Degenerative Cervical Myelopathy (DCM) induces sex-specific dysbiosis in the mouse gut bacterial microbiome, altering abundance and function

Background: Degenerative cervical myelopathy (DCM) represents the commonest cause of spinal cord impairment induced by non-traumatic events in the elderly population. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel functions, as well as gastrointestinal dysfunction. The gut microbiota has been increasingly recognized as an environmental factor that can modulate both the central nervous system and immune response through the microbiota-gut-brain axis. Changes in gut microbiota composition or in the microbiota producing factors have been linked in the progression and development of several different pathologies such as traumatic spinal cord injury (SCI). Little is known about the molecular mechanisms that trigger DCM manifestation, and the potential role of the gut microbiota.

Results: Herein DCM was induced in female and male C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of DCM-induced changes in microbiota composition, also known as dysbiosis, was assessed by 16S rRNA sequencing from fecal samples at 3 different time points (6, 9 and 12 weeks after DCM induction). Several bacterial members were identified based on BLAST against the largest collection of metagenome-derived genomes from the mouse gut up to date. In both, female and males DCM caused gut dysbiosis compared with the sham group. However, dysbiosis was more pronounced in males than females, where several bacterial members of the families Lachnospiraceae and Muribaculaceae were significantly altered in the DCM group. These changes were also associated with altered immune cell composition in gut-associated lymphoid tissue, blood, and microbe-derived metabolic changes in propionate, butyrate, and lactate-producing bacterial members.

Conclusions: Our results demonstrate for the first time that DCM causes dynamic changes over time in the gut microbiota. Furthermore, we identify specie-specific abundance changes during DCM progression. DCM strongly reduces the abundance of butyrate-producing bacteria, and lactate-producing bacteria in much less extent. Sequence-based pangenomics cores were not resolved between the latter bacteria, but the gap-filling reactions and metabolic modelling successfully identified pyruvate-to-butanoate and pyruvate-to-propionate genes such as Buk and ACH1, respectively. These results aid to better understand markers and the molecular mechanisms that over time trigger DCM manifestation in females and males.