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. 2024 Oct 9;32(10):1853-1867.e5.
doi: 10.1016/j.chom.2024.08.016. Epub 2024 Sep 17.

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species- and strain-level diversity and evolution

Zhenrun J Zhang  1 , Cody G Cole  1 , Michael J Coyne  1 , Huaiying Lin  2 , Nicholas Dylla  2 , Rita C Smith  2 , Téa E Pappas  2 , Shannon A Townson  2 , Nina Laliwala  2 , Emily Waligurski  1 , Ramanujam Ramaswamy  2 , Che Woodson  2 , Victoria Burgo  2 , Jessica C Little  2 , David Moran  2 , Amber Rose  2 , Mary McMillin  2 , Emma McSpadden  2 , Anitha Sundararajan  2 , Ashley M Sidebottom  2 , Eric G Pamer  3 , Laurie E Comstock  4
Affiliations

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species- and strain-level diversity and evolution

Zhenrun J Zhang et al. Cell Host Microbe. .

Abstract

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome, with diverse impacts on human health. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, metabolomic, and horizontal gene transfer analyses. Families, genera, and species could be grouped based on many distinctive features. We also observed extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-species diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses represents a valuable resource to facilitate informed selection of strains for microbiome reconstitution.

Keywords: Bacteroidales; MGE; T6SS; bacterial isolates; biobank; culture collection; metabolomics; microbiome.

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Conflict of interest statement

Declaration of interests E.G.P. serves on the advisory board of Diversigen; is an inventor on patent applications WPO2015179437A1, titled “Methods and compositions for reducing Clostridium difficile infection,” and WO2017091753A1, titled “Methods and compositions for reducing vancomycin-resistant enterococci infection or colonization”; and receives royalties from Seres Therapeutics, Inc.

Figures

Figure 1.
Figure 1.. Phylogeny and genomic characterization of the 127 unique gut Bacteroidales isolates.
A. Phylogenetic tree of unique gut Bacteroidales isolates and type strains based on concatenated single-copy core gene sequences. Escherichia coli serves as an outgroup. Scale bar indicates phylogenetic distance. 127 isolates (circles), type strains (triangles). B. Genomic size of human gut Bacteroidales isolates (circles) and type strains (triangles), arranged by decreasing average genome size of species from top to bottom. C. Genomic %GC content of human gut Bacteroidales isolates (circles) and type strains (triangles), arranged by decreasing average %GC content of species from top to bottom.
Figure 2.
Figure 2.. Core genomes of Bacteroidales isolates at various taxonomic levels.
The number of core gene clusters shared by isolates grouped at different taxonomic ranks is plotted. Color indicates core gene clusters in different taxonomic ranks. Bacteroidales collection isolates (circles) or type strains (triangles).
Figure 3.
Figure 3.. UMAP analysis of the genomic diversity of Bacteroidales isolates.
UMAP plot based on the presence or absence of gene clusters in whole-genome protein coding sequences of all Bacteroidales human isolates and type strains in our collection. Bacteroidales collection isolates (circles) or type strains (triangles).
Figure 4.
Figure 4.. CAZyme and PUL analyses of Bacteroidales isolates.
A. Total numbers of CAZymes in each Bacteroidales isolate, arranged by species from most (top) to least (bottom). CAZyme families are categorized into five major classes according to CAZy database, each panel representing one class. B. UMAP plot based on the presence or absence of CAZyme families in all Bacteroidales human isolates and type strains used here. Color indicates species identity. Bacteroidales collection isolates (circles) or type strains (triangles). C. Number of PULs in all Bacteroidales isolates and type strains, ranked by their average PUL numbers from most (top) to least (bottom).
Figure 5.
Figure 5.. Metabolomic profiles of Bacteroidales isolates.
A. Quantitative metabolomics of SCFAs among Bacteroidales isolates. Each column represents one SCFA. Numbers in cells indicate relative concentration changes in mM compared to BHIS medium. Color squares on the left indicate species identity. B. Semi-quantitative metabolomics of 24 metabolites among Bacteroidales isolates. Each column represents one metabolite. Columns are grouped by hierarchical clustering. Color scale indicates log2(fold change) of metabolite concentration relative to BHIS medium. Color squares on the left indicate species identity. C. Final OD600 of Bacteroidales isolates. Each point represents mean of OD600 reading of wells of corresponding isolates grown in 96-well plates at the harvest time in one biological replicate. Colors of each bar indicate species identity. Bacteroidales isolates and species are in the same order in A, B and C.
Figure 6.
Figure 6.. Strain evolution in the human gut microbiota due to DNA transfer events.
A. Phage/genetic elements that transferred between the various species of the DFI.9 microbiome. B. Divergence and evolution due to DNA acquisitions of four B. thetaiotaomicron isolates of DFI.6 of the same clonal lineage. Sites of insertion of the elements in each of the genomes is shown. The MGE is 29,213 bp, the phage is 10,545 bp and all isolates contain plasmids of 98,230 bp, 4,971 bp, 4,148 bp and 2,750 bp, and three of the four isolates also contain a 44,031 bp plasmid shown in pink. C. Extensive divergence of isolates of clonal lineage 2 of Ph. vulgatus of ecosystem MSK.19 due to differential DNA acquisitions/losses. Fourteen isolates are differentiated based on the 14 transferred elements listed across the top. Isolates that are the same in regard to the presence or absence of these elements are shaded green and orange. Unshaded strains are each unique. Red X indicates presence of the element and black O indicates the element is absent in that isolate. Number in parenthesis refers to the region listed in Table S6, which also contains details of the genes of these regions. AID – acquired interbacterial defense element. LCP – large conjugative plasmid. Created with BioRender.com.
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