Production of trimethylamine-N-oxide (TMAO) via the gut microbiota has recently been proposed as an important pathophysiological mechanism linking ingestion of ‘unhealthy foods’, such as beef (containing carnitine) and eggs (containing choline), and the development of atherosclerosis. Hence, TMAO has gained attention as a novel biomarker for cardiovascular disease. However, fish and seafood contain considerable amounts of TMAO and are generally accepted as cardioprotective: a puzzling paradox that seems to have been neglected. We suspect that the TMAO story may be a red herring.

Irritable bowel syndrome (IBS) is often accompanied by extra-intestinal symptoms, including fatigue and musculoskeletal pain. The present study aimed to investigate whether these symptoms were associated with markers of enterocyte disintegrity, endotoxemia and inflammation. Patients with IBS were recruited consecutively from our outpatient clinic (n=94) and compared with a group of healthy controls (n=20). Habitual symptoms were assessed using the IBS Severity Scoring System, the Fatigue Impact Scale and Visual Analogue Scales for measuring musculoskeletal pain. A lactulose challenge test was performed to induce post-prandial symptoms, and blood samples were obtained prior to and 90 min following lactulose ingestion to determine levels of intestinal fatty acid binding protein (iFABP), lipopolysaccharide (LPS), the LPS co-receptor soluble cluster of differentiation (sCD) 14, monocyte chemoattractant protein-1 (MCP-1) and calprotectin. Habitual symptom scores were high among the included patients, and lactulose ingestion induced significantly more symptoms in the patient group compared with the healthy control group (P=0.0001). Serum levels of iFABP were reduced in IBS patients compared with healthy controls, prior to and following lactulose ingestion (P=0.0002 and P=0.0001, respectively). Following lactulose ingestion, iFABP levels decreased in IBS patients (P=0.0001) and in healthy controls (P=0.02). Fasting levels of LPS, sCD14, MCP-1 and calprotectin were not significantly different between IBS patients and healthy controls. However, following lactulose ingestion, LPS levels increased in healthy controls (P=0.03), whereas MCP-1 levels decreased in IBS patients (P=0.008). Intestinal and extra-intestinal symptom severities were not correlated with levels of circulating biomarkers. No assessed biomarker in the present study appeared to be associated with symptom development in IBS patients. However, the implications of the low levels of iFABP observed require further investigation.

For almost 20 years we have produced a human intestinal microbiota under strict anaerobic conditions, as an in vitro batch culture. This cultivated microbial ecosystem designated anaerobic cultivated human intestinal microbiota (ACHIM) has been reinoculated every second week during the years into new production batches. The cultivated microbiota has retained a microbial diversity comparable to that of feces from healthy donors, containing the major bacterial phyla Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria, as confirmed by gene sequencing. This batch-cultured microbial ecosystem has been tested for safety and clinical efficacy for many years in more than 400 patients, most of them suffering from recurrent Clostridium difficile-infection (RCDI). No adverse events and a cure-rate of more than 90 % have been reported in these patients, most of which received the cultivated microbiota administered into the upper duodenum by gastro scope. Results will be presented from an ongoing randomized controlled clinical study in Sweden, in which the efficacy of ACHIM is being compared to vancomycin in the treatment of RCDI. Clinical results from patients suffering from other diseases associated with gut dysbiosis will be reported briefly.

Background/Aims: Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may relieve symptoms in patients with irritable bowel syndrome (IBS). We investigated whether this diet alters microbial fermentation, a process that may be involved in IBS symptom generation. Methods: Patients with IBS were included consecutively to participate in a 4-week FODMAP restricted diet. IBS symptoms were evaluated by using the IBS severity scoring system (IBS-SSS). Short-chain fatty acids (SCFAs) were analyzed in fecal samples before and after the dietary intervention, both at baseline and after in vitro fermentation for 24 h. Results: Sixty-three patients completed the study. Following the dietary intervention, IBS-SSS scores improved significantly (p < 0.0001). Total SCFA levels were reduced in fecal samples analyzed both at baseline (p = 0.005) and after in vitro fermentation for 24 h (p = 0.013). Following diet, baseline levels of acetic (p = 0.003) and n-butyric acids (p = 0.009) decreased, whereas 24 h levels of i-butyric (p = 0.003) and i-valeric acids (p = 0.003) increased. Fecal SCFA levels and IBS symptom scores were not correlated. Conclusion: Dietary FODMAP restriction markedly modulated fecal fermentation in patients with IBS. Saccharolytic fermentation decreased, while proteolytic fermentation increased, apparently independent of symptoms.

Valeur, Jørgen MD, PhD1; Undseth, Ragnhild MD2; Berstad, Arnold MD, PhD1 Author Information

No abstract available. (Published: 29 May 2015) Citation: Microbial Ecology in Health & Disease 2015, 26: 27637 - http://dx.doi.org/10.3402/mehd.v26.27637

Two cases of post-infectious IBS were successfully treated with transplantation of an anaerobic cultivated human intestinal microbiota. This suggests that a dysbiosis of the intestinal microbiota could be the culprit at least in some cases of IBS. Resetting the gut microbiota might be a possible solution for these patients that otherwise may face a life-long reduction in quality of life. Studies have suggested that conditions as varied as chronic constipation, metabolic syndrome, autoimmunity, asthma, cardiovascular disease and Crohn's disease may be caused by intestinal dysbiosis. If this is the case we would like to suggest a new term: Dysbiotic Bowel Syndrome (DBS).

Background: Ingestion of low-digestible carbohydrates triggers symptoms in patients with irritable bowel syndrome (IBS). These carbohydrates become substrates for microbial fermentation in the colon, yielding short-chain fatty acids (SCFAs) that are readily absorbed. Aiming to compare colonic fermentation in patients with IBS and healthy controls, we analyzed the concentrations of SCFA in serum at fasting and 90 minutes following ingestion of an unabsorbable, but fermentable carbohydrate, lactulose.Methods: Patients with IBS according to Rome III criteria (n=22) and healthy controls (n=20) ingested 10 g lactulose dissolved in water. Symptoms were graded by questionnaires and SCFA were analyzed using hollow fiber-supported liquid membrane extraction coupled with gas chromatography.Results: Lactulose induced more symptoms in patients with IBS than in healthy controls (P=0.0001). Fasting serum levels of SCFA did not differ between patients with IBS and controls. However, the postprandial levels of total SCFA (P=0.0002), acetic acid (P=0.005), propionic acid (P=0.0001), and butyric acid (P=0.01) were significantly lower in patients with IBS compared with healthy controls. There was no correlation between the levels of serum SCFA and symptom severity.Conclusion: Low-serum levels of SCFA after lactulose ingestion may indicate impaired colonic fermentation in patients with IBS. Conceivably, this disturbance is related to symptom generation, but the mechanism is not clear.

IntroductionTryptophan is an ‘essential’ amino acid: humanscannot make it themselves, but must obtain it inthe form of food. In addition to being a buildingblock in the biosynthesis of proteins, this aromaticsubstance can be converted into a number of meta-bolites of great clinical importance. The best known isthe enzymatic conversion to serotonin. However, inrecent years, attention has increasingly focused on themedical significance of the enzymatic oxidation oftryptophan to form indole compounds collectivelyknown as kynurenines. Both excessive kynurenineproduction and an accompanying deficiency of thesubstrate, tryptophan, may be the cause of a numberof pathological conditions. In addition, the oxidationitself may affect the body’s redox balance. In thisarticle, we hypothesize that tryptophan is ‘essential’inthepathogenesisofirritablebowelsyndrome (IBS).Indolamine dioxygenaseIndolamine dioxygenase (IDO) is the key enzymeinvolved in the conversion of tryptophan in the intes-tine. The enzyme catalyses oxidation of tryptophan tokynurenine in a reaction that produces peroxide andgives rise to highly reactive and potentially harmfuloxygen and hydroxyl radicals. The IDO reaction maytherefore contribute to what is generally calledoxidative stress [1,2]. Oxygen and hydroxyl radicalsformed as a result of the IDO reaction will acceleratethe oxidation of nitrogen monoxide (NO) to nitrite(NO

Background: Patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome (IBS) suffer from several health complaints, including fatigue. The aim of the present study was to validate a Norwegian translation of the Fatigue Impact Scale (FIS), and to assess the impact of fatigue in patients with self-reported food hypersensitivity and IBS, as compared with healthy controls.Methods: Thirty-eight patients with unexplained self-reported food hypersensitivity and IBS, who participated in the validation of the FIS completed the following additional questionnaires: the Short Form of Nepean Dyspepsia Index for assessment of quality of life, the Subjective Health Complaint Inventory, and questionnaires for diagnosis and severity of IBS. Impact of fatigue was studied in 43 patients with unexplained self-reported food hypersensitivity, 70% diagnosed with IBS, and 42 healthy controls.Results: Cronbach's a for the FIS was 0.98, indicating excellent agreement between individual items. Scores on the FIS correlated with scores on the Short Form of Nepean Dyspepsia Index (r= 0.50, P=0.001), indicating good convergent validity, and were higher in patients (median 85.0, interquartile range 36.8-105.3) than in controls (median 14.0, interquartile range 3.0-29.0, P <= 0.0001).Conclusion: The Norwegian translation of the FIS performed excellently in patients with unexplained self-reported food hypersensitivity and IBS, with patients reporting significantly more impact of chronic fatigue than healthy controls.

BACKGROUND:Metabolic surgery causes the remission of type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to varying degrees, depending on the patient characteristics and the surgical procedure. The aim of this study was to find predictors for the remission of T2DM and hypertension after biliopancreatic diversion with duodenal switch (BPDDS).METHODS:Eighty patients with T2DM were followed up for 2 years or more after BPDDS, and changes in body weight and metabolic status were noted. Remission was defined as fasting glucose <7 mmol/l with HbA1C <6.5 %, blood pressure <140/90 mmHg, and low-density lipoprotein (LDL) <2.6 mmol without the use of medication.RESULTS:Preoperatively, the mean age was 44 years, body mass index (BMI) was 48 kg/m(2), and duration of diabetes was 5 years. Of the 80 patients, 38 patients were using insulin, 48 patients were using antihypertensives, and 38 patients were using a lipid-lowering drug. Five percent of the patients had recommended levels for HbA1C, blood pressure, and LDL prior to the operation. The remission rate at 2 years was 94 % for T2DM, 54 % for hypertension, and 86 % for LDL hyperlipidemia. Preoperative predictors for nonremission of T2DM were a higher BMI, insulin usage, and low insulin C-peptide, and for hypertension, older age and more severe hypertension. Postoperative weight loss was important for both.CONCLUSIONS:Surgical intervention with BPDDS is an effective treatment of T2DM, hypertension, and hyperlipidemia. The duration of T2DM and age of the patient are the most important preoperative predictors for the remission of T2DM and hypertension, respectively.

2276 - 8 Irritable bowel syndrome is a commonly occurring symptom complex of unknown cause. The condition is characterised by gastrointestinal problems, but is often accompanied by functional disorders in several organ systems. Disruption of the intestinal flora may be a causal factor, and this possibility should be further researched, not least as a basis for treatment.

"Fecal fat excretion in irritable bowel syndrome." Scandinavian Journal of Gastroenterology, 47(8-9), pp. 1120–1121

Background: Food hypersensitivity is commonly suspected, but seldom verified. Patients with subjective food hypersensitivity suffer from both intestinal and extraintestinal health complaints. Abnormalities of the enterochromaffin cells may play a role in the pathogenesis. The aim of this study was to investigate enterochromaffin cell function in patients with subjective food hypersensitivity by measuring serum chromogranin A (CgA) and 5-hydroxytryptamine (5-HT, serotonin) in gut lavage fluid.Methods: Sixty-nine patients with subjective food hypersensitivity were examined. -Twenty-three patients with inflammatory bowel disease and 35 healthy volunteers were included as comparison groups. CgA was measured in serum by enzyme-linked immunosorbent assay. Gut lavage fluid was obtained by administering 2 L of polyethylene glycol solution intraduodenally. The first clear fluid passed per rectum was collected and 5-HT was analyzed by liquid chromatography tandem mass spectrometry.Results: Serum levels of CgA were significantly lower in patients with subjective food hypersensitivity than in healthy controls (P = 0.04). No differences were found in 5-HT levels in gut lavage fluid between patients with subjective food hypersensitivity and the control groups. There was no correlation between serum CgA and gut lavage 5-HT.Conclusion: Decreased blood levels of CgA suggest neuroendocrine alterations in patients with subjective food hypersensitivity. However, 5-HT levels in gut lavage fluid were normal.

Self-reported hypersensitivity to food is a common condition and many of these patients have indications of intestinal immune activation. Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells involved in both initiating immune responses and maintaining tolerance. The aims of this study were to evaluate the DC populations with their phenotype and T cell stimulatory capacity in patients with food hypersensitivity and to study its relationship with atopic disease. Blood samples from 10 patients with self-reported food hypersensitivity, divided into atopic and nonatopic subgroups, and 10 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood Dendritic cells kit. Monocyte-derived DCs (moDCs) were evaluated concerning their phenotype and T cell stimulatory capacity. DC populations and cell surface markers were not significantly different between patients and healthy controls, but moDCs from atopic patients expressed significantly more CD38 compared to moDCs from nonatopic patients. Moreover, lipopolysaccharide stimulated moDCs from atopic patients produced significantly more interleukin-10 compared to nonatopic patients. CD38 expression was correlated to total serum immunoglobulin E levels. These findings support the notion of immune activation in some patients with self-reported food hypersensitivity. They need to be confirmed in a larger cohort.

The biliopancreatic diversion with duodenal switch can be performed by different combinations of restriction and malabsorption. The aim of this study was to evaluate weight loss and potential side effects for two variants of the procedure.