Spontaneous axon regeneration is preserved despite gut microbiota disruption after spinal cord injury in lampreys

Traumatic spinal cord injuries (SCIs) often result in permanent disabilities in humans. One major reason for the lack of recovery is the inability of adult mammalian descending neurons to regenerate their axons after injury. In contrast, several fish species, such as the sea lamprey, exhibit spontaneous axon regeneration and successful functional recovery following a complete SCI. Recent studies have shown that a SCI in rodents and humans induces gut microbiome dysbiosis, which can impair recovery. Therefore, our goal was to examine how the microbiome changes after SCI in a regenerating animal model (the larval sea lamprey) and whether these changes influence the spontaneous regeneration of descending neuropeptidergic (cholecystokinergic) axons. Our data show that a complete SCI triggers an initial shift (5 weeks post-injury) in gut microbial communities in larval lampreys, characterized by an expansion of Legionellaceae family members. However, a treatment with broad-spectrum antibiotic gentamicin during the first 5 weeks post-injury, which completely disrupted the gut microbiome (eliminating Legionellaceae and promoting Bradyrhizobiaceae expansion), did not affect the spontaneous regeneration of descending cholecystokinergic axons at 10 weeks post-injury. This finding indicates that changes in the intestinal microbial communities following a complete SCI probably do not influence the spontaneous regeneration of descending axons in lampreys.