The gut-brain axis and beyond: Microbiome control of spinal cord injury pain in humans and rodents

Bannerman, Courtney A.; Douchant, Katya; Sheth, Prameet M.; Ghasemlou, Nader

doi:10.1016/j.ynpai.2020.100059

Cited by 19 publications

(20 citation statements)

References 242 publications

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“…Clostridium saccharogumia produces enterolactone in the gut of rats (Woting et al, 2010) which is associated with reducing the risk of cardiovascular disease which might indirectly improve hippocampal neurogenesis. Several studies have analyzed SCIinduced changes in the microbiota (Kigerl et al, 2018;Bannerman et al, 2021;Du et al, 2021), although, it is unclear how these changes can impact hippocampal neurogenesis. Determining the influence of SCI-induced changes to the microbiota and altering it to increase hippocampal neurogenesis is a developing area of research (Jogia and Ruitenberg, 2020;Tang et al, 2021).…”

Section: Gastrointestinal-renal Disorders and Neurogenesismentioning

confidence: 99%

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Sefiani

Geoffroy

2021

Front. Neurosci.

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Currently there are approximately 291,000 people suffering from a spinal cord injury (SCI) in the United States. SCI is associated with traumatic changes in mobility and neuralgia, as well as many other long-term chronic health complications, including metabolic disorders, diabetes mellitus, non-alcoholic steatohepatitis, osteoporosis, and elevated inflammatory markers. Due to medical advances, patients with SCI survive much longer than previously. This increase in life expectancy exposes them to novel neurological complications such as memory loss, cognitive decline, depression, and Alzheimer’s disease. In fact, these usually age-associated disorders are more prevalent in people living with SCI. A common factor of these disorders is the reduction in hippocampal neurogenesis. Inflammation, which is elevated after SCI, plays a major role in modulating hippocampal neurogenesis. While there is no clear consensus on the mechanism of the decline in hippocampal neurogenesis and cognition after SCI, we will examine in this review how SCI-induced inflammation could modulate hippocampal neurogenesis and provoke age-associated neurological disorders. Thereafter, we will discuss possible therapeutic options which may mitigate the influence of SCI associated complications on hippocampal neurogenesis.

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Section: Gastrointestinal-renal Disorders and Neurogenesismentioning

confidence: 99%

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Sefiani

Geoffroy

2021

Front. Neurosci.

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“…4,55,107,116 The GIM also plays an important role in immune system maturation and activation, 70,81,113,129 a key driver of central and neuropathic pain. 6,55,75,76,116 Given its multifaceted role, we first sought to perform a longitudinal analysis of the GIM in the compression and contusion models of SCI, which exhibit differing pain profiles. A significant shift in the overall bacterial population was observed in mice that underwent a compression injury (PERMANOVA, P < 0.012), but not in those that received a contusion injury (PERMANOVA, P = 0.057; Figs.…”

Section: Resultsmentioning

confidence: 99%

“…29 It is possible that the increased dysbiosis in our compression model is affecting the immune system, resulting in differing pain outcomes because of the prominent role of the GIM in immune system regulation. 6 Various studies have provided detailed characterizations of the development and maintenance of pain-like response in rodents after clip-compression injury, 17,61 with some studies having assessed longitudinal changes in pain. 41,69,83 Mechanical hypersensitivity is most often observed by 14dpi, although some have found it to develop as early as 7dpi or late as 28dpi.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner

Bannerman

Douchant

Segal

et al. 2021

Pain

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Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was performed on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days postinjury, concomitant with reduced locomotor function, compared with those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared with those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C 1 monocytes) after compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in patients with SCI and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusioncompression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.

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“… 111 , 116 The reduction of butyrate-producing microbes seen after SCI can result in more microglia with the M1 phenotype. 117 M1 microglia release proinflammatory cytokines and recruit immune cells to the injury, altogether leading to inflammation, cell death, demyelination, nociceptive activation, and hypersensitivity. 117 The mice with both SCI and dysbiosis have an increased total number of infiltrating lymphocytes.…”

Section: Spinal Cord Injurymentioning

confidence: 99%

“… 117 M1 microglia release proinflammatory cytokines and recruit immune cells to the injury, altogether leading to inflammation, cell death, demyelination, nociceptive activation, and hypersensitivity. 117 The mice with both SCI and dysbiosis have an increased total number of infiltrating lymphocytes. 104 These mice also have increased expression of the spinal cord and colon TLR4, MyD88, p-p65 and p-I κ B α , important molecules in the inflammatory pathway that responds to LPS.…”

Section: Spinal Cord Injurymentioning

confidence: 99%

Gut microbiome and neurosurgery: Implications for treatment

Willman

Reddy

et al. 2022

Clinical and Translational Dis

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Introduction: The aim of this review is to summarize the current understanding of the gut-brain axis (GBA), its impact on neurosurgery, and its implications for future treatment. Background: An abundance of research has established the existence of a collection of pathways between the gut microbiome and the central nervous system (CNS), commonly known as the GBA. Complicating this relationship, the gut microbiome bacterial diversity appears to change with age, antibiotic exposure and a number of external and internal factors. Methods: In this paper, we present the current understanding of the key protective and deleterious roles the gut microbiome plays in the pathogenesis of several common neurosurgical concerns. Results: Specifically, we examine how spinal cord injury, traumatic brain injury and stroke may cause gut microbial dysbiosis. Furthermore, this link appears to be bidirectional as gut dysbiosis contributes to secondary CNS injury in each of these ailment settings. This toxic cycle may be broken, and the future secondary damage rescued by timely, therapeutic, gut microbiome modification. In addition, a robust gut microbiome appears to improve outcomes in brain tumour treatment. There are several primary routes by which microbiome dysbiosis may be ameliorated, including faecal microbiota transplant, oral probiotics, bacteriophages, genetic modification of gut microbiota and vagus nerve stimulation. Conclusion: The GBA represents an important component of patient care in the field of neurosurgery. Future research may illuminate ideal methods of therapeutic microbiome modulation in distinct pathogenic settings.

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The gut-brain axis and beyond: Microbiome control of spinal cord injury pain in humans and rodents

Cited by 19 publications

References 242 publications

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

The Potential Role of Inflammation in Modulating Endogenous Hippocampal Neurogenesis After Spinal Cord Injury

Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner

Gut microbiome and neurosurgery: Implications for treatment

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