Dietary intake and nutritional status in patients with newly diagnosed inflammatory bowel disease: insights from the IBSEN III study.

BACKGROUND: Dietary recommendations in inflammatory bowel disease (IBD) are inconclusive, and patients may follow restrictive diets with increased risk of malnutrition. The aim of this study was to compare dietary intakes and nutritional status in men and women with newly diagnosed IBD with a general population sample, and to investigate whether intakes were in line with the Nordic Nutrition Recommendations. METHODS: This was a cross-sectional study including adults≥ 40 years with IBD from the Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III cohort study. A validated food frequency questionnaire (FFQ) was used in dietary data collection, and a sample from the seventh survey of the Tromsø Study was included as a comparison group. RESULTS: A total of 227 men and women with IBD were included. IBD patients had higher intake of grain products, sweetened beverages, energy, fat and polyunsaturated fat (PUFA), but lower intake of dairy products, alcohol and iodine compared to adults from the comparison sample (p < 0.01). Intakes of saturated fat and carbohydrates in both genders, and vitamin D in women were not within recommended levels. Anemia and hypoalbuminemia were more prevalent in IBD patients than in the comparison sample. CONCLUSIONS: Dietary intakes in newly diagnosed IBD patients were mostly in line with Nordic Nutrition Recommendations. Higher proportion of IBD patients exceeded recommended allowances of fat and added sugar than the comparison sample. Insufficient micronutrient intake, anemia and hypoalbuminemia are present challenges in IBD patients that require monitoring.

Self-prescribed dietary restrictions in patients with inflammatory bowel disease (IBD) due to inconclusive dietary guidance may influence their risk of malnutrition. Comprehensive assessment of both dietary intake and nutritional status as early as time of diagnosis may help identify challenges in this patient group and implement appropriate interventions.

Effects of a low FODMAP diet on gut microbiota in individuals with treated coeliac disease having persistent gastrointestinal symptoms - a randomised controlled trial.

Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD (n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject ß-diversity, P < 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes (Pgroup < 0·001) and class Erysipelotrichia (Pgroup = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline (Pinteraction ≤ 0·009). No differences were found in faecal bacterial α-diversity (Pgroup ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation (Pgroup = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).

Diet-microbiota interaction in irritable bowel syndrome: looking beyond the low-FODMAP approach.

BACKGROUND: Diet is one of the main modulators of the gut microbiota, and dietary patterns are decisive for gut-microbiota-related diseases, including irritable bowel syndrome (IBS). The low-FODMAP diet (LFD) is commonly used to treat IBS, but its long-term effects on microbiota, symptoms and quality of life (QoL) are unclear. Alternative dietary strategies promoting beneficial gut microbiota, combined with reduced symptoms and improved QoL, are therefore of interest. AIMS: To review current evidence on the diet-microbiota-interaction as a modulator of IBS pathophysiology, and dietary management of IBS, with particular emphasis on strategies targeting the gut microbiota, beyond the LFD. METHODS: Literature was identified through PubMed-searches with relevant keywords. RESULTS: Dietary patterns with a low intake of processed foods and a high intake of plants, such as the Mediterranean diet, promote gut microbiota associated with beneficial health outcomes. In contrast, Western diets with a high intake of ultra-processed foods promote a microbiota associated with disease, including IBS. Increasing evidence points towards dietary strategies consistent with the Mediterranean diet being equal to the LFD in alleviating IBS-symptoms and having a less negative impact on QoL. Timing of food intake is suggested as a gut microbiota modulator, but little is known about its effects on IBS. CONCLUSIONS: Dietary recommendations in IBS should aim to target the gut microbiota by focusing on improved dietary quality, considering the impact on both IBS-symptoms and QoL. Increased intake of whole foods combined with a regular meal pattern and limitation of ultra-processed foods can be beneficial strategies beyond the LFD.

Increased plasma levels of non-sugar sweeteners in patients with symptomatic carotid atherosclerosis.

Purpose. The non-sugar sweeteners acesulfame K and saccharin are considered safe, but there is conflicting evidence on their effects on cardiovascular health. Materials and methods. In this explorative pilot study, we measured plasma levels of acesulfame K and saccharin in 15 patients with symptomatic carotid atherosclerosis, 18 asymptomatic patients and 15 control subjects. Fecal microbiota and short-chain fatty acids were analyzed. Dietary and medical history was assessed. Results. Symptomatic patients had higher levels of acesulfame K and saccharin compared to controls. Acesulfame K was associated with increased leukocyte count. Saccharin was associated with more severe carotid stenosis, as well as lower fecal butyric acid.

Short-chain fatty acids as a link between diet and cardiometabolic risk: a narrative review.

AIM: Diet has a profound impact on cardiometabolic health outcomes such as obesity, blood glucose, blood lipids and blood pressure. In recent years, the gut microbiota has emerged as one of several potential key players explaining dietary effects on these outcomes. In this review we aim to summarise current knowledge of interaction between diet and gut microbiota focusing on the gut-derived microbial metabolites short-chain fatty acids and their role in modulating cardiometabolic risk. FINDINGS: Many observational and interventional studies in humans have found that diets rich in fibre or supplemented with prebiotic fibres have a favourable effect on the gut microbiota composition, with increased diversity accompanied by enhancement in short-chain fatty acids and bacteria producing them. High-fat diets, particularly diets high in saturated fatty acids, have shown the opposite effect. Several recent studies indicate that the gut microbiota modulates metabolic responses to diet in, e.g., postprandial blood glucose and blood lipid levels. However, the metabolic responses to dietary interventions, seem to vary depending on individual traits such as age, sex, ethnicity, and existing gut microbiota, as well as genetics. Studies mainly in animal models and cell lines have shown possible pathways through which short-chain fatty acids may mediate these dietary effects on metabolic regulation. Human intervention studies appear to support the favourable effect of short-chain fatty acid in animal studies, but the effects may be modest and vary depending on which cofactors were taken into consideration. CONCLUSION: This is an expanding and active field of research that in the near future is likely to broaden our understanding of the role of the gut microbiota and short-chain fatty acids in modulating metabolic responses to diet. Nevertheless, the findings so far seem to support current dietary guidelines encouraging the intake of fibre rich plant-based foods and discouraging the intake of animal foods rich in saturated fatty acids.

Prebiotic effect of inulin-type fructans on faecal microbiota and short-chain fatty acids in type 2 diabetes: a randomised controlled trial.

PURPOSE: Compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this study was to evaluate the prebiotic effect of inulin-type fructans on the faecal microbiota and short-chain fatty acids (SCFA) in patients with type 2 diabetes. METHODS: The study was a placebo controlled crossover study, where 25 patients (15 men) aged 41-71 years consumed 16 g of inulin-type fructans (a mixture of oligofructose and inulin) and 16-g placebo (maltodextrin) for 6 weeks in randomised order. A 4-week washout separated the 6 weeks treatments. The faecal microbiota was analysed by high-throughput 16S rRNA amplicon sequencing and SCFA in faeces were analysed using vacuum distillation followed by gas chromatography. RESULTS: Treatment with inulin-type fructans induced moderate changes in the faecal microbiota composition (1.5%, p = 0.045). A bifidogenic effect was most prominent, with highest positive effect on operational taxonomic units (OTUs) of Bifidobacterium adolescentis, followed by OTUs of Bacteroides. Significantly higher faecal concentrations of total SCFA, acetic acid and propionic acid were detected after prebiotic consumption compared to placebo. The prebiotic fibre had no effects on the concentration of butyric acid or on the overall microbial diversity. CONCLUSION: Six weeks supplementation with inulin-type fructans had a significant bifidogenic effect and induced increased concentrations of faecal SCFA, without changing faecal microbial diversity. Our findings suggest a moderate potential of inulin-type fructans to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT02569684).

Correction to: Prebiotic effect of inulin­type fructans on faecal microbiota and short­chain fatty acids in type 2 diabetes: a randomised controlled trial.

The original version of this article unfortunately contained a mistake. The presentation of Fig. 4 was incorrect.

Attention deficit and hyperactivity disorder symptoms respond to gluten-free diet in patients with coeliac disease.

Introduction: Patients with coeliac disease commonly report symptoms of 'brain fog'. The aim of this study was to assess self-reported symptoms of impaired concentration in coeliac disease before and after treatment with gluten-free diet, compared with healthy controls and patient controls. Methods: Patients with newly diagnosed coeliac disease were included consecutively from two out-patient clinics. The patients completed the questionnaires Adult ADHD Self-Report Scale v1.1 Symptoms Checklist (ASRS), Hospital Anxiety and Depression Scale (HADS) and Gastrointestinal Symptom Rating Scale (GSRS) prior to start of a gluten-free diet and after at least 12 months on the diet. Patients with an established diagnosis of inflammatory bowel disease served as patient controls (n = 36). Health care personnel at Oslo University Hospital served as healthy controls (n = 60) and filled out ASRS and HADS. Results: A total of 31 newly diagnosed coeliac patients were included in the study. Of these, 26 patients met for follow-up and repeated the questionnaires. Prior to treatment, patients with coeliac disease had significantly higher scores than healthy controls on both the ASRS (p = .0014) and HADS (p=.0004). After a gluten-free diet, their scores improved and were not significantly different from healthy controls. There were no significant differences between patients with coeliac disease prior to treatment and patient controls with inflammatory bowel disease. Conclusion: Prior to treatment, coeliac disease patients reported significantly more symptoms than healthy controls on ASRS and HADS. The differences disappeared after a minimum of 12 months on a gluten-free diet.

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.

Persistent symptoms in patients with Crohn's disease in remission: An exploratory study on the role of diet.

OBJECTIVES: Patients with Crohn's disease (CD) often report food hypersensitivities with gastrointestinal (GI) symptoms despite being in clinical remission. We aimed to identify the most frequent symptoms and dietary triggers in such patients, and also explored whether a strict elimination diet may reduce their GI symptoms. METHODS: We assessed GI symptoms and dietary triggers in 16 patients with CD in clinical remission. Of these, 12 patients subsequently participated in a dietary intervention trial: two weeks on a habitual diet including wheat and dairy products followed by two weeks of a strict elimination diet. The severity of seven symptoms (overall symptoms, abdominal pain, bloating, abnormal feces, wind, fatigue, and musculoskeletal pain) was measured by using visual analog scales throughout the four weeks intervention period. MAIN RESULTS: The most common symptoms were abdominal pain, wind, bloating, odorous wind/feces, and diarrhea. Dairy and wheat products were reported as the most frequent dietary symptom triggers. All symptoms improved (p < .05) during the elimination diet period, especially in patients with small intestinal affection. CONCLUSION: Our exploratory study suggests that dietary interventions such as an elimination diet may reduce GI symptoms in patients with CD in remission.

Exploring Gut Microbiota Composition as an Indicator of Clinical Response to Dietary FODMAP Restriction in Patients with Irritable Bowel Syndrome.

BACKGROUND: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may relieve symptoms of irritable bowel syndrome (IBS). However, nutritional counseling is resource-demanding and not all patients will benefit. AIMS: To explore whether gut microbial composition may identify symptom response to a low-FODMAP diet in patients with IBS. METHODS: Patients were recruited consecutively to participate in a 4-week FODMAP-restricted diet. Response to diet was defined as ≥ 50% decrease in IBS symptom severity scores (IBS-SSS) compared to baseline. Fecal microbiota were analyzed by a commercially available method (the GA-map™ Dysbiosis Test), assessing 54 bacterial markers targeting more than 300 bacteria at different taxonomic levels. RESULTS: Sixty-one patients (54 F; 7 M) were included: 32 (29 F; 3 M) classified as responders and 29 (25 F; 4 M) as non-responders. Ten of the 54 bacterial markers differed significantly between responders and non-responders. Based on median values (used as cutoff) of responders for these 10 bacterial markers, we constructed a Response Index (RI): Each patient was given a point when the value for each selected bacterial marker differed from the cutoff. These points were summed up, giving an RI from 0 to 10. Patients with RI > 3 were 5 times more likely to respond (OR = 5.05, 95% CI [1.58; 16.10]), and the probability to respond was 83.4%, 95% CI [61.2-94%]. CONCLUSIONS: Gut microbial composition, assessed by using a new RI, may constitute a tool to identify patients that are likely to respond to dietary FODMAP restriction.

Evaluation of a faecal dysbiosis test for irritable bowel syndrome in subjects with and without obesity.

Biomarkers for irritable bowel syndrome (IBS) are demanded. An altered faecal microbiome has been reported in subjects with IBS and could be a valuable biomarker. This study evaluated the diagnostic properties of a new test for faecal dysbiosis, designed to distinguish IBS from healthy volunteers and compared the prevalence rates of dysbiosis related to IBS and morbid obesity. Subjects with and without morbid obesity and IBS were included. The faecal microbiota was assessed with GA-mapTM Dysbiosis Test (Genetic Analysis AS, Oslo, Norway). The test result was given as dysbiosis (yes/no). Comparisons were made between four groups: subjects with IBS and morbid obesity (IBS+/MO+); subjects without IBS and with morbid obesity (IBS-/MO+); subjects with IBS and without morbid obesity (IBS+/MO-); and healthy volunteers (IBS-/MO-).The prevalence rates of dysbiosis in the groups IBS+/MO+, IBS-/MO+, IBS+/MO- and IBS-/MO- were 18/28 (64%), 45/71 (63%), 31/63 (49%) and 38/91 (42%). Dysbiosis was more prevalent in subjects with morbid obesity, both in those with and without IBS, than in healthy volunteers (p values .04 and .006). Used as a diagnostic test for IBS in subjects without morbid obesity, the positive and negative likelihood ratios (LR) were 1.18 (0.83-1.67) and 0.87 (0.65-1.18), respectively, and in subjects with morbid obesity the LR were 1.01 (95% CI: 0.73-1.41) and 0.98 (0.54-1.75) respectively. The dysbiosis test was unsuitable as a diagnostic test for IBS. Dysbiosis was statistically significantly associated with morbid obesity, but not with IBS.

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.

Chronic alcohol overconsumption may alter gut microbial metabolism: a retrospective study of 719 13C-D-xylose breath test results.

Objective: Alterations of gut microbiota composition or function may participate in the pathophysiology of several diseases. We aimed to explore the effect of chronic alcohol overconsumption on gut microbial metabolism, as assessed by evaluating 13C-D-xylose breath test results. Materials and methods: We investigated all 13C-D-xylose breath tests performed at Lovisenberg Diaconal Hospital during the years 2005 to 2011, using patient files for diagnosing the patients into one of three patient categories: alcohol overconsumption, coeliac disease and functional bowel disorder. In addition, a group of healthy controls was included. The time curves of 13CO2 excretion in breath samples were divided into two phases, evaluating small intestinal absorption (0-60 min) and colonic microbial metabolism (90-240 min), respectively. Results: A total of 719 patients underwent 13C-D-xylose breath testing during the inclusion period. Thirty-five had a history of alcohol overconsumption, 66 had coeliac disease, and 216 had a functional bowel disorder, while 44 healthy controls were included for comparison. The alcohol overconsumption group had similar small intestinal phase results as the group of patients with untreated coeliac disease. During the colonic phase, the group of patients with alcohol overconsumption differed from all the other groups in terms of 13C-xylose recovery, with significantly less 13CO2 excretion compared to the other groups. Conclusion: The results suggest that patients with a history of alcohol overconsumption suffer from both small intestinal malabsorption and impaired colonic microbial metabolism. The role of gut microbiota in chronic alcohol overconsumption should be investigated further.

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.

Extra-intestinal symptoms in patients with irritable bowel syndrome: related to high total IgE levels and atopic sensitization?

Objective We have previously found that high levels of total IgE, but not atopic sensitization, was a significant predictor for functional gastrointestinal (GI) symptoms. In this study, we aimed to assess the prevalence of extra-intestinal symptoms in IBS patients, and explore their relation to total IgE levels and atopic sensitization. Materials and methods Seventy-one patients with functional GI complaints were included. Severity of GI symptoms, fatigue and musculoskeletal pain was evaluated using the following questionnaires: IBS-Severity Scoring System (IBS-SSS), Fatigue Impact Scale (FIS), FibroFatigue Scale (FFS), and Visual Analog Scales (VAS) for musculoskeletal pain. Levels of total IgE and specific IgE-antibodies were analyzed. Results Fatigue and musculoskeletal pain were demonstrated in 78.9 and 43.7% of the patients, respectively. IBS-SSS scores were significantly correlated with fatigue scores and musculoskeletal pain. Patients with fatigue and musculoskeletal pain had significantly higher IBS-SSS scores than patients without fatigue and musculoskeletal pain. Total IgE levels were significantly higher in IBS patients compared to a healthy control group from a previous study. However, neither total IgE nor atopic sensitization was significantly associated with extra-intestinal symptoms. Conclusions IBS, fatigue, and musculoskeletal pain were significantly associated. Total IgE levels were higher in IBS patients than healthy controls, but not related to intestinal or extra-intestinal symptom severity. Atopy was not associated with any of the co-morbidities. Thus, the clinical significance of high IgE levels in IBS remains unclear and further studies are warranted to explore a common underlying mechanism for the co-morbid triad of IBS, fatigue, and musculoskeletal pain.

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.