Gabriel Fernandes

Bio: Gabriel Fernandes is an academic researcher from Oswaldo Cruz Foundation. The author has contributed to research in topics: Calorie restriction & Fish oil. The author has an hindex of 51, co-authored 185 publications receiving 12341 citations. Previous affiliations of Gabriel Fernandes include Universidade Federal de Minas Gerais & Universidade Católica de Brasília.

Enterotypes of the human gut microbiome

Abstract: Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

Biological effects of conjugated linoleic acids in health and disease.

Abstract: Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of octadecadienoic acid [linoleic acid (LA), 18:2n-6] commonly found in beef, lamb and dairy products. The most abundant isomer of CLA in nature is the cis-9, trans-11 (c9t11) isomer. Commercially available CLA is usually a 1:1 mixture of c9t11 and trans-10, cis-12 (t10c12) isomers with other isomers as minor components. Conjugated LA isomer mixture and c9t11 and t10c12 isomers alone have been attributed to provide several health benefits that are largely based on animal and in vitro studies. Conjugated LA has been attributed many beneficial effects in prevention of atherosclerosis, different types of cancer, hypertension and also known to improve immune function. More recent literature with availability of purified c9t11 and t10c12 isomers suggests that t10c12 is the sole isomer involved in antiadipogenic role of CLA. Other studies in animals and cell lines suggest that the two isomers may act similarly or antagonistically to alter cellular function and metabolism, and may also act through different signaling pathways. The effect of CLA and individual isomers shows considerable variation between different strains (BALB/C mice vs. C57BL/6 mice) and species (e.g., rats vs. mice). The dramatic effects seen in animal studies have not been reflected in some clinical studies. This review comprehensively discusses the recent studies on the effects of CLA and individual isomers on body composition, cardiovascular disease, bone health, insulin resistance, mediators of inflammatory response and different types of cancer, obtained from both in vitro and animal studies. This review also discusses the latest available information from clinical studies in these areas of research.

Dietary n‐3 Fatty Acids Decrease Osteoclastogenesis and Loss of Bone Mass in Ovariectomized Mice

Abstract: UNLABELLED The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis This finding supports a beneficial effect of FO on the attenuation of osteoporosis INTRODUCTION Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described METHODS Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO) Bone mineral density was analyzed by DXA The serum lipid profile was analyzed by gas chromatography Receptor activator of NF-kappaB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3 NF-kappaB activation in BM macrophages was measured by an electrophoretic mobility shift assay RESULTS AND CONCLUSION Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice Significantly increased bone mineral density loss (20% in distal left femur and 226% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]) DHA and EPA also inhibited BM macrophage NF-kappaB activation induced by RANKL in vitro TNF-alpha, interleukin (IL)-2, and interferon (IFN)-gamma concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice

Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats

Abstract: Obesity is a multifactor disease associated with cardiovascular disorders such as hypertension. Recently, gut microbiota was linked to obesity pathogenesisand shown to influence the host metabolism. Moreover, several factors such as host-genotype and life-style have been shown to modulate gut microbiota composition. Exercise is a well-known agent used for the treatment of numerous pathologies, such as obesity and hypertension; it has recently been demonstrated to shape gut microbiota consortia. Since exercise-altered microbiota could possibly improve the treatment of diseases related to dysfunctional microbiota, this study aimed to examine the effect of controlled exercise training on gut microbial composition in Obese rats (n = 3), non-obese Wistar rats (n = 3) and Spontaneously Hypertensive rats (n = 3). Pyrosequencing of 16S rRNA genes from fecal samples collected before and after exercise training was used for this purpose. Exercise altered the composition and diversity of gut bacteria at genus level in all rat lineages. Allobaculum (Hypertensive rats), Pseudomonas and Lactobacillus (Obese rats) were shown to be enriched after exercise, while Streptococcus (Wistar rats), Aggregatibacter and Sutturella (Hypertensive rats) were more enhanced before exercise. A significant correlation was seen in the Clostridiaceae and Bacteroidaceae families and Oscillospira and Ruminococcus genera with blood lactate accumulation. Moreover, Wistar and Hypertensive rats were shown to share a similar microbiota composition, as opposed to Obese rats. Finally, Streptococcus alactolyticus, Bifidobacterium animalis, Ruminococcus gnavus, Aggregatibacter pneumotropica and Bifidobacterium pseudolongum were enriched in Obese rats. These data indicate that non-obese and hypertensive rats harbor a different gut microbiota from obese rats and that exercise training alters gut microbiota from an obese and hypertensive genotype background.

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

Abstract: Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFNγ on glucose tolerance. In IFNγ-deficient mice, A. muciniphila is significantly increased and restoration of IFNγ levels reduces A. muciniphila abundance. We further show that IFNγ-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFNγ-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFNγ-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFNγ, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans.

phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data.

Abstract: Background The analysis of microbial communities through DNA sequencing brings many challenges: the integration of different types of data with methods from ecology, genetics, phylogenetics, multivariate statistics, visualization and testing. With the increased breadth of experimental designs now being pursued, project-specific statistical analyses are often needed, and these analyses are often difficult (or impossible) for peer researchers to independently reproduce. The vast majority of the requisite tools for performing these analyses reproducibly are already implemented in R and its extensions (packages), but with limited support for high throughput microbiome census data. Results Here we describe a software project, phyloseq, dedicated to the object-oriented representation and analysis of microbiome census data in R. It supports importing data from a variety of common formats, as well as many analysis techniques. These include calibration, filtering, subsetting, agglomeration, multi-table comparisons, diversity analysis, parallelized Fast UniFrac, ordination methods, and production of publication-quality graphics; all in a manner that is easy to document, share, and modify. We show how to apply functions from other R packages to phyloseq-represented data, illustrating the availability of a large number of open source analysis techniques. We discuss the use of phyloseq with tools for reproducible research, a practice common in other fields but still rare in the analysis of highly parallel microbiome census data. We have made available all of the materials necessary to completely reproduce the analysis and figures included in this article, an example of best practices for reproducible research. Conclusions The phyloseq project for R is a new open-source software package, freely available on the web from both GitHub and Bioconductor.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Diet rapidly and reproducibly alters the human gut microbiome

Abstract: Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

Human gut microbiome viewed across age and geography

Abstract: Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.

Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes

Abstract: Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.