Antibiotic prophylaxis dysregulates dental implant placement surgery-induced osteoimmune wound healing and attenuates the alveolar bone-implant interface in mice.

AIM: Antimicrobial-induced shifts in commensal oral microbiota can dysregulate helper T-cell oral immunity to affect osteoclast-osteoblast actions in alveolar bone. Antibiotic prophylaxis is commonly performed with dental implant placement surgery to prevent post-surgical complications. However, antibiotic prophylaxis effects on osteoimmune processes supporting dental implant osseointegration are unknown. The aim of the study was to discern the impact of antibiotic prophylaxis on dental implant placement surgery-induced osteoimmune wound healing and osseointegration. MATERIALS AND METHODS: We performed SHAM or dental implant placement surgery in mice. Groups were administered prophylactic antibiotics (amoxicillin or clindamycin) or vehicle. Gingival bacteriome was assessed via 16S sequencing. Helper T-cell oral immunity was evaluated by flow cytometry. Osteoclasts and osteoblasts were assessed via histomorphometry. Implant osseointegration was evaluated by micro-computed tomography. RESULTS: Dental implant placement surgery up-regulated TH 1, TH 2 and TREG cells in cervical lymph nodes (CLNs), which infers helper T-cell oral immunity contributes to dental implant placement osseous wound healing. Prophylactic antibiotics with dental implant placement surgery caused a bacterial dysbiosis, suppressed TH 1, TH 2 and TREG cells in CLNs, reduced osteoclasts and osteoblasts lining peri-implant alveolar bone, and attenuated the alveolar bone-implant interface. CONCLUSIONS: Antibiotic prophylaxis dysregulates dental implant placement surgery-induced osteoimmune wound healing and attenuates the alveolar bone-implant interface in mice.

Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice.

Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor-fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity.

Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice.

Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone. Our purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific pathogen-free (SPF) and germ-free (GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor/fibroblast growth factor 15 axis, a gut/liver endocrine axis supporting systemic bile acid homeostasis. Minocycline-treated SPF mice had increased serum conjugated bile acids that were farnesoid X receptor (FXR) antagonists, suppressed osteoblast function, decreased bone mass, and impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR signaling. This work introduces bile acids as a potentially novel mediator of gut/liver signaling actions contributing to gut microbiota effects on bone.