Journal article
Antibiotic Perturbation of Gut Microbiota Dysregulates Osteoimmune Cross Talk in Postpubertal Skeletal Development
The American journal of pathology, Vol.189(2), pp.370-390
02/01/2019
DOI: 10.1016/j.ajpath.2018.10.017
PMCID: PMC6360355
PMID: 30660331
Abstract
Commensal gut microbiota host immune responses are experimentally delineated via gnotobiotic animal models or alternatively by antibiotic perturbation of gut microbiota. Osteoimmunology investigations in germ-free mice, revealing that gut microbiota immunomodulatory actions critically regulate physiologic skeletal development, highlight that antibiotic perturbation of gut microbiota may dysregulate normal osteoimmunological processes. We investigated the impact of antibiotic disruption of gut microbiota on osteoimmune response effects in postpubertal skeletal development. Sex-matched C57BL/6T mice were administered broad-spectrum antibiotics or vehicle-control from the age of 6 to 12 weeks. Antibiotic alterations in gut bacterial composition and skeletal morphology were sex dependent. Antibiotics did not influence osteoblastogenesis or endochondral bone formation, but notably enhanced osteoclastogenesis. Unchanged Tnf or Ccl3 expression in marrow and elevated tumor necrosis factor-a and chemokine (C-C motif) ligand 3 in serum indicated that the pro-osteoclastic effects of the antibiotics are driven by increased systemic inflammation. Antibiotic-induced broad changes in adaptive and innate immune cells in mesenteric lymph nodes and spleen demonstrated that the perturbation of gut microbiota drives a state of dysbiotic hyperimmune response at secondary lymphoid tissues draining Local gut and systemic circulation. Antibiotics up-regulated the myeloid-derived suppressor cells, immature myeloid progenitor cells known for immunosuppressive properties in pathophysiologic inflammatory conditions. Myeloid derived suppressor cell mediated immunosuppression can be antigen specific. Therefore, antibiotic induced broad suppression of major histocompatibility complex class II antigen presentation genes in bone marrow discerns that antibiotic perturbation of gut microbiota dysregulates critical osteoimmune cross talk.
Details
- Title: Subtitle
- Antibiotic Perturbation of Gut Microbiota Dysregulates Osteoimmune Cross Talk in Postpubertal Skeletal Development
- Creators
- Jessica D. Hathaway-Schrader - Medical University of South CarolinaHeidi M. Steinkamp - Medical University of South CarolinaMichael B. Chavez - Medical University of South CarolinaNicole A. Poulides - Medical University of South CarolinaJoy E. Kirkpatrick - Medical University of South CarolinaMichael E. Chew - University of South CarolinaEmily Huang - Medical University of South CarolinaAlexander Alekseyenko - Medical University of South CarolinaJose Aguirre - University of FloridaChad M. Novince - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.189(2), pp.370-390
- Publisher
- Elsevier
- DOI
- 10.1016/j.ajpath.2018.10.017
- PMID
- 30660331
- PMCID
- PMC6360355
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Number of pages
- 21
- Grant note
- P30GM103331 / NIH/National Institute of General Medical Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) K08DE025337; R01DE021423; T32DE017551; R25DE022677 / NIH/National Institute of Dental and Craniofacial Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) American Society for Bone and Mineral Research Rising Star Award R25DE022677 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) R01LM012517 / NATIONAL LIBRARY OF MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Library of Medicine (NLM) P30GM103331 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 02/01/2019
- Academic Unit
- Pediatric Dentistry
- Record Identifier
- 9984367620302771
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