Neanderthals occupied Western Eurasia between 350 ka and 40 ka ago, during the climatically volatile Pleistocene. A key issue is to what extent Neanderthal populations expanded into areas of Western ...Eurasia and what conditions facilitated such range expansions. The range extent of Neanderthals is generally based on the distribution of Neanderthal material, but the land-altering nature of glacial periods has erased much of the already sparse material evidence of Neanderthals, particularly in the northern latitudes. To overcome this obstacle species distribution models can estimate past distributions of Neanderthals, however, most implementations are generally constrained spatially and temporally and may be artificially truncating the Neanderthal niche space. Using dated contexts from Neanderthal sites from across Western Eurasia, millennial-scale paleoclimate reconstructions, and a spatiotemporal species distribution model, we infer the fundamental climatic niche space of Neanderthals and estimate the extent of Neanderthal occupation. We find that (a.) despite the long timeframe, Neanderthals occupy a relatively narrow fundamental climatic niche space, (b.) the estimated projected potential Neanderthal niche space suggests a larger geographic range than the material record suggests, and (c.) that there was a general decline in the size of the projected potential Neanderthal niche from 145 ka ago onward, possibly contributing to their extinction.
The effects of probiotic supplementation on fecal microbiota composition in healthy adults have not been well established. We aimed to provide a systematic review of the potential evidence for an ...effect of probiotic supplementation on the composition of human fecal microbiota as assessed by high-throughput molecular approaches in randomized controlled trials (RCTs) of healthy adults.
The survey of peer-reviewed papers was performed on 17 August 2015 by a literature search through PubMed, SCOPUS, and ISI Web of Science. Additional papers were identified by checking references of relevant papers. Search terms included healthy adult, probiotic, bifidobacterium, lactobacillus, gut microbiota, fecal microbiota, intestinal microbiota, intervention, and (clinical) trial. RCTs of solely probiotic supplementation and placebo in healthy adults that examined alteration in composition of overall fecal microbiota structure assessed by shotgun metagenomic sequencing, 16S ribosomal RNA sequencing, or phylogenetic microarray methods were included. Independent collection and quality assessment of studies were performed by two authors using predefined criteria including methodological quality assessment of reports of the clinical trials based on revised tools from PRISMA/Cochrane and by the Jadad score.
Seven RCTs investigating the effect of probiotic supplementation on fecal microbiota in healthy adults were identified and included in the present systematic review. The quality of the studies was assessed as medium to high. Still, no effects were observed on the fecal microbiota composition in terms of α-diversity, richness, or evenness in any of the included studies when compared to placebo. Only one study found that probiotic supplementation significantly modified the overall structure of the fecal bacterial community in terms of β-diversity when compared to placebo.
This systematic review of the pertinent literature demonstrates a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults. Future studies would benefit from pre-specifying the primary outcome and transparently reporting the results including effect sizes, confidence intervals, and P values as well as providing a clear distinction of between-group and within-group comparisons.
Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin ...resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or ...protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference ...databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Multispecies theory is employed to explore the cultural and phenomenological dimensions of Neanderthal-carnivore co-existence.•Neanderthal life and adaptation are re-framed in terms of shifting ...carnivore ecologies.•We show that raptors, hyenas and bears were not merely competitors but likely constituted socially significant others and were thus an integral part of Neanderthal society.•Neanderthal-carnivore coevolution is argued to have resulted in specific behavioral and material strategies to negotiate carnivore neighborhoods.•Neanderthal material culture previously interpreted as ‘symbolic’ or as a proxy for ‘behavioral modernity’ is redressed as an emergent product of situated hominin-animal intersections.•The emergence of developed Upper Paleolithic techno-complexes is proposed to herald a key transition in hominin-carnivore relations with hitherto overlooked implications for the development of representational art and visual culture.•Anthropologically informed, ‘more-than-human’ theory-building can yield novel and surprising perspectives on long-standing debates in Paleolithic archaeology.
Late Pleistocene hominins co-evolved with non-analogue assemblages of carnivores and carnivorous omnivores. Although previous work has carefully examined the ecological and adaptive significance of living in such carnivore-saturated environments, surprisingly little attention has been paid to the social and cultural consequences of being-with, and adapting to, other charismatic predators and keystone carnivores. Focusing on Neanderthal populations in Western Eurasia, this paper draws together mounting archaeological evidence that suggests that some Late Pleistocene hominins devised specific behavioral strategies to negotiate their place within the vibrant carnivore guilds of their time. We build on integrative multispecies theory and broader re-conceptualizations of human-nature relations to argue that otherwise puzzling evidence for purported ‘symbolic’ behavior among Neanderthals can compellingly be re-synthesized with their ecology, settlement organization and lifeworld phenomenology. This re-framing of Neanderthal lifeways in the larger context of startling carnivore environments reveals that these hominins likely developed intimate, culturally mediated, and hence varied, bonds with raptor, hyena and bear others, rather than merely competing with them for resources, space and survival. This redressing of human-carnivore relations in the Middle Paleolithic yields important challenges for current narratives on evolving multispecies systems in the Late Pleistocene, complicating our understanding of Late Quaternary megafaunal extinctions and the roles of hominins in these processes.
Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose ...metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
Aims/hypothesis
Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared with non-diabetic individuals. However, these alterations may be confounded by ...medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men with the primary aim of investigating metformin-induced compositional changes in the non-diabetic state. A secondary aim was to examine whether the pre-treatment gut microbiota was related to gastrointestinal adverse effects during metformin treatment.
Methods
Twenty-seven healthy young Danish men were included in an 18-week one-armed crossover trial consisting of a pre-intervention period, an intervention period and a post-intervention period, each period lasting 6 weeks. Inclusion criteria were men of age 18–35 years, BMI between 18.5 kg/m
2
and 27.5 kg/m
2
, HbA
1c
< 39 mmol/mol (5.7%) and plasma creatinine within the normal range. No prescribed medication, including antibiotics, for 2 months prior to recruitment were allowed and no previous gastrointestinal surgery, discounting appendectomy or chronic illness requiring medical treatment. During the intervention the participants were given metformin up to 1 g twice daily. Participants were examined five times in the fasting state with blood sampling and recording of gastrointestinal symptoms. Examinations took place at Frederiksberg Hospital, Denmark before and after the pre-intervention period, halfway through and immediately after the end of intervention and after the wash-out period. Faecal samples were collected at nine evenly distributed time points, and bacterial DNA was extracted and subjected to 16S rRNA gene amplicon sequencing in order to evaluate gut microbiota composition. Subjective gastrointestinal symptoms were reported at each visit.
Results
Data from participants who completed visit 1 (
n
=23) are included in analyses. For the primary outcome the relative abundance of 11 bacterial genera significantly changed during the intervention but returned to baseline levels after treatment cessation. In line with previous reports, we observed a reduced abundance of
Intestinibacter
spp. and
Clostridium
spp., as well as an increased abundance of
Escherichia/Shigella
spp. and
Bilophila wadsworthia
. The relative abundance at baseline of 12 bacterial genera predicted self-reported gastrointestinal adverse effects.
Conclusions/interpretation
Intake of metformin changes the gut microbiota composition in normoglycaemic young men. The microbiota changes induced by metformin extend and validate previous reports in individuals with type 2 diabetes. Secondary analyses suggest that pre-treatment gut microbiota composition may be a determinant for development of gastrointestinal adverse effects following metformin intake. These results require further investigation and replication in larger prospective studies.
Trial registration
Clinicaltrialsregister.eu 2015-000199-86 and ClinicalTrials.gov NCT02546050
Funding
This project was funded by Danish Diabetes Association and The Novo Nordisk Foundation
Infants with Noonan Syndrome and hypertrophic cardiomyopathy have a poor prognosis and a high mortality especially when diagnosed before six months of age. As for the majority of the RASopathies, no ...medical treatment has been approved for Noonan Syndrome. Meanwhile, several approved agents targeting the same RAS/MAPK signaling pathway are used in cancer treatment. In this case report we describe a child with Noonan Syndrome caused by a pathogenic RIT1 variant, who developed severe early-onset hypertrophic cardiomyopathy and pulmonary valve stenosis. She received off-label treatment with the MEK-inhibitor trametinib which resulted in complete remission of the cardiac hypertrophy and a significant improvement of the pulmonary valve stenosis. Our case emphasizes the potential of existing cancer agents targeting the RAS/MAPK signaling pathway as successful treatment for RASopathy manifestations.
Proteoglycans (PGs) are complex macromolecules consisting of a core protein and glycosaminoglycan (GAG) side chains. PGs are important for the constitution and functioning of the connective tissue. ...The normal composition of the GAG side chains defines the nature of the PGs and a wide range of biological events. Deficiencies of specific enzymes involved in the linkage of GAGs to the core protein to form functional PGs, lead to a heterogeneous disease group called Linkeropathies. This is a group of multisystem conditions characterized by different phenotypes that include skeletal dysplasia and various extra-skeletal features: developmental delay/intellectual disability, ophthalmological abnormalities including blue sclerae, facial characteristics, cardiac defects, abdominal wall defects (hernias), cutis laxa, hypermobility and hypotonia. The conditions show variable severity and often overlapping phenotypes. The enzyme β-1,3-glucuronyltransferase 3, encoded by B3GAT3, is involved in the linkage process to form functional PGs. Biallelic pathogenic variants in B3GAT3 hence lead to Linkeropathy due to loss of function or decreased activity of this enzyme.
We describe a 22-year-old female patient, born of consanguineous parents. The disease history includes congenital severe joint malalignment of elbows, hips, knees and feet, hypermobility, severe kyphoscoliosis, osteoporosis with multiple fractures in childhood, congenital diaphragmatic hernia, minor dental anomalies, digital malformations, and characteristic facial features.
Whole exome sequencing was performed, and homozygosity for a novel in-frame deletion in B3GAT3, (c.61_63delCTC (p.(Leu21del))) was detected. Both unaffected parents (double second cousins) were shown to be heterozygous carriers.
This is the first report to describe homozygosity for this specific in-frame deletion in B3GAT3 (p.(Leu21del)). We present a young adult phenotype and a summary of previous reported patients with other biallelic B3GAT3-variants for comparison. Previously described patients of B3GAT3-deficiency were, however, all children with phenotypes ranging from prenatal manifestation and early lethality to less severe. We suggest that this novel homozygous in-frame deletion in B3GAT3 may be the cause of a recessive form of Linkeropathy.
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