Читать книгу Nutrition and Growth - Группа авторов - Страница 24

Hathaway-Schrader JD^1,2, Steinkamp HM^1,4, Chavez MB^1,5, Poulides NA^1,2, Kirkpatrick JE¹, Chew ME¹, Huang E¹, Alekseyenko AV^1,3, Aguirre JI⁶, Novince CM^1,2

¹Department of Oral Health Sciences, Medical University of South Carolina College of Dental Medicine, Charleston, SC, USA; ²Endocrinology Division, Department of Pediatrics, Medical University of South Carolina College of Medicine, Charleston, SC, USA; ³Department of Public Health Sciences, Medical University of South Carolina College of Medicine, Charleston, SC, USA; ⁴Division of Pediatric Dentistry, The Ohio State University College of Dentistry, Columbus, OH, USA; ⁵Division of Biosciences, The Ohio State University College of Dentistry, Columbus, OH, USA; ⁶Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA

Am J Pathol 2019;89:370–390

Background: Recent research show that host gut microbiota may have an influence on pathological states of the gastrointestinal tract and also impact on distant organs (e.g., liver, brain, heart and skeleton). Throughout the lifespan, various lifestyle factors may lead to changes in gut microbiota, which includes medications like antibiotics. Pro-inflammatory immune states can suppress osteoblastic bone formation and increase bone resorption. Antibiotic administration has been shown to lead to disruption of gut microbiota leading to a pro-inflammatory hyperimmune state. The osteoimmune mechanism linking antibiotic and skeletal development is unclear. The aim of this study was to investigate the effect of antibiotic disruption of gut microbiota in mice (C57BL/6 strain) from 6 to 12 weeks.

Methods: Mice were administered antibiotics (vancomycin, imipenem/cliastin and neomycin) or vehicle in drinking water from 6 to 12 weeks. Mice were euthanized at 12 weeks of age. MicroCT and histomorphometry (static and dynamic) of tibia were performed.

Results: Antibiotic therapy led to reduction in bacterial load in male and female mice but composition changes were sex dependent. Male mice treated with antibiotics showed significant increase in α-protobacteria and γ-proteobacteria but decrease in Bacteroidetes. On the other hand, female mice treated with antibiotics showed significant increase in a-proteobacteria and decrease in Bacteroidetes and Firmicutes. Trabecular microarchitecture deficits were observed in mice treated with antibiotics at 12 weeks, with greater deficits in male mice. Antibiotic treated mice did not show any evidence of growth impairment (tibia length, growth plate chondrocyte height and zone morphology). Static and dynamic studies of bone formation on histomorphometry did not show any abnormalities in osteoblastogenesis. However, histomorphometric studies of osteoclastogenesis with TRAP-stained proximal tibia showed increased osteoclast size and number. Increased systemic inflammation was observed with antibiotic administration in the mice (increased tumour necrosis factor and chemokines, CCL3). In addition, changes in adaptive and innate immune cells were also noted in mesenteric lymph nodes and spleen.

Conclusion: This study demonstrated that broad spectrum antibiotic administration led to disruption of gut microbiota composition altering host immune response which in turn modulates the developing skeleton. Deficits in trabecular microarchitecture and increased osteoclastogenesis were observed with no impairment in linear growth.

Reprinted with permission from Elsevier.

Comments

This current study extends work that show that antibiotic perturbation of gut microbiota can influence bone mass by demonstrating that the potential mechanism is via alteration in systemic and local osteoimmune processes. The sex differences in alteration in gut microbiota and bone mass are intriguing and suggest the possible influence of sex steroid. The clinical implications of these results remain to be seen. In groups of children with chronic disorders requiring long-term treatment with prophylactic antibiotics, this maybe another mechanism of abnormalities in bone development.

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