Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization

To understand how a bacterium ultimately succeeds or fails in adapting to a new host, it is essential to assess the temporal dynamics of its fitness over the course of colonization. Here, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron (Bt), into the guts of germ-free m...

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Published in:	Cell reports (Cambridge) Vol. 42; no. 8; p. 113009
Main Authors:	Kennedy, Megan S., Zhang, Manjing, DeLeon, Orlando, Bissell, Jacie, Trigodet, Florian, Lolans, Karen, Temelkova, Sara, Carroll, Katherine T., Fiebig, Aretha, Deutschbauer, Adam, Sidebottom, Ashley M., Lake, Joash, Henry, Chris, Rice, Phoebe A., Bergelson, Joy, Chang, Eugene B.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 29-08-2023 Elsevier
Subjects:	Acclimatization Animals Bacteroides thetaiotaomicron Bacteroides thetaiotaomicron - genetics BarSeq BASIC BIOLOGICAL SCIENCES Biological Assay commensal bacteria CP: Microbiology Gene Expression Profiling gut colonization Humans insertion sequence IS elements Mice microbial adaptation microbial metabolism microbiome-based therapy Microbiota insertion sequence microbial metabolism microbiome-based therapy Bacteroides thetaiotaomicron BarSeq gut colonization CP: Microbiology IS elements microbial adaptation commensal bacteria
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Summary:	To understand how a bacterium ultimately succeeds or fails in adapting to a new host, it is essential to assess the temporal dynamics of its fitness over the course of colonization. Here, we introduce a human-derived commensal organism, Bacteroides thetaiotaomicron (Bt), into the guts of germ-free mice to determine whether and how the genetic requirements for colonization shift over time. Combining a high-throughput functional genetics assay and transcriptomics, we find that gene usage changes drastically during the first days of colonization, shifting from high expression of amino acid biosynthesis genes to broad upregulation of diverse polysaccharide utilization loci. Within the first week, metabolism becomes centered around utilization of a predominant dietary oligosaccharide, and these changes are largely sustained through 6 weeks of colonization. Spontaneous mutations in wild-type Bt also evolve around this locus. These findings highlight the importance of considering temporal colonization dynamics in developing more effective microbiome-based therapies. [Display omitted] •B. thetaiotaomicron adaptation to the germ-free mouse gut is a dynamic process•Early selective pressures are distinct from intermediate and long-term pressures•Selective pressure for efficient dietary resource use dominates in the long term•Changes in Bt spatial localization parallel changes in resource use Kennedy et al. evaluate temporal dynamics of Bacteroides thetaiotaomicron (Bt) adaptation to a new host. Bt metabolic priorities shift over the course of colonization, culminating in strong selective pressure to efficiently consume dietary resources. This work highlights the importance of considering temporal dynamics in developing better microbiome-based therapies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 National Institutes of Health (NIH) AC02-06CH11357; T32DK007074; RC2DK122394; T32GM00728; P30 DK042086 USDOE Office of Science (SC), Biological and Environmental Research (BER) AUTHOR CONTRIBUTIONS Conceptualization, M.S.K., M.Z., E.B.C., and J.B.; methodology, M.S.K., M.Z., and E.B.C.; formal analysis, M.S.K., M.Z., O.D., F.T., and A.M.S.; investigation, M.S.K., M.Z., J.B., K.L., S.T., K.T.C., A.M.S., and J.L.; resources, A.D.; data curation, M.S.K. and M.Z.; writing – original draft, M.S.K. and M.Z.; writing – review & editing, M.S.K., M.Z., E.B.C., A.F., J.B., C.H., and P.A.R.; visualization, M.S.K., M.Z., O.D., and F.T.; funding acquisition, E.B.C.
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2023.113009