The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition

Li, Xuanji; Stokholm, Jakob; Brejnrod, Asker; Vestergaard, Gisle; Russel, Jakob; Trivedi, Urvish; Thorsen, Jonathan; Gupta, Shashank; Hjelmsø, Mathis Hjort; Shah, Shiraz A.; Rasmussen, Morten Arendt; Bisgaard, Hans; Sørensen, Søren J.

doi:10.1016/j.chom.2021.03.017

Cited by 77 publications

(112 citation statements)

References 81 publications

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“…A total of 660 participants delivered a fecal sample 1-year after birth. Each fecal sample was mixed with 10% vol/vol glycerol broth and stored at -80°C until DNA extraction for metagenomes 31 , and virome extraction. Extraction and sequencing of virions was done using a previously described protocol 64 .…”

Section: Methodsmentioning

confidence: 99%

“…Bacterial hosts for the vOTUs were predicted using 318k CRISPR spacers from our metagenome assembled genomes 30 , CRISPRopenDB 32 and WIsH 33 , and the three predictions were integrated by taking the last common ancestor (LCA). 63% of the vOTUs yielded host predictions at the bacterial genus-level, while 77% were covered at the bacterial order-level (Figure 2A) and 79% at the phylum level.…”

Section: Votu Host Distributions Mimic the Bacterial Compositionmentioning

confidence: 99%

“…The children are monitored by clinicians who diagnose eventual conditions, and multi-omics data is collected routinely to shed light on disease mechanisms. A total of 647 children had a fecal sample obtained at 1 year of age where the virome was characterised, and deep metagenomes for the samples were sequenced in parallel 31 .…”

Section: Study Populationmentioning

confidence: 99%

“…Bacterial hosts for the vOTUs were predicted using 318k CRISPR spacers from our metagenome assembled genomes (MAGs) 31 and the 11M spacers from the CRISPR spacer database 33 as well as by using WIsH 34 . The three host predictions were merged by selecting the last common ancestor (LCA).…”

Section: Votu Host Distributions Mimic Sample Bacterial Compositionmentioning

confidence: 99%

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Hundreds of viral families in the healthy infant gut

Shah

Deng

Thorsen

et al. 2021

Preprint

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The gut microbiome (GM) is shaped through infancy and plays a major role in determining susceptibility to chronic diseases later in life. Bacteriophages (phage) are known to modulate bacterial populations in numerous ecosystems, including the gut. However, virome data is difficult to analyse because it mostly consists of unknown viruses, i.e. viral dark matter. Here, we manually resolved the viral dark matter in the largest human virome study published to date. Fecal viromes from a cohort of 647 infants at 1 year of age were deeply sequenced and analysed through successive rounds of clustering and curation. This uncovered more than ten thousand viral species distributed over 248 viral families falling within 17 viral order-level clusters. Most of the defined viral families and orders were novel and belonged to the Caudoviricetes viral class. Bacterial hosts were predicted for 79% of the viral species using CRISPR spacers in metagenomes from the same fecal samples. While Bacteroides-infecting Crassphages were present, novel viral families were more predominant, including phages infecting Clostridiales and Bifidobacterium. Phage lifestyles were determined for more than three thousand caudoviral species. Lifestyles were homogeneous at the family level for 149 caudiviral families. 32 families were found to be virulent, while 117 families were temperate. Virulent phage families were more abundant but temperate phage families were more diverse and widespread. Together, the viral families found in this study represent a major expansion of current bacteriophage taxonomy, and the sequences have been put online for use and validation by the community.

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Section: Methodsmentioning

confidence: 99%

Section: Votu Host Distributions Mimic the Bacterial Compositionmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Section: Votu Host Distributions Mimic Sample Bacterial Compositionmentioning

confidence: 99%

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Hundreds of viral families in the healthy infant gut

Shah

Deng

Thorsen

et al. 2021

Preprint

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“…For virome sequencing they were filtered through a 0.45 µm pore size PES filter (Minisart® High Flow Syringe Filter, Sartorius, Göttingen, Germany). For the metagenome sequencing DNA was extracted using the method of Mortensen et al [42] and the DNA was sequenced, and genomes assembled as described in Li et al [43]. Sequencing reads have previously been deposited in the SRA under the accession: PRJNA715601.…”

Section: Metagenome and Virome Sequencing And Assemblymentioning

confidence: 99%

Prophages in the infant gut are largely induced, and may be functionally relevant to their hosts

Redgwell

Thorsen

Petit

et al. 2021

Preprint

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Background: Bacteriophages are the most abundant biological entity on the planet, and are key components of any ecosystem they are present in. The gut virome is increasingly being implicated in disease states although these studies largely focus on lytic phages in adults. Here we identify prophages from a large infant cohort and investigate their potential functions. Results: We identified 10645 vOTUs from 662 metagenomes. No core virome was found: the most prevalent vOTU was identified in 70% of the samples. The most abundant and prevalent group of phages are a novel group closely related to Bacteroides phage Hanky p00. Functional annotation of this group revealed the presence of genes in the dDTP-L-rhamnose pathway, possibly involved in the production of capsular polysaccharides. We also found an abundance of diversity generating retroelements in the phages. Additionally, paired virome data allowed us to show that the majority of prophages are induced in at least one sample and that this is not affected by the use of antibiotics in the 4 weeks prior to sampling. Conclusions: Prophages in the infant gut are largely unique to the individual and not shared. Most of them appear to be induced and so may be key drivers in shaping the bacterial microbiome. The most abundant group of phages are novel, and possess elements that may allow them to maintain differentially susceptible subpopulations of their host bacterium; whilst also containing diversity generating retroelements that could expand their host range. Prophages are important components of the infant gut that may have far reaching influences on the composition and function of the microbiome.

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Metagenomic Insight into The Global Dissemination of The Antibiotic Resistome

Zhang,

Xu,

Lei

et al. 2023

Advanced Science

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The global crisis in antimicrobial resistance continues to grow. Estimating the risks of antibiotic resistance transmission across habitats is hindered by the lack of data on mobility and habitat‐specificity. Metagenomic samples of 6092 are analyzed to delineate the unique core resistomes from human feces and seven other habitats. This is found that most resistance genes (≈85%) are transmitted between external habitats and human feces. This suggests that human feces are broadly representative of the global resistome and are potentially a hub for accumulating and disseminating resistance genes. The analysis found that resistance genes with ancient horizontal gene transfer (HGT) events have a higher efficiency of transfer across habitats, suggesting that HGT may be the main driver for forming unique but partly shared resistomes in all habitats. Importantly, the human fecal resistome is historically different and influenced by HGT and age. The most important routes of cross‐transmission of resistance are from the atmosphere, buildings, and animals to humans. These habitats should receive more attention for future prevention of antimicrobial resistance. The study will disentangle transmission routes of resistance genes between humans and other habitats in a One Health framework and can identify strategies for controlling the ongoing dissemination and antibiotic resistance.

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The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition

Cited by 77 publications

References 81 publications

Hundreds of viral families in the healthy infant gut

Hundreds of viral families in the healthy infant gut

Prophages in the infant gut are largely induced, and may be functionally relevant to their hosts

Metagenomic Insight into The Global Dissemination of The Antibiotic Resistome

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