The Gut Microbiome In Multiple Sclerosis

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Welcome to my blog entitled ‘The Microbiome In Multiple Sclerosis”.

Before we start, other blogs that you might be interested in, include:

There is mounting evidence in preliminary human studies suggesting that a dysbiotic Multiple Sclerosis gut microbiome could affect disease progression. (2)

There are many ways that the microbiome may contribute to Multiple Sclerosis:

  • The Gut-Brain Axis
  • Microbial metabolites
  • Modulation of the immune system
  • Maintaining a healthy gut barrier (preventing leaky gut)

The Gut-Brain Axis in Multiple Sclerosis

The enteric nervous system has long been recognised as a ‘second brain’. More recently, the gut–brain axis has been recognised as a bi-directional communication system from the central nervous system to the gut and vice versa; this communication is mediated by veracious substances including neuronal connections, neuroendocrine signals, and immune signaling. (1)

The CNS regulates gut function by promoting gut motility via a dense innervation system and by orchestrating local immune responses through the high numbers of immune cells that are present in the gut. (1)

These signals are delivered by the utilisation of substances, such as pro-inflammatory cytokines, neuropeptides (like cholecystokinin (CCK) and leptin), and neurotransmitters (like dopamine and serotonin. (1)

Conversely, structures in immediate proximity to the microbiome—such as the intestinal epithelial cells and immune cells in gut-associated lymphatic tissue (GALT) and the enteric nervous system (ENS)—mediate the transmission of signaling pathways from the gut towards the CNS. (1)

In this respect, gut microbiota may modulate the host via several pathways that originate in parts of the neuroendocrine, neural, and immune systems. (1)

Gut Microbiome, Immunity And Multiple Sclerosis

Microbial Metabolites And Multiple Sclerosis

Apart from microbial structural components that may shape immune responses in the intestine with implications for systemic disease, other molecular mediators also exhibit the capacity to induce pro- or anti-inflammatory reactions. (1)

Metabolites of microbial origin are present in the intestine, often as a by-product of nutrient degradation; these molecules may stimulate immune cells towards activated phenotype and cytokine production.

Short chain fatty acids are metabolites produced by intestinal microbes that mediate a well-known anti-inflammatory effect. (1)

Leaky Gut And Multiple Sclerosis

Intestinal dysbiosis appears to mediate barrier dysfunction.

Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia.

We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis

Microbiome Diversity, Leaky Gut, And Multiple Sclerosis

Concomitant reduction in SCFAs associated to dysbiosis, that is, reduced microbial diversity, a condition frequently described in MS, results in compromised intestinal barrier and thus predisposes towards systemic pro-inflammatory reactions.(1)

The Hygiene Hypothesis And Multiple Sclerosis

The hygiene hypothesis postulates that individuals living in environments that are too “clean” lack the requisite exposure to “immune-tolerising” microbial products, resulting in poorly regulated immune systems and increased immune-mediated diseases. (3)

Interestingly, few studies have linked MS with the hygiene hypothesis.

Conclusions: The Gut Microbiome In Multiple Sclerosis

In addition to the classical paradigm of immune–brain interaction in the context of Multiple Sclerosis, the intestine has emerged as an additional regulating organ of responses that take place both in the immunological and the nervous (central and peripheral) counterparts. In this respect, the gut commensal microbiota may serve as environmental factors that shape the intestinal milieu.

The modification of gut microbiota by either dietary (e.g., probiotic supplementation) or medicinal approaches (e.g., antibiotic administration) may serve as additional therapeutic strategies for MS prophylaxis.

More interventional approaches, such as FMT, have also been proposed.

References

  1. Microbiome in Multiple Sclerosis: Where Are We, What We Know and Do Not Know (click here)
  2. The Gut Microbiome and Multiple Sclerosis (click here)
  3. Multiple sclerosis, the microbiome, TLR2, and the hygiene hypothesis (click here)
  4. Gut microbiome in multiple sclerosis: The players involved and the roles they play (click here)
  5. The gut microbiome in neurological disorders (click here)
  6. Gut microbiome and multiple sclerosis: New insights and perspective (click here)
  7. Alterations of the human gut microbiome in multiple sclerosis (click here)
  8. A probiotic modulates the microbiome and immunity in multiple sclerosis (click here)
  9. Multiple sclerosis and faecal microbiome transplantation: are you going to eat that? (click here)
  10. The Gut-CNS Axis in Multiple Sclerosis (click here)
  11. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics (click here)
  12. Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome (click here)
  13. Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis (click here)
  14. The “Gut Feeling”: Breaking Down the Role of Gut Microbiome in Multiple Sclerosis (click here)
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