@article{1e2f6b81eda245f9b45745dbe46008ac,
title = "Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization",
abstract = "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.",
keywords = "Bacteroides thetaiotaomicron, BarSeq, CP: Microbiology, IS elements, commensal bacteria, gut colonization, insertion sequence, microbial adaptation, microbial metabolism, microbiome-based therapy",
author = "Kennedy, {Megan S.} and Manjing Zhang and Orlando DeLeon and Jacie Bissell and Florian Trigodet and Karen Lolans and Sara Temelkova and Carroll, {Katherine T.} and Aretha Fiebig and Adam Deutschbauer and Sidebottom, {Ashley M.} and Joash Lake and Chris Henry and Rice, {Phoebe A.} and Joy Bergelson and Chang, {Eugene B.}",
note = "Funding Information: We thank Hualan Liu for invaluable experimental help with the RB-TnSeq libraries. We thank David Hershey and A. Murat Eren for helpful scientific input. We also thank the Chang lab members for scientific support received. The graphical abstract was created using BioRender. This work was performed with support from NIH T32DK007074 (M.Z. M.S.K.), NIH RC2DK122394 (E.B.C.), NIH T32GM007281 (M.S.K.), and the Host-Microbe and Tissue and Cell Engineering cores of the UChicago DDRCC, Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) (NIDDK P30 DK042086). 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. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. Funding Information: We thank Hualan Liu for invaluable experimental help with the RB-TnSeq libraries. We thank David Hershey and A. Murat Eren for helpful scientific input. We also thank the Chang lab members for scientific support received. The graphical abstract was created using BioRender. This work was performed with support from NIH T32DK007074 (M.Z., M.S.K.), NIH RC2DK122394 (E.B.C.), NIH T32GM007281 (M.S.K.), and the Host-Microbe and Tissue and Cell Engineering cores of the UChicago DDRCC , Center for Interdisciplinary Study of Inflammatory Intestinal Disorders (C-IID) (NIDDK P30 DK042086 ). Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = aug,
day = "29",
doi = "10.1016/j.celrep.2023.113009",
language = "English (US)",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}