Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale

Zlitni, Soumaya; Bishara, Alex; Moss, Eli L.; Ткаченко, Е. И.; Kang, Joyce B.; Culver, Rebecca; Andermann, Tessa M.; Weng, Ziming; Wood, Christina M.; Handy, Christine; Ji, Hanlee P.; Batzoglou, Serafim; Bhatt, Ami S.

doi:10.1186/s13073-020-00747-0

Cited by 48 publications

(34 citation statements)

References 74 publications

(96 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent metagenomic studies have highlighted the importance of mobile genetic elements like phage and transposons for population-level evolution (Hackl et al, 2020;Kent et al, 2020;Zlitni et al, 2020). While mobile elements did not feature strongly in our data, this may be due to methodological choices designed to increase our confidence in MAG quality at the expense of biasing against retaining mobile elements due to difficulties in confidently assigning them to a single population based solely on differential coverage and tetranucleotide frequency (Quince et al 2017).…”

Section: Discussionmentioning

confidence: 66%

Gene- and genome-centric dynamics shape the diversity of oral bacterial populations

Utter

Cavanaugh

Borisy³

2021

Preprint

View full text Add to dashboard Cite

Two major viewpoints have been put forward for how microbes adapt to a niche, differing in whether adaptation is driven principally by gene-centric or genome-centric processes. Longitudinal sampling at microbially-relevant timescales, i.e., days to weeks, is critical for distinguishing these mechanisms. Because of its significance for both microbial ecology and human health and its accessibility and high level of curation, we used the oral microbiota to evaluate evolutionary mechanisms. Metagenomes were generated by shotgun sequencing of total community DNA from the healthy tongues of 17 volunteers at four to seven timepoints obtained over intervals of days to weeks. We obtained 390 high-quality metagenome-assembled genomes (MAGs) defining population genomes from 55 genera, the majority of which were temporally stable at the MAG level. Decomposing MAG-defined populations by single nucleotide variant frequencies revealed MAGs were composed of up to 5 haplotypes, putatively distinct strain- or subpopulation-level genotypes. Most haplotypes were stable over time, yet we found examples of individual haplotypes sweeping from low abundance to dominance in a population over a period of days, a pattern suggestive of genome-centric adaptation. At the gene level, the vast majority of genes in each MAG were tightly linked over the two-week sampling window based on their frequency in the metagenomes of different mouths. The few genes that changed in abundance independently from nearby genes did not change in a directional manner, nor did nonsynonymous codon variants within such genes. Altogether, these observations characterize the intrapopulation genomic dynamics of the oral microbiota at microbially-relevant timescales. Our results demonstrate that both gene- and genome-wide sweeps occur on daily timescales but likely with different ecological ramifications. We infer that genome-wide selection of ecotypes is the dominant mode of adaptation in the oral populations, with short-term changes in gene frequency also occurring.

show abstract

Section: Discussionmentioning

confidence: 66%

Gene- and genome-centric dynamics shape the diversity of oral bacterial populations

Utter

Cavanaugh

Borisy³

2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Besides, MetaSAG can subdivide genomes of individual strains, even for species that cannot be divided into strain levels by metagenomic bins. Single-cell based strain-resolved genome analysis will contribute to our understanding of intraspecies diversity and distribution of non-chromosomal elements[29,33–35].…”

Section: Discussionmentioning

confidence: 99%

“…Using SAGs as references, contigs that have been erroneously removed or included by conventional binners can be correctly assigned, suggesting that even uncultured bacterial genomes can be validated for showing their reliability at the strain-level.DiscussionHQ reference genomes are essential for understanding the phylogeny and function of uncultured microbes in complex microbial ecosystems. In a changing environment, microbes acquire adaptive evolution through repeated genetic mutations and horizontal transfer, etc [27][28][29][30]. .…”

mentioning

confidence: 99%

Recovery of high-quality assembled genomes via metagenome binning guided with single-cell amplified genomes

Arikawa¹,

Ide

Kogawa

et al. 2021

Preprint

View full text Add to dashboard Cite

High-quality (HQ) reference genomes are essential for understanding the phylogeny and function of uncultured microbes in complex microbial ecosystems. However, existing metagenomic binners often fail to reconstruct a reasonable number of reliable HQ genomes owing to a lack of ideal binning guides. Here, we present a single-cell genome-guided binning of metagenomic assemblies (SIGMA) to reconstruct the HQ genomes of multiple strains from microbial communities at once. SIGMA generates self-reference sequences from the same sample by single-cell sequencing and uses them as guides to reconstruct metagenomic bins. The single-cell genome guide enabled precise binning and sequence integration and produced the largest number of HQ genomes from mock community and human microbiota samples in comparison with conventional binners. SIGMA can recover rRNA and tRNA genes and link plasmids to the host. This ability will contribute to understanding intraspecies diversity and distribution of mobile genetic elements in uncultured microbes.

show abstract

“…Since it is not currently possible to predict which donor may be a super donor, or which donor material may increase likelihood of success, most FMT studies currently use an accepted best strategy combining donor material into a single batch (Wilson et al, 2019). This is the technique that we used in this efficacy study, however, this method could introduce niche competition between microbiota resulting in altered implantation (Zlitni et al, 2020). Future studies of FMT should include a comparison of benefits gained through combination of donor materials versus the risk of potential niche competition.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Ross

Reveles

2020

American J Primatol

View full text Add to dashboard Cite

Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition. K E Y W O R D S aging, fecal microbiota transplantation, gut microbiota, healthspan 1 | BACKGROUND In 2030, when the last baby boomer turns 65, one out of every five Americans (about 72 million people) will be 65 years or older (Centers for Disease & Prevention, 2003, 2015). This shift to an aged population is likely to increase overall economic burden, including costs of medical care and an increase in the percentage of the population not working (Dall et al., 2013; Weil, 1997). Due to the dynamic alteration of human population needs in the near future, aging researchers are no longer simply focused on extending human lifespan; they are interested in increasing quality of life, extending the length of time people are living independently, and overall healthspan for the aging population. Therefore, the focus of aging research has now shifted to treating aging as a systemic problem and determining whether an increase in lifespan alters the ability for that individual to remain disease free. The hope is that the treatment for multiple age-related diseases including diabetes, cardiovascular disease, Alzheimer's disease, dementia, and sarcopenia could be

show abstract

Strain-resolved microbiome sequencing reveals mobile elements that drive bacterial competition on a clinical timescale

Cited by 48 publications

References 74 publications

Gene- and genome-centric dynamics shape the diversity of oral bacterial populations

Gene- and genome-centric dynamics shape the diversity of oral bacterial populations

Recovery of high-quality assembled genomes via metagenome binning guided with single-cell amplified genomes

Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets

Contact Info

Product

Resources

About