Examining Emerging Gut Microbiota Biomarkers for MS

Recent research has suggested that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. Other immune-related disorders are linked to gut dysbiosis including type 1 diabetes, Sjögren’s syndrome, and cardiovascular disease. We explore the potential of gut microbiota biomarkers in multiple sclerosis (MS) and their potential applications in the diagnosis, prognosis, and management of MS.  

What Is Gut Dysbiosis and How Could It Be Linked to MS?
Gut microbiota is a complex ecosystem of microorganisms that live in the gastrointestinal tract that facilitates homeostasis through regulation of the immune system, metabolism, and other physiological processes. Gut dysbiosis, which is an imbalance of microbial diversity, may be caused by changes in one’s diet and the use of medications, like antibiotics, infections, and gastrointestinal surgery. Understandably, such changes can set off a pro-inflammatory cascade activating the immune system. It’s been suggested that this response might be an additional disease mechanism in MS. 

Alterations that may originate from gut dysbiosis can alter Th17 immune-mediated responses and IL-10 production, both mediators are known to be linked to MS disease activity and/or CNS autoimmunity. Additionally, studies have identified the modulation of neurotransmitters, like GABA (γ-aminobutyric acid), and short-chain fatty acids are critical to the structure, function, and regulation of the intestinal mucosa/barrier and the blood-brain barrier.   

Observed Gut Microbiota Alterations in Patients with MS
Several studies have identified specific gut microbiota changes associated with MS. Here are some findings so far. 

• Patients with MS have distinct gut microbiota compared to healthy controls 
• Concentration of short-chain fatty acids were lower in patients with MS 
• Beneficial bacteria, such as Actinobacteria like Bifidobacterium, and Firmicutes like Lactobacillus, Clostridium, and Faecalibacterium were decreased in patients with MS  
• Proinflammatory bacteria, such as Akkermansia and Methanobrevibacter, associated with disease activity and severity were increased in patients with MS  
• Higher counts of Pedobacteria, Flavobacterium, Pseudomonas, among other species were present in patients with relapsing-remitting MS 

Applications of Gut Microbiota Biomarkers in MS
As with many diseases, early diagnosis, careful monitoring, and prognosis of MS is a necessary challenge that is critical to improve patient outcomes. As technology continues to progress, emerging biomarkers are needed to meet the challenge. Gut microbiota biomarkers can be used as diagnostic and prognostic tools in MS. They could also be used to monitor disease activity and response to treatment. Let’s look at the focus of current studies exploring the utility of gut microbiota as biomarkers in MS. 

• Diagnosis: Changes in the microbial composition of the gut microbiota may be used in the diagnosis of MS susceptibility. Further, the lack of beneficial bacteria and their metabolites, such as short-chain fatty acids, have anti-inflammatory properties that are being investigated for its protective autoimmunity potential.  
• Monitoring: Markers of MS activity can be monitored by increases in Methanobrevivacter smithii and Akkermansia muciniphila, which are associated with increased proinflammatory Th17 activation and degradation of intestinal mucosa, respectively. Similarly, lower levels of metabolites, including short-chain fatty acids, nitric oxide, and/or hydrogen sulfide, may be indicative of blood-brain barrier integrity, which can be monitored for disease activity and responses to treatment.  
• Prognosis: Ongoing low diversity of microbiome could be indicative of increased disease progression and disability. Brain atrophy may be predictive of the alterations of specific strains, which may be used as markers of prognosis. Variability of serum antibodies to microbiota antigens may also be a predictor of MS progression in relation to CNS inflammation.    

Current Challenges and Limitations of Using Gut Microbiota Biomarkers in MS
As with any new findings, large-scale studies and validated collection and testing methodologies are in their infancy. However, gut microbiota biomarkers have the potential as diagnostic and prognostic tools in MS. In fact, studies suggest they could also be used to monitor disease activity and response to treatment. Further research is ongoing to explore the validity of gut microbiota as a biomarker in MS, but its potential is exciting in this and other autoimmune diseases. In doing so, these biomarkers could be used to improve the management of MS by providing a non-invasive and cost-effective way to diagnose and monitor the disease. They could also be used to identify patients who are at risk of developing MS and to monitor the response to treatment.