Dynamic genetic adaptation of Bacteroides thetaiotaomicron during murine gut colonization

Megan S. Kennedy, Manjing Zhang, Orlando DeLeon, Jacie Bissell, Florian Trigodet, Karen Lolans, Sara Temelkova, Katherine T. Carroll, Aretha Fiebig, Adam Deutschbauer, Ashley M. Sidebottom, Joash Lake, Chris Henry, Phoebe A. Rice, Joy Bergelson, Eugene B. Chang

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number113009
JournalCell Reports
Issue number8
StatePublished - Aug 29 2023


  • Bacteroides thetaiotaomicron
  • BarSeq
  • CP: Microbiology
  • IS elements
  • commensal bacteria
  • gut colonization
  • insertion sequence
  • microbial adaptation
  • microbial metabolism
  • microbiome-based therapy

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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