Insights Into the Human Gut Microbiome and its Link with Obesity and Cardiometabolic Diseases

The gut microbiome is a complex microbial community that inhabits the gastrointestinal tract comprising archaea, bacteria, viruses and fungi. This community lies at the interface between our environment and our cells. As such, it plays an important role in multiple nutritional, physiological and immune processes, including the synthesis of vitamins and other compounds, the energy harvest from food, and the tight regulation of innate and adaptive immunity. The gut microbiome is implicated in the pathophysiology of obesity, type 2 diabetes and cardiovascular disease. This is of particular relevance in the context of the epidemiologic and dietary transition that characterizes westernization, a process in which low- and middle-income countries shift towards increased consumption of processed foods and reduced physical activity with a concomitant increase in non-communicable diseases. This thesis contributes to our understanding of the role of the gut microbiome in cardiometabolic disease and obesity

Influence of fly ash blending on hydration and physical behavior of Belite-Alite-Ye'elimite cements

A cement powder, composed of belite, alite and ye’elimite, was blended with 0, 15 and 30 wt% of fly ash and the resulting lended cements were further characterized. During hydration, the presence of fly ash caused the partial inhibition of both AFt degradation and belite reactivity, even after 180 days. The compressive strength of the corresponding mortars increased by increasing the fly ash content (68, 73 and 82 MPa for mortars with 0, 15 and 30 wt% of fly ash, respectively, at 180 curing days), mainly due to the diminishing porosity and pore size values. Although pozzolanic reaction has not been directly proved there are indirect evidences.This work is part of the Ph.D. of D. Londono-Zuluaga funded by Beca Colciencias 646—Doctorado en el exterior and Enlaza Mundos 2013 program grant. Cement and Building materials group (CEMATCO) from National University of Colombia is acknowledged for providing the calorimetric measurements. Funding from Spanish MINECO BIA2017-82391-R and I3 (IEDI-2016-0079) grants, co-funded by FEDER, are acknowledged

Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis

Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes

Shells and humans: molluscs and other coastal resources from the earliest human occupations at the Mesolithic shell midden of El Mazo (Asturias, Northern Spain)

Human populations exploited coastal areas with intensity during the Mesolithic in Atlantic Europe, resulting in the accumulation of large shell middens. Northern Spain is one of the most prolific regions, and especially the so-called Asturian area. Large accumulations of shellfish led some scholars to propose the existence of intensification in the exploitation of coastal resources in the region during the Mesolithic. In this paper, shell remains (molluscs, crustaceans and echinoderms) from stratigraphic units 114 and 115 (dated to the early Mesolithic c. 9 kys cal BP) at El Mazo cave (Asturias, northern Spain) were studied in order to establish resource exploitation patterns and environmental conditions. Species representation showed that limpets, top shells and sea urchins were preferentially exploited. One-millimetre mesh screens were crucial in establishing an accurate minimum number of individuals for sea urchins and to determine their importance in exploitation patterns. Environmental conditions deduced from shell assemblages indicated that temperate conditions prevailed at the time of the occupation and the morphology of the coastline was similar to today (rocky exposed shores). Information recovered relating to species representation, collection areas and shell biometry reflected some evidence of intensification (reduced shell size, collection in lower areas of exposed shores, no size selection in some units and species) in the exploitation of coastal resources through time. However, the results suggested the existence of changes in collection strategies and resource management, and periods of intense shell collection may have alternated with times of shell stock recovery throughout the Mesolithic.This research was performed as part of the project “The human response to the global climatic change in a littoral zone: the case of the transition to the Holocene in the Cantabrian coast (10,000–5000 cal BC) (HAR2010-22115-C02-01)” funded by the Spanish Ministry of Economy and Competitiveness. AGE was funded by the University of Cantabria through a predoctoral grant and IGZ was funded by the Spanish Ministry of Economy and Competitiveness through a Juan de la Cierva grant. We also would like to thank the University of Cantabria and the IIIPC for providing support, David Cuenca-Solana, Alejandro García Moreno and Lucia Agudo Pérez for their help. We also thank Jennifer Jones for correcting the English. Comments from two anonymous reviewers helped to improve the paper

Incorporating genome-based phylogeny and functional similarity into diversity assessments helps to resolve a global collection of human gut metagenomes

Tree-based diversity measures incorporate phylogenetic or functional relatedness into comparisons of microbial communities. This can improve the identification of explanatory factors compared to tree-agnostic diversity measures. However, applying tree-based diversity measures to metagenome data is more challenging than for single-locus sequencing (e.g. 16S rRNA gene). Utilizing the Genome Taxonomy Database for species-level metagenome profiling allows for functional diversity measures based on genomic content or traits inferred from it. Still, it is unclear how metagenome-based assessments of microbiome diversity benefit from incorporating phylogeny or function into measures of diversity. We assessed this by measuring phylogeny-based, function-based and tree-agnostic diversity measures from a large, global collection of human gut metagenomes composed of 30 studies and 2943 samples. We found tree-based measures to explain phenotypic variation (e.g. westernization, disease status and gender) better or equivalent to tree-agnostic measures. Ecophylogenetic and functional diversity measures provided unique insight into how microbiome diversity was partitioned by phenotype. Tree-based measures greatly improved machine learning model performance for predicting westernization, disease status and gender, relative to models trained solely on tree-agnostic measures. Our findings illustrate the usefulness of tree- and function-based measures for metagenomic assessments of microbial diversity, which is a fundamental component of microbiome science

Struo: a pipeline for building custom databases for common metagenome profilers

Taxonomic and functional information from microbial communities can be efficiently obtained by metagenome profiling, which requires databases of genes and genomes to which sequence reads are mapped. However, the databases that accompany metagenome profilers are not updated at a pace that matches the increase in available microbial genomes, and unifying database content across metagenome profiling tools can be cumbersome. To address this, we developed Struo, a modular pipeline that automatizes the acquisition of genomes from public repositories and the construction of custom databases for multiple metagenome profilers. The use of custom databases that broadly represent the known microbial diversity by incorporating novel genomes results in a substantial increase in mappability of reads in synthetic and real metagenome datasets

Impact of DNA extraction, sample dilution, and reagent contamination on 16S rRNA gene sequencing of human feces

Culture-independent methods have granted the possibility to study microbial diversity in great detail, but technical issues pose a threat to the accuracy of new findings. Biases introduced during DNA extraction can result in erroneous representations of the microbial community, particularly in samples with low microbial biomass. We evaluated the DNA extraction method, initial sample biomass, and reagent contamination on the assessment of the human gut microbiota. Fecal samples of 200 mg were subjected to 1:10 serial dilutions; total DNA was obtained using two commercial kits and the microbiota assessed by 16S ribosomal RNA (rRNA) gene sequencing. In addition, we sequenced multiple technical controls. The two kits were efficient in extracting DNA from samples with as low as 2 mg of feces. However, in instances of lower biomass, only one kit performed well. The number of reads from negative controls was negligible. Both DNA extraction kits allowed inferring microbial consortia with similar membership but different abundances. Furthermore, we found differences in the taxonomic profile of the microbial community. Unexpectedly, the effect of sample dilution was moderate and did not introduce severe bias into the microbial inference. Indeed, the microbiota inferred from fecal samples was distinguishable from that of negative controls. In most cases, samples as low as 2 mg did not result in a dissimilar representation of the microbial community compared with the undiluted sample. Our results indicate that the gut microbiota inference is not much affected by contamination with laboratory reagents but largely impacted by the protocol to extract DNA

Reclassification of Catabacter hongkongensis as Christensenella hongkongensis comb. nov. based on whole genome analysis

The genera Catabacter (family 'Catabacteraceae') and Christensenella (family Christensenellaceae) are close relatives within the phylum Firmicutes. Members of these genera are strictly anaerobic, non-spore-forming and short straight rods with diverse phenotypes. Phylogenetic analysis of 16S rRNA genes suggest that Catabacter splits Christensenella into a polyphyletic clade. In an effort to ensure that family/genus names represent monophyletic clades, we performed a whole-genome based analysis of the genomes available for the cultured representatives of these genera: four species of Christensenella and two strains of Catabacter hongkongensis. A concatenated alignment of 135 shared protein sequences of single-copy core genes present in the included strains indicates that C. hongkongensis is indeed nested within the Christensenella clade. Based on their evolutionary relationship, we propose the transfer of Catabacter hongkongensis to the genus Christensenella as Christensenella hongkongensis comb. nov

Gut microbiota is associated with obesity and cardiometabolic disease in a population in the midst of Westernization

Westernization and its accompanying epidemiological transitions are associated with changes in gut microbiota. While the extremes of this lifestyle spectrum have been compared (hunter-gatherers, industrialized countries), populations undergoing such shifts have received little attention. To fill the gap of knowledge about the microbiome evolution following broad lifestyle changes and the emergence of disease-associated dysbiosis, we performed a cross-sectional study in which we characterized the microbiota of 441 Colombian adults through 16S rRNA gene sequencing and determined its relationship with demographic, health-related and dietary parameters. We showed that in the gut microbiota of this cohort thrive taxa proper of both hunter-gatherers (Prevotella, Treponema) and citizens of industrialized countries (Bacteroides, Bifidobacterium, Barnesiella); the relative abundances of these taxa differed from those in Western and non-Western populations. We also showed that the Colombian gut microbiota is composed of five consortia of co-abundant microorganisms that are differentially associated with lifestyle, obesity and cardiometabolic disease, and highlighted metabolic pathways that might explain associations between microbiota and host health. Our results give insights into the evolution of the gut microbiota, and underscore the importance of this community to human health. Promoting the growth of specific microbial consortia could help ameliorating physiological conditions associated with Western lifestyles