| 1. |
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| 2. |
- Bakker, G. J., et al.
(författare)
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Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile
- 2017
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Ingår i: Microbiology Spectrum. - 2165-0497. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.
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| 3. |
- Bakker, G. J., et al.
(författare)
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Gut microbiota and energy expenditure in health and obesity
- 2015
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Ingår i: Journal of Clinical Gastroenterology. - 0192-0790 .- 1539-2031. ; 49
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of intestinal bacterial strains (gut microbiota) to the development of obesity and obesity-related disorders is increasingly recognized as a potential diagnostic and pharmacologic target. Alterations in the intestinal bacterial composition have been associated with presence of chronic low-grade inflammation, a known feature of insulin resistance and type 2 diabetes mellitus. However, causality still needs to be proven. Fecal transplantation studies in germ-free mice have provided crucial insight into the causality of gut microbiota in development of obesity and obesity-related disorders. Moreover, fecal transplantation studies in conjunction with fecal sampling in prospectively followed cohorts will help identify causally involved intestinal bacterial strains in human obesity. Results from these studies will lead to characterization of novel diagnostic markers as well as therapeutic strategies that aim to treat obesity and obesityrelated disorders Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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| 4. |
- Bakker, G. J., et al.
(författare)
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Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects
- 2019
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:16
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Tidskriftsartikel (refereegranskat)abstract
- Intake of a high-fat meal induces a systemic inflammatory response in the postprandial which is augmented in obese subjects. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on postprandial inflammatory response in lean and obese subjects. Ten lean and ten obese subjects with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Oral high-fat meal tests (50 g fat/m(2) body surface area) were performed before and after vancomycin intervention. Gut microbiota composition, leukocyte counts, plasma lipopolysaccharides (LPS), LPS-binding protein (LBP), IL-6 and MCP-1 concentrations and monocyte CCR2 and cytokine expression were determined before and after the high-fat meal. Oral vancomycin treatment resulted in profound changes in gut microbiota composition and significantly decreased bacterial diversity in both groups (phylogenetic diversity pre- versus post-intervention: lean, 56.9 +/- 7.8 vs. 21.4 +/- 6.6, P < 0.001; obese, 53.9 +/- 7.8 vs. 21.0 +/- 5.9, P < 0.001). After intervention, fasting plasma LPS significantly increased (lean, median [IQR] 0.81 [0.63-1.45] EU/mL vs. 2.23 [1.33-3.83] EU/mL, P = 0.017; obese, median [IQR] 0.76 [0.45-1.03] EU/mL vs. 1.44 [1.11-4.24], P = 0.014). However, postprandial increases in leukocytes and plasma LPS were unaffected by vancomycin in both groups. Moreover, we found no changes in plasma LBP, IL-6 and MCP-1 or in monocyte CCR2 expression. Despite major vancomycin-induced disruption of the gut microbiota and increased fasting plasma LPS, the postprandial inflammatory phenotype in lean and obese subjects was unaffected in this study.
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| 5. |
- Bakker, G. J., et al.
(författare)
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Pancreatic 18 F-FDG uptake is increased in type 2 diabetes patients compared to non-diabetic controls
- 2019
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Increasing evidence indicates that the development of type 2 diabetes is driven by chronic low grade beta-cell inflammation. However, it is unclear whether pancreatic inflammation can be noninvasively visualized in type 2 diabetes patients. We aimed to assess pancreatic 18 F-FDG uptake in type 2 diabetes patients and controls using 18 F-fluorodeoxylglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT). Material and methods In this retrospective cross-sectional study, we enrolled 20 type 2 diabetes patients and 65 controls who had undergone a diagnostic 18 F-FDG PET/CT scan and obtained standardized uptake values (SUVs) of pancreas and muscle. Pancreatic SUV was adjusted for background uptake in muscle and for fasting blood glucose concentrations. Results The maximum pancreatic SUVs adjusted for background muscle uptake (SUV max.m ) and fasting blood glucose concentration (SUV glucose ) were significantly higher in diabetes patients compared to controls (median 2.86 [IQR 2.24–4.36] compared to 2.15 [IQR 1.51–2.83], p = 0.006 and median 2.76 [IQR 1.18–4.34] compared to 1.91 [IQR 1.27–2.55], p<0.001, respectively). In linear regression adjusting for age and body mass index, diabetes remained the main predictor of SUV max.m and SUV glucose . Conclusion Pancreatic 18 F-FDG uptake adjusted for background muscle uptake and fasting blood glucose concentration was significantly increased in type 2 diabetes patients. © 2019 Bakker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 6. |
- Bakker, G. J., et al.
(författare)
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Relationship Between Gut Microbiota, Energy Metabolism, and Obesity
- 2016
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Ingår i: The Microbiota in Gastrointestinal Pathophysiology Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis. - 9780128040621 ; , s. 255-258
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The gut microbiota is increasingly recognized as an important regulator of energy metabolism. Alterations in gut microbiota composition have been associated with the presence of obesity, which is accompanied by a low-grade inflammatory state and increases the risk of several diseases, including type 2 diabetes mellitus. Although causality still needs to be proven, there is a large body of evidence supporting a role for the gut microbiota in the development of obesity and the associated diseases. In this regard, prospective human trials targeting the gut microbiota, using, for example, probiotics or fecal transplantation, are needed. This approach may yield exciting novel diagnostic markers as well as therapeutic targets. In this chapter, we will describe several mechanisms, which may contribute to the influence of the gut microbiota on metabolism, including direct energy extraction from the diet, production of short-chain fatty acids, and bacterial translocation. © 2017 Elsevier Inc. All rights reserved.
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| 7. |
- Bouter, K. E., et al.
(författare)
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Role of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction
- 2017
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 152:7, s. 1671-1678
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Tidskriftsartikel (refereegranskat)abstract
- The potential role of intestinal microbiota in the etiology of various human diseases has attracted massive attention in the last decade. As such, the intestinal microbiota has been advanced as an important contributor in the development of obesity and obesity-related metabolic dysfunctions, amongst others. Experiments in animal models have produced evidence for a causal role of intestinal microbiota in the etiology of obesity and insulin resistance. However, with a few exceptions, such causal relation is lacking for humans and most publications merely report associations between intestinal microbial composition and metabolic disorders such as obesity and type 2 diabetes. Thus, the reciprocal relationship between the bacteria and these metabolic disorders remains a matter of debate. The main objective of this review is to critically assess the driving role of intestinal microbe composition in the etiology, prevention, and treatment of obesity and obesity-related metabolic dysfunction, including type 2 diabetes. © 2017 AGA Institute
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| 8. |
- Cammarota, G., et al.
(författare)
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European consensus conference on faecal microbiota transplantation in clinical practice
- 2017
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 66:4, s. 569-580
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Tidskriftsartikel (refereegranskat)abstract
- Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
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| 9. |
- de Clercq, N. C., et al.
(författare)
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Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome
- 2017
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Ingår i: Psychosomatic Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0033-3174 .- 1534-7796. ; 79:8, s. 874-879
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome. Methods: A selective literature review was conducted to evaluate GI and brain interactions. Results: Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear. Conclusions: One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.
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| 10. |
- de Clercq, N. C., et al.
(författare)
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Gut microbiota in obesity and undernutrition
- 2016
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Ingår i: Advances in Nutrition. - : Elsevier BV. - 2161-8313. ; 7:6, s. 1080-1089
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Tidskriftsartikel (refereegranskat)abstract
- Malnutrition is the result of an inadequate balance between energy intake and energy expenditure that ultimately leads to either obesity or undernutrition. Several factors are associated with the onset and preservation of malnutrition. One of these factors is the gut microbiota, which has been recognized as an important pathophysiologic factor in the development and sustainment of malnutrition. However, to our knowledge, the extent to which the microbiota influences malnutrition has yet to be elucidated. In this review, we summarize the mechanisms via which the gut microbiota may influence energy homeostasis in relation to malnutrition. In addition, we discuss potential therapeutic modalities to ameliorate obesity or undernutrition. © 2016 American Society for Nutrition.
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| 11. |
- de Clercq, N. C., et al.
(författare)
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The effect of having Christmas dinner with in-laws on gut microbiota composition
- 2019
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Ingår i: Human Microbiome Journal. - : Elsevier BV. - 2452-2317. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The Christmas season can have a major impact on human health. Especially increased contact with in-laws during the holiday season is an important environmental factor known to affect both physical and mental health (Mirza et al., 2004). However, the mechanism through which in-laws influence host health is not yet understood. Emerging evidence has identified the intestinal microbiota as an important mediator for both physical and mental health. Here, we performed a prospective observational study to examine the impact of contact with in-laws on the gut microbiome during the Christmas season. We conducted 16S ribosomal DNA sequencing of fecal samples collected at two separate time points (December 23rd and December 27th 2016) from a group of 28 healthy volunteers celebrating Christmas. To discriminate between participants who visited their own family versus their in-laws, we built a multivariate statistical model that identified microbial biomarker species. We observed two distinct microbial-biomarker signatures discriminating the participants that visited their in-laws versus their own family over the Christmas season. We identified seven bacterial species whose relative-change profile differed significantly among these two groups. In participants visiting in-laws, there was a significant decrease in all Ruminococcus species, known to be associated with psychological stress and depression. A larger randomized controlled study is needed to reproduce these findings before we can recognize in-laws as a potential risk factor for the gut microbiota composition and subsequently host health. © 2019 Elsevier Ltd
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| 12. |
- de Groot, P. F., et al.
(författare)
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Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.
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| 13. |
- de Groot, P. F., et al.
(författare)
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Fecal microbiota transplantation in metabolic syndrome: History, present and future
- 2017
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Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 8:3, s. 253-267
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Tidskriftsartikel (refereegranskat)abstract
- The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects. © 2017 The Author(s). Published with license by Taylor & Francis © 2017, © P. F. de Groot, M. N. Frissen, N. C. de Clercq, and M. Nieuwdorp.
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| 14. |
- Deschasaux, M., et al.
(författare)
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Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography
- 2018
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:10, s. 1526-31
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Tidskriftsartikel (refereegranskat)abstract
- Trillions of microorganisms inhabit the human gut and are regarded as potential key factors for health(1,2). Characteristics such as diet, lifestyle, or genetics can shape the composition of the gut microbiota(2-6) and are usually shared by individuals from comparable ethnic origin. So far, most studies assessing how ethnicity relates to the intestinal microbiota compared small groups living at separate geographical locations(7-10). Using fecal 16S ribosomal RNA gene sequencing in 2,084 participants of the Healthy Life in an Urban Setting (HELIUS) study(11,12), we show that individuals living in the same city tend to share similar gut microbiota characteristics with others of their ethnic background. Ethnicity contributed to explain the interindividual dissimilarities in gut microbiota composition, with three main poles primarily characterized by operational taxonomic units (OTUs) classified as Prevotella (Moroccans, Turks, Ghanaians), Bacteroides (African Surinamese, South-Asian Surinamese), and Clostridiales (Dutch). The Dutch exhibited the greatest gut microbiota alpha-diversity and the South-Asian Surinamese the smallest, with corresponding enrichment or depletion in numerous OTUs. Ethnic differences in alpha-diversity and interindividual dissimilarities were independent of metabolic health and only partly explained by ethnic-related characteristics including sociodemographic, lifestyle, or diet factors. Hence, the ethnic origin of individuals may be an important factor to consider in microbiome research and its potential future applications in ethnic-diverse societies.
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| 15. |
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| 16. |
- Fluitman, Kristina S., et al.
(författare)
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The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids
- 2017
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Ingår i: Expert Review of Endocrinology and Metabolism. - : Informa UK Limited. - 1744-6651 .- 1744-8417. ; 12:3, s. 215-226
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Malnutrition refers to both over- and undernutrition and results from a disruption in energy balance. It affects one in three people worldwide and is associated with increased morbidity and mortality. The intestinal microbiota represents a newly identified factor that might contribute to the development of malnutrition, as it harbors traits that complement the human metabolic and endocrine capabilities, thereby influencing energy balance. Areas covered: In the current review, we aim to give a comprehensive overview on the microbiota, its development and its possible influence on energy balance, with emphasis the role of short-chain fatty acids. We also consider microbial characteristics associated with obesity and undernutrition and evaluate microbial manipulating strategies. The PubMed database was searched using the terms: ‘gastrointestinal microbiota’, ‘volatile fatty acids’, ‘malnutrition’, ‘undernutrition’, ‘obesity’, ‘insulin resistance’, ‘prebiotics’, ‘probiotics’, ‘antibiotics’ and ‘fecal microbiota transplantation’. Expert commentary: Microbiota make important contributions to the regulation of energy balance, whereas microbial disturbances might predispose to malnutrition. If we manage to manipulate the microbiota to our benefit, it could lead to preventive or therapeutic strategies targeting malnutrition. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 17. |
- Groen, R. N., et al.
(författare)
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Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives
- 2018
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Ingår i: Critical Reviews in Clinical Laboratory Sciences. - : Informa UK Limited. - 1040-8363 .- 1549-781X. ; 55:4, s. 283-293
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Forskningsöversikt (refereegranskat)abstract
- Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders.
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| 18. |
- Hartstra, A. V., et al.
(författare)
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Insights Into the Role of the Microbiome in Obesity and Type 2 Diabetes
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:1, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.
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| 19. |
- Hartstra, A. V., et al.
(författare)
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Interplay between gut microbiota, its metabolites and human metabolism: Dissecting cause from consequence
- 2016
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Ingår i: Trends in Food Science & Technology. - : Elsevier BV. - 0924-2244. ; 57, s. 233-243
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alterations in gut microbiota composition and bacterial metabolites have been increasingly recognized to affect host metabolism and are at the basis of metabolic diseases such as obesity and type 2 diabetes (DM2). Intestinal enteroendocrine cells (EEC's) sense gut luminal content and accordingly secrete hormones that modulate glucose and lipid metabolism and affect satiety. It has become evident that microbial metabolic products significantly affect EEC function. Scope and approach: In this review, we will discuss current insights in the role of the gut microbiota and its metabolites in development of obesity and DM2 and elaborate on interventions that modulate EEC action. Key findings and conclusions: Studies including fecal transplantation and Roux-en-Y gastric bypass (RYGB) in humans and animal models suggest that the gut microbiota and its metabolites causally contribute to development of obesity and DM2. Emerging evidence suggests that the gut microbiota and its metabolites can modulate secretion of EEC hormones that regulate appetite and insulin secretion. Dispersed intestinal expression and low abundance make EEC's difficult to study. Since current intestinal sampling methods in humans are mostly limited to the colon, this leaves a large part of EEC function understudied. It would therefore be relevant to develop means to extend sampling methods throughout to entire GI tract. (C) 2016 Elsevier Ltd. All rights reserved.
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| 20. |
- Herrema, H., et al.
(författare)
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Emerging role of intestinal microbiota and microbial metabolites in metabolic control
- 2017
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 60:4, s. 613-617
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Tidskriftsartikel (refereegranskat)abstract
- The role of the intestinal microbiota and microbial metabolites in the maintenance of host health and development of metabolic disease has gained significant attention over the past decade. Mechanistic insight revealing causality, however, is scarce. Work by Ussar and co-workers demonstrates that a complex interaction between microbiota, host genetics and environmental factors is involved in metabolic disease development in mice. In addition, Perry and coworkers show that the microbial metabolite acetate augments insulin resistance in rats. These studies underscore an important role of the microbiota in the development of obesity and symptoms of type 2 diabetes in rodents. If causality can be demonstrated in humans, development of novel diagnostic and therapeutic tools that target the gut microbiota will have high potential.
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| 21. |
- Koh, Ara, et al.
(författare)
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Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1
- 2018
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 175:4
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38 gamma MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
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| 22. |
- Koopen, Annefleur M., et al.
(författare)
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Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk
- 2016
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Ingår i: Current Opinion in Lipidology. - 0957-9672 .- 1473-6535. ; 27, s. 615-622
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Forskningsöversikt (refereegranskat)abstract
- Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Purpose of review: The absolute burden of cardiovascular risk remains high despite currently available preventive and therapeutic options. In search for novel therapeutic leads, mounting evidence has linked the gut microbiota as well as their metabolites to the development of cardiometabolic diseases. Recent findings: The intestinal microbiota influences the host via different metabolic pathways as inducer of endotoxemia, formation of trimethylamine-N-oxide, production of short chain fatty acids, and is a regulator in intestinal bile acid metabolism. Disruption of the gut microbiome may disturb the homeostasis of the microbial ecosystem to an alternative stable state associated with pathophysiological traits in microbiota and host. However, causality has not been shown yet. Summary: We are just beginning to understand how the gut microbiota influence our cardiometabolic health and various innovative therapeutic options are in the developing (preclinical) phase. This review focuses on the current evidence whether and to what extent the intestinal microbiota are involved in cardiovascular disease and whether this is based on merely association or causal relations.
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| 23. |
- Kootte, R. S., et al.
(författare)
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Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition
- 2017
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 26:4, s. 611-619
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as gamma-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
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| 24. |
- König, Julia, 1983-, et al.
(författare)
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Consensus report: faecal microbiota transfer - clinical applications and procedures
- 2017
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Ingår i: Alimentary Pharmacology & Therapeutics. - Hoboken, USA : Wiley. - 0269-2813 .- 1365-2036. ; 45:2, s. 222-239
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Tidskriftsartikel (refereegranskat)abstract
- Background Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
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| 25. |
- Li, S. S., et al.
(författare)
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Durable coexistence of donor and recipient strains after fecal microbiota transplantation
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6285, s. 586-589
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Tidskriftsartikel (refereegranskat)abstract
- Fecal microbiota transplantation (FMT) has shown efficacy in treating recurrent Clostridium difficile infection and is increasingly being applied to other gastrointestinal disorders, yet the fate of native and introduced microbial strains remains largely unknown. To quantify the extent of donor microbiota colonization, we monitored strain populations in fecal samples from a recent FMT study on metabolic syndrome patients using single-nucleotide variants in metagenomes. We found extensive coexistence of donor and recipient strains, persisting 3 months after treatment. Colonization success was greater for conspecific strains than for new species, the latter falling within fluctuation levels observed in healthy individuals over a similar time frame. Furthermore, same-donor recipients displayed varying degrees of microbiota transfer, indicating individual patterns of microbiome resistance and donor-recipient compatibilities.
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