes were expressed as standardized mean differences (Cohen's d). RESULTS: Fifty-four patients completed the 8-week treatment (n = 28 mesalamine, n = 26 placebo), 49 (91%) were male, and age range 23-71 years (mean ± SD 43 ± 13). Mesalamine demonstrated superior efficacy compared to placebo on the primary outcome variable, overall BSS (Cohen's d = 0.57, p = 0.042). Mesalamine was also superior for the secondary outcome of how much IBS affects your life in general (d = 0.72, p = 0.01). For the secondary outcomes of IBS symptoms, 7 of the 7 symptoms had trends of mesalamine superiority. For the secondary outcomes of IBS-QOL subscales, 8 of 9 had trends of mesalamine superiority. CONCLUSION: In patients with PI-IBS, long-acting mesalamine demonstrated to be effective in reducing IBS symptoms and improving QOL.

A Double-Humanized Mouse Model for Studying Host Gut Microbiome-Immune Interactions in Gulf War Illness.

Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1ß, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1ß, 6, 8 (IL-1ß, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.

Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome.

BACKGROUND & AIMS: Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS. METHODS: We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials. CONCLUSIONS: Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.

Fecal microbiota transplant delivered via invasive routes in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) results in significant loss of quality of life. Management guidelines do not recommend fecal microbiota transplant (FMT) for IBS based on weak evidence as refined data is lacking. We performed a systematic review and meta-analysis to ascertain the pooled clinical outcomes of FMT in IBS, delivered via invasive routes. METHODS: Multiple databases were searched through January 2023 to identify studies that reported on FMT treatment in IBS by invasive routes. Standard meta-analysis methodology using the random-effects model was used. Heterogeneity was assessed by I2% and 95% predication interval. RESULTS: Five studies were included. As many as 377 IBS patients were assessed, of which 238 received FMT and 139 received placebo. One study used nasojejunal tubes, one esophagogastroduodenoscopy and three colonoscopy for FMT delivery. FMT via colonoscopy was performed as a one-time procedure instilled into the cecum. Two studies used 30 g of stool from a single universal donor and one study used 50-80 g of pooled donor feces. The pooled odds ratio of improvement in IBS symptoms with FMT was significantly better as compared to that of placebo OR = 2.9 (95% CI [1.6-5.2, I2 = 62%, p < 0.001]). This was true for studies that exclusively used colonoscopy (OR = 2.1 [1.1-4.2, p = 0.04]). In the FMT arm, 10 patients (10.6%) reported abdomen pain and worsening of symptoms with bloating and six patients (6.3%) reported diarrhea. CONCLUSION: FMT delivered via invasive routes, especially colonoscopy, demonstrated significant improvement in IBS symptoms. A single FMT consisting of 30 g or more of single universal donor feces instilled into the cecum is the predominant modality.

Microbiome Dysbiosis Shows Strong Association of Gut-Derived Altered Metabolomic Profile in Gulf War Chronic Multisymptom Illness Symptom Persistence Following Western Diet Feeding and Development of Obesity.

The pathophysiology of Gulf War Illness (GWI) remains elusive even after three decades. The persistence of multiple complex symptoms along with metabolic disorders such as obesity worsens the health of present Gulf War (GW) Veterans often by the interactions of the host gut microbiome and inflammatory mediators. In this study, we hypothesized that the administration of a Western diet might alter the host metabolomic profile, which is likely associated with the altered bacterial species. Using a five-month symptom persistence GWI model in mice and whole-genome sequencing, we characterized the species-level dysbiosis and global metabolomics, along with heterogenous co-occurrence network analysis, to study the bacteriome-metabolomic association. Microbial analysis at the species level showed a significant alteration of beneficial bacterial species. The beta diversity of the global metabolomic profile showed distinct clustering due to the Western diet, along with the alteration of metabolites associated with lipid, amino acid, nucleotide, vitamin, and xenobiotic metabolism pathways. Network analysis showed novel associations of gut bacterial species with metabolites and biochemical pathways that could be used as biomarkers or therapeutic targets to ameliorate symptom persistence in GW Veterans.

Randomized, Double-Blind Placebo-Controlled Trial to Assess the Effect of Probiotics on Irritable Bowel Syndrome in Veterans With Gulf War Illness.

Background: Many veterans who served in Operation Desert Storm (August 1990 to March 1991) experienced a complex of symptoms of unknown etiology called Gulf War illness (GWI), which significantly impacts the health and quality of life (QOL) and may have contributed to irritable bowel syndrome (IBS). Methods: We performed a prospective, double-blind placebocontrolled study to determine the efficacy of the multistrain De Simone Formulation probiotic containing 8 strains of bacteria on symptoms of IBS and GWI. Veterans of Operation Desert Storm who had IBS and ≥ 2 nonintestinal symptoms of GWI were included. The primary study endpoint was change in bowel symptom score. The secondary endpoints were mean change in symptoms, QOL, and extra-intestinal and posttraumatic stress disorder (PTSD) symptoms. Results: A total of 101 Gulf War veterans with IBS and GWI were screened at the Veteran Affairs Medical Center in Salt Lake City, Utah. The study was completed by 53 veterans; 47 (89%) were male with a mean (SD) age of 55 (8) years. The probiotic did not improve IBS symptoms or other extra-intestinal symptoms common to IBS and GWI. Conclusions: Our study did not demonstrate statistically significant improvement in IBS symptoms or QOL after treatment with the probiotic. We also did not find any improvement in symptoms of GWI or PTSD.

Risk factors for upper and lower functional gastrointestinal disorders in Persian Gulf War Veterans during and post-deployment.

BACKGROUND: Gastroenteritis is a risk factor for irritable bowel syndrome (IBS), but its role in other functional gastrointestinal disorders (FGIDs) is less clear. The aim of this study was to determine the prevalence of FGIDs in Gulf War (GW) Veterans before, during, and after deployment and to determine whether gastroenteritis was a risk factor for upper and lower FGIDs. METHODS: The Veterans who served during the Persian GW were mailed validated questionnaires inquiring about their bowel habits, psychological and extra-intestinal symptoms, and quality of life (QOL). The lactulose hydrogen breath test (LBT) was performed for small intestinal bacterial overgrowth. KEY RESULTS: Data were analyzed from 468 GW Veterans. The prevalence of FGID before, during, and 16 years after deployment was 15.7%, 49.9%, and 64.2%, respectively. New FGIDs during deployment was reported by 41.2%, and during 16 years after deployment, 43.7% acquired new FGIDs. FGIDs were associated with psychological disorders, extra-intestinal symptoms, and lower QOL. Gastroenteritis was reported by 44.3% of deployed Veterans and was a risk factor for IBS, dyspepsia, and functional diarrhea post-deployment. The cases and controls did not differ significantly in the frequency of positive LBT. CONCLUSIONS AND INFERENCES: There is an increase in the prevalence of FGIDs during deployment, and it persists after deployment. There is a further increase in the prevalence of FGIDs after deployment. In addition to IBS, gastroenteritis during deployment is a risk factor for dyspepsia and functional diarrhea post-deployment. Therefore, prevention of gastroenteritis during deployment and screening of Veterans for FGIDs post-deployment would be of value for Veterans' long-term health.

Double-Blind Placebo-Controlled Study of Rifaximin and Lactulose Hydrogen Breath Test in Gulf War Veterans with Irritable Bowel Syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) occurs in up to 33% of Gulf War (GW) Veterans. Alterations in gut microflora including small intestinal bacterial overgrowth (SIBO) during deployment may play a role in development of IBS. Rifaximin is a minimally absorbed antibiotic speculated to improve IBS symptoms, in part, by restoring normal gut microflora. The aim of this study was to compare rifaximin to placebo on IBS symptoms and quality of life (QOL) in GW Veterans with IBS without constipation. METHODS: A double-blind, placebo-controlled study was performed. One hundred and twenty-two GW Veterans with IBS (Rome III) from our database and referral to gastroenterology and internal medicine clinics were screened. After a 2-week run-in period, 50 patients were randomized (1:1) to receive either rifaximin 550 gm or placebo twice daily for 2 weeks in a double-blind study. Patients were advised not to change their diet or medications during the study. The symptoms assessed were: (1) stool frequency, (2) stool consistency (Bristol stool scale, 1-7, very hard to watery), (3) urgency (1 = yes/0 = no daily for 7 days), (4) severity of abdominal pain (0-4, none to severe), (5) severity of bloating (1-4, none to severe), and (6) global improvement scale (1-7, substantially worse to substantially improved). These were recorded for 7 consecutive days and then averaged across the 7 days, to generate a continuous variable. The symptom data were compared after 2 weeks of treatment. QOL was assessed using IBS-QOL. The lactulose hydrogen breath test (LHBT) was performed at baseline and after 2 weeks of treatment. RESULTS: Fifty Veterans were randomized to receive treatment; 3 withdrew and 3 were lost to follow-up. Data were analyzed from 44 patients (38 men, 6 women, median age 52, range 33-77 years). Rifaximin was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all P ≥ 0.25) or QOL (all P ≥ 0.26). Normalization of SIBO by LHBT was not different between rifaximin- and placebo-treated Veterans (7 vs. 22%, P = 0. 54). CONCLUSION: Rifaximin was not effective in improving IBS symptoms and QOL in GW Veterans with non-constipated IBS.

Investigating Clinical Benefits of a Novel Sleep-Focused Mind-Body Program on Gulf War Illness Symptoms: A Randomized Controlled Trial.

OBJECTIVE: Mind-Body Bridging (MBB) has been shown to be effective for improving disturbed sleep. In this prospective randomized controlled trial, we evaluated the efficacy of sleep-focused MBB compared with sleep education control (SED) for improving sleep in previously deployed Gulf War veterans. METHODS: US military service members with sleep and physical health complaints who were deployed in 1990-1991 were randomized to receive three weekly sessions of either MBB (n = 33) or SED (n = 27) between 2012 and 2015. The primary outcome of Medical Outcomes Study Sleep Scale was completed at baseline, weekly during treatment, postintervention, and 3-month follow-up. Secondary outcome measures for posttraumatic stress disorder, depression, fatigue, quality of life, symptom severity, and mindfulness were completed at baseline, postintervention and 3-month follow-up. Salivary samples were collected at five time points per day at each visit for cortisol and α-amylase assessment. Clinician-administered assessments of sleep and co-occurring conditions were conducted at baseline and postintervention. RESULTS: MBB was significantly more efficacious than SED in reducing disturbed sleep at follow-up (F(1,180.54) = 4.04, p = .046). In addition, self-reported posttraumatic stress disorder (F(1,56.42) = 4.50, p = .038) for the treatment effect, depression (F(1,93.70) = 4.44, p = .038), and fatigue symptoms (F(1,68.58) = 3.90, p = .050) at follow-up improved in MBB compared with those in SED. Consistently higher percentages of veterans in MBB reported improvements of sleep, pain, and composite sleep/general co-occurring symptoms at the postclinical evaluation, as compared with veterans in SED. Finally, the mean waking level of salivary α-amylase in the MBB declined to a greater extent than that in the SED, at follow-up (F(1,88.99) = 3.78, p = .055), whereas no effects were found on cortisol. CONCLUSIONS: Sleep-focused MBB can improve sleep and possibly also co-occurring symptoms in Gulf War veterans. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01543997.

Irritable Bowel Syndrome and Quality of Life in Women With Fecal Incontinence.

OBJECTIVES: The objectives of this work were to determine the prevalence of irritable bowel syndrome (IBS) and IBS subtypes in women presenting for fecal incontinence (FI) treatment and to assess the impact of IBS on FI symptoms and quality of life (QOL). METHODS: In this multicenter prospective cohort study, women reported at least monthly solid, liquid, or mucus FI. Rome III clinical criteria defined IBS. Women also self-reported having an IBS diagnosis. Baseline questionnaires included the following: Modified Manchester Health Questionnaire, Fecal Incontinence Severity Index, Bristol Stool Scale, Pelvic Floor Distress Inventory, and the Pelvic Floor Impact Questionnaire. RESULTS: Of the 133 women enrolled, 119 completed Rome III IBS questionnaires, and 111 reported on whether they had a previous diagnosis of IBS. The prevalence of IBS was 31% (95% confidence interval [CI], 22.9%-40.2%) according to the Rome III IBS criteria. The most common subtypes were IBS-mixed (41%) and IBS-diarrhea (35%). Twenty-four (22%) of 111 patients had a previous diagnosis of IBS. Among women who met Rome III IBS criteria, 23 (66%) of 35 women had never had a diagnosis of IBS. Women with FI and IBS reported significantly worse QOL compared to women without IBS despite similar FI severity and stool consistency. CONCLUSIONS: Irritable bowel syndrome negatively affects QOL and affects one third of women with FI presenting for care in tertiary centers. Our findings suggest that assessment of IBS symptoms and diagnosis may be important for women presenting for FI treatment.

Disorders of gastrointestinal hypomotility.

Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.

Overexpression of mutant amyloid-ß protein precursor and presenilin 1 modulates enteric nervous system.

Alzheimer's disease (AD) is a neurodegenerative disorder histologically characterized by amyloid-ß (Aß) protein accumulation and activation of associated microglia. Although these features are well described in the central nervous system, the process and consequences of Aß accumulation in the enteric nervous system have not been extensively studied. We hypothesized that Aß also may accumulate in the enteric nervous system and lead to immune cell activation and neuronal dysfunction in the digestive tract not unlike that observed in diseased brain. To test this hypothesis, ileums of the small intestine of thirteen month old AßPP/PS1 and C57BL/6 (wild type) mice were collected and analyzed using immunohistochemistry, western blot analysis, cytokine arrays, and ELISA. AßPP/PS1 mice demonstrated no differences in intestinal motility or water absorption but elevated luminal IgA levels compared to wild type mice. They also had increased protein levels of AßPP and the proteolytic enzyme, BACE, corresponding to an increase in Aß1-40 in the intestinal lysate as well as an increase in both Aß1-40 and Aß1-42 in the stool. This correlated with increased protein markers of proinflammatory and immune cell activation. Histologic analysis localized AßPP within enteric neurons but also intestinal epithelial cells with elevated Aß immunoreactivity in the AßPP/PS1 mice. The presence of AßPP, Aß, and CD68 immunoreactivity in the intestines of some patients with neuropathologically-confirmed AD are consistent with the findings in this mouse model. These data support the hypothesis that in AD the intestine, much like the brain, may develop proinflammatory and immune changes related to AßPP and Aß.

Minimum important differences for scales assessing symptom severity and quality of life in patients with fecal incontinence.

OBJECTIVES: The objective of this study was to estimate the minimum important difference (MID) for the Fecal Incontinence Severity Index (FISI), the Colorectal-Anal Distress Inventory (CRADI) scale of the Pelvic Floor Distress Inventory, the Colorectal-Anal Impact Questionnaire (CRAIQ) scale of the Pelvic Floor Impact Questionnaire, and the Modified Manchester Health Questionnaire (MMHQ). METHODS: We calculated the MIDs using anchor-based and distribution-based approaches from a multicenter prospective cohort study investigating adaptive behaviors among women receiving nonsurgical and surgical management for fecal incontinence (FI). Patient responses were primarily anchored using a Global Impression of Change scale. The MID was defined as the difference in mean change from baseline between those who indicated they were "a little better" and those who reported "no change" on the Global Impression of Change scale 3 months after treatment. The effect size and SE of measurement were the distribution methods used. RESULTS: The mean changes (SD) in FISI, CRADI, CRAIQ, and MMHQ scores from baseline to 3 months after treatment were -8.8 (12.0), -52.7 (70.0), -60.6 (90.0), and -12.6 (19.2), respectively. The anchor-based MID estimates suggested by an improvement from no change to a little better were -3.6, -11.4 and -4.7, -18.1 and -8.0, and -3.2 for the FISI, CRADI (long and short version), CRAIQ (long and short version), and MMHQ, respectively. These data were supported by 2 distribution-based estimates. CONCLUSIONS: The MID values for the FISI are -4, CRADI (full version, -11; short version, -5), CRAIQ (full version, -18; short version, -8), and MMHQ -3. Statistically significant improvements that meet these thresholds are likely to be clinically important.

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome--a pilot study.

OBJECTIVE: Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. MATERIAL AND METHODS: Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. RESULTS: One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22-45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). CONCLUSIONS: There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.