scholarly journals Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 393-393
Author(s):  
Moamen Elmassry ◽  
Eunhee Chung ◽  
Abdul Hamood ◽  
Chwan-Li Shen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Alpha Diversity ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Microbiome Composition ◽  
And Function

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

scholarly journals Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 482
Author(s):  
Jae-Kwon Jo ◽  
Seung-Ho Seo ◽  
Seong-Eun Park ◽  
Hyun-Woo Kim ◽  
Eun-Ju Kim ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
High Fat Diet ◽  
Amplicon Sequencing ◽  
Gas Chromatography Mass Spectrometry ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Underlying Mechanisms ◽  
Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

scholarly journals Metformin Strongly Affects Gut Microbiome Composition in High-Fat Diet-Induced Type 2 Diabetes Mouse Model of Both Sexes

2021 ◽  
Vol 12 ◽  
Author(s):  
Laila Silamiķele ◽  
Ivars Silamiķelis ◽  
Monta Ustinova ◽  
Zane Kalniņa ◽  
Ilze Elbere ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Abundant Species ◽  
Metformin Treatment ◽  
High Fat ◽  
Microbiome Composition ◽  
Before And After ◽  
Diabetes Mouse

Effects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mouse models, depending on sex and metabolic status in well controlled experimental setting. Our study aimed to examine metformin-induced alterations in gut microbiome diversity, composition, and functional implications of high-fat diet-induced type 2 diabetes mouse model, using, for the first time in mice study, the shotgun metagenomic sequencing that allows estimation of microorganisms at species level. We also employed a randomized block, factorial study design, and including 24 experimental units allocated to 8 treatment groups to systematically evaluate the effect of sex and metabolic status on metformin interaction with microbiome. We used DNA obtained from fecal samples representing gut microbiome before and after ten weeks-long metformin treatment. We identified 100 metformin-related differentially abundant species in high-fat diet-fed mice before and after the treatment, with most of the species relative abundances increased. In contrast, no significant changes were observed in control diet-fed mice. Functional analysis targeted to carbohydrate, lipid, and amino acid metabolism pathways revealed 14 significantly altered hierarchies. We also observed sex-specific differences in response to metformin treatment. Males experienced more pronounced changes in metabolic markers, while in females the extent of changes in gut microbiome representatives was more marked, indicated by 53 differentially abundant species with more remarkable Log fold changes compared to the combined-sex analysis. The same pattern manifested regarding the functional analysis, where we discovered 5 significantly affected hierarchies in female groups but not in males. Our results suggest that both sexes of animals should be included in future studies focusing on metformin effects on the gut microbiome.

scholarly journals Metformin strongly affects gut microbiome composition in high-fat diet-induced type 2 diabetes mouse model of both sexes

2020 ◽  
Author(s):  
Laila Silamiķele ◽  
Ivars Silamiķelis ◽  
Monta Ustinova ◽  
Zane Kalniņa ◽  
Ilze Elbere ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Abundant Species ◽  
Metformin Treatment ◽  
High Fat ◽  
Microbiome Composition ◽  
Before And After ◽  
Diabetes Mouse

AbstractEffects of metformin, the first-line drug for type 2 diabetes therapy, on gut microbiome composition in type 2 diabetes have been described in various studies both in human subjects and animals. However, the details of the molecular mechanisms of metformin action have not been fully understood. Moreover, there is a significant lack of information on how metformin affects gut microbiome composition in female mice models, as most of the existing studies have focused on males only.Our study aimed to examine metformin-induced alterations in gut microbiome diversity and composition of high-fat diet-induced type 2 diabetes mouse model, employing a randomized block, factorial study design, and including 24 experimental units allocated to 8 treatment groups. We performed shotgun metagenomic sequencing using DNA obtained from fecal samples representing gut microbiome before and after ten weeks-long metformin treatment.We identified 100 metformin-related differentially abundant species in high-fat diet-fed mice before and after the treatment, with most of the species abundances increased. In contrast, no significant changes were observed in control diet-fed mice.We also observed sex-specific differences in response to metformin treatment. Males experienced more pronounced changes in metabolic markers, while, in females, the extent of changes in gut microbiome representatives was more marked, indicated by 53 differentially abundant species with more remarkable Log fold changes compared to the combined-sex analysis. Our results suggest that both sexes of animals should be included in future studies focusing on metformin effects on the gut microbiome.

Alterations of gut microbiome in patients with type 2 diabetes mellitus who had undergone cholecystectomy

2021 ◽  
Vol 320 (1) ◽  
pp. E113-E121
Author(s):  
Bin Wei ◽  
Yakun Wang ◽  
Shoukui Xiang ◽  
Yan Jiang ◽  
Rong Chen ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Microbiome Composition ◽  
Stool Samples ◽  
Rrna Gene Sequencing ◽  
And Function ◽  
New Onset

The gut microbiome of long-term T2DM patients who had undergone cholecystectomy and age- and/or sex-matched subjects of new-onset and long-term T2DM without cholecystectomy was assessed using 16S rRNA gene sequencing in stool samples. The findings suggest that, cholecystectomy could partially alleviate long-term diabetes-induced dysbiosis of gut microbiome composition and function.

scholarly journals Gut Microbiome in Chronic Coronary Syndrome Patients

2021 ◽  
Vol 10 (21) ◽  
pp. 5074
Author(s):  
Emilia Sawicka-Smiarowska ◽  
Kinga Bondarczuk ◽  
Witold Bauer ◽  
Magdalena Niemira ◽  
Anna Szalkowska ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Health Assessment ◽  
Study Groups ◽  
Cholesterol Concentration ◽  
Control Group ◽  
Rrna Gene ◽  
Microbiome Composition ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
And Function

Despite knowledge of classical coronary artery disease (CAD) risk factors, the morbidity and mortality associated with this disease remain high. Therefore, new factors that may affect the development of CAD, such as the gut microbiome, are extensively investigated. This study aimed to evaluate gut microbiome composition in CAD patients in relation to the control group. We examined 169 CAD patients and 166 people in the control group, without CAD, matched in terms of age and sex to the study group. Both populations underwent a detailed health assessment. The microbiome analysis was based on the V3–V4 region of the 16S rRNA gene (NGS method). Among 4074 identified taxonomic units in the whole population, 1070 differed between study groups. The most common bacterial types were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Furthermore, a higher Firmicutes/Bacteroidetes ratio in the CAD group compared with the control was demonstrated. Firmicutes/Bacteroidetes ratio, independent of age, sex, CAD status, LDL cholesterol concentration, and statins treatment, was related to altered phosphatidylcholine concentrations obtained in targeted metabolomics. Altered alpha-biodiversity (Kruskal–Wallis test, p = 0.001) and beta-biodiversity (Bray–Curtis metric, p < 0.001) in the CAD group were observed. Moreover, a predicted functional analysis revealed some taxonomic units, metabolic pathways, and proteins that might be characteristic of the CAD patients’ microbiome, such as increased expressions of 6-phospho-β-glucosidase and protein-N(pi)-phosphohistidine-sugar phosphotransferase and decreased expressions of DNA topoisomerase, oxaloacetate decarboxylase, and 6-beta-glucosidase. In summary, CAD is associated with altered gut microbiome composition and function.

scholarly journals Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Sandra Mrozinska ◽  
Piotr Radkowski ◽  
Tomasz Gosiewski ◽  
Magdalena Szopa ◽  
Malgorzata Bulanda ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiome ◽  
Bacterial Flora ◽  
Control Group ◽  
16S Sequencing ◽  
Microbiome Composition ◽  
Colonic Flora

Background. Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY).Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed.Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006) and the amount of Bacteroidetes was lower (p=0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group.Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

Abstract 18: Gut Microbiome Modifies the Protective Effects of a Mediterranean Dietary Pattern Against Diabetes Mellitus in US Hispanics/ Latinos: The Hispanic Community Health Study/ Study of Latinos (HCHS/SOL)

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Dong Wang ◽  
Qibin Qi ◽  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Daniela Sotres-Alvarez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Relative Abundance ◽  
Gut Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Health Study ◽  
Rrna Gene ◽  
Inverse Association ◽  
Protective Effects ◽  
Acid Fermentation ◽  
Microbiome Composition

Introduction: Little is known about whether the effect of a healthy diet on diabetes mellitus (DM) is modified by the gut microbiome in human. Hypothesis: We hypothesize that the gut microbiome modifies the inverse association between the Mediterranean diet (MedDiet) and risk of DM. Methods: This study included 543 DM cases, 805 with impaired glucose tolerance (IGT) and 394 with normal glucose regulation (NGR) in adults 23-83yrs old from the HCHS/SOL. Fecal samples were profiled using 16s rRNA gene sequencing. We applied QIIME 2 to cluster sequences into OTUs and assign taxonomies, and PICRUSt to predict metagenomic gene functions. Adherence to the MedDiet was evaluated by a MedDiet index using the average of two 24-hr dietary recalls. We applied MaAsLin2 to quantify associations between the MedDiet index and microbial features with adjustment for confounding factors listed in the caption of Fig. 1. Results: MedDiet was associated with phylogenetically diverse, rare, and abundant gut microbes (Fig. 1a). For example, a higher MedDiet index was associated with a higher relative abundance of Faecalibacterium Prausnitzii [FDR-adjusted p (q) =0.002], but a lower relative abundance of Collinsella aerofaciens ( q =0.009). We found that several microbial functions related to plant-derived polysaccharide degradation such as fructuronate reductase ( q =0.02), and short-chain fatty acid fermentation such as butyryl-CoA dehydrogenase ( q =0.002) were enriched in participants with higher MedDiet index. We found that the inverse association between MedDiet and risk of DM was more pronounced in participants with greater abundance of Prevotella copri , but weaker in participants whose gut microbial communities were dominated by Bacteroides ( P interaction =0.02 for IGT/DM vs NGR, Fig. 1b). Conclusions: Adherence to the MedDiet is associated with diverse gut microorganisms and microbial functions. The inverse association between MedDiet and risk of DM might be modified by gut microbiome composition. 1

scholarly journals Impacts of Aging and Blackcurrant Supplementation on the Gut Microbiome Profile of Female Mice (P20-031-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sang Gil Lee ◽  
Cao Lei ◽  
Melissa Melough ◽  
Junichi Sakaki ◽  
Kendra Maas ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Health Benefits ◽  
Alpha Diversity ◽  
Young Female ◽  
Rrna Gene ◽  
Fecal Samples ◽  
Female Mice ◽  
Aged Mice ◽  
Young Mice

Abstract Objectives Blackcurrant, an anthocyanin-rich berry, has multiple health benefits. The purpose of this study was to examine the impacts of blackcurrant supplementation and aging on gut bacterial communities in female mice. Methods Three-month and 18-month old female mice were provided standard chow diets with or without anthocyanin-rich blackcurrant extract (BC) (1% w/w) for four months. Upon study completion, fecal samples were collected directly from the animals’ colons. Microbiome DNA was extracted from the fecal samples and the V3-V4 regions of their 16S rRNA gene were amplified and sequenced using Results Taxonomic analysis showed a significantly decrease in alpha diversity in aged female mice, compared to young counterparts. BC consumption did not alter the alpha diversity in either young or aged mice compared to control diets. For beta diversity, we observed the clustering was associated with age but not diet. The phylogenic abundance analysis showed that the relative abundance of several phyla, including Firmicutes, Bacteroidetes, Cyanobacteria, Proteobacteria, and Tenericutes was higher in aged compared to young mice. Among them, the abundance of Firmicutes was downregulated by BC in the young but not the aged mice. The abundance of Bacteroidetes was increased by BC in both the young and the aged groups. Noticeably, Verrucomicrobia was the only phylum whose relative abundance was upregulated in the aged female mice compared to the young mice. Meanwhile, its relative abundance in the aged group was suppressed by BC. Interestingly, Desulfovibrio, which is the most representative sulfate-reducing genus, was detectable only in young female mice, and BC increased its relative abundance. Conclusions Our results characterized the gut microbiome compositions in young and aged female mice, and indicated that the gut microbiome of young and aged female mice responded differently to four month BC administration. Through additional research, the microbial alterations observed in this study should be further investigated to inform our understanding of the effect of BC on the gut microbiome, the possible health benefits related to these changes, and the differing effects of BC supplementation across populations. Funding Sources This study was supported by the USDA NIFA Seed Grant (#2016-67018-24492) and the University of Connecticut Foundation Esperance Funds to Dr. Ock K. Chun. We thank the National Institute on Aging for providing aged mice for the project and Just the Berries Ltd. for providing the blackcurrant extract.

scholarly journals Dysbiosis of Gut Microbiota with Increased Trimethylamine N-oxide Level in Patients with Large Artery Atherosclerotic and Cardioembolic Strokes

2020 ◽  
Author(s):  
Dong-Juan Xu ◽  
Kai Cheng Wang ◽  
Lin-Bo Yuan ◽  
Qiong-Qiong Lin ◽  
Hong-Fei Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Control Group ◽  
Large Artery ◽  
Microbiome Composition ◽  
Plaque Area ◽  
Liquid Chromatography Tandem Mass ◽  
And Function ◽  
Dietary Choline ◽  
Asymptomatic Control

Abstract Background — With the establishment of the concept of the gut–brain axis, increasing evidence has shown that the gut microbiome plays an important role in the pathogenesis of cardiovascular diseases. Gut bacteria can transform dietary choline, L-carnitine, and trimethylamine N -oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver and participate in atherogenesis. However, only few studies have described alterations in the gut microbiota composition and function in cardioembolic (CE) and large artery atherosclerotic (LAA) strokes. Methods and Results — A case–control study was performed on patients with LAA and CE strokes. TMAO was determined via liquid chromatography tandem mass spectrometry. Gut microbiome was profiled through Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions). The TMAO levels in the plasma of patients with LAA and CE strokes were significantly increased (TMAO: LAA stroke, 2931±456.4 ng/mL vs. CE stroke, 4220±577.6 ng/mL vs. control, 1663±117.8 ng/mL; P < 0.05). The TMAO level in patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% confidence interval = 0.08 to 0.55, and P = 0.0093). The composition and function of gut microbiomes in the LAA and CE stroke groups were significantly different from those of the asymptomatic control. In addition to the significantly increased α and β diversities, the gut microbiome composition and function showed that the LAA group had more microorganisms than the asymptomatic control group; such microorganisms convert dietary source choline, TMAO to TMA. Parabacteroides and Streptococcus exhibited the strongest association with LAA and CE strokes. Conclusions — This study established the compositional and functional alterations of gut microbiomes in patients with LAA and CE strokes and the relationship between plasma TMAO and gut microbiota. The findings suggest the potential of using gut microbiota as a biomarker for patients with LAA and CE strokes.

scholarly journals The long non-coding RNA Pax6os1/PAX6-AS1 modulates pancreatic β-cell identity and function

2020 ◽  
Author(s):  
Livia Lopez-Noriega ◽  
Rebecca Callingham ◽  
Aida Martinez-Sánchez ◽  
Grazia Pizza ◽  
Nejc Haberman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
High Glucose ◽  
High Fat Diet ◽  
High Fat ◽  
Β Cell ◽  
And Function

AbstractLong non-coding RNAs (lncRNAs) are emerging as crucial regulators of β-cell development and function. Consequently, the mis-expression of members of this group may contribute to the risk of type 2 diabetes (T2D). Here, we investigate roles for an antisense lncRNA expressed from the Pax6 locus (annotated as Pax6os1 in mice and PAX6-AS1 in humans) in β-cell function. The transcription factor Pax6 is required for the development of pancreatic islets and maintenance of a fully differentiated β-cell phenotype. Pax6os1/PAX6-AS1 expression was increased in pancreatic islets and β-cell lines at high glucose concentrations, in islets from mice fed a high fat diet, and in those from patients with type 2 diabetes. Silencing or deletion of Pax6os1/PAX6-AS1 in MIN6 cells and EndoC-βH1cells, respectively, upregulated β-cell signature genes, including insulin. Moreover, shRNA-mediated silencing of PAX6-AS1 in human islets not only increased insulin mRNA, but also enhanced glucose-stimulated insulin secretion and calcium dynamics. In contrast, inactivation of Pax6os1 in mice was largely without effect on glucose homeostasis, though female Pax6os1 null mice on high fat diet (HFD) showed a tendency towards enhanced glucose clearance. Together, our results suggest that increased expression of PAX6-AS1 at high glucose levels may contribute to β-cell dedifferentiation and failure in some forms of type 2 diabetes. Thus, targeting PAX6-AS1 may provide a promising strategy to enhance insulin secretion and improve glucose homeostasis in type 2 diabetes.

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