Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including ...neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina.
Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing.
We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota.
These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut-brain and gut-retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life. Video abstract.
Eukaryotes are habitats for bacterial organisms where the host colonization and dispersal among individual hosts have consequences for the bacterial ecology and evolution. Vertical symbiont ...transmission leads to geographic isolation of the microbial population and consequently to genetic isolation of microbiotas from individual hosts. In contrast, the extent of geographic and genetic isolation of horizontally transmitted microbiota is poorly characterized. Here we show that chemosynthetic symbionts of individual Bathymodiolus brooksi mussels constitute genetically isolated subpopulations. The reconstruction of core genome-wide strains from high-resolution metagenomes revealed distinct phylogenetic clades. Nucleotide diversity and strain composition vary along the mussel life span and individual hosts show a high degree of genetic isolation. Our results suggest that the uptake of environmental bacteria is a restricted process in B. brooksi, where self-infection of the gill tissue results in serial founder effects during symbiont evolution. We conclude that bacterial colonization dynamics over the host life cycle is thus an important determinant of population structure and genome evolution of horizontally transmitted symbionts.
The taxonomic composition of microbial communities can be assessed using universal marker amplicon sequencing. The most common taxonomic markers are the 16S rDNA for bacterial communities and the ...internal transcribed spacer (ITS) region for fungal communities, but various other markers are used for barcoding eukaryotes. A crucial step in the bioinformatic analysis of amplicon sequences is the identification of representative sequences. This can be achieved using a clustering approach or by denoising raw sequencing reads. DADA2 is a widely adopted algorithm, released as an R library, that denoises marker-specific amplicons from next-generation sequencing and produces a set of representative sequences referred to as 'Amplicon Sequence Variants' (ASV). Here, we present Dadaist2, a modular pipeline, providing a complete suite for the analysis that ranges from raw sequencing reads to the statistics of numerical ecology. Dadaist2 implements a new approach that is specifically optimised for amplicons with variable lengths, such as the fungal ITS. The pipeline focuses on streamlining the data flow from the command line to R, with multiple options for statistical analysis and plotting, both interactive and automatic.
Genetic diversity of closely related free-living microorganisms is widespread and underpins ecosystem functioning, but most evolutionary theories predict that it destabilizes intimate mutualisms. ...Accordingly, strain diversity is assumed to be highly restricted in intracellular bacteria associated with animals. Here, we sequenced metagenomes and metatranscriptomes of 18 Bathymodiolus mussel individuals from four species, covering their known distribution range at deep-sea hydrothermal vents in the Atlantic. We show that as many as 16 strains of intracellular, sulfur-oxidizing symbionts coexist in individual Bathymodiolus mussels. Co-occurring symbiont strains differed extensively in key functions, such as the use of energy and nutrient sources, electron acceptors and viral defence mechanisms. Most strain-specific genes were expressed, highlighting their potential to affect fitness. We show that fine-scale diversity is pervasive in Bathymodiolus sulfur-oxidizing symbionts, and hypothesize that it may be widespread in low-cost symbioses where the environment, rather than the host, feeds the symbionts.
Many animals live in intimate associations with a species-rich microbiome. A key factor in maintaining these beneficial associations is fidelity, defined as the stability of associations between ...hosts and their microbiota over multiple host generations. Fidelity has been well studied in terrestrial hosts, particularly insects, over longer macroevolutionary time. In contrast, little is known about fidelity in marine animals with species-rich microbiomes at short microevolutionary time scales, that is at the level of a single host population. Given that natural selection acts most directly on local populations, studies of microevolutionary partner fidelity are important for revealing the ecological and evolutionary processes that drive intimate beneficial associations within animal species.
In this study on the obligate symbiosis between the gutless marine annelid Olavius algarvensis and its consortium of seven co-occurring bacterial symbionts, we show that partner fidelity varies across symbiont species from strict to absent over short microevolutionary time. Using a low-coverage sequencing approach that has not yet been applied to microbial community analyses, we analysed the metagenomes of 80 O. algarvensis individuals from the Mediterranean and compared host mitochondrial and symbiont phylogenies based on single-nucleotide polymorphisms across genomes. Fidelity was highest for the two chemoautotrophic, sulphur-oxidizing symbionts that dominated the microbial consortium of all O. algarvensis individuals. In contrast, fidelity was only intermediate to absent in the sulphate-reducing and spirochaetal symbionts with lower abundance. These differences in fidelity are likely driven by both selective and stochastic forces acting on the consistency with which symbionts are vertically transmitted.
We hypothesize that variable degrees of fidelity are advantageous for O. algarvensis by allowing the faithful transmission of their nutritionally most important symbionts and flexibility in the acquisition of other symbionts that promote ecological plasticity in the acquisition of environmental resources. Video Abstract.
The gut microbiota’s function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). ...This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development.
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•Microbiota disturbances promote tumor growth in several breast cancer models•Increased tumor volume positively correlates with stromal mast cell density•Supplementation with a commensal restores tumor growth to normal
Pathophysiology; Microbiology; Cancer
The human intestinal microbiota is abundant in viruses, comprising mainly bacteriophages, occasionally outnumbering bacteria 10:1 and is termed the virome. Due to their high genetic diversity and the ...lack of suitable tools and reference databases, the virome remains poorly characterised and is often referred to as "viral dark matter". However, the choice of sequencing platforms, read lengths and library preparation make study design challenging with respect to the virome. Here we have compared the use of PCR and PCR-free methods for sequence-library construction on the Illumina sequencing platform for characterising the human faecal virome. Viral DNA was extracted from faecal samples of three healthy donors and sequenced. Our analysis shows that most variation was reflecting the individually specific faecal virome. However, we observed differences between PCR and PCR-free library preparation that affected the recovery of low-abundance viral genomes. Using three faecal samples in this study, the PCR library preparation samples led to a loss of lower-abundance vOTUs evident in their PCR-free pairs (vOTUs 128, 6202 and 8364) and decreased the alpha-diversity indices (Chao1
-value = 0.045 and Simpson
-value = 0.044). Thus, differences between PCR and PCR-free methods are important to consider when investigating "rare" members of the gut virome, with these biases likely negligible when investigating moderately and highly abundant viruses.
Fungi and the mycobiome are a fundamental part of the human microbiome that contributes to human health and development. Despite this, relatively little is known about the mycobiome of the preterm ...infant gut. Here, we have characterised faecal fungal communities present in 11 premature infants born with differing degrees of prematurity and mapped how the mycobiome develops during early infancy. Using an ITS1 sequencing-based approach, the preterm infant gut mycobiome was found to be often dominated by a single species, typically a yeast.
was the most abundant genus, with the pathobionts
and
highly prevalent and persistent in these infants. Gestational maturity at birth affected the distribution and abundance of these
, with hospital-associated
more prevalent and abundant in infants born at less than 31 weeks. Fungal diversity was lowest at 6 months, but increased with age and change of diet, with food-associated
most abundant in infants post weaning. This study provides a first insight into the fungal communities present within the preterm infant gut, identifying distinctive features including the prominence of pathobiont species, and the influence age and environmental factors play in shaping the development of the mycobiome.
Over the last decades, the world of communication underwent drastic changes, and internet and social media emerged as essential vehicles for exchanging information. Following these trends, it is ...important that scientists adapt to changes and adopt optimal strategies to communicate with colleagues, lay people and institutions. We conducted an online survey to investigate the communication strategies of microbiologists and their colleagues from other disciplines. We collected data from 527 scholars from 57 countries, with ∼42% of them being microbiologists. We focused particularly on social media and found that >80% of participants used them for work, and that ∼50% of interviewed actively shared and gathered scientific contents from social media. Compared to colleagues from other fields, microbiologists were less averse to use social media for work and were also less accustomed to use pre-prints as a source and vehicle of information. However, a large proportion of microbiologists declared to have planned pre-print publications in the future. Surprisingly, our data revealed that age is a poor predictor of social media usage, but it is strongly associated with the type of social media used, the activity undertaken on them and the attitude towards pre-print publications. Considering the kaleidoscopic variety of scientific communication tools, our data might help to optimize the scientific promotion strategies among microbiologists.
The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To disentangle the inherent complexity and ...capture the ecological spectrum of microbiome variability, we used 5,230 gut metagenomes to characterize signatures of bacteria commonly co-occurring, termed enterosignatures (ESs). We find five generalizable ESs dominated by either Bacteroides, Firmicutes, Prevotella, Bifidobacterium, or Escherichia. This model confirms key ecological characteristics known from previous enterotype concepts, while enabling the detection of gradual shifts in community structures.
Temporal analysis implies that the Bacteroides-associated ES is “core” in the resilience of westernized gut microbiomes, while combinations with other ESs often complement the functional spectrum. The model reliably detects atypical gut microbiomes correlated with adverse host health conditions and/or the presence of pathobionts. ESs provide an interpretable and generic model that enables an intuitive characterization of gut microbiome composition in health and disease.
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•The human gut microbiome is described as combinations of five enterosignatures•Enterosignatures represent microbial guilds, complementary in their metabolism•Enterosignature composition is dynamic and changes with host’s age•Gut microbiomes deviating from this model could indicate dysbiotic states
Frioux et al. introduce enterosignatures as microbial guilds whose assemblies are accurate descriptors of the human gut microbiome composition. Enterosignature composition relates to changes and perturbations in the microbiome over a lifetime. The model generalizes to diverse human populations and can be used to detect anomalies in the gut microbiome.
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