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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.

The development and application of next generation sequencing technologies for clinical gastroenterology research has provided evidence that microbial dysbiosis is of relevance for the pathogenesis of gastrointestinal and extra-intestinal diseases. Microbial dysbiosis is characterized as alterations of diversity, function, and density of the intestinal microbes. Emerging evidence suggests that alterations of the gastrointestinal microbiome are important for the pathophysiology of a variety of functional gastrointestinal conditions, e.g., irritable bowel syndrome (IBS) and functional dyspepsia (FD), also known as disorders of brain-gut axis interaction. Clinicians have for many years recognized that small intestinal bacterial overgrowth (SIBO) is typified by a microbial dysbiosis that is underpinned by abnormal bacterial loads in these sites. SIBO presents with symptoms which overlap with symptoms of FD and IBS, point toward the possibility that SIBO is either the cause or the consequence of functional gastrointestinal disorders (FGIDs). More recently, new terms including “intestinal methanogen overgrowth” and “small intestinal fungal overgrowth” have been introduced to emphasize the contribution of methane production by archea and fungi in small intestinal dysbiosis. There is emerging data that targeted antimicrobial treatment of SIBO in patients with FD who simultaneously may or may not have IBS, results in symptom improvement and normalization of positive breath tests. However, the association between SIBO and FGIDs remains controversial, since widely accepted diagnostic tests for SIBO are lacking. Culture of jejunal fluid aspirate has been proposed as the “traditional gold standard” for establishing the diagnosis of SIBO. Utilizing jejunal fluid culture, the results can potentially be affected by cross contamination from oropharyngeal and luminal microbes, and there is controversy regarding the best cut off values for SIBO diagnosis. Thus, it is rarely used in routine clinical settings. These limitations have led to the development of breath tests, which when compared with the “traditional gold standard,” have sub-optimal sensitivity and specificity for SIBO diagnosis. With newer diagnostic approaches–based upon applications of the molecular techniques there is an opportunity to characterize the duodenal and colonic mucosa associated microbiome and associated gut microbiota dysbiosis in patients with various gastrointestinal and extraintestinal diseases. Furthermore, the role of confounders like psychological co-morbidities, medications, dietary practices, and environmental factors on the gastrointestinal microbiome in health and disease also needs to be explored.

Figure S1. Bacterial load on the small intestinal mucosa in all patients. Figure S2. Bacterial diversity (Chao1 index) within the mucosa-associated microbiota from duodenal biopsies from patients classified as having a functional dyspepsia (FD), iron deficiency (ID), or Crohn’s disease (CD). Figure S3. Bacterial diversity (Chao1 index) within the mucosa-associated microbiota from duodenal biopsies from patients with Crohn’s disease (CD). Table S1. Additional characteristics for the functional/iron deficiency patients included in the cohort (n = 82). Table S2. Additional characteristics for the 20 CD patients included in the cohort, including CD medications. Table S3. OTU table with raw read counts used for subsequent data analysis. Table S4. Relative abundances of bacterial phyla present in the duodenal mucosal microbiota of all patients. Table S5. Relative abundances of bacterial genera present in the duodenal mucosal microbiota of all patients. Table S6. Bacterial phyla present in the duodenal mucosal microbiota of all patients. Table S7. Bacterial genera present in the duodenal mucosal microbiota of all patients. Table S8. Bacterial OTUs that were observed to have significantly different relative abundances in the duodenal mucosal microbiota of all patients. Table S9. p values comparing relative abundances of bacterial genera present in the duodenal mucosal microbiota of either functional dyspepsia (FD) and iron deficiency (ID) patients (Table A), or Crohn’s disease (CD) patients (Table B). Patients were grouped based on smoking status (current smoker, previous smoker, or having never smoked). (PDF 822 kb)

Supplementary Methods. (PDF 163 kb)

Supplementary Methods. (PDF 163 kb)

Figure S1. Bacterial load on the small intestinal mucosa in all patients. Figure S2. Bacterial diversity (Chao1 index) within the mucosa-associated microbiota from duodenal biopsies from patients classified as having a functional dyspepsia (FD), iron deficiency (ID), or Crohn’s disease (CD). Figure S3. Bacterial diversity (Chao1 index) within the mucosa-associated microbiota from duodenal biopsies from patients with Crohn’s disease (CD). Table S1. Additional characteristics for the functional/iron deficiency patients included in the cohort (n = 82). Table S2. Additional characteristics for the 20 CD patients included in the cohort, including CD medications. Table S3. OTU table with raw read counts used for subsequent data analysis. Table S4. Relative abundances of bacterial phyla present in the duodenal mucosal microbiota of all patients. Table S5. Relative abundances of bacterial genera present in the duodenal mucosal microbiota of all patients. Table S6. Bacterial phyla present in the duodenal mucosal microbiota of all patients. Table S7. Bacterial genera present in the duodenal mucosal microbiota of all patients. Table S8. Bacterial OTUs that were observed to have significantly different relative abundances in the duodenal mucosal microbiota of all patients. Table S9. p values comparing relative abundances of bacterial genera present in the duodenal mucosal microbiota of either functional dyspepsia (FD) and iron deficiency (ID) patients (Table A), or Crohn’s disease (CD) patients (Table B). Patients were grouped based on smoking status (current smoker, previous smoker, or having never smoked). (PDF 822 kb)

If you haven’t measured something, you really don’t know much about it. —Karl Pearson (attributed) Gastrointestinal (GI) symptoms represent an important and often unappreciated cause of morbidity in diabetes, although the significance of this burden across the spectrum of patients and the underlying pathophysiology, including the relationship of symptoms with glycemic control, remain poorly defined. The relevance of GI symptoms and the necessity for their accurate assessment have increased with the greater focus on the gut as a therapeutic target for glucose lowering. This review addresses the prevalence, assessment, pathogenesis, and management of GI symptoms in diabetes, beginning with broad principles and then focusing on specific segments of the GI tract. We initially performed a literature search of PubMed by using synonyms and combinations of the following search terms: “gastrointestinal symptoms”, “diabetes”, “prevalence”, “pathogenesis”, “diagnosis”, and “management”. We restricted the search results to English only. Review papers and meta-analyses are presented as the highest level of evidence where possible followed by randomized controlled trials, uncontrolled trials, retrospective and observational data, and expert opinion.

BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Nav1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without (controls). Mutant forms of SCN5A were expressed in HEK-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study (GWAS) was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13/584 patients (2.2%, probands). Diarrhea-predominant IBS (IBS-D) was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (IBS-C, 31%) than IBS-D (10%, P

Background/Objectives: In patients with functional dyspepsia (FD), symptoms are frequently triggered, or exacerbated, by fatty foods. We hypothesized that in FD patients, a high-fat (high-FAT) meal would induce more symptoms than a high-carbohydrate (high-CHO) meal, associated with an altered secretion of cholecystokinin (CCK), peptide-YY (PYY), and ghrelin and an increased antral size, when compared to healthy subjects (HS). Methods: FD symptoms, appetite perceptions, plasma hormones, and antral area were measured in 8 FD patients and 8 HS on three separate days after the ingestion of high-CHO or high-FAT (500 kcal/400 g) meals, or a low-nutrient control (180 kcal/400 g); the energy intake was quantified 60 min later. Results: Nausea (P < 0.01) and pain (P = 0.05) were greater in FD after the high-FAT, when compared to high-CHO and control meals and in HS. Discomfort was greater after all meals in FD when compared to HS (P < 0.05). Fasting CCK and stimulation of CCK by the high-FAT (P < 0.01) meal were greater in FD, while fasting and postprandial PYY were lower (P < 0.001) in FD than in HS, with no differences in fasting, or postprandial, plasma ghrelin between FD and HS. Fasting antral area was greater in FD (P < 0.05), with no differences postprandially between FD and HS. There were no differences in the energy intake between the two groups. Conclusions: In FD patients: (a) a high-FAT meal induces more symptoms than an isocaloric high-CHO meal, and(b) fasting and postprandial plasma CCK concentrations are greater and PYY concentrations are less. Our findings have important implications for the development of diet-based therapies for the treatment of FD. Refereed/Peer-reviewed