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      Enterotype May Drive the Dietary-Associated Cardiometabolic Risk Factors

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          Abstract

          Analyses of typical bacterial clusters in humans named enterotypes may facilitate understanding the host differences in the cardiometabolic profile. It stills unknown whether the three previously described enterotypes were present in populations living below the equator. We examined how the identification of enterotypes could be useful to explain the dietary associations with cardiometabolic risk factors in Brazilian subjects. In this cross-sectional study, a convenience sample of 268 adults (54.2% women) reported their dietary habits and had clinical and biological samples collected. In this study, we analyzed biochemical data and metagenomics of fecal microbiota (16SrRNA sequencing, V4 region). Continuous variables were compared using ANOVA, and categorical variables using chi-square test. Vsearch clustered the operational taxonomic units, and Silva Database provided the taxonomic signatures. Spearman coefficient was used to verify the correlation between bacteria abundances within each enterotype. One hundred subjects were classified as omnivore, 102 lacto-ovo-vegetarians, and 66 strict vegetarians. We found the same structure as the three previously described enterotypes: 111 participants were assigned to Bacteroides, 55 to Prevotella, and 102 to Ruminococcaceae enterotype. The Prevotella cluster contained higher amount of strict vegetarians individuals than the other enterotypes (40.0 vs. 20.7 and 20.6, p = 0.04). Subjects in this enterotype had a similar anthropometric profile but a lower mean LDL-c concentration than the Bacteroides enterotype (96 ± 23 vs. 109 ± 32 mg/dL, p = 0.04). We observed significant correlations between bacterial abundances and cardiometabolic risk factors, but coefficients differed depending on the enterotype. In Prevotella enterotype, Eubacterium ventriosum (r BMI = −0.33, p = 0.03, and r HDL-c = 0.33, p = 0.04), Akkermansia (r 2h glucose = −0.35, p = 0.02), Roseburia (r BMI = −0.36, p = 0.02 and r waist = −0.36, p = 0.02), and Faecalibacterium (r insulin = −0.35, p = 0.02) abundances were associated to better cardiometabolic profile. The three enterotypes previously described are present in Brazilians, supporting that those bacterial clusters are not population-specific. Diet-independent lower LDL-c levels in subjects from Prevotella than in other enterotypes suggest that a protective bacterial cluster in the former should be driving this association. Enterotypes seem to be useful to understand the impact of daily diet exposure on cardiometabolic risk factors. Prospective studies are needed to confirm their utility for predicting phenotypes in humans.

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          Most cited references27

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          FLASH: fast length adjustment of short reads to improve genome assemblies.

          Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome. We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds. The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash. t.magoc@gmail.com.
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            Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

            The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
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              Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice

              Recent evidence indicates that the gut microbiota plays a key role in the pathophysiology of obesity. Indeed, diet-induced obesity (DIO) has been associated to substantial changes in gut microbiota composition in rodent models. In the context of obesity, enhanced adiposity is accompanied by low-grade inflammation of this tissue but the exact link with gut microbial community remains unknown. In this report, we studied the consequences of high-fat diet (HFD) administration on metabolic parameters and gut microbiota composition over different periods of time. We found that Akkermansia muciniphila abundance was strongly and negatively affected by age and HFD feeding and to a lower extend Bilophila wadsworthia was the only taxa following an opposite trend. Different approaches, including multifactorial analysis, showed that these changes in Akkermansia muciniphila were robustly correlated with the expression of lipid metabolism and inflammation markers in adipose tissue, as well as several circulating parameters (i.e., glucose, insulin, triglycerides, leptin) from DIO mice. Thus, our data shows the existence of a link between gut Akkermansia muciniphila abundance and adipose tissue homeostasis on the onset of obesity, thus reinforcing the beneficial role of this bacterium on metabolism.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                23 February 2017
                2017
                : 7
                : 47
                Affiliations
                [1] 1Department of Epidemiology, School of Public Health, University of São Paulo São Paulo, Brazil
                [2] 2René Rachou Research Center, Oswaldo Cruz Foundation Belo Horizonte, Brazil
                [3] 3Department of Preventive Medicine, Federal University of São Paulo São Paulo, Brazil
                [4] 4Laboratory of Genetics and Molecular Cardiology, Heart Institute (Incor), University of São Paulo Medical School São Paulo, Brazil
                Author notes

                Edited by: Michele Marie Kosiewicz, University of Louisville, USA

                Reviewed by: Valerio Iebba, Sapienza University of Rome, Italy; Gena D. Tribble, University of Texas Health Science Center at Houston, USA

                *Correspondence: Sandra R. G. Ferreira sandrafv@ 123456usp.br
                Article
                10.3389/fcimb.2017.00047
                5322172
                28280715
                3bbd2a20-38cc-417f-9db9-093b7c90ae59
                Copyright © 2017 de Moraes, Fernandes, da Silva, Almeida-Pititto, Gomes, Pereira and Ferreira.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 October 2016
                : 07 February 2017
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 58, Pages: 9, Words: 6436
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo 10.13039/501100001807
                Award ID: 2012/12626-9
                Award ID: 2012/03880-9
                Categories
                Microbiology
                Original Research

                Infectious disease & Microbiology
                gut microbiota,enterotype,cardiometabolic risk,diet,lipid profile

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