From prediction to function using evolutionary genomics: Human-specific ecotypes of lactobacillus reuterihave diverse probiotic functions

Jennifer K. Spinler, Amrita Sontakke, Emily B. Hollister, Susan F. Venable, Phaik Lyn Oh, Miriam A. Balderas, Delphine M A Saulnier, Toni Ann Mistretta, Sridevi Devaraj, Jens Walter, James Versalovic, Sarah K. Highlander

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


The vertebrate gut symbiont Lactobacillus reuteri has diversified into separate clades reflecting host origin. Strains show evidence of host adaptation, but howhost-microbe coevolution influencesmicrobial-derived effects on hosts is poorly understood. Emphasizing human-derived strains of L. reuteri,we combined comparative genomic analyses with functional assays to examine variations in host interaction among genetically distinct ecotypes. Within clade II or VI, the genomes of human-derived L. reuteri strains are highly conserved in gene content and at the nucleotide level. Nevertheless, they share only 70-90% of total gene content, indicating differences in functional capacity. Human-associated lineages are distinguished by genes related to bacteriophages, vitamin biosynthesis, antimicrobial production, and immunomodulation. Differential production of reuterin, histamine, and folate by 23 clade II and VI strainswas demonstrated. These strains also differed with respect to their ability tomodulate human cytokine production (tumor necrosis factor, monocyte chemoattractant protein-1, interleukin [IL]-1b, IL-5, IL-7, IL-12, and IL-13) by myeloid cells. Microarray analysis of representative clade II and clade VI strains revealed global regulation of genes within the reuterin, vitamin B12, folate, and arginine catabolism gene clusters by the AraC family transcriptional regulator, PocR. Thus, human-derived L. reuteri clade II and VI strains are genetically distinct and their differences affect their functional repertoires and probiotic features. These findings highlight the biological impact of microbe:host coevolution and illustrate the functional significance of subspecies differences in the human microbiome. Consideration of host origin and functional differences at the subspecies level may have major impacts on probiotic strain selection and considerations of microbial ecology in mammalian species.

Original languageEnglish (US)
Pages (from-to)1772-1789
Number of pages18
JournalGenome Biology and Evolution
Issue number7
StatePublished - Jul 2014


  • Anti-inflammatory
  • Histamine
  • Host-based evolution
  • Immunostimulatory
  • PocR transcriptional regulation
  • Reuterin

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics


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