Nutritional intervention by a novel slow-release niacin formulation beneficially alters the gut microbiome and promotes systemic metabolic effects in humans

2017 ◽  
Vol 12 (S 01) ◽  
pp. S1-S84
Author(s):  
D Fangmann ◽  
EM Theismann ◽  
K Türk ◽  
DM Schulte ◽  
I Relling ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Slow Release ◽  
Nutritional Intervention ◽  
Metabolic Effects

scholarly journals Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Edward C. Deehan ◽  
Eloisa Colin-Ramirez ◽  
Lucila Triador ◽  
Karen L. Madsen ◽  
Carla M. Prado ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Randomized Controlled Trial ◽  
Combination Therapy ◽  
Gut Microbiome ◽  
Controlled Trial ◽  
Fecal Microbiota ◽  
Metabolic Effects ◽  
Microbiota Composition ◽  
Randomized Controlled ◽  
Secondary Outcomes

Abstract Background Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. Methods This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12–18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. Discussion This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. Trial registration ClinicalTrials.gov NCT04578652. Registered on 8 October 2020.

scholarly journals 11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet

2017 ◽  
Vol 232 (2) ◽  
pp. 273-283 ◽  
Author(s):  
Jethro S Johnson ◽  
Monica N Opiyo ◽  
Marian Thomson ◽  
Karim Gharbi ◽  
Jonathan R Seckl ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Inflammatory Responses ◽  
Hydroxysteroid Dehydrogenase ◽  
Western Diet ◽  
Metabolic Effects ◽  
Chow Diet ◽  
The Family ◽  
The Impact

The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched ‘Western’ diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae. Our results demonstrate that (i) genetic effects on host–microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency.

scholarly journals Gut Microbiota and Metabolic Specificity in Ulcerative Colitis and Crohn's Disease

2020 ◽  
Vol 7 ◽  
Author(s):  
Jagadesan Sankarasubramanian ◽  
Rizwan Ahmad ◽  
Nagavardhini Avuthu ◽  
Amar B. Singh ◽  
Chittibabu Guda
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Meta Analysis ◽  
Metabolic Effects ◽  
Taxonomic Rank ◽  
Disease Specific

Background: Inflammatory bowel disease (IBD) represents multifactorial chronic inflammatory conditions in the gastrointestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Despite similarities in pathobiology and disease symptoms, UC and CD represent distinct diseases and exhibit diverse therapeutic responses. While studies have now confirmed that IBD is associated with dramatic changes in the gut microbiota, specific changes in the gut microbiome and associated metabolic effects on the host due to CD and UC are less well-understood.Methods: To address this knowledge gap, we performed an extensive unbiased meta-analysis of the gut microbiome data from five different IBD patient cohorts from five different countries using QIIME2, DIAMOND, and STAMP bioinformatics platforms. In-silico profiling of the metabolic pathways and community metabolic modeling were carried out to identify disease-specific association of the metabolic fluxes and signaling pathways.Results: Our results demonstrated a highly conserved gut microbiota community between healthy individuals and IBD patients at higher phylogenetic levels. However, at or below the order level in the taxonomic rank, we found significant disease-specific alterations. Similarly, we identified differential enrichment of the metabolic pathways in CD and UC, which included enriched pathways related to amino acid and glycan biosynthesis and metabolism, in addition to other metabolic pathways.Conclusions: In conclusion, this study highlights the prospects of harnessing the gut microbiota to improve understanding of the etiology of CD and UC and to develop novel prognostic, and therapeutic approaches.

scholarly journals Effects of a Microbiome Restoration Strategy on Metabolic Markers in Healthy Adults

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1147-1147
Author(s):  
Anissa Armet ◽  
Fuyong Li ◽  
Tianna Rusnak ◽  
Janis Cole ◽  
Adele Gagnon ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Gut Microbiome ◽  
Repeated Measures ◽  
Bacterial Species ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Healthy Adults ◽  
Metabolic Effects ◽  
Metabolic Markers ◽  
Lipid Panel

Abstract Objectives Industrialization has increased chronic disease prevalence, potentially due to lifestyle-induced disruptions of the gut microbiome. Decreased intake of dietary fibers is likely a key factor as they play an important role in chronic disease prevention and are growth substrates for the gut microbiota. Strategies that restore microbiome diversity, such as reintroducing health-promoting bacterial species and microbiota accessible carbohydrates (MACs), have been proposed to improve health but have not yet been systematically tested. The objective of this study was to determine the effects of a microbiome restoration strategy on metabolic markers in healthy adults. Methods Using a randomized controlled pilot study, 30 subjects consumed either a MAC-rich diet or their usual diet for three weeks each in a crossover fashion, with a three-week washout following each diet period. Participants were further divided into three groups and consumed either a single dose of one of two Limosilactobacillus reuteri strains, a rare species in industrialized microbiomes, or a placebo on day four of each diet period. Metabolic markers (standard lipid panel, glucose, insulin, C-reactive protein (CRP)) were assessed in blood collected at the start and end of each diet period. Data were analyzed using repeated measures ANOVA. Results Compared to baseline, the MAC-rich diet induced substantial metabolic changes, as it reduced total cholesterol (P < 0.0001), low density lipoprotein cholesterol (P < 0.0001), high density lipoprotein (HDL) cholesterol (P < 0.0001), non-HDL cholesterol (P < 0.0001), and glucose (P < 0.01). Other metabolic markers, such as insulin and CRP, were not significantly affected. Though the MAC-rich diet increased L. reuteri persistence in the gut for eight days (P < 0.05), the metabolic effects were independent of L. reuteri supplementation. Conclusions Our results show that a MAC-rich diet significantly benefited metabolic markers and transiently enhanced the persistence of a lost bacterial species in the gut. Ongoing analyses are exploring how the gut microbiome specifically contributes to the observed health effects of the MAC-rich diet. Funding Sources This work was supported by the Weston Family Microbiome Initiative, CIHR, Alberta Innovates Postgraduate Fellowship, and Science Foundation Ireland.

scholarly journals Changes in the Gut Microbiome and Predicted Functional Metabolic Effects in an Australian Parkinson’s Disease Cohort

2021 ◽  
Vol 15 ◽  
Author(s):  
Jade E. Kenna ◽  
Eng Guan Chua ◽  
Megan Bakeberg ◽  
Alfred Tay ◽  
Sarah McGregor ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Metabolic Effects ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Kegg Analysis ◽  
Cohort Differences

Background: There has been increasing recognition of the importance of the gut microbiome in Parkinson’s disease (PD), but the influence of geographic location has received little attention. The present study characterized the gut microbiota and associated changes in host metabolic pathways in an Australian cohort of people with PD (PwP).Methods: The study involved recruitment and assessment of 87 PwP from multiple Movement Disorders Clinics in Australia and 47 healthy controls. Illumina sequencing of the V3 and V4 regions of the 16S rRNA gene was used to distinguish inter-cohort differences in gut microbiota; KEGG analysis was subsequently performed to predict functional changes in host metabolic pathways.Results: The current findings identified significant differences in relative abundance and diversity of microbial operational taxonomic units (OTUs), and specific bacterial taxa between PwP and control groups. Alpha diversity was significantly reduced in PwP when compared to controls. Differences were found in two phyla (Synergistetes and Proteobacteria; both increased in PwP), and five genera (Colidextribacter, Intestinibacter, Kineothrix, Agathobaculum, and Roseburia; all decreased in PwP). Within the PD cohort, there was no association identified between microbial composition and gender, constipation or use of gastrointestinal medication. Furthermore, KEGG analysis identified 15 upregulated and 11 downregulated metabolic pathways which were predicted to be significantly altered in PwP.Conclusion: This study provides the first comprehensive characterization of the gut microbiome and predicted functional metabolic effects in a southern hemisphere PD population, further exploring the possible mechanisms whereby the gut microbiota may exert their influence on this disease, and providing evidence for the incorporation of such data in future individualized therapeutic strategies.

scholarly journals Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3709 ◽  
Author(s):  
Piero Portincasa ◽  
Agostino Di Ciaula ◽  
Gabriella Garruti ◽  
Mirco Vacca ◽  
Maria De Angelis ◽  
...  
Keyword(s):  
Bile Acids ◽  
Gut Microbiome ◽  
Portal Tract ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Remnant Liver ◽  
Prevention Measures ◽  
Distal Intestine ◽  
Gene Environment ◽  
Fat Soluble Vitamins

Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.

scholarly journals Gut Microbiota Regulates the Interaction between Diet and Genetics to Influence Glucose Tolerance

Medicines ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 34
Author(s):  
Jeralyn Franson ◽  
Julianne Grose ◽  
Kaitlyn Larson ◽  
Laura Bridgewater
Keyword(s):  
Weight Gain ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Nutrient Sensing ◽  
Metabolic Effects ◽  
High Fat ◽  
Serine Threonine Kinase ◽  
16S Sequencing ◽  
Triglyceride Accumulation ◽  
Pas Kinase

Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per–Arnt–Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK−/−) protects against triglyceride accumulation, insulin resistance, and weight gain on a high-fat diet; conditions that are associated with dysbiosis of the gut microbiome. Methods: Herein, we report the metabolic effects of the interplay of diet (high fat high sugar, HFHS), genotype (PASK−/−), and microbiome (16S sequencing). Results: Microbiome analysis identified a diet-induced, genotype-independent forked shift, with two discrete clusters of HFHS mice having increased beta and decreased alpha diversity. A “lower” cluster contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres, and was associated with increased weight gain, glucose intolerance, triglyceride accumulation, and decreased claudin-1 expression. Genotypic effects were observed within the clusters, lower cluster PASK−/− mice displayed increased weight gain and decreased triglyceride accumulation, whereas upper PASK−/− were resistant to decreased claudin-1. Conclusions: These results confirm previous reports that PAS kinase deficiency can protect mice against the deleterious effects of diet, and they suggest that microbiome imbalances can override protection. In addition, these results support a healthy diet for beneficial microbiome maintenance and suggest microbial culprits associated with metabolic disease.

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