Gut Microbiota Are Disease-Modifying Factors After Traumatic Spinal Cord Injury

Abstract

Spinal cord injury (SCI) disrupts the autonomic nervous system (ANS), impairing its ability to coordinate organ function throughout the body. Emerging data indicate that the systemic pathology that manifests from ANS dysfunction exacerbates intraspinal pathology and neurological impairment. Precisely how this happens is unknown, although new data, in both humans and in rodent models, implicate changes in the composition of bacteria in the gut (i.e., the gut microbiota) as disease-modifying factors that are capable of affecting systemic physiology and pathophysiology. Recent data from rodents indicate that SCI causes gut dysbiosis, which exacerbates intraspinal inflammation and lesion pathology leading to impaired recovery of motor function. Postinjury delivery of probiotics containing various types of "good" bacteria can partially overcome the pathophysiologal effects of gut dysbiosis; immune function, locomotor recovery, and spinal cord integrity are partially restored by a sustained regimen of oral probiotics. More research is needed to determine whether gut dysbiosis varies across a range of clinically relevant variables, including sex, injury level, and injury severity, and whether changes in the gut microbiota can predict the onset or severity of common postinjury comorbidities, including infection, anemia, metabolic syndrome, and, perhaps, secondary neurological deterioration. Those microbial populations that dominate the gut could become "druggable" targets that could be manipulated via dietary interventions. For example, personalized nutraceuticals (e.g., pre- or probiotics) could be developed to treat the above comorbidities and improve health and quality of life after SCI.

Keywords: Intestinal dysbiosis; Microbiome; Neuroinflammation; Probiotics; Spinal cord injury.

Fig. 1

Spinal cord injury (SCI) disrupts brain and brainstem control over the sympathetic preganglionic neurons (SPNs) that are located in the thoracic spinal cord. This break in executive control over SPNs breaks homeostasis and control over postganglionic neurons (e.g., projecting from celiac ganglia) that innervate the gastrointestinal (GI) tract. Loss of coordinated neural control over the GI tract will impair motility, mucous secretion, immune surveillance, and epithelial barrier permeability in the small and large intestines. Together, these changes in the GI tract can cause bacterial translocation and gut dysbiosis (a). After SCI, probiotic treatment may normalize the gut microbiota leading to improvements in gut barrier integrity (b)

Fig. 2

Gut dysbiosis is a disease-modifying comorbidity that likely causes or exacerbates many other comorbidities associated with spinal cord injury (SCI). Gut microbiota can directly influence immune function, neurocognitive function, and mood, metabolism, and energy/fatigue. Each of these can, in turn, influence the gut microbiota. Thus, gut dysbiosis creates a feed-forward cycle that can contribute to lasting pathophysiology, which will impair function and quality of life after SCI