Diet-microbiome interactions promote enteric nervous system resilience following spinal cord injury.

Spinal cord injury (SCI) results in numerous systemic dysfunctions, including intestinal dysmotility and enteric nervous system (ENS) atrophy. The ENS has capacity to recover following perturbation, yet intestinal pathologies persist. With emerging evidence demonstrating SCI-induced alterations to gut microbiome composition, we hypothesized that microbiome modulation contributes to post-injury enteric recovery. Here, we show that intervention with the dietary fiber, inulin, prevents SCI-induced ENS atrophy and dysmotility in mice. While SCI-associated microbiomes and specific injury-sensitive gut microbes are not sufficient to modulate intestinal dysmotility after injury, intervention with microbially-derived short-chain fatty acid (SCFA) metabolites prevents ENS dysfunctions in injured mice. Notably, inulin-mediated resilience is dependent on IL-10 signaling, highlighting a critical diet-microbiome-immune axis that promotes ENS resilience post-injury. Overall, we demonstrate that diet and microbially-derived signals distinctly impact ENS survival after traumatic spinal injury and represent a foundation to uncover etiological mechanisms and future therapeutics for SCI-induced neurogenic bowel.

Modulatory effects of gut microbiota on innate and adaptive immune responses following spinal cord injury.

Spinal cord injury (SCI) represents a highly debilitating trauma to the central nervous system, currently lacking effective therapeutic strategies. The cascade of inflammatory responses induced by secondary damage following SCI disrupts the local immune environment at the injury site, ultimately exacerbating functional impairments post-injury. With advancing research on the gut-brain axis, evidence suggests that dysbiosis of the gut microbiota post-SCI amplifies inflammatory responses and plays a pivotal role in modulating post-injury immune-inflammatory responses. In this review article, we will explore the significant role of the gut microbiota and its metabolic products in modulating the responses of central and peripheral immune cells post-SCI, as well as their potential as therapeutic interventions for SCI treatment.

Understanding the impact of spinal cord injury on the microbiota of healthy skin and pressure injuries.

Pressure injuries (PI) are a common issue among individuals with spinal cord injury (SCI), especially in the sitting areas of the body. Considering the risk of infections occurring to PI during the wound healing process, the skin microbiome is likely to be a source of bacteria. We investigated the relationship between skin and PI microbiomes, and assessed any correlation with clinically relevant outcomes related to PI. Samples were isolated from SCI patients undergoing reconstructive surgery of PI, severity grades III and IV. DNA samples from skin and PI were analysed using 16S rRNA gene sequencing. Our results showed disparities in microbiome composition between skin and PI. The skin had lower diversity, while PI showed increased bacterial homogeneity as the severity grade progressed. The skin bacterial composition varied based on its location, influenced by Cutibacterium. Compositional differences were identified between PI grades III and IV, with clusters of bacteria colonizing PI, characterized by Pseudomonas, Proteus and Peptoniphilus. The skin and PI microbiomes were not affected by the level of the SCI. Our study highlights the differences in the microbiome of skin and PI in SCI patients. These findings could be used to target specific bacteria for PI treatment in clinical practice.

Systematic review of the changes in the microbiome following spinal cord injury: animal and human evidence.

STUDY DESIGN: Systematic review. OBJECTIVES: To investigate the changes in the microbiome among human and animal populations with spinal cord injury (SCI). METHODS: Four databases (EMBASE, Medline (Ovid), Web of Science, Cochrane Central Register of Trials (CENTRAL)) and Google Scholar were searched. No language restrictions were applied. Data extraction was done in parallel and independently by two reviewers. The search was last conducted on 07 April 2021. RESULTS: There were 6869 studies retrieved, 43 full-text studies reviewed, and 19 studies included. There were seven animal gut studies, six human gut studies, and six urinary tract studies identified. There were no publications found on other body sites. Among the included studies, we observed a consistent and significant difference in gut microbiome composition between populations with SCI and able-bodied populations. This is characterized by a decrease in beneficial butyrate-producing bacteria (Faecalbacterium, Megamonas, Roseburia) and an increase in inflammation-associated bacteria (Alistipes, Anaerotruncus, and Lachnoclostridium). On the other hand, the urine of individuals with SCI was polymicrobial and members of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae) were frequently observed. Probiotics were shown to induce a significant but transient shift in the urinary tract microbiome. The studies had low to moderate risks of bias. CONCLUSIONS: There are limited studies on the changes in microbiome among SCI populations. The gut microbiome was characterized by bacterial profiles associated with chronic inflammation and metabolic disorder while the studies of the urinary tract microbiome show the dominance of bacterial genera associated with urinary tract infection.

Profile of gut microbiota in patients with traumatic thoracic spinal cord injury and its clinical implications: a case-control study in a rehabilitation setting.

Gut microbiota are the candidate biomarkers for neurogenic bowel dysfunction (NBD) in patients with spinal cord injury (SCI). We aimed to identify the common features between patients with varying degree of thoracic SCI and healthy individuals and subpopulations of microbiota correlated with the serum biomarkers. Twenty-one patients with complete thoracic SCI (CTSCI), 24 with incomplete thoracic SCI (ITSCI), and 24 healthy individuals (HC) were enrolled in this study. Fresh stool samples and clinical data were collected from all participants, and their bowel functions with SCI were assessed. Microbial diversity and composition were analyzed by sequencing the 16S rRNA gene. The features of gut microbiota correlated with the serum biomarkers and their functions were investigated. The mean NBD score of patients with CTSCI was higher than that of patients with ITSCI. Diversity of the gut microbiota in SCI group was reduced, and with an increase in the degree of damage, alpha diversity had decreased gradually. The composition of gut microbiota in patients with SCI was distinct from that in healthy individuals, and CTSCI group exhibited further deviation than ITSCI group compared to healthy individuals. Four serum biomarkers were found to be correlated with most differential genera. Patients with thoracic SCI present gut dysbiosis, which is more pronounced in patients with CTSCI than in those with ITSCI. Therefore, the gut microbiota profile may serve as the signatures for bowel and motor functions in patients with thoracic SCI.

Changes in gut microbiota in the acute phase after spinal cord injury correlate with severity of the lesion.

After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.

Influence of patient isolation due to colonization with multidrug-resistant organisms on functional recovery after spinal cord injury.

STUDY DESIGN: Chart reviews were combined with neurological and functional outcome data obtained from the prospective European Multicenter Study on Spinal Cord Injury (EMSCI, www.emsci.org). OBJECTIVES: To determine if strict physical isolation of multidrug-resistant organisms (MDRO)-positive patients negatively affects neurological recovery and functional outcome in the first year after acute spinal cord injury (SCI). SETTING: SCI Center Heidelberg University Hospital. METHODS: Individuals with acute (< 6 weeks) traumatic or ischemic SCI were included. During primary comprehensive care, isolated MDRO-positive patients (n = 13) were compared with a MDRO-negative control group (n = 13) matched for functional (Spinal Cord Independence Measure-SCIM) and neurological impairment (motor scores based on the International Standards for Neurological Classification of Spinal Cord Injury-ISNCSCI) at an early stage up to 40 days after SCI. SCIM scores and motor scores were obtained at 12 weeks (intermediate stage) and 24 or 48 weeks (late stage) after SCI. RESULTS: Isolated MDRO-positive (median duration of hospitalization: 175 days, 39% of inpatient stay under isolation measures) and non-isolated MDRO-negative (median duration of hospitalization: 161 days) patients showed functional and neurological improvements, which were not statistically different between groups at the intermediate and late stage. CONCLUSION: Prolonged isolation due to MDRO colonization for over a third of the inpatient comprehensive care period does not appear to impair neurological recovery and functional outcome within the first year after SCI.

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention.

Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.

Spinal cord injury and gut microbiota: A review.

After spinal cord injury (SCI), intestinal dysfunction has a serious impact on physical and mental health, quality of life, and social participation. Recent data from rodent and human studies indicated that SCI causes gut dysbiosis. Remodeling gut microbiota could be beneficial for the recovery of intestinal function and motor function after SCI. However, few studies have explored SCI with focus on the gut microbiota and "microbiota-gut-brain" axis. In this review, the complications following SCI, including intestinal dysfunction, anxiety and depression, metabolic disorders, and neuropathic pain, are directly or indirectly related to gut dysbiosis, which may be mediated by "gut-brain" interactions. Furthermore, we discuss the research strategies that can be beneficial in this regard, including germ-free animals, fecal microbiota transplantation, probiotics, phages, and brain imaging techniques. The current microbial research has shifted from descriptive to mechanismal perspective, and future research using new technologies may further demonstrate the pathophysiological mechanism of association of SCI with gut microbiota, elucidate the mode of interaction of gut microbiota and hosts, and help develop personalized microbiota-targeted therapies and drugs based on microbiota or corresponding metabolites.

Alterations in the fecal microbiota of patients with spinal cord injury.

OBJECTIVES: Spinal cord injury (SCI) is associated with severe autonomic dysfunction. Patients with SCI often suffer from a lack of central nervous system control over the gastrointestinal system. Therefore, we hypothesized that patients with SCI would cause intestinal flora imbalance. We investigated alterations in the fecal microbiome in a group of patients with SCI. METHODS: Microbial communities in the feces of 23 patients and 23 healthy controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The relative abundances between the fecal microbiota at the genus level in patients with SCI and healthy individuals were determined using cluster analysis. RESULTS: The structure and quantity of fecal microbiota differed significantly between patients with SCI and healthy controls, but the richness and diversity were not significantly different. A two-dimensional heatmap showed that the relative abundances of forty-five operational taxonomic units (OTUs) were significantly enriched either in SCI or healthy samples. Among these, 18 OTUs were more abundant in healthy controls than in patients with SCI, and 27 OTUs were more abundant in the SCI group than in healthy controls. CONCLUSION: Our study showed that patients with SCI exhibited microbiome dysbiosis.