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

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.

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Gut microbiota composition explains more variance in the host cardiometabolic risk than genetic ancestry

10.1101/394726 ◽

2018 ◽

Cited By ~ 3

Author(s):

Sandra J. Guzmán-Castañeda ◽

Esteban L. Ortega-Vega ◽

Jacobo de la Cuesta-Zuluaga ◽

Eliana P. Velásquez-Mejía ◽

Winston Rojas ◽

...

Keyword(s):

Gut Microbiota ◽

Disease Risk ◽

Community Dwelling ◽

Genetic Ancestry ◽

Cardiometabolic Disease ◽

Cardiometabolic Health ◽

Genetic Composition ◽

Gut Microbes ◽

Host Health ◽

Cardiometabolic Disease Risk

AbstractBackgroundCardiometabolic affections greatly contribute to the global burden of disease. The susceptibility to these conditions associates with the ancestral genetic composition and gut microbiota. However, studies explicitly testing associations between genetic ancestry and gut microbes are rare. We examined whether the ancestral genetic composition was associated with gut microbiota, and split apart the effects of genetic and non-genetic factors on host health.ResultsWe performed a cross-sectional study of 441 community-dwelling Colombian mestizos from five cities. We characterized the host genetic ancestry using 40 ancestry informative markers and gut microbiota through 16S rRNA gene sequencing. We measured variables related to cardiometabolic health (adiposity, blood chemistry and blood pressure), diet (calories, macronutrients and fiber) and lifestyle (physical activity, smoking and medicament consumption). The ancestral genetic composition of the studied population was 67±6% European, 21±5% Native American and 12±5% African. While we found limited evidence of associations between genetic ancestry and gut microbiota or disease risk, we observed a strong link between gut microbes and cardiometabolic health. Multivariable-adjusted linear models indicated that gut microbiota was more likely to explain variance in host health than genetic ancestry. Further, we identified 9 OTUs associated with increased disease risk and 11 with decreased risk.ConclusionsGut microbiota seems to be more meaningful to explain cardiometabolic disease risk than genetic ancestry in this mestizo population. Our study suggests that novel ways to control cardiometabolic disease risk, through modulation of the gut microbial community, could be applied regardless of the genetic ancestry of the intervened population.

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Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients

10.1101/2021.04.20.440658 ◽

2021 ◽

Author(s):

André Moreira-Rosário ◽

Cláudia Marques ◽

Hélder Pinheiro ◽

João Ricardo Araújo ◽

Pedro Ribeiro ◽

...

Keyword(s):

Risk Factors ◽

Gut Microbiota ◽

Disease Severity ◽

Severe Disease ◽

Clinical Severity ◽

Rrna Gene ◽

C Reactive Protein ◽

Clinical Progression ◽

Reactive Protein ◽

Microbiota Diversity

AbstractRisk factors for COVID-19 disease severity are still poorly understood. Considering the pivotal role of gut microbiota on host immune and inflammatory functions, we investigated the association between changes in gut microbiota composition and the clinical severity of COVID-19. We conducted a multicentre cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: 1) WHO Clinical Progression Scale - mild 19 (16.5%), moderate 37 (32.2%) or severe 59 (51.3%); and 2) location of recovery from COVID-19 - ambulatory 14 (household isolation; 12.2%), hospitalized in ward 40 (34.8%) or intensive care unit 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing and data obtained was further related with clinical parameters of COVID-19 patients. Risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models.In comparison with mild COVID-19 patients, the gut microbiota of moderate and severe patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera. Multivariable regression analysis showed that Shannon index diversity (odds ratio [OR] 2.85 [95% CI 1.09-7.41]; p=0.032) and C-Reactive Protein (OR 3.45 [95% CI 1.33-8.91]; p=0.011) were risk factors for COVID-19 severe disease (a score of 6 or higher in WHO clinical progression scale).In conclusion, our results demonstrated that hospitalised moderate and severe COVID-19 patients have microbial signatures of gut dysbiosis and for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker for COVID-19 disease severity.

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Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients

Frontiers in Microbiology ◽

10.3389/fmicb.2021.705020 ◽

2021 ◽

Vol 12 ◽

Author(s):

André Moreira-Rosário ◽

Cláudia Marques ◽

Hélder Pinheiro ◽

João Ricardo Araújo ◽

Pedro Ribeiro ◽

...

Keyword(s):

Risk Factors ◽

Gut Microbiota ◽

Diversity Index ◽

Clinical Severity ◽

Rrna Gene ◽

C Reactive Protein ◽

Clinical Progression ◽

Cross Sectional ◽

Reactive Protein ◽

Microbiota Diversity

The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale—mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19—ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09–7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33–8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.

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

Metabolites ◽

10.3390/metabo11080482 ◽

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.

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Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability

Nutrients ◽

10.3390/nu12051488 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1488 ◽

Cited By ~ 3

Author(s):

Anna Mas-Capdevila ◽

Joan Teichenne ◽

Cristina Domenech-Coca ◽

Antoni Caimari ◽

Josep M Del Bas ◽

...

Keyword(s):

Risk Factors ◽

Gut Microbiota ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Current Evidence ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Beneficial Effects ◽

High Interindividual Variability

Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin’s beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin’s contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.

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The Prebiotic Inulin Beneficially Alters the Gut Microbiome and Associated Metabolites in an APOE4 Mouse Model (P08-133-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-133-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Lucille Yanckello ◽

Jared Hoffman ◽

Ishita Parikh ◽

Jessie Hoffman ◽

Stefan Green ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Dietary Intervention ◽

Disease Risk ◽

Short Chain Fatty Acids ◽

Apoe4 Allele ◽

Funding Sources ◽

Tryptophan Metabolites ◽

Host Metabolism ◽

Microbiota Diversity

Abstract Objectives The APOE4 allele is a genetic risk factor for certain diseases, due in part to alterations in lipid and glucose metabolism. The gut microbiota is also known to impact metabolic and can be beneficially modulated by prebiotics. Prebiotics are fermented into metabolites by the gut microbiota. These metabolites act as gut-brain axis components. However, the interaction of the APOE4 allele, gut microbiota, and prebiotics are unknown. The goal of the study was to use prebiotic diet to restore the gut microbiome of mice with human APOE4 (E4FAD) genes. We hypothesized that the microbial compositions of E4 mice fed inulin, compared to control fed, will correlate to metabolites being produced by the microbiome that confer benefit to host metabolism. Methods At 3 months of age the E4FAD mice were fed for 4 months with either control or inulin diet. We used 16S rRNA sequencing to determine gut microbiota diversity and species variations; non-targeted UPLC-MS/MS and GC-MS analysis was used to determine metabolic profiles of blood. Results The inulin fed mice showed a more beneficial microbial taxa profile than those mice that were control fed. Control mice showed higher levels of dimethylglycine, choline, creatine and the polyamine spermine. Higher levels of spermine, specifically, correlate to higher levels of the Proteobacteria which has been implicated in GI disorders. E4 inulin fed mice showed higher levels of bile acids, short chain fatty acids and metabolites involved in energy, increased levels of tryptophan metabolites and robust increases in sphingomyelins. Specifically in E4 inulin fed mice we saw increases in certain genera of bacteria, all of which have been implicated in being beneficial to the composition of the microbiome and producing one or more of the above mentioned metabolites. Conclusions We believe the disparities of microbial metabolite production between E4 inulin fed mice and E4 control fed mice can be attributed to differences in certain taxa that produce these metabolites, and that higher levels of these taxa are due to the dietary intervention of inulin. Despite the APOE4 allele increasing one's risk for certain diseases, we believe that beneficially modulating the gut microbiota may be one way to enhance host metabolism and decrease disease risk over time. Funding Sources NIH/NIDDK T323048107792, NIH/NIA R01AG054459, NIEHS/NIH P42ES007380. Supporting Tables, Images and/or Graphs

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Does dog acquisition improve physical activity, sedentary behaviour and biological markers of cardiometabolic health? Results from a three-arm controlled study

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2019-000703 ◽

2020 ◽

Vol 6 (1) ◽

pp. e000703

Author(s):

Lauren Powell ◽

Kate M Edwards ◽

Adrian Bauman ◽

Paul McGreevy ◽

Anthony Podberscek ◽

...

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Cardiometabolic Risk ◽

Community Dwelling ◽

Cardiometabolic Risk Factors ◽

Analysis Of Covariance ◽

Controlled Study ◽

Cardiometabolic Health ◽

Community Control ◽

Sit To Stand

ObjectivesDog ownership has been associated with improved cardiometabolic risk factors, including physical activity. Most of the evidence originates from cross-sectional studies or populations with established disease. This study investigated changes in physical activity and other cardiometabolic risk factors following dog acquisition in a sample of 71 community-dwelling adults.MethodsParticipants self-allocated to three groups: 17 individuals acquired a dog within 1 month of baseline (dog acquisition), 29 delayed dog acquisition until study completion (lagged control) and 25 had no interest in dog acquisition (community control). Self-reported and thigh-worn accelerometer-based physical activity patterns, systolic and diastolic blood pressures, resting heart rate and VO2max were measured three times: baseline, 3 months and 8 months. Data were analysed using repeated measures analysis of covariance with owner age, season, sex and education included as covariates. Post hoc between-group tests were performed where there were significant overall effects (p<0.05).ResultsWe found significant effects in mean daily steps (F(4,64)=3.02, p=0.02) and sit-to-stand transitions (F(4,66)=3.49, p=0.01). The dog acquisition group performed an additional 2589 steps (p=0.004) and 8.2 sit-to-stand transitions (p=0.03) per day at 3 months, although these effects were not maintained at 8 months. We found a significant effect in self-reported weekly walking duration (F(4,130)=2.84, p=0.03) among the lagged control group with an 80 min increase between 3 and 8 months (p=0.04). Other cardiometabolic risk factors were unchanged following dog acquisition.ConclusionOur study provides encouraging results that suggest a positive influence of dog acquisition on physical activity in the short term but larger and more generalisable controlled studies are needed.Trial registration numberACTRN12617000967381.

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Influence of Quercetin Supplementation on Disease Risk Factors in Community-Dwelling Adults

Journal of the American Dietetic Association ◽

10.1016/j.jada.2011.01.013 ◽

2011 ◽

Vol 111 (4) ◽

pp. 542-549 ◽

Cited By ~ 24

Author(s):

Amy M. Knab ◽

R. Andrew Shanely ◽

Dru A. Henson ◽

Fuxia Jin ◽

Serena A. Heinz ◽

...

Keyword(s):

Risk Factors ◽

Disease Risk ◽

Community Dwelling

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Synthetic dietary inulin, Fuji FF, delays development of diet-induced obesity by improving gut microbiota profiles and increasing short-chain fatty acid production

PeerJ ◽

10.7717/peerj.8893 ◽

2020 ◽

Vol 8 ◽

pp. e8893 ◽

Cited By ~ 1

Author(s):

Miki Igarashi ◽

Miku Morimoto ◽

Asuka Suto ◽

Akiho Nakatani ◽

Tetsuhiko Hayakawa ◽

...

Keyword(s):

Energy Metabolism ◽

Gut Microbiota ◽

Propionic Acid ◽

Short Chain ◽

Rrna Gene ◽

High Fat ◽

Fermentation Products ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

Background Dietary fiber, including inulin, promotes health via fermentation products, such as short-chain fatty acids (SCFAs), produced from the fiber by gut microbiota. SCFAs exert positive physiological effects on energy metabolism, gut immunity, and the nervous system. Most of the commercial inulin is extracted from plant sources such as chicory roots, but it can also be enzymatically synthesized from sucrose using inulin producing enzymes. Studies conducted on rodents fed with a cafeteria diet have suggested that while increasing plasma propionic acid, synthetic inulin modulates glucose and lipid metabolism in the same manner as natural inulin. Therefore, this study aimed to determine the effects of a synthetic inulin, Fuji FF, on energy metabolism, fecal SCFA production, and microbiota profiles in mice fed with a high-fat/high-sucrose diet. Methods Three-week-old male C57BL/6J mice were fed a high-fat/high-sucrose diet containing cellulose or Fuji FF for 12 weeks, and the effects on energy metabolism, SCFA production, and microbiota profiles were evaluated. Results Body weight gain was inhibited by Fuji FF supplementation in high-fat/high-sucrose diet-fed C57BL/6J mice by reducing white adipose tissue weight while increasing energy expenditure, compared with the mice supplemented with cellulose. Fuji FF also elevated levels of acetic, propionic and butyric acids in mouse feces and increased plasma propionic acid levels in mice. Moreover, 16S rRNA gene amplicon sequencing of fecal samples revealed an elevated abundance of Bacteroidetes and a reduced abundance of Firmicutes at the phylum level in mice supplemented with Fuji FF compared to those supplemented with cellulose. Fuji FF also resulted in abundance of the family Bacteroidales S24-7 and reduction of Desulfovibrionaceae in the feces. Conclusion Long term consumption of Fuji FF improved the gut environment in mice by altering the composition of the microbiota and increasing SCFA production, which might be associated with its anti-obesity effects.

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The effect of different drinking water in culture medium on feces microbiota diversity

Journal of Water and Health ◽

10.2166/wh.2020.075 ◽

2020 ◽

Author(s):

Kun Zhou ◽

Weili Liu ◽

Zhaoli Chen ◽

Dong Yang ◽

Zhigang Qiu ◽

...

Keyword(s):

Drinking Water ◽

Gut Microbiota ◽

Mineral Water ◽

Culture Medium ◽

Diversity Index ◽

Tap Water ◽

Brain Heart Infusion ◽

Rrna Gene ◽

16S Rrna Gene Analysis ◽

Microbiota Diversity

Abstract The human gut harbors trillions of microbes, which are extremely important to the health of the host. However, the effect of drinking water on gut microbiota has been poorly understood. In this study, we explored the response of BALB/c mice gut bacterial community (feces) to the different types of drinking water, including commercial bottled mineral water (MW), natural water (NW), purified water (PW) and tap water (TW). Feces were cultured with Brain Heart Infusion Broth dissolved in four types of drinking water. 16S rRNA gene analysis was performed. Our results reveal that the microbiota composition is different among culturing with four types of drinking water. As the culture time increases, the number of OTUs significantly decreased, except under the aerobic condition of MW. Under aerobic conditions on the 5th day, the considerable differences of alpha diversity index are found between MW and three others, and there are the most unique taxa in MW group. Importantly, the LEfSe analysis discovers that the Bacteroidetes taxa dominate the differences between MW and the other water types. Our findings demonstrate that the mineral water as a culture medium may lead to a progressive increase of the gut microbiota diversity by providing the growth convenience to Bacteroidetes.

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