Format

Send to

Choose Destination
Am J Pathol. 2019 Feb;189(2):370-390. doi: 10.1016/j.ajpath.2018.10.017. Epub 2019 Jan 16.

Antibiotic Perturbation of Gut Microbiota Dysregulates Osteoimmune Cross Talk in Postpubertal Skeletal Development.

Author information

1
Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Endocrinology Division, Department of Pediatrics, Medical University of South Carolina College of Medicine, Charleston, South Carolina.
2
Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Division of Pediatric Dentistry, The Ohio State University College of Dentistry, Columbus, Ohio.
3
Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Division of Biosciences, The Ohio State University College of Dentistry, Columbus, Ohio.
4
Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina.
5
Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Department of Public Health Sciences, Medical University of South Carolina College of Medicine, Charleston, South Carolina.
6
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.
7
Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, South Carolina; Endocrinology Division, Department of Pediatrics, Medical University of South Carolina College of Medicine, Charleston, South Carolina. Electronic address: novincec@musc.edu.

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-α 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.

PMID:
30660331
PMCID:
PMC6360355
[Available on 2020-02-01]
DOI:
10.1016/j.ajpath.2018.10.017

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center