Skip to content
2000
Volume 22, Issue 40
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Background: Alterations in gut microbiota, coupled to increased gut permeability are now widely recognized as having a role in the etiology, course and treatment of many medical conditions, including autoimmune and neurodegenerative disorders. Methods: In this review, the role that such gut changes play over the course of multiple sclerosis (MS) is detailed. Results: Given the wide array of biological factors and processes that have been shown to be altered in MS, including changes in the gut, this allows for a better integration of the diverse array of pathophysiological processes linked to MS. Such pathophysiological processes include increases in oxidative and nitrosative stress, pro-inflammatory immune responses, especially T helper (Th)17 cell proliferation and activation, tryptophan catabolites, pain, fatigue and increased levels of depression. By raising levels of immune activation, increased gut permeability and alterations in gut microbiota impact on all of these MS-associated processes. Alterations in the regulation of local melatonergic pathway activation is proposed to be an important hub for such pathophysiological processes in MS, allowing for the increased frequency of depression that may be prodromal in MS, both in the first episode as well as in relapses, to become more intimately associated with the etiology and course of MS. We propose this occurs by decreasing serotonin availability as a precursor for the melatoninergic pathways. Conclusion: Changes in the gut are evident in the early stages of MS, including in paediatric MS, and may interact with pro-inflammatory genetic susceptibility genes to drive the biological underpinnings of MS. Such a conceptualization of the biological underpinnings of MS also has treatment implications.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/1381612822666160915160520
2016-11-01
2024-11-23
Loading full text...

Full text loading...

/content/journals/cpd/10.2174/1381612822666160915160520
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test