Antibiotic administration decreases microglia and macrophage recruitment in a sex-dependent manner following Degenerative Cervical Myelopathy.

Degenerative Cervical Myelopathy (DCM), the leading cause of spinal cord dysfunction in adults, results from progressive compression of the spinal cord and is characterized by motor, sensory, and autonomic impairments. Histopathological features include neuroinflammation, apoptosis, ischemia, and microvascular remodeling. The primary treatment for DCM is surgical decompression. Despite a higher prevalence in men and pronounced gut dysbiosis in male DCM mice, most experimental studies rely on female or mixed-sex models, highlighting the need for sex-specific research on gut dysbiosis in DCM. Here, we used a mouse model of DCM at the C5-6 level and administered broad-spectrum antibiotics to reduce microbiota diversity after DCM induction. Neuromotor activity was assessed using the open field and ladder walk tests. Neuroinflammation and gut integrity were evaluated though immunohistochemistry. Antibiotic treatment did not significantly worsen coordination in either sex, although females exhibited greater speed and increased distance traveled than males after DCM induction. Astrogliosis was unaffected by antibiotic in both sexes. In contrast, microglial recruitment decreased in males, whereas macrophages were reduced in females after treatment. Microglia/macrophage morphology became less ramified in males, whereas in females it became more ramified after antibiotic treatment. At the colonic level, females showed reduced macrophage infiltration without significant changes activation markers (CD206, CD86 and Arg-I) or in epithelial integrity assessed by occluding expression. These findings underscore sex-specific effects of gut disbiosis in DCM, where distinct modulation of microglia and macrophages may explain the motor benefits restricted to females.