Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome

Nature Microbiology, Journal Year: 2021, Volume and Issue: 6(7), P. 960 - 970

Published: June 24, 2021

Bacteriophages have important roles in the ecology of human gut microbiome but are under-represented reference databases. To address this problem, we assembled Metagenomic Gut Virus catalogue that comprises 189,680 viral genomes from 11,810 publicly available stool metagenomes. Over 75% represent double-stranded DNA phages infect members Bacteroidia and Clostridia classes. Based on sequence clustering identified 54,118 candidate species, 92% which were not found existing The improves detection viruses metagenomes accounts for nearly 40% CRISPR spacers Bacteria Archaea. We also produced a 459,375 protein clusters to explore functional potential virome. This revealed tens thousands diversity-generating retroelements, use error-prone reverse transcription mutate target genes may be involved molecular arms race between their bacterial hosts.

Language: Английский

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Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation

Cell, Journal Year: 2022, Volume and Issue: 185(16), P. 2879 - 2898.e24

Published: Aug. 1, 2022

Language: Английский

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iPHoP: An integrated machine learning framework to maximize host prediction for metagenome-derived viruses of archaea and bacteria

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(4), P. e3002083 - e3002083

Published: April 21, 2023

The extraordinary diversity of viruses infecting bacteria and archaea is now primarily studied through metagenomics. While metagenomes enable high-throughput exploration the viral sequence space, metagenome-derived sequences lack key information compared to isolated viruses, in particular host association. Different computational approaches are available predict host(s) uncultivated based on their genome sequences, but thus far individual limited either precision or recall, i.e., for a number they yield erroneous predictions no prediction at all. Here, we describe iPHoP, two-step framework that integrates multiple methods reliably taxonomy genus rank broad range archaea, while retaining low false discovery rate. Based large dataset virus genomes from IMG/VR database, illustrate how iPHoP can provide extensive guide further characterization viruses.

Language: Английский

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Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes

Cell, Journal Year: 2023, Volume and Issue: 186(14), P. 3111 - 3124.e13

Published: June 21, 2023

The gut microbiome modulates immune and metabolic health. Human data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers Tanzania comparative populations in Nepal California. We recovered 91,662 genomes bacteria, archaea, bacteriophages, eukaryotes, 44% which absent existing unified datasets. identified 124 gut-resident species vanishing highlighted distinct aspects related to situ replication rates, signatures selection, strain sharing. Industrialized microbes were found be enriched genes associated with oxidative stress, possibly a result adaptation inflammatory processes. This unparalleled view provides valuable resource, expands capable colonizing human gut, clarifies extensive perturbation induced by lifestyle.

Language: Английский

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PhaTYP: predicting the lifestyle for bacteriophages using BERT

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 24(1)

Published: Oct. 17, 2022

Bacteriophages (or phages), which infect bacteria, have two distinct lifestyles: virulent and temperate. Predicting the lifestyle of phages helps decipher their interactions with bacterial hosts, aiding phages' applications in fields such as phage therapy. Because experimental methods for annotating cannot keep pace fast accumulation sequenced phages, computational method predicting lifestyles has become an attractive alternative. Despite some promising results, prediction remains difficult because limited known annotations sheer amount contigs assembled from metagenomic data. In particular, most existing tools precisely predict short contigs. this work, we develop PhaTYP (Phage TYPe tool) to improve accuracy on We design different training tasks, self-supervised fine-tuning overcome difficulties. rigorously tested compared four state-of-the-art methods: DeePhage, PHACTS, PhagePred BACPHLIP. The results show that outperforms all these achieves more stable performance addition, demonstrated utility analyzing human neonates' gut This application shows is a useful means studying data extend our understanding microbial communities.

Language: Английский

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PhageLeads: Rapid Assessment of Phage Therapeutic Suitability Using an Ensemble Machine Learning Approach

Viruses, Journal Year: 2022, Volume and Issue: 14(2), P. 342 - 342

Published: Feb. 8, 2022

The characterization of therapeutic phage genomes plays a crucial role in the success rate therapies. There are three checkpoints that need to be examined for selection candidates, namely, presence temperate markers, antimicrobial resistance (AMR) genes, and virulence genes. However, currently, no single-step tools available this purpose. Hence, we have developed tool capable checking all conditions required suitable candidates. This consists an ensemble machine-learning-based predictors determining markers (integrase, Cro/CI repressor, immunity DNA partitioning protein A, antirepressor) along with integration ABRicate determine antibiotic genes Using biological features were able predict high MCC scores (>0.70), corresponding lifestyle phages accuracy 96.5%. Additionally, screening 183 lytic revealed six found contain AMR or showing not used therapy. suite predictors, PhageLeads, integrated tool, can accessed online silico candidates from single genome metagenomic contigs.

Language: Английский

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Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(6), P. 1064 - 1078

Published: May 15, 2023

Language: Английский

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Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 5, 2023

Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers both pathogens exhibit high disease activity poor clinical outcomes. Colonization PSC-derived Kp specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets sustained suppressive effect vitro. Oral administration the lowers levels Kp-colonized germ-free SPF mice, without off-target dysbiosis. Furthermore, demonstrate oral intravenous successfully suppresses attenuates severity mice. These results collectively suggest using shows promise for targeting PSC.

Language: Английский

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Antimicrobial resistance crisis: could artificial intelligence be the solution?

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: Jan. 23, 2024

Abstract Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced priority list of most threatening pathogens against which novel antibiotics need to be developed. The discovery introduction are time-consuming expensive. According WHO’s report antibacterial agents in clinical development, only 18 have been approved since 2014. Therefore, critically needed. Artificial intelligence (AI) rapidly applied drug development its recent technical breakthrough dramatically improved efficiency antibiotics. Here, we first summarized recently marketed antibiotics, antibiotic candidates development. In addition, systematically reviewed involvement AI utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well mechanism prediction, stewardship.

Language: Английский

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The gut virome is associated with stress-induced changes in behaviour and immune responses in mice

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(2), P. 359 - 376

Published: Feb. 5, 2024

The microbiota-gut-brain axis has been shown to play an important role in the stress response, but previous work focused primarily on of bacteriome. gut virome constitutes a major portion microbiome, with bacteriophages having potential remodel bacteriome structure and activity. Here we use mouse model chronic social stress, employ 16S rRNA whole metagenomic sequencing faecal pellets determine how is modulated by contributes effects stress. We found that led behavioural, immune alterations mice were associated changes bacteriophage class Caudoviricetes unassigned viral taxa. To whether these causally related stress-associated behavioural or physiological outcomes, conducted transplant from before autochthonously transferred it undergoing transfer protected against behaviour sequelae restored stress-induced select circulating cell populations, cytokine release, gene expression amygdala. These data provide evidence plays modulation during indicating populations should be considered when designing future microbiome-directed therapies.

Language: Английский

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