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19 pages, 3911 KiB

Open AccessArticle

Loss of Diurnal Oscillatory Rhythms in Gut Microbiota Correlates with Changes in Circulating Metabolites in Type 2 Diabetic db/db Mice

by Eleni Beli, Samantha Prabakaran, Preethi Krishnan, Carmella Evans-Molina and Maria B. Grant

Nutrients 2019, 11(10), 2310; https://doi.org/10.3390/nu11102310 - 29 Sep 2019

Cited by 33 | Viewed by 5018

Abstract

Our hypothesis is that diabetes leads to loss of diurnal oscillatory rhythms in gut microbiota altering circulating metabolites. We performed an observational study where we compared diurnal changes of the gut microbiota with temporal changes of plasma metabolites. Metadata analysis from bacterial DNA [...] Read more.

Our hypothesis is that diabetes leads to loss of diurnal oscillatory rhythms in gut microbiota altering circulating metabolites. We performed an observational study where we compared diurnal changes of the gut microbiota with temporal changes of plasma metabolites. Metadata analysis from bacterial DNA from fecal pellets collected from 10-month old control (db/m) and type 2 diabetic (db/db) mice every 4 h for a 24-h period was used for prediction analysis. Blood plasma was collected at a day and night time points and was used for untargeted global metabolomic analysis. Feeding and activity behaviors were recorded. Our results show that while diabetic mice exhibited feeding and activity behavior similar to control mice, they exhibited a loss of diurnal oscillations in bacteria of the genus Akkermansia, Bifidobacterium, Allobaculum, Oscillospira and a phase shift in the oscillations of g.Prevotella, proteobacteria, and actinobacteria. Analysis of the circulating metabolites showed alterations in the diurnal pattern of metabolic pathways where bacteria have been implicated, such as the histidine, betaine, and methionine/cysteine pathway, mitochondrial function and the urea cycle. Functional analysis of the differential microbes revealed that during the day, when mice are asleep, the microbes of diabetic mice were enriched in processing carbon and pyruvate metabolic pathways instead of xenobiotic degradation as was observed for control mice. Altogether, our study suggests that diabetes led to loss of rhythmic oscillations of many gut microbiota with possible implications for temporal regulation of host metabolic pathways. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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22 pages, 3166 KiB

Open AccessArticle

Green Coffee Extract Improves Cardiometabolic Parameters and Modulates Gut Microbiota in High-Fat-Diet-Fed ApoE^-/- Mice

by Erika Caro-Gómez, Jelver A. Sierra, Juan S. Escobar, Rafael Álvarez-Quintero, Mauricio Naranjo, Sonia Medina, Eliana P. Velásquez-Mejía, Jorge H. Tabares-Guevara, Julio C. Jaramillo, Yudy M. León-Varela, Katalina Muñoz-Durango and José R. Ramírez-Pineda

Nutrients 2019, 11(3), 497; https://doi.org/10.3390/nu11030497 - 27 Feb 2019

Cited by 29 | Viewed by 8377

Abstract

Chlorogenic acids (CGA) are the most abundant phenolic compounds in green coffee beans and in the human diet and have been suggested to mitigate several cardiometabolic risk factors. Here, we aimed to evaluate the effect of a water-based standardized green coffee extract (GCE) [...] Read more.

Chlorogenic acids (CGA) are the most abundant phenolic compounds in green coffee beans and in the human diet and have been suggested to mitigate several cardiometabolic risk factors. Here, we aimed to evaluate the effect of a water-based standardized green coffee extract (GCE) on cardiometabolic parameters in ApoE^-/- mice and to explore the potential underlying mechanisms. Mice were fed an atherogenic diet without (vehicle) or with GCE by gavage (equivalent to 220 mg/kg of CGA) for 14 weeks. We assessed several metabolic, pathological, and inflammatory parameters and inferred gut microbiota composition, diversity, and functional potential. Although GCE did not reduce atherosclerotic lesion progression or plasma lipid levels, it induced important favorable changes. Specifically, improved metabolic parameters, including fasting glucose, insulin resistance, serum leptin, urinary catecholamines, and liver triglycerides, were observed. These changes were accompanied by reduced weight gain, decreased adiposity, lower inflammatory infiltrate in adipose tissue, and protection against liver damage. Interestingly, GCE also modulated hepatic IL-6 and total serum IgM and induced shifts in gut microbiota. Altogether, our results reveal the cooccurrence of these beneficial cardiometabolic effects in response to GCE in the same experimental model and suggest potential mediators and pathways involved. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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13 pages, 1585 KiB

Open AccessArticle

Limited Effects of Low-to-Moderate Aerobic Exercise on the Gut Microbiota of Mice Subjected to a High-Fat Diet

by Filipe M. Ribeiro, Camila F. A. Ribeiro, Ana C. M. Garcia, Alinne P. Castro, Jeeser A. Almeida, Octavio L. Franco and Bernardo A. Petriz

Nutrients 2019, 11(1), 149; https://doi.org/10.3390/nu11010149 - 11 Jan 2019

Cited by 21 | Viewed by 4565

Abstract

Several studies have indicated that diet and exercise may modulate the gut microbiota in obese subjects. Both interventions were shown to alter the microbiota orthogonally. However, this relationship has not been fully explored. This study analyzed the effects of low-to-moderate aerobic training on [...] Read more.

Several studies have indicated that diet and exercise may modulate the gut microbiota in obese subjects. Both interventions were shown to alter the microbiota orthogonally. However, this relationship has not been fully explored. This study analyzed the effects of low-to-moderate aerobic training on the fecal microbiota of mice subjected to a high-fat diet (HFD). Here, 40 male mice (C57Bl/6) were divided into two groups with standard diet (SD; 12.4% lipid) and HFD (60.3% lipid) for four months. These groups were divided into four, named SD control, HF control, SD trained and HF trained. All animals were submitted to an incremental test to estimate low-to-moderate maximum speed. Training consisted of 30 min·day⁻¹, 5 days/week, for 8 weeks. The HFD increased the body weight (p < 0.0001) and adiposity index (p < 0.05). HFD also negatively influenced performance in exercise training. Moreover, the diversity of gut microbiota was reduced by the HFD in all groups. A low-to-moderate exercise was ineffective in modulating the gut microbiota composition in mice subjected to HFD. These findings suggest that two months of low-to-moderate exercise does not achieve a preponderant modulatory effect on shaping microbiota when submitted to the high-fat diet. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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16 pages, 1927 KiB

Open AccessArticle

Higher Fecal Short-Chain Fatty Acid Levels Are Associated with Gut Microbiome Dysbiosis, Obesity, Hypertension and Cardiometabolic Disease Risk Factors

by Jacobo De la Cuesta-Zuluaga, Noel T. Mueller, Rafael Álvarez-Quintero, Eliana P. Velásquez-Mejía, Jelver A. Sierra, Vanessa Corrales-Agudelo, Jenny A. Carmona, José M. Abad and Juan S. Escobar

Nutrients 2019, 11(1), 51; https://doi.org/10.3390/nu11010051 - 27 Dec 2018

Cited by 308 | Viewed by 18605

Abstract

Fiber fermentation by gut microbiota yields short-chain fatty acids (SCFAs) that are either absorbed by the gut or excreted in feces. Studies are conflicting as to whether SCFAs are beneficial or detrimental to cardiometabolic health, and how gut microbiota associated with SCFAs is [...] Read more.

Fiber fermentation by gut microbiota yields short-chain fatty acids (SCFAs) that are either absorbed by the gut or excreted in feces. Studies are conflicting as to whether SCFAs are beneficial or detrimental to cardiometabolic health, and how gut microbiota associated with SCFAs is unclear. In this study of 441 community-dwelling adults, we examined associations of fecal SCFAs, gut microbiota diversity and composition, gut permeability, and cardiometabolic outcomes, including obesity and hypertension. We assessed fecal microbiota by 16S rRNA gene sequencing, and SCFA concentrations by gas chromatography/mass spectrometry. Fecal SCFA concentrations were inversely associated with microbiota diversity, and 70 unique microbial taxa were differentially associated with at least one SCFA (acetate, butyrate or propionate). Higher SCFA concentrations were associated with a measure of gut permeability, markers of metabolic dysregulation, obesity and hypertension. Microbial diversity showed association with these outcomes in the opposite direction. Associations were significant after adjusting for measured confounders. In conclusion, higher SCFA excretion was associated with evidence of gut dysbiosis, gut permeability, excess adiposity, and cardiometabolic risk factors. Studies assessing both fecal and circulating SCFAs are needed to test the hypothesis that the association of higher fecal SCFAs with obesity and cardiometabolic dysregulation is due to less efficient SCFA absorption. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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23 pages, 2292 KiB

Open AccessArticle

Gut Microbiota and Endothelial Dysfunction Markers in Obese Mexican Children and Adolescents

by Khemlal Nirmalkar, Selvasankar Murugesan, María Luisa Pizano-Zárate, Loan Edel Villalobos-Flores, Cristina García-González, Rosa María Morales-Hernández, Jorge Arturo Nuñez-Hernández, Fernando Hernández-Quiroz, María del Socorro Romero-Figueroa, César Hernández-Guerrero, Carlos Hoyo-Vadillo and Jaime García-Mena

Nutrients 2018, 10(12), 2009; https://doi.org/10.3390/nu10122009 - 19 Dec 2018

Cited by 74 | Viewed by 8997

Abstract

Obesity is a metabolic disease characterized by low-grade inflammation and accompanied by dyslipidemia and up-regulation of other bioactive molecules, creating a predisposition to endothelial dysfunction and metabolic syndrome. We studied the association between gut microbiota diversity and endothelial dysfunction (EDF) markers in obese [...] Read more.

Obesity is a metabolic disease characterized by low-grade inflammation and accompanied by dyslipidemia and up-regulation of other bioactive molecules, creating a predisposition to endothelial dysfunction and metabolic syndrome. We studied the association between gut microbiota diversity and endothelial dysfunction (EDF) markers in obese Mexican children and adolescents. We examined clinical data including metabolic factors and EDF markers in blood samples. Gut bacterial diversity was characterized by high-throughput sequencing of V3-16S rDNA libraries. Triglycerides, insulin, homeostasis model assessment-insulin resistant (HOMA-IR), leptin, C-reactive protein (CRP), and EDF marker intercellular adhesion molecule 1 (ICAM-1) were significantly higher in obese children and adolescents. Multivariate analysis showed statistically significant positive associations between vascular cell adhesion molecule 1 (VCAM-1) and Veillonellaceae, and between ICAM-1 and Ruminococcus in obese children. In obese adolescents, there was a statistically significant positive association between total cholesterol and Ruminococcus, and between ICAM-1 and Bacteroides. LEfSe analysis showed that the genus Lactobacillus and family Coriobacteriaceae were enriched in children, and genera Collinsella and Prevotella were enriched in obese adolescents. Obese children and adolescents had higher levels of insulin resistance and metabolic syndrome. These results suggest that obese Mexican children and adolescents had increased levels of CRP and a reduction of adiponectin, which causes higher expression of EDF markers, affecting endothelial function and associating with changes in the gut microbiota. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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12 pages, 1324 KiB

Open AccessArticle

Low Salivary Amylase Gene (AMY1) Copy Number Is Associated with Obesity and Gut Prevotella Abundance in Mexican Children and Adults

by Paola León-Mimila, Hugo Villamil-Ramírez, Blanca E. López-Contreras, Sofía Morán-Ramos, Luis R. Macias-Kauffer, Víctor Acuña-Alonzo, Blanca E. Del Río-Navarro, Jorge Salmerón, Rafael Velazquez-Cruz, Teresa Villarreal-Molina, Carlos A. Aguilar-Salinas and Samuel Canizales-Quinteros

Nutrients 2018, 10(11), 1607; https://doi.org/10.3390/nu10111607 - 01 Nov 2018

Cited by 33 | Viewed by 5724

Abstract

Genome-wide association studies (GWAS) have identified copy number variants (CNVs) associated with obesity in chromosomal regions 1p31.1, 10q11.22, 11q11, 16p12.3, and recently 1p21.1, which contains the salivary amylase gene (AMY1). Recent evidence suggests this enzyme may influence gut microbiota composition through [...] Read more.

Genome-wide association studies (GWAS) have identified copy number variants (CNVs) associated with obesity in chromosomal regions 1p31.1, 10q11.22, 11q11, 16p12.3, and recently 1p21.1, which contains the salivary amylase gene (AMY1). Recent evidence suggests this enzyme may influence gut microbiota composition through carbohydrate (mainly starch) degradation. The role of these CNVs in obesity has been scarcely explored in the Latino population, and thus the aim of our study was to evaluate the association of 1p31.1, 10q11.22, 11q11, 16p12.3 and 1p21.1 CNVs with obesity in 921 Mexican children, to replicate significant associations in 920 Mexican adults, and to analyze the association of AMY1 copy number with gut microbiota in 75 children and 45 adults. Of the five CNVs analyzed, 1q11 CNV was significantly associated with obesity in children, but not in adults. Only AMY1 CNV was significantly associated with obesity in both age groups. Moreover, gut microbiota analyses revealed a positive correlation between AMY1 copy number and Prevotella abundance. This genus has enzymes and gene clusters essential for complex polysaccharide degradation and utilization. To our knowledge, this is the first study to analyze the association of these five CNVs in the Mexican population and to report a correlation between AMY1 CN and gut microbiota in humans. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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Review

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16 pages, 1455 KiB

Open AccessReview

Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome—A Systematic Review

by Zhengxiao Zhang, Valentin Mocanu, Chenxi Cai, Jerry Dang, Linda Slater, Edward C. Deehan, Jens Walter and Karen L. Madsen

Nutrients 2019, 11(10), 2291; https://doi.org/10.3390/nu11102291 - 25 Sep 2019

Cited by 132 | Viewed by 11361

Abstract

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as [...] Read more.

Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m², fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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14 pages, 267 KiB

Open AccessReview

Is It Time to Use Probiotics to Prevent or Treat Obesity?

by Andrea Brusaferro, Rita Cozzali, Ciriana Orabona, Anna Biscarini, Edoardo Farinelli, Elena Cavalli, Ursula Grohmann, Nicola Principi and Susanna Esposito

Nutrients 2018, 10(11), 1613; https://doi.org/10.3390/nu10111613 - 01 Nov 2018

Cited by 79 | Viewed by 9946

Abstract

In recent years, attention has been given to the role potentially played by gut microbiota in the development of obesity. Several studies have shown that in individuals with obesity, the gut microbiota composition can be significantly different from that of lean individuals, that [...] Read more.

In recent years, attention has been given to the role potentially played by gut microbiota in the development of obesity. Several studies have shown that in individuals with obesity, the gut microbiota composition can be significantly different from that of lean individuals, that faecal bacteria can exert a fundamental role in modulating energy metabolism, and that modifications of gut microbiota composition can be associated with increases or reductions of body weight and body mass index. Based on this evidence, manipulation of the gut microbiota with probiotics has been considered a possible method to prevent and treat obesity. However, despite a great amount of data, the use of probiotics to prevent and treat obesity and related problems remains debated. Studies have found that the probiotic effect on body weight and metabolism is strain specific and that only some of the species included in the Lactobacillus and Bifidobacterium genera are effective, whereas the use of other strains can be deleterious. However, the dosage, duration of administration, and long-term effects of probiotics administration to prevent overweight and obesity are not known. Further studies are needed before probiotics can be rationally prescribed for the prevention or treatment of obesity. Control of the diet and environmental and life-style factors that favour obesity development remain the best solution to problems related to weight gain. Full article

(This article belongs to the Special Issue Gut Microbiota and Obesity)

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