From IBS to ME - The dysbiotic march hypothesis.

Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown. Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a "dysbiotic march". In analogy with "the atopic march" in allergic diseases, we suggest "a dysbiotic march" in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.

Microbial trimethylamine-N-oxide as a disease marker: something fishy?

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.

Systemic symptoms in irritable bowel syndrome: An investigative study on the role of enterocyte disintegrity, endotoxemia and inflammation.

Irritable bowel syndrome (IBS) is often accompanied by extra­intestinal 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 post­prandial 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 co­receptor soluble cluster of differentiation (sCD) 14, monocyte chemoattractant protein­1 (MCP­1) 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, MCP­1 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 MCP­1 levels decreased in IBS patients (P=0.008). Intestinal and extra­intestinal 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.

Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.

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.

Probiotic lactic acid bacteria - the fledgling cuckoos of the gut?

It is tempting to look at bacteria from our human egocentric point of view and label them as either 'good' or 'bad'. However, a microbial society has its own system of government - 'microcracy' - and its own rules of play. Lactic acid bacteria are often referred to as representatives of the good ones, and there is little doubt that those belonging to the normal intestinal flora are beneficial for human health. But we should stop thinking of lactic acid bacteria as always being 'friendly' - they may instead behave like fledgling cuckoos.

Oatmeal porridge: impact on microflora-associated characteristics in healthy subjects.

Oatmeal porridge has been consumed for centuries and has several health benefits. We aimed to investigate the effect of oatmeal porridge on gut microflora functions. A total of ten healthy subjects ingested 60 g oatmeal porridge daily for 1 week. The following microflora-associated characteristics were assessed before and after the intervention: intestinal gas production following lactulose ingestion, faecal excretion of SCFA and faecal levels of urease and ß-galactosidase. In addition, rectal levels of PGE2 were measured. Microbial fermentation as evaluated by intestinal gas production and excretion of SCFA did not change significantly following the dietary intervention. However, faecal levels of ß-galactosidase and urease decreased after eating oatmeal porridge (P=0·049 and 0·031, respectively). Host inflammatory state, as measured by rectal levels of PGE2, also decreased, but the change was not significant (P=0·168). The results suggest that oatmeal porridge has an effect on gut microbial functions and may possess potential prebiotic properties that deserve to be investigated further.

Low serum levels of short-chain fatty acids after lactulose ingestion may indicate impaired colonic fermentation in patients with irritable bowel syndrome.

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.

Indole - the scent of a healthy 'inner soil'.

Tryptophan is an essential amino acid with an indole nucleus. Humans cannot produce this amino acid themselves, but must obtain it through their diet. Much attention is currently paid to the wide physiological and clinical implications of the tryptophan-derived substances, serotonin and kynurenines, generated by human enzymes following the intestinal absorption of tryptophan. However, even before being absorbed, several microbial metabolites of tryptophan are formed, mainly from 'malabsorbed' (incompletely digested) proteins within the colon. The normal smell of human faeces is largely due to indole, one of the major metabolites. Recent studies indicate that this foul-smelling substance is also of utmost importance for our health.

[Underlying dysbiosis may be the cause of some forms of IBS. Patients were free of symptoms after the administration of microbiota]. / Bakomliggande dysbios kan vara orsak till vissa former av IBS - Patienter blev symtomfria efter tillförsel av mikrobiota.

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).

The effect of body position on postprandial perceptions, gastric emptying, and intragastric meal distribution: an ultrasonographic study in reclining healthy subjects.

OBJECTIVE: Postprandial dyspepsia is common and may be associated with abnormal intragastric distribution of food. We aimed to determine the effect of body position on gastric emptying, meal distribution, and postprandial perceptions in healthy subjects. MATERIAL AND METHODS: Eight adolescents (4 females and 4 males aged 14 years) were investigated using three-dimensional ultrasonography. The subjects were studied twice in a random order: once in the right lateral recumbent (RLR) position and once in the left lateral recumbent (LLR) position. Postprandial perceptions, gastric volumes, and antral areas were recorded immediately after the ingestion of 500 ml of a low-caloric meat soup over 4 min, and at 10 and 20 min following the meal. RESULTS: Postprandial perceptions (epigastric pain, nausea, and fullness) were more pronounced in the RLR position compared to the LLR position, particularly at the end of the meal ingestion (p < 0.01). Gastric volumes were significantly smaller in the RLR position compared to the LLR position at 10 min (p < 0.01) and 20 min (p < 0.05). Antral areas were significantly wider in the RLR position compared to the LLR position at 10 min (p < 0.05) and 20 min (p < 0.01). CONCLUSION: Postprandial perceptions are more pronounced, gastric emptying is faster, and antral area is wider in the RLR position compared to the LLR position. The results suggest that lying on the left side after a meal may be a measure to reduce postprandial dyspeptic sensations.

Chronic fatigue in patients with unexplained self-reported food hypersensitivity and irritable bowel syndrome: validation of a Norwegian translation of the Fatigue Impact Scale.

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 α 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.

Predictors for remission of major components of the metabolic syndrome after biliopancreatic diversion with duodenal switch (BPDDS).

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.