Abstract:
:Interaction between disease-microbiome associations and ageing has not been explored in detail. Here, using age/region-matched sub-sets, we analysed the gut microbiome differences across five major diseases in a multi-cohort dataset constituting more than 2500 individuals from 20 to 89 years old. We show that disease-microbiome associations display specific age-centric trends. Ageing-associated microbiome alterations towards a disease-like configuration occur in colorectal cancer patients, thereby masking disease signatures. We identified a microbiome disease response shared across multiple diseases in elderly subjects that is distinct from that in young/middle-aged individuals, but also a novel set of taxa consistently gained in disease across all age groups. A subset of these taxa was associated with increased frailty in subjects from the ELDERMET cohort. The relevant taxa differentially encode specific functions that are known to have disease associations. :The human body is an ecosystem made up of both human cells and trillions of microbes, and the largest microbial community is in the gut. This community of gut microbes helps harvest nutrients from our food, modulates our immune system, and even affects our mood. Infectious and chronic diseases appear to cause changes in the make-up of the gut microbiome, while microbiome changes may increase the risk of some non-infectious diseases. Learning more about these disease-linked changes in the gut microbiome may therefore help scientists to develop new tests and treatments. To do this, scientists need to understand which microbes play a role in individual diseases, if risk-related microbes are gained or helpful microbes lost in patients with particular diseases, and if certain changes in gut microbes occur across many diseases. Ageing also changes the gut microbes. This may happen because older individuals eat a less complex diet and are likely to take many medications that may alter the microbes in their gut. Because of this, age may affect changes in gut microbes associated with diseases. This highlights the need for studies that tease apart the importance of ageing-related and disease-related changes in the gut microbiome. Now, Ghosh et al. show that gut microbe changes linked to diseases may vary with a person’s age. The analysis compared the gut microbiomes of more than 2,500 individuals aged 20 to 89. This included individuals with inflammatory bowel disease, colorectal cancer, type 2 diabetes, intestinal polyps and liver cirrhosis. The study revealed that younger people gradually gain disease-associated gut microbes, while older people tend to lose the gut microbes usually found in a healthy gut. Ghosh et al. also identified a set of gut microbes that were gained in many diseases and across age-groups. This set of microbes was also associated with frailty in elderly people. The characteristics of the microbes in this set are all known to have detrimental effects on human health. This analysis shows how important it is to control for age and other factors that may skew the results of microbiome projects. Future studies are needed to understand why these gut microbe changes occur and what the consequences of these changes are for a person’s health and the course of their disease. This may lead to the development of treatment strategies that help promote a healthy gut microbiome and fight disease throughout life.
journal_name
Elifejournal_title
eLifeauthors
Ghosh TS,Das M,Jeffery IB,O'Toole PWdoi
10.7554/eLife.50240subject
Has Abstractpub_date
2020-03-11 00:00:00issn
2050-084Xpii
50240journal_volume
9pub_type
杂志文章相关文献
eLife文献大全abstract::During inflammation, serum amyloid A proteins transport retinol to infected tissues. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.04246
更新日期:2014-09-02 00:00:00
abstract::Experiments on flies suggest that a gain-of-function mechanism in a protein called CSPɑ contributes to the progressive brain disease CLN4. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.53233
更新日期:2019-12-06 00:00:00
abstract::Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the absence of CSF1R. Here, we analyzed mpeg1:GFP-expressing macrophages in csf1r-deficient zebrafish and report that embryonic macrophages emerg...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.53403
更新日期:2020-05-05 00:00:00
abstract::Axonal conduction velocity can change substantially during ongoing activity, thus modifying spike interval structures and, potentially, temporal coding. We used a biophysical model to unmask mechanisms underlying the history-dependence of conduction. The model replicates activity in the unmyelinated axon of the crusta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.25382
更新日期:2017-07-10 00:00:00
abstract::The dynamic tyrosination-detyrosination cycle of α-tubulin regulates microtubule functions. Perturbation of this cycle impairs mitosis, neural physiology, and cardiomyocyte contraction. The carboxypeptidases vasohibins 1 and 2 (VASH1 and VASH2), in complex with the small vasohibin-binding protein (SVBP), mediate α-tub...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.58157
更新日期:2020-08-10 00:00:00
abstract::Neurons coding for head-direction are crucial for spatial navigation. Here we explored the cellular basis of head-direction coding in the rat dorsal presubiculum (PreS). We found that layer2 is composed of two principal cell populations (calbindin-positive and calbindin-negative neurons) which targeted the contralater...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14592
更新日期:2016-06-10 00:00:00
abstract::The integrity of the nuclear membranes coupled to the selective barrier of nuclear pore complexes (NPCs) are essential for the segregation of nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation to NPC assembly triggers an ESCRT-dependent surveillance system that seals nuclear pores: how these por...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45284
更新日期:2019-04-03 00:00:00
abstract::The light environment greatly impacts human alertness, mood, and cognition by both acute regulation of physiology and indirect alignment of circadian rhythms. These processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), but the relevant downstream brain areas involved...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.44358
更新日期:2019-07-23 00:00:00
abstract::Responses of sensory neurons are often modeled using a weighted combination of rectified linear subunits. Since these subunits often cannot be measured directly, a flexible method is needed to infer their properties from the responses of downstream neurons. We present a method for maximum likelihood estimation of subu...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.45743
更新日期:2020-03-09 00:00:00
abstract::Multi-modal MRI techniques have identified biomarkers that could help to predict whether someone will develop epilepsy. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.29853
更新日期:2017-07-26 00:00:00
abstract::Sex-specific synaptic connectivity is beginning to emerge as a remarkable, but little explored feature of animal brains. We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode Caenorhabditis elegans. We demonstrate that a ph...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.59614
更新日期:2020-10-06 00:00:00
abstract::Peptidoglycan (PG) is the main component of bacterial cell walls and the target for many antibiotics. PG biosynthesis is tightly coordinated with cell wall growth and turnover, and many of these control activities depend upon PASTA-domain containing eukaryotic-like serine/threonine protein kinases (PASTA-eSTK) that se...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.56048
更新日期:2020-05-29 00:00:00
abstract::Two recently discovered transcription factors stop cells from dividing when plants face extreme heat and DNA damage. ...
journal_title:eLife
pub_type: 评论,杂志文章
doi:10.7554/eLife.46781
更新日期:2019-04-09 00:00:00
abstract::Mechanical force and Wnt signaling activate β-catenin-mediated transcription to promote proliferation and tissue expansion. However, it is unknown whether mechanical force and Wnt signaling act independently or synergize to activate β-catenin signaling and cell division. We show that mechanical strain induced Src-depe...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.19799
更新日期:2016-10-26 00:00:00
abstract::Decisions are accompanied by a degree of confidence that a selected option is correct. A sequential sampling framework explains the speed and accuracy of decisions and extends naturally to the confidence that the decision rendered is likely to be correct. However, discrepancies between confidence and accuracy suggest ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.12192
更新日期:2016-02-01 00:00:00
abstract::In the fruit fly optic lobe, T4 and T5 cells represent the first direction-selective neurons, with T4 cells responding selectively to moving brightness increments (ON) and T5 cells to brightness decrements (OFF). Both T4 and T5 cells comprise four subtypes with directional tuning to one of the four cardinal directions...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.29044
更新日期:2017-08-22 00:00:00
abstract::Beige/brite adipocytes are induced within white adipose tissues (WAT) and, when activated, consume glucose and fatty acids to produce heat. Classically, two stimuli have been used to trigger a beiging response: cold temperatures and β3-adrenergic receptor (Adrb3) agonists. These two beiging triggers have been used int...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.30329
更新日期:2017-10-11 00:00:00
abstract::PKMζ is a persistently active PKC isoform proposed to maintain late-LTP and long-term memory. But late-LTP and memory are maintained without PKMζ in PKMζ-null mice. Two hypotheses can account for these findings. First, PKMζ is unimportant for LTP or memory. Second, PKMζ is essential for late-LTP and long-term memory i...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.14846
更新日期:2016-05-17 00:00:00
abstract::Major depressive disorder (MDD) is a prevalent illness that can be precipitated by acute or chronic stress. Studies of patients with Wolfram syndrome and carriers have identified Wfs1 mutations as causative for MDD. The medial prefrontal cortex (mPFC) is known to be involved in depression and behavioral resilience, al...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.08752
更新日期:2015-09-15 00:00:00
abstract::Activation of systemic acquired resistance in plants is associated with transcriptome reprogramming induced by the unstable coactivator NPR1. Immune-induced ubiquitination and proteasomal degradation of NPR1 are thought to facilitate continuous delivery of active NPR1 to target promoters, thereby maximising gene expre...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47005
更新日期:2019-10-07 00:00:00
abstract::The vascular pathogen Verticillium dahliae infects the roots of plants to cause Verticillium wilt. The molecular mechanisms underlying V. dahliae virulence and host resistance remain elusive. Here, we demonstrate that a secretory protein, VdSCP41, functions as an intracellular effector that promotes V. dahliae virulen...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.34902
更新日期:2018-05-14 00:00:00
abstract::GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRL...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.47178
更新日期:2019-06-06 00:00:00
abstract::Segmentation of the axial skeleton in amniotes depends on the segmentation clock, which patterns the paraxial mesoderm and the sclerotome. While the segmentation clock clearly operates in teleosts, the role of the sclerotome in establishing the axial skeleton is unclear. We severely disrupt zebrafish paraxial segmenta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.33843
更新日期:2018-04-06 00:00:00
abstract::When a human catches a ball, they estimate future target location based on the current trajectory. How animals, small and large, encode such predictive processes at the single neuron level is unknown. Here we describe small target-selective neurons in predatory dragonflies that exhibit localized enhanced sensitivity f...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.26478
更新日期:2017-07-25 00:00:00
abstract::The Fluc family of F(-) ion channels protects prokaryotes and lower eukaryotes from the toxicity of environmental F(-). In bacteria, these channels are built as dual-topology dimers whereby the two subunits assemble in antiparallel transmembrane orientation. Recent crystal structures suggested that Fluc channels conta...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.18767
更新日期:2016-07-23 00:00:00
abstract::Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by ...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.31502
更新日期:2018-02-20 00:00:00
abstract::Adhesion molecules hold cells together but also couple cell membranes to a contractile actomyosin network, which limits the expansion of cell contacts. Despite their fundamental role in tissue morphogenesis and tissue homeostasis, how adhesion molecules control cell shapes and cell patterns in tissues remains unclear....
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.22796
更新日期:2017-05-24 00:00:00
abstract::Hawaiian isolates of the nematode species Caenorhabditis elegans have long been known to harbor genetic diversity greater than the rest of the worldwide population, but this observation was supported by only a small number of wild strains. To better characterize the niche and genetic diversity of Hawaiian C. elegans a...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.50465
更新日期:2019-12-03 00:00:00
abstract::The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear. Using electron microscopy, we have determined the structure of the CMG in the presence of ATPγS and a DNA duplex bearing a 3' single-stranded tail. The struc...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.03273
更新日期:2014-08-12 00:00:00
abstract::The precise pattern of motor neuron (MN) activation is essential for the execution of motor actions; however, the molecular mechanisms that give rise to specific patterns of MN activity are largely unknown. Phrenic MNs integrate multiple inputs to mediate inspiratory activity during breathing and are constrained to fi...
journal_title:eLife
pub_type: 杂志文章
doi:10.7554/eLife.52859
更新日期:2020-01-16 00:00:00