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1.
  • Attaye, I., et al. (författare)
  • A Crucial Role for Diet in the Relationship Between Gut Microbiota and Cardiometabolic Disease
  • 2020
  • Ingår i: Annual Review of Medicine. - : Annual Reviews. - 0066-4219 .- 1545-326X. - 9780824305710 ; , s. 149-161
  • Bokkapitel (refereegranskat)abstract
    • Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly tomorbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been shown to considerably alter gut microbiota composition and function. Moreover, several diet-derived microbial metabolites are able to modulate human metabolism and thereby alter CMD risk. Dietary interventions that affect gut microbiota composition and function are therefore a promising, novel, and cost-efficient method to reduce CMD risk. Studies suggest that fermentable carbohydrates can beneficially alter gut microbiota composition and function, whereas high animal protein and high fat intake negatively impact gut microbiota function and composition. This review focuses on the role of macronutrients (i.e., carbohydrate, protein, and fat) and dietary patterns (e.g., vegetarian/vegan and Mediterranean diet) in gut microbiota composition and function in the context of CMD.
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2.
  • Attaye, Ilias, et al. (författare)
  • Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes
  • 2023
  • Ingår i: ISCIENCE. - 2589-0042. ; 26:8
  • Tidskriftsartikel (refereegranskat)abstract
    • High-protein diets are promoted for individuals with type 2 diabetes (T2D). How-ever, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized -controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and-derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure.
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3.
  • Aydin, Oemruem, et al. (författare)
  • Post-Bariatric Hypoglycemia: an Impaired Metabolic Response to a Meal
  • 2024
  • Ingår i: OBESITY SURGERY. - 0960-8923 .- 1708-0428.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/Hypothesis Post-bariatric hypoglycemia (PBH) is caused by postprandial hyperinsulinemia, due to anatomical alterations and changes in post-prandial metabolism after bariatric surgery. The mechanisms underlying the failing regulatory and compensatory systems are unclear. In this study, we investigated the differences in post-prandial hormones and metabolic profiles between patients with and without PBH. Methods We performed a mixed meal test (MMT) in 63 subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery. Blood was withdrawn at 0, 10, 20, 30, 60, and 120 min after ingestion of a standardized meal. Glucose, insulin, GLP-1, FGF-19, and FGF-21 were measured and untargeted metabolomics analysis was performed on blood plasma to analyze which hormonal and metabolic systems were altered between patients with and without PBH. Results Out of 63, a total of 21 subjects (33%) subjects developed PBH (glucose < 3.1 mmol/L) after surgery. Decreased glucose and increased insulin excursions during MMT were seen in PBH (p < 0.05). GLP-1, FGF-19, and FGF-21 were elevated after surgery (p < 0.001), but did not differ between PBH and non-PBH groups. We identified 20 metabolites possibly involved in carbohydrate metabolism which differed between the two groups, including increased carnitine and acylcholines in PBH. Conclusion Overall, 33% of the subjects developed PBH 1 year after RYGB surgery. While GLP-1, FGF-19, and FGF-21 were similar in PBH and non-PBH patients, metabolomics analysis revealed changes in carnitine and acyclcholines that are possibly involved in energy metabolism, which may play a role in the occurrence of PBH. [GRAPHICS] .
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5.
  • Bakker, G. J., et al. (författare)
  • Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity
  • 2022
  • Ingår i: Obesity Science & Practice. - : Wiley. - 2055-2238. ; 8:1, s. 56-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. Material and Methods: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m(2)) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. Results: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. Conclusions: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.
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6.
  • Bakker, G. J., et al. (författare)
  • Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile
  • 2017
  • Ingår i: Microbiology Spectrum. - 2165-0497. ; 5:4
  • 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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7.
  • Bakker, G. J., et al. (författare)
  • Gut microbiota and energy expenditure in health and obesity
  • 2015
  • Ingår i: Journal of Clinical Gastroenterology. - 0192-0790 .- 1539-2031. ; 49
  • 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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8.
  • Bakker, G. J., et al. (författare)
  • Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects
  • 2019
  • Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:16
  • 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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9.
  • Bakker, G. J., et al. (författare)
  • Pancreatic 18 F-FDG uptake is increased in type 2 diabetes patients compared to non-diabetic controls
  • 2019
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
  • 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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10.
  • Bakker, G. J., et al. (författare)
  • Relationship Between Gut Microbiota, Energy Metabolism, and Obesity
  • 2016
  • Ingår i: The Microbiota in Gastrointestinal Pathophysiology Implications for Human Health, Prebiotics, Probiotics, and Dysbiosis. - 9780128040621 ; , s. 255-258
  • 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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11.
  • Bouter, K. E., et al. (författare)
  • Role of the Gut Microbiome in the Pathogenesis of Obesity and Obesity-Related Metabolic Dysfunction
  • 2017
  • Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 152:7, s. 1671-1678
  • 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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12.
  • Byndloss, Mariana, et al. (författare)
  • The gut microbiota and diabetes : research, translation, and clinical applications – 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum
  • 2024
  • Ingår i: Diabetologia. - 0012-186X.
  • Forskningsöversikt (refereegranskat)abstract
    • This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.
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13.
  • Cammarota, G., et al. (författare)
  • European consensus conference on faecal microbiota transplantation in clinical practice
  • 2017
  • Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 66:4, s. 569-580
  • 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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14.
  • de Clercq, N. C., et al. (författare)
  • Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome
  • 2017
  • Ingår i: Psychosomatic Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0033-3174 .- 1534-7796. ; 79:8, s. 874-879
  • 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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15.
  • de Clercq, N. C., et al. (författare)
  • Gut microbiota in obesity and undernutrition
  • 2016
  • Ingår i: Advances in Nutrition. - : Elsevier BV. - 2161-8313. ; 7:6, s. 1080-1089
  • 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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16.
  • de Clercq, N. C., et al. (författare)
  • The effect of having Christmas dinner with in-laws on gut microbiota composition
  • 2019
  • Ingår i: Human Microbiome Journal. - : Elsevier BV. - 2452-2317. ; 13
  • 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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17.
  • de Groot, P. F., et al. (författare)
  • Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
  • 2017
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
  • 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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18.
  • de Groot, P. F., et al. (författare)
  • Fecal microbiota transplantation in metabolic syndrome: History, present and future
  • 2017
  • Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 8:3, s. 253-267
  • 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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19.
  • Deschasaux, M., et al. (författare)
  • Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography
  • 2018
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 24:10, s. 1526-31
  • 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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20.
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21.
  • Fluitman, Kristina S., et al. (författare)
  • The intestinal microbiota, energy balance, and malnutrition: emphasis on the role of short-chain fatty acids
  • 2017
  • Ingår i: Expert Review of Endocrinology and Metabolism. - : Informa UK Limited. - 1744-6651 .- 1744-8417. ; 12:3, s. 215-226
  • 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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22.
  • Grimnes, G., et al. (författare)
  • Impact of a Vancomycin-Induced Shift of the Gut Microbiome in a Gram-Negative Direction on Plasma Factor VIII:C Levels: Results from a Randomized Controlled Trial
  • 2022
  • Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 122:4, s. 540-551
  • Tidskriftsartikel (refereegranskat)abstract
    • Rationale Inflammation is present in several conditions associated with risk of venous thromboembolism. The gut microbiome might be a source of systemic inflammation and activation of coagulation, by translocation of lipopolysaccharides from gram-negative bacteria to the systemic circulation. Objective To investigate whether a vancomycin-induced shift of the gut microbiome in a gram-negative direction influences systemic inflammation and plasma factor (F) VIII procoagulant activity (FVIII:C). Methods and Results We performed a randomized controlled trial including 43 healthy volunteers aged 19 to 37 years. Twenty-one were randomized to 7 days of oral vancomycin intake and 22 served as controls. Feces and blood were sampled at baseline, the day after the end of intervention, and 3 weeks after intervention. Gut microbiome composition was assessed by amplicon sequencing. FVIII:C was measured using an activated partial thromboplastin time-based assay, cytokines were measured using multiplex technology, complement activation was measured using the enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (CRP) was measured by an immunoturbidimetric assay. Vancomycin intake reduced gut microbiome diversity and increased the abundance of gram-negative bacteria. Change in FVIII:C in the intervention group was +4IU/dL versus -6IU/dL ( p =0.01) in the control group. A similar change was observed for log-transformed CRP (+0.21 mg/dL vs. -0.25mg/dL, p =0.04). The cytokines and complement activation markers remained similar in the two groups. Conclusion The found slight increases in FVIII:C and CRP levels might support the hypothesis that a vancomycin-induced gram-negative shift in the gut microbiome could induce increased systemic inflammation and thereby a procoagulant state.
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23.
  • Groen, R. N., et al. (författare)
  • Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives
  • 2018
  • Ingår i: Critical Reviews in Clinical Laboratory Sciences. - : Informa UK Limited. - 1040-8363 .- 1549-781X. ; 55:4, s. 283-293
  • 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.
  •  
24.
  • Hartstra, A. V., et al. (författare)
  • Insights Into the Role of the Microbiome in Obesity and Type 2 Diabetes
  • 2015
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:1, s. 159-165
  • 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.
  •  
25.
  • Hartstra, A. V., et al. (författare)
  • Interplay between gut microbiota, its metabolites and human metabolism: Dissecting cause from consequence
  • 2016
  • Ingår i: Trends in Food Science & Technology. - : Elsevier BV. - 0924-2244. ; 57, s. 233-243
  • 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.
  •  
26.
  • Hassing, H. C., et al. (författare)
  • SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus
  • 2014
  • Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:5, s. 1309-1316
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Methods: Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Results: Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). Conclusions: These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM.
  •  
27.
  • Herrema, H., et al. (författare)
  • Emerging role of intestinal microbiota and microbial metabolites in metabolic control
  • 2017
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 60:4, s. 613-617
  • 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.
  •  
28.
  • Khan, M. T., et al. (författare)
  • Microbial Modulation of Insulin Sensitivity
  • 2014
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 20:5, s. 753-760
  • Tidskriftsartikel (refereegranskat)abstract
    • The gut microbiota has emerged as an integral factor that impacts host metabolism and has been suggested to play a vital role in metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. In humans, cross-sectional studies have identified microbiota profiles associated with metabolic diseases, whereas causation mainly has been demonstrated in animal models. Recent studies involving microbiota-based interventions in humans, or transfer of disease-associated microbiota into germ-free mice, underscore that an altered microbiota may directly modulate host metabolism in humans. However, it will be essential to determine whether an altered gut microbiota precedes development of insulin resistance and diabetes and to identify the underlying molecular mechanisms. Increased mechanistic insights of how the microbiota modulates metabolic disease in humans may pave the way for identification of innovative microbiota-based diagnostics and/or therapeutics.
  •  
29.
  • Koh, Ara, et al. (författare)
  • Microbially Produced Imidazole Propionate Impairs Insulin Signaling through mTORC1
  • 2018
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 175:4
  • 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.
  •  
30.
  • Koopen, Annefleur M., et al. (författare)
  • Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk
  • 2016
  • Ingår i: Current Opinion in Lipidology. - 0957-9672 .- 1473-6535. ; 27, s. 615-622
  • 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.
  •  
31.
  • Koopen, A. M., et al. (författare)
  • Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition
  • 2020
  • Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial-metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn
  •  
32.
  • Kootte, R. S., et al. (författare)
  • Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition
  • 2017
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 26:4, s. 611-619
  • 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.
  •  
33.
  • Kullberg, R. F. J., et al. (författare)
  • Gut microbiota of adults with asthma is broadly similar to non-asthmatics in a large population with varied ethnic origins
  • 2021
  • Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0976 .- 1949-0984. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial gut communities might predispose children to develop asthma. Yet, little is known about the role of these micro-organisms in adult asthmatics. We aimed to profile the relationship between fecal microbiota and asthma in a large-scale, ethnically diverse, observational cohort of adults. Fecal microbiota composition of 1632 adults (172 asthmatics and 1460 non-asthmatics) was analyzed using 16S ribosomal RNA gene sequencing. Using extremely randomized trees machine learning models, we assessed the discriminatory ability of gut bacterial features to identify asthmatics from non-asthmatics. Asthma contributed 0.019% to interindividual dissimilarities in intestinal microbiota composition, which was not significant (P = .97). Asthmatics could not be distinguished from non-asthmatics based on individual microbiota composition by an extremely randomized trees classifier model (area under the receiver operating characteristic curve = 0.54). In conclusion, there were no prominent differences in fecal microbiota composition in adult asthmatics when compared to non-asthmatics in an urban, large-sized and ethnically diverse cohort.
  •  
34.
  • König, Julia, 1983-, et al. (författare)
  • Consensus report: faecal microbiota transfer - clinical applications and procedures
  • 2017
  • Ingår i: Alimentary Pharmacology & Therapeutics. - Hoboken, USA : Wiley. - 0269-2813 .- 1365-2036. ; 45:2, s. 222-239
  • 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.
  •  
35.
  • Lappa, Dimitra, 1988, et al. (författare)
  • Self-organized metabotyping of obese individuals identifies clusters responding differently to bariatric surgery
  • 2023
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 18:3, s. e0279335-
  • Tidskriftsartikel (refereegranskat)abstract
    • Weight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients' stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments.
  •  
36.
  • Li, S. S., et al. (författare)
  • Durable coexistence of donor and recipient strains after fecal microbiota transplantation
  • 2016
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6285, s. 586-589
  • 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.
  •  
37.
  • Louca, Panayiotis, et al. (författare)
  • The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery
  • 2023
  • Ingår i: Cell Reports Medicine. - 2666-3791. ; 4:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
  •  
38.
  • Meijnikman, A. S., et al. (författare)
  • Evaluating causality of gut microbiota in obesity and diabetes in humans
  • 2018
  • Ingår i: Endocrine reviews. - : The Endocrine Society. - 0163-769X .- 1945-7189. ; 39:2, s. 133-153
  • Forskningsöversikt (refereegranskat)abstract
    • The pathophysiology of obesity and obesity-related diseases such as type 2 diabetes mellitus (T2DM) is complex and driven by many factors. One of the most recently identified factors in development of these metabolic pathologies is the gut microbiota. The introduction of affordable, high-throughput sequencing technologies has substantially expanded our understanding of the role of the gut microbiome in modulation of host metabolism and (cardio)metabolic disease development. Nevertheless, evidence for a role of the gut microbiome as a causal, driving factor in disease development mainly originates from studies in mouse models: data showing causality in humans are scarce. In this review, we will discuss the quality of evidence supporting a causal role for the gut microbiome in the development of obesity and diabetes, in particular T2DM, in humans. Considering overlap in potential mechanisms, the role of the gut microbiome in type 1 diabetes mellitus will also be addressed. We will elaborate on factors that drive microbiome composition in humans and discuss how alterations in microbial composition or microbial metabolite production contribute to disease development. Challenging aspects in determining causality in humans will be postulated together with strategies that might hold potential to overcome these challenges. Furthermore, we will discuss means to modify gut microbiome composition in humans to help establish causality and discuss systems biology approaches that might hold the key to unravelling the role of the gut microbiome in obesity and T2DM. © 2018 Endocrine Society.
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39.
  • Männistö, Ville, et al. (författare)
  • Protein Phosphatase 1 Regulatory Subunit 3B Genotype at rs4240624 Has a Major Effect on Gallbladder Bile Composition
  • 2021
  • Ingår i: Hepatology Communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 5, s. 244-257
  • Tidskriftsartikel (refereegranskat)abstract
    • The protein phosphatase 1 regulatory subunit 3B (PPP1R3B) gene is a target of farnesoid X receptor (FXR), which is a major regulator of bile acid metabolism. Both PPP1R3B and FXR have been suggested to take part in glycogen metabolism, which may explain the association of PPP1R3B gene variants with altered hepatic computed tomography attenuation. We analyzed the effect of PPP1R3B rs4240624 variant on bile acid composition in individuals with obesity. The study cohort consisted of 242 individuals from the Kuopio Obesity Surgery Study (73 men, 169 women, age 47.6±9.0years, body mass index 43.2±5.4kg/m2) with PPP1R3B genotype and liver RNA sequencing (RNA-seq) data available. Fasting plasma and gallbladder bile samples were collected from 50 individuals. Bile acids in plasma did not differ based on the PPP1R3B rs4240624 genotype. However, the concentration of total bile acids (109±55 vs. 35±19mM; P=1.0×10−5) and all individual bile acids (also 7α-hydroxy-4-cholesten-3-one [C4]) measured from bile were significantly lower in those with the AG genotype compared to those with the AA genotype. In addition, total cholesterol (P=0.011) and phospholipid (P=0.001) levels were lower in individuals with the AG genotype, but cholesterol saturation index did not differ, indicating that the decrease in cholesterol and phospholipid levels was secondary to the change in bile acids. Liver RNA-seq data demonstrated that expression of PPP1R3B, tankyrase (TNKS), Homo sapiens chromosome 8 clone RP11-10A14.5 (AC022784.1 [LOC157273]), Homo sapiens chromosome 8 clone RP11-375N15.1 (AC021242.1), and Homo sapiens chromosome 8, clone RP11-10A14 (AC022784.6) associated with the PPP1R3B genotype. In addition, genes enriched in transmembrane transport and phospholipid binding pathways were associated with the genotype. Conclusion: The rs4240624 variant in PPP1R3B has a major effect on the composition of gallbladder bile. Other transcripts in the same loci may be important mediators of the variant effect.
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40.
  • Männistö, Ville T, et al. (författare)
  • Protein Phosphatase 1 Regulatory Subunit 3 Beta rs4240624 Genotype Is Associated With Gallstones and With Significant Changes in Bile Lipidome.
  • 2024
  • Ingår i: Gastro hep advances. - 2772-5723. ; 3:5, s. 594-601
  • Tidskriftsartikel (refereegranskat)abstract
    • Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta (PPP1R3B) rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD.Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m2) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery.The G allele of PPP1R3B rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of PPP1R3B genotype on minor lipids.The PPP1R3B rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the PPP1R3B genotype contributes to the risk of gallstones by altering the bile lipidome.
  •  
41.
  • Nieuwdorp, Max (författare)
  • Faecal microbiota transplantation
  • 2014
  • Ingår i: British Journal of Surgery. - : John Wiley and Sons Ltd. - 0007-1323 .- 1365-2168. ; 101:8, s. 887-888
  • Tidskriftsartikel (refereegranskat)abstract
    • Research opportunities in a variety of surgical conditions
  •  
42.
  • Nieuwdorp, Max, et al. (författare)
  • Role of the microbiome in energy regulation and metabolism
  • 2014
  • Ingår i: Gastroenterology. - : W.B. Saunders. - 0016-5085 .- 1528-0012. ; 146:6, s. 1525-1533
  • Tidskriftsartikel (refereegranskat)abstract
    • Intestinal microbes regulate metabolic function and energy balance; an altered microbial ecology is believed to contribute to the development of several metabolic diseases. Relative species abundance and metabolic characteristics of the intestinal microbiota change substantially in those who are obese or have other metabolic disorders and in response to ingested nutrients or therapeutic agents. The mechanisms through which the intestinal microbiota and its metabolites affect host homeostasis are just beginning to be understood. We review the relationships between the intestinal microbiota and host metabolism, including energy intake, use, and expenditure, in relation to glucose and lipid metabolism. These associations, along with interactions among the intestinal microbiota, mucus layer, bile acids, and mucosal immune responses, reveal potential mechanisms by which the microbiota affect metabolism. We discuss how controlled studies involving direct perturbations of microbial communities in human and animal models are required to identify effective therapeutic targets in the microbiota. © 2014 by the AGA Institute.
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43.
  • Schnitzler, J. G., et al. (författare)
  • Nile Red Quantifier: A novel and quantitative tool to study lipid accumulation in patient-derived circulating monocytes using confocal microscopy
  • 2017
  • Ingår i: Journal of Lipid Research. - 0022-2275. ; 58:11, s. 2210-2219
  • Tidskriftsartikel (refereegranskat)abstract
    • The inflammatory profile of circulating monocytes is an important biomarker for atherosclerotic plaque vulnerability. Recent research revealed that peripheral lipid uptake by monocytes alters their phenotype toward an inflammatory state and this coincides with an increased lipid droplet (LD) content. Determination of lipid content of circulating monocytes is, however, not very well established. Based on Nile Red (NR) neutral LD imaging, using confocal microscopy and computational analysis, we developed NR Quantifier (NRQ), a novel quantification method to assess LD content in monocytes. Circulating monocytes were isolated from blood and used for the NR staining procedure. In monocytes stained with NR, we clearly distinguished, based on 3D imaging, phospholipids and exclusively intracellular neutral lipids. Next, we developed and validated NRQ, a semi-automated quantification program that detects alterations in lipid accumulation. NRQ was able to detect LD alterations after ex vivo exposure of isolated monocytes to freshly isolated LDL in a time-and dose-dependent fashion. Finally, we validated NRQ in patients with familial hypercholesterolemia and obese subjects in pre-and postprandial state. In conclusion, NRQ is a suitable tool to detect even small differences in neutral LD content in circulating monocytes using NR staining. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.
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44.
  • Singh, R., et al. (författare)
  • Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: A proof of principle study ISRCTN48328635 ISRCTN
  • 2018
  • Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Infections with multidrug-resistant microorganisms are associated with increased hospitalization, medication costs and mortality. Based on our fecal microbiota transplantation (FMT) experience for Clostridium difficile infection, we treated 15 patients carrying ESBL-producing Enterobacteriaceae (ESBL-EB) with FMT. Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained, amounting to a total number of 22 transplants. The objective was decolonization of ESBL-EB. Results: Three out of fifteen (20%) patients were ESBL-negative at 1, 2 and 4 weeks after the first transplant, while six out of 15 (40%) were negative after the second transplant. Comparison of fecal microbiota at baseline and 4 weeks after FMT revealed restoration of microbial diversity after FMT and a microbial shift towards donor composition. Finally, we suggest several possible factors of response to therapy, such as donor-recipient microbiota match and number of FMTs. Therefore, FMT can be an effective treatment in patients carrying ESBL-EB. Response may be determined by microbiota composition and number of FMT procedures. Trial registration ISRCTN ISRCTN48328635 Registered 11 October 2017, retrospectively registered. © 2018 The Author(s).
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45.
  • Smits, L. P., et al. (författare)
  • Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome
  • 2018
  • Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 7:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIntestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. Methods and ResultsWe performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2weeks thereafter, we determined the ability to produce TMAO from d(6)-choline and d(3)-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. F-18-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as exvivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic F-18-fluorodeoxyglucose uptake, or exvivo cytokine production from peripheral blood mononuclear cells. ConclusionsSingle lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation.
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46.
  • Smits, Mark M., et al. (författare)
  • Biliary effects of liraglutide and sitagliptin, a 12-week randomized placebo-controlled trial in type 2 diabetes patients
  • 2016
  • Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 18, s. 1217-1225
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. Aims: Treatment with glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors might increase gallstone formation; however, the mechanisms involved are unknown. We aimed to assess the effects of these drugs on gallbladder volume and bile acid profile. Materials and methods: A total of 57 type 2 diabetes patients (mean ± SD age, 62.8 ± 6.9 years; BMI, 31.8 ± 4.1 kg/m2; HbA1c, 7.3% ± 0.6%), treated with metformin and/or sulfonylureas, were included in this 12-week randomized, placebo-controlled, double-blind, single-centre trial between July 2013 and August 2015 at the VU University Medical Center, the Netherlands. Patients received the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebo for 12 weeks. Gallbladder fasting volume and ejection fraction were measured using ultrasonography after a high-fat meal. Serum bile acids were measured in the fasting and postprandial state and in faecal samples. The trial was registered at ClinicalTrials.gov (NCT01744236). Results: Neither liraglutide nor sitagliptin had an effect on gallbladder fasting volume and ejection fraction (p >.05). Liraglutide increased serum levels of deoxycholic acid in the fasting state [0.20 µmol/L (95% CI 0.027-0.376), p = 0.024] and postprandial state [AUC 40.71 (13.22-68.21), p = 0.005] and in faeces [ratio 1.5 (1.03-2.19); p = 0.035]. Sitagliptin had no effect on serum bile acids, but increased faecal levels of chenodeoxycholic acid [ratio 3.42 (1.33-8.79), p = 0.012], cholic acid [ratio 3.32 (1.26-8.87), p = 0.017] and ursodeoxycholic acid [ratio 3.81 (1.44-10.14), p = 0.008]. Conclusions: Neither liraglutide nor sitagliptin has an effect on gallbladder volume. Observed changes in bile acids with liraglutide suggest alterations in the intestinal microbiome, while sitagliptin appears to increase hepatic bile acid production.
  •  
47.
  • Udayappan, S. D., et al. (författare)
  • Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and type 2 diabetes mellitus
  • 2014
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 177:1, s. 24-29
  • Forskningsöversikt (refereegranskat)abstract
    • The prevalence of obesity and diabetes mellitus type 2 is increasing rapidly around the globe. Recent insights have generated an entirely new perspective that the intestinal microbiota may play a significant role in the development of these metabolic disorders. Alterations in the intestinal microbiota composition promote systemic inflammation that is a hallmark of obesity and subsequent insulin resistance. Thus, it is important to understand the reciprocal relationship between intestinal microbiota composition and metabolic health in order to eventually prevent disease progression. In this respect, faecal transplantation studies have implicated that butyrate-producing intestinal bacteria are crucial in this process and be considered as key players in regulating diverse signalling cascades associated with human glucose and lipid metabolism.
  •  
48.
  • Udayappan, S. D., et al. (författare)
  • Intestinal Ralstonia pickettii augments glucose intolerance in obesity
  • 2017
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.
  •  
49.
  • Udayappan, Shanthadevi, et al. (författare)
  • Oral treatment with Eubacterium hallii improves insulin sensitivity in db/db mice
  • 2016
  • Ingår i: npj Biofilms and Microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • © The Author(s) 2016. An altered intestinal microbiota composition is associated with insulin resistance and type 2 diabetes mellitus. We previously identified increased intestinal levels of Eubacterium hallii, an anaerobic bacterium belonging to the butyrate-producing Lachnospiraceae family, in metabolic syndrome subjects who received a faecal transplant from a lean donor. To further assess the effects of E. hallii on insulin sensitivity, we orally treated obese and diabetic db/db mice with alive E. hallii and glycerol or heatinactive E. hallii as control. Insulin tolerance tests and hyperinsulinemic-euglycemic clamp experiments revealed that alive E. hallii treatment improved insulin sensitivity compared control treatment. In addition, E. hallii treatment increased energy expenditure in db/db mice. Active E. hallii treatment was found to increase faecal butyrate concentrations and to modify bile acid metabolism compared with heat-inactivated controls. Our data suggest that E. hallii administration potentially alters the function of the intestinal microbiome and that microbial metabolites may contribute to the improved metabolic phenotype.
  •  
50.
  • van Baar, A. C. G., et al. (författare)
  • Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites
  • 2018
  • Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 7:5, s. 673-680
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS) and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naive males with MetS using machine-learning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven) pathophysiology behind insulin resistance in human obesity.
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