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Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose-response effects on glucose metabolism in human subjects with metabolic syndrome.
Gilijamse, PW, Hartstra, AV, Levin, E, Wortelboer, K, Serlie, MJ, Ackermans, MT, Herrema, H, Nederveen, AJ, Imangaliyev, S, Aalvink, S, et al
NPJ biofilms and microbiomes. 2020;(1):16
Abstract
Dysbiosis of the intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic strain Anaerobutyricum soehngenii on glucose metabolism in 24 subjects with metabolic syndrome. We found that treatment with A. soehngenii was safe and observed a significant correlation between the measured fecal abundance of administered A. soehngenii and improvement in peripheral insulin sensitivity after 4 weeks of treatment. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehngenii (defined as improved insulin sensitivity 4 weeks after A. soehngenii intake) is dependent on microbiota composition at baseline. These data in humans are promising, but additional studies are needed to reproduce our findings and to investigate long-term effects, as well as other modes of delivery.
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Red wine polyphenols modulate fecal microbiota and reduce markers of the metabolic syndrome in obese patients.
Moreno-Indias, I, Sánchez-Alcoholado, L, Pérez-Martínez, P, Andrés-Lacueva, C, Cardona, F, Tinahones, F, Queipo-Ortuño, MI
Food & function. 2016;(4):1775-87
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Abstract
This study evaluated the possible prebiotic effect of a moderate intake of red wine polyphenols on the modulation of the gut microbiota composition and the improvement in the risk factors for the metabolic syndrome in obese patients. Ten metabolic syndrome patients and ten healthy subjects were included in a randomized, crossover, controlled intervention study. After a washout period, the subjects consumed red wine and de-alcoholized red wine over a 30 day period for each. The dominant bacterial composition did not differ significantly between the study groups after the two red wine intake periods. In the metabolic syndrome patients, red wine polyphenols significantly increased the number of fecal bifidobacteria and Lactobacillus (intestinal barrier protectors) and butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) at the expense of less desirable groups of bacteria such as LPS producers (Escherichia coli and Enterobacter cloacae). The changes in gut microbiota in these patients could be responsible for the improvement in the metabolic syndrome markers. Modulation of the gut microbiota by using red wine could be an effective strategy for managing metabolic diseases associated with obesity.
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Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook.
Kelly, CR, Kahn, S, Kashyap, P, Laine, L, Rubin, D, Atreja, A, Moore, T, Wu, G
Gastroenterology. 2015;(1):223-37
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Abstract
The community of microorganisms within the human gut (or microbiota) is critical to health and functions with a level of complexity comparable to that of an organ system. Alterations of this ecology (or dysbiosis) have been implicated in a number of disease states, and the prototypical example is Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) has been demonstrated to durably alter the gut microbiota of the recipient and has shown efficacy in the treatment of patients with recurrent CDI. There is hope that FMT may eventually prove beneficial for the treatment of other diseases associated with alterations in gut microbiota, such as inflammatory bowel disease, irritable bowel syndrome, and metabolic syndrome, to name a few. Although the basic principles that underlie the mechanisms by which FMT shows therapeutic efficacy in CDI are becoming apparent, further research is needed to understand the possible role of FMT in these other conditions. Although relatively simple to perform, questions regarding both short-term and long-term safety as well as the complex and rapidly evolving regulatory landscape has limited widespread use. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future.
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The malabsorption of commonly occurring mono and disaccharides: levels of investigation and differential diagnoses.
Raithel, M, Weidenhiller, M, Hagel, AF, Hetterich, U, Neurath, MF, Konturek, PC
Deutsches Arzteblatt international. 2013;(46):775-82
Abstract
BACKGROUND Adverse food reactions (AFR) have has recently attracted increased attention from the media and are now more commonly reported by patients. Its classification, diagnostic evaluation, and treatment are complex and present a considerable challenge in clinical practice. Non-immune-mediated types of food intolerance have a cumulative prevalence of 30% to 40%, while true (immune-mediated) food allergies affect only 2% to 5% of the German population. METHOD We selectively searched the literature for pertinent publications on carbohydrate malabsorption, with special attention to published guidelines and position papers. RESULTS Carbohydrate intolerance can be the result of a rare, systemic metabolic defect (e.g., fructose intolerance, with a prevalence of 1 in 25,000 persons) or of gastrointestinal carbohydrate malabsorption. The malabsorption of simple carbohydrates is the most common type of non-immune-mediated food intolerance, affecting 20% to 30% of the European population. This condition is caused either by deficient digestion of lactose or by malabsorption of fructose and/or sorbitol. Half of all cases of gastrointestinal carbohydrate intolerance have nonspecific manifestations, with a differential diagnosis including irritable bowel syndrome, intolerance reactions, chronic infections, bacterial overgrowth, drug side effects, and other diseases. The diagnostic evaluation includes a nutritional history, an H2 breath test, ultrasonography, endoscopy, and stool culture. CONCLUSION The goals of treatment for carbohydrate malabsorption are to eliminate the intake of the responsible carbohydrate substance or reduce it to a tolerable amount and to assure the physiological nutritional composition of the patient's diet. In parallel with these goals, the patient should receive extensive information about the condition, and any underlying disease should be adequately treated.
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Effect of Lactobacillus salivarius Ls-33 on fecal microbiota in obese adolescents.
Larsen, N, Vogensen, FK, Gøbel, RJ, Michaelsen, KF, Forssten, SD, Lahtinen, SJ, Jakobsen, M
Clinical nutrition (Edinburgh, Scotland). 2013;(6):935-40
Abstract
BACKGROUND & AIMS This study is a part of the clinical trials with probiotic bacterium Lactobacillus salivarius Ls-33 conducted in obese adolescents. Previously reported clinical studies showed no effect of Ls-33 consumption on the metabolic syndrome in the subject group. The aim of the study was to investigate the impact of L. salivarius Ls-33 on fecal microbiota in obese adolescents. METHODS The study was a double-blinded intervention with 50 subjects randomized to intake of L. salivarius Ls-33 or placebo for 12 weeks. The fecal microbiota was assessed by real-time quantitative PCR before and after intervention. Concentrations of fecal short chain fatty acids were determined using gas chromatography. RESULTS Ratios of Bacteroides-Prevotella-Porphyromonas group to Firmicutes belonging bacteria, including Clostridium cluster XIV, Blautia coccoides_Eubacteria rectale group and Roseburia intestinalis, were significantly increased (p ≤ 0.05) after administration of Ls-33. The cell numbers of fecal bacteria, including the groups above as well as Clostridium cluster I, Clostridium cluster IV, Faecalibacterium prausnitzii, Enterobacteriaceae, Enterococcus, the Lactobacillus group and Bifidobacterium were not significantly altered by intervention. Similarly, short chain fatty acids remained unaffected. CONCLUSION L. salivarius Ls-33 might modify the fecal microbiota in obese adolescents in a way not related to metabolic syndrome. CLINICAL TRIAL NUMBER NCT 01020617.
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The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome 'at-risk' population.
Fava, F, Gitau, R, Griffin, BA, Gibson, GR, Tuohy, KM, Lovegrove, JA
International journal of obesity (2005). 2013;(2):216-23
Abstract
INTRODUCTION AND OBJECTIVES An obese-type human microbiota with an increased Firmicutes:Bacteroidetes ratio has been described that may link the gut microbiome with obesity and metabolic syndrome (MetS) development. Dietary fat and carbohydrate are modifiable risk factors that may impact on MetS by altering the human microbiome composition. We determined the effect of the amount and type of dietary fat and carbohydrate on faecal bacteria and short chain fatty acid (SCFA) concentrations in people 'at risk' of MetS. DESIGN A total of 88 subjects at increased MetS risk were fed a high saturated fat diet (HS) for 4 weeks (baseline), then randomised onto one of the five experimental diets for 24 weeks: HS; high monounsaturated fat (MUFA)/high glycemic index (GI) (HM/HGI); high MUFA/low GI (HM/LGI); high carbohydrate (CHO)/high GI (HC/HGI); and high CHO/low GI (HC/LGI). Dietary intakes, MetS biomarkers, faecal bacteriology and SCFA concentrations were monitored. RESULTS High MUFA diets did not affect individual bacterial population numbers but reduced total bacteria and plasma total and LDL-cholesterol. The low fat, HC diets increased faecal Bifidobacterium (P=0.005, for HC/HGI; P=0.052, for HC/LGI) and reduced fasting glucose and cholesterol compared to baseline. HC/HGI also increased faecal Bacteroides (P=0.038), whereas HC/LGI and HS increased Faecalibacterium prausnitzii (P=0.022 for HC/HGI and P=0.018, for HS). Importantly, changes in faecal Bacteroides numbers correlated inversely with body weight (r=-0.64). A total bacteria reduction was observed for high fat diets HM/HGI and HM/LGI (P=0.023 and P=0.005, respectively) and HS increased faecal SCFA concentrations (P<0.01). CONCLUSION This study provides new evidence from a large-scale dietary intervention study that HC diets, irrespective of GI, can modulate human faecal saccharolytic bacteria, including bacteroides and bifidobacteria. Conversely, high fat diets reduced bacterial numbers, and in the HS diet, increased excretion of SCFA, which may suggest a compensatory mechanism to eliminate excess dietary energy.
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Metabonomic understanding of probiotic effects in humans with irritable bowel syndrome.
Hong, YS, Hong, KS, Park, MH, Ahn, YT, Lee, JH, Huh, CS, Lee, J, Kim, IK, Hwang, GS, Kim, JS
Journal of clinical gastroenterology. 2011;(5):415-25
Abstract
GOALS This study was undertaken to evaluate the effects of probiotics on adult patients with irritable bowel syndrome (IBS) through clinical parameters and H nuclear magnetic resonance (NMR)-based metabonomics. BACKGROUND As systematic effect of probiotics on inflammatory bowel disease through metabonomics approach has been extensively studied to date, metabonomic characterization of the probiotics effect on IBS is also needed for better understanding the effect with respect to host metabolic mechanism. STUDY Seventy-four IBS patients meeting Rome criteria were randomized to receive probiotics and placebo through a parallel-group, double-blind, randomized, placebo-controlled clinical study. Probiotic fermented milk and placebo were administered 3 times daily for 8 weeks. Improvements of IBS were assessed according to Rome III questionnaires and H NMR metabolic profiling of serum and fecal samples from all participants was used to characterize a significant change in serum and fecal metabolome before and after probiotics. RESULTS Fecal counts of the Lactobacilli, but not Bifidobacteria species, which included in the probiotic milk, were increased significantly in feces of IBS patients receiving treatment (P=0.014). NMR data set coupled with multivariate statistical analysis identified intrinsically elevated serum levels of glucose (P=0.0265) and tyrosine (P=0.0016) in IBS patients. These levels normalized to those of healthy individuals in the probiotic administration group, but not the placebo group. CONCLUSIONS This metabonomic study suggests that in a subset of IBS patients there exists a potential dysregulation in energy homeostasis (serum glucose) and liver function (serum tyrosine) that may be improved through probiotics supplementation. Moreover, global metabolic profiling highlights the potential of metabonomic approach for assessing bowel diseases or symptoms with respect to host metabolic perturbation.