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Effects of faecal microbiota transplantation on the small intestinal mucosa in systemic sclerosis.
Strahm, N, Didriksen, H, Fretheim, H, Molberg, Ø, Midtvedt, Ø, Farstad, IN, Midtvedt, T, Lundin, KEA, Aabakken, L, Błyszczuk, P, et al
Rheumatology (Oxford, England). 2023;(8):2918-2929
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Abstract
OBJECTIVES In SSc, gastrointestinal tract (GIT) involvement is a major concern, with no disease-modifying and limited symptomatic therapies available. Faecal microbiota transplantation (FMT) represents a new therapeutic option for GIT-affliction in SSc, showing clinical promise in a recent controlled pilot trial. Here, we aim to investigate effects of FMT on duodenal biopsies collected from SSc patients by immunohistochemistry and transcriptome profiling. METHODS We analysed duodenal biopsies obtained pre-intervention (week 0) and post-intervention (weeks 2 and 16) from nine SSc patients receiving an intestinal infusion of FMT (n = 5) or placebo (n = 4). The analysis included immunohistochemistry (IHC) with a selected immune function and fibrosis markers, and whole biopsy transcriptome profiling. RESULTS In patients receiving FMT, the number of podoplanin- and CD64-expressing cells in the mucosa were lower at week 2 compared with baseline. This decline in podoplanin- (r = 0.94) and CD64-positive (r = 0.89) cells correlated with improved patient-reported lower GIT symptoms. Whole biopsy transcriptome profiling from week 2 showed significant enrichment of pathways critical for cellular and endoplasmic reticulum stress responses, microvillus and secretory vesicles, vascular and sodium-dependent transport, and circadian rhythm. At week 16, we found enrichment of pathways mandatory for binding activity of immunoglobulin receptors, T cell receptor complexes, and chemokine receptors, as well as response to zinc-ions. We found that 25 genes, including Matrix metalloproteinase-1 were upregulated at both week 2 and week 16. CONCLUSION Combining selective IHC and unbiased gene expression analyses, this exploratory study highlights the potential for disease-relevant organ effects of FMT in SSc patients with GIT involvement. TRIAL REGISTRATION ClinicalTrials.gov, http://clinicaltrials.gov, NCT03444220.
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Oatmeal porridge: impact on microflora-associated characteristics in healthy subjects.
Valeur, J, Puaschitz, NG, Midtvedt, T, Berstad, A
The British journal of nutrition. 2016;(1):62-7
Abstract
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 β-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 β-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.
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Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.
Valeur, J, Røseth, AG, Knudsen, T, Malmstrøm, GH, Fiennes, JT, Midtvedt, T, Berstad, A
Digestion. 2016;(1):50-6
Abstract
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.
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Exclusive Enteral Nutrition Does Not Normalize Gut Microflora Function in Pediatric Perianal Crohn Disease.
Tjellström, B, Stenhammar, L, Magnusson, KE, Midtvedt, T, Norin, E, Sundqvist, T, Högberg, L
Journal of pediatric gastroenterology and nutrition. 2015;(1):e4
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Epigenomic programing: a future way to health?
Shenderov, BA, Midtvedt, T
Microbial ecology in health and disease. 2014
Abstract
It is now generally accepted that the 'central genome dogma' (i.e. a causal chain going from DNA to RNA to proteins and downstream to biological functions) should be replaced by the 'fluid genome dogma', that is, complex feed-forward and feed-back cycles that interconnect organism and environment by epigenomic programing - and reprograming - throughout life and at all levels, sometimes also down the generations. The epigenomic programing is the net sum of interactions derived from own metabolism and microbiota as well as external factors such as diet, pharmaceuticals, environmental compounds, and so on. It is a growing body of results indicating that many chronic metabolic and degenerative disorders and diseases - often called 'civilization diseases' - are initiated and/or influenced upon by non-optimal epigenomic programing, often taking place early in life. In this context, the first 1,000 days of life - from conception into early infancy - is often called the most important period of life. The following sections present some major mechanisms for epigenomic programing as well as some factors assumed to be of importance. The need for more information about own genome and metagenome, as well as a substantial lack of adequate information regarding dietary and environmental databases are also commented upon. However, the mere fact that we can influence epigenomic health programing opens up the way for prophylactic and therapeutic interventions. The authors underline the importance of creating a 'Human Gut Microbiota and Epigenomic Platform' in order to facilitate interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics and metabolomics as well as in disease epidemiology, prevention and treatment.
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The effects of oats on the function of gut microflora in children with coeliac disease.
Tjellström, B, Stenhammar, L, Sundqvist, T, Fälth-Magnusson, K, Hollén, E, Magnusson, KE, Norin, E, Midtvedt, T, Högberg, L
Alimentary pharmacology & therapeutics. 2014;39(10):1156-60
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Plain language summary
Oats have been allowed in the gluten-free diet of patients with coeliac disease (CD), however concerns have been raised that they may not be safe to eat in a subset of these patients. Short chain fatty acids (SFCAs) have been identified as a marker of inflammation and gut metabolism. Recent studies have found that children with CD often have elevated SCFA levels, indicating a disturbance in the gut microflora. The aim of this study was to identify the effect of consuming oats in children recently diagnosed with CD by examining faecal SCFAs. 116 children were treated with or without oats in their gluten-free diet for one year to see if oats affect the gut microflora. The findings of this study indicate that the children consuming oats had higher faecal SCFA concentration after one year than those not consuming oats. Based on this study, the authors’ conclude that oats do affect the gut microflora metabolism and that some coeliac children consuming oats may develop gut mucosal inflammation, leading to further future complications.
Abstract
BACKGROUND Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. AIM: To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats. METHODS This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed. RESULTS The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group. CONCLUSIONS Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.
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Probiotics and clinical effects: is the number what counts?
Bertazzoni, E, Donelli, G, Midtvedt, T, Nicoli, J, Sanz, Y
Journal of chemotherapy (Florence, Italy). 2013;(4):193-212
Abstract
Probiotics are defined as 'live microorganisms that when administered in adequate amounts confer health benefits on the host', underlining the need of microbial viability and the requirement of a suitable dose to obtain a health benefit. The dose and the administration regimen are critical issues for probiotics either ingested as foods claiming health benefits or used as drugs in clinics. In fact, regulatory authorities demand to guarantee consumers that a probiotic is effective in the recommended conditions of use and responds to its specific claims. Thus, a proper identification of probiotic strain(s), a definition of the amount of microorganisms surviving by the end of the product shelf-life, and a demonstration of their beneficial effects by appropriate human trials are required. The current knowledge on the effective dose of different probiotic strains used for several disorders is here reviewed.