Gut bacteria could help patients recover from spinal cord injury
Spinal cord injuries disrupt the microbiome, and reintroducing good bacteria may be key to improving recovery.
ResearchGate: How do spinal cord injuries alter the makeup of gut bacteria??
Phillip Popovich and Kristina Kigerl: Spinal cord injury causes severe neurological and psychological complications that can predispose individuals to gut dysbiosis, a disruption of the microbial community. For example, acute and often chronic stress are expected due to the sudden and dramatic life changes experienced by someone with a spinal cord injury. Bladder and bowel function are impaired after a spinal cord injury because of damage to the autonomic nervous system. A spinal cord injury also impairs immune function, increasing the need for repeat antibiotic dosing to fight infections. All of these factors can contribute to gut dysbiosis.
We found changes in the abundance of the two major bacterial communities that make up the gut microbiome: Bacteria from Bacteroidales decreased while those of Clostridiales increased after a spinal cord injury. These changes became more pronounced several weeks after the injury. ???
RG: How does dysbiosis in turn impact recovery from spinal cord injuries?
Popovich and Kigerl: We found that if normal (uninjured) mice were given a?cocktail of broad-spectrum antibiotics before they receive a spinal cord injury, the cocktail caused gut dysbiosis. When these mice then received a spinal cord injury, they were unable to recover locomotor function as efficiently as mice with injured spinal cords that had a normal gut microbiota before the injury. This dysbiosis also increased spinal inflammation and activated immune cells found with the gut.
RG: Could you describe your study on probiotics in mice?
Popovich and Kigerl: In an effort to restore a healthy gut microbiota and block the detrimental effects of dysbiosis after a spinal cord injury, we treated mice with VSL#3, a medical-grade probiotic, starting immediately after the injury and continuing daily for the duration of the study.
RG: What did you find?
Popovich and Kigerl: We found that VSL#3 treatment improved neurological recovery and reduced spinal cord pathology, while simultaneously increasing gut-associated regulatory T cells, a type of immune cell that can suppress inflammation. Furthermore, we were able to boost the levels of probiotic bacteria – Lactobacilllales and Bifidobacteriales – in the gut microbiome after injury.
RG: What kind of probiotic is VSL#3?
Popovich and Kigerl: We used VSL#3 from Sigma Tau Pharmaceuticals. It’s a commercially available probiotic formulation that has been tested in models of irritable bowel syndrome and ulcerative colitis. VSL#3 consists of eight strains of live bacteria: Streptococcus thermophiles, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, and Lactobacillus delbrueckii subsp. Bulgaricus.
RG: Why do those particular bacteria help?
Popovich and Kigerl: One of the challenging aspects of choosing a probiotic is that many effects are strain specific. VSL#3 appealed to us because it contains eight different species of live bacteria, which broadens the potential mechanisms of action.
The probiotics, containing large numbers of lactic acid-producing bacteria, activated a regulatory T cells, a type of immune cell that can suppress inflammation. These cells may prevent damage to the spinal cord after injury. Additionally, the probiotic bacteria may boost spinal cord recovery by secreting factors that enhance neuronal growth and function. Both of these mechanisms could explain how post-injury disruption of the gut microbiome contributes to the pathology of spinal cord injuries, and how probiotics block or reverse these effects.
RG: What are the next steps in this research?
Popovich and Kigerl: We hope that these data will help increase awareness in pre-clinical and clinical research programs about the important role of biochemical signaling among the gut, immune system, and central nervous system in recovery from spinal cord injury. Future studies should consider the role of gut dysbiosis in other organ systems and functions affected by spinal cord injury. For example, in addition to affecting motor function, sensory and autonomic dysfunction occur after a spinal cord injury. Also, there is profound immune suppression, metabolic and cardiovascular disease and various nutritional deficiencies that could be traced back to changes in the gut microbiota. Probiotics are one of many possible approaches for treating or at least reducing the detrimental effects of dysbiosis after a spinal cord injury.
Featured image: Neurons from a mouse spinal cord. Credit: NICHD and S. Jeong