Microbiota-independent ameliorative effects of antibiotics on spontaneous Th2-associated pathology of the small intestine

Daehee Han, Matthew C. Walsh, Kwang Soon Kim, Sung Wook Hong, Junyoung Lee, Jaeu Yi, Gloriany Rivas, Charles D. Surh, Yongwon Choi

Research output: Contribution to journalArticlepeer-review


We have previously generated a mouse model of spontaneous Th2-associated disease of the small intestine called TRAF6ΔDC, in which dendritic cell (DC)-intrinsic expression of the signaling mediator TRAF6 is ablated. Interestingly, broad-spectrum antibiotic treatment ameliorates TRAF6 ΔDC disease, implying a role for commensal microbiota in disease development. However, the relationship between the drug effects and commensal microbiota status remains to be formally demonstrated. To directly assess this relationship, we have now generated TRAF6 ΔDC bone marrow chimera mice under germ-free (GF) conditions lacking commensal microbiota, and found, unexpectedly, that Th2-associated disease is actually exacerbated in GF TRAF6 ΔDC mice compared to specific pathogen-free (SPF) TRAF6Δ DC mice. At the same time, broad-spectrum antibiotic treatment of GF TRAF6ΔDC mice has an ameliorative effect similar to that observed in antibiotics-treated SPF TRAF6Δ DC mice, implying a commensal microbiota-independent effect of broad-spectrum antibiotic treatment. We further found that treatment of GF TRAF6ΔDC mice with broadspectrum antibiotics increases Foxp3 + Treg populations in lymphoid organs and the small intestine, pointing to a possible mechanism by which treatment may directly exert an immunomodulatory effect. To investigate links between the exacerbated phenotype of the small intestines of GF TRAF6ΔDC mice and local microbiota, we performed microbiotic profiling of the luminal contents specifically within the small intestines of diseased TRAF6ΔDC mice, and, when compared to co-housed control mice, found significantly increased total bacterial content characterized by specific increases in Firmicutes Lactobacillus species. These data suggest a protective effect of Firmicutes Lactobacillus against the spontaneous Th2-related inflammation of the small intestine of the TRAF6ΔDC model, and may represent a potential mechanism for related disease phenotypes.

Original languageEnglish
Article numbere0118795
JournalPloS one
Issue number2
Publication statusPublished - 2015 Feb 17

Bibliographical note

Publisher Copyright:
© 2015 Han et al.

All Science Journal Classification (ASJC) codes

  • General


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