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The key to treating Multiple Sclerosis may lie in the gut

Multiple Sclerosis

Multiple sclerosis (MS) is a degenerative neurological condition, whose incidence seems to be rising. A 2015 study from Norway found that the incidence had increased 10-fold over a 40-year time period, and currently affects around 200 in every 100,000 people [1]. Multiple sclerosis affects the myelin sheath surrounding nerve fibres. Myelin acts as in insulator, with neural signals ‘jumping’ insulated areas, thus allowing the signal to pass more rapidly along nerve fibres. When myelin is destroyed by Multiple sclerosis, signals pass much more slowly.

Depending which nerves are affected, symptoms might range from blurred vision to numbness, tingling or weakness. For many patients, the disease follows a ‘relapsing-remitting’ course, meaning that symptoms occur, then slowly resolve. The patient then has a symptom-free period, which can last for many years before another attack occurs. Sometimes the symptoms do not completely resolve, leaving behind some residual problems. Over years symptoms can build-up and the time interval between attacks often becomes shorter. In many cases patients go on to develop the progressive form of Multiple sclerosis where symptom-free periods no longer occur, and neurological symptoms gradually worsen.

Multiple sclerosis is an autoimmune disorder, meaning that the immune system is wrongly primed to attack an element of the patient’s own body. In the case of Multiple sclerosis, it is the myelin around nerves which is destroyed. The causes of Multiple sclerosis are unclear, but seem to involve a combination of genetic predisposition with environmental influences such as smoking or exposure to certain viruses [2]. There is no cure for MS, with treatment revolving around symptom relief, along with some medications which aim to reduce the frequency of attacks [3].

The gut microbiome

Gut flora or the gut microbiome contains staggering numbers of bacteria. In the colon, there are estimated to be up to 1012 bacteria per gram of intestinal content. These bacteria are acquired during the first two years of life, and are specific to the individual, their diet, their age and general health. Gut flora are not merely tolerated by us, they are necessary to and nurtured by the gut. For example, some bacteria contain enzymes which breakdown complex fibre or carbohydrates, allowing them to be absorbed, whilst others help protect us from more harmful organisms [4].

There is a growing appreciation that the gut microbiome plays a role in regulating how our body reacts to disease; in particular the working of the immune system and how the body responds to inflammation. Differences in the gut biome between healthy individuals and people suffering from autoimmune gut conditions (such as Crohn’s Disease) have been observed [5].  We know that MS has both an immune and an inflammatory component, raising the possibility of a role for gut flora in the condition.

Evidence of the influence of gut microbiome on Multiple sclerosis

Recent observational studies have compared the gut biome between health ‘control’ individuals and those with MS. Although everyone’s gut flora is different, using groups of genetically similar individuals with similar diets allow comparisons to be made and ‘group differences’ to be detected. These studies have shown that the gut biome in patients with MS really does seem to be different. Although the studies thus far have been small, and haven’t looked at patients in different stages of the disease or on different treatments, the findings have been interesting enough to prompt further investigation [6,7].

In a paper recently published in the Proceedings of the National Academy of Sciences of the United States of America, a group from a range of Universities across America looked at the functions of the bacteria that have been found to be either increased or decreased in the gut of Multiple sclerosis patients. They found that the levels of several bacteria known to be linked to increased inflammation were increased, while some thought to reduce inflammation were lowered [8]. As we know that inflammation is important in modulating the progression and course of Multiple sclerosis, this was a very interesting finding.

The group then went further, and looked to see if changing the gut flora of mice with an artificially induced form of Multiple sclerosis could alter the course of their disease. They transplanted the gut flora of healthy mice into diseased animals and found that this really could reduce the disease progression.

In a similar study, a group from Germany reported complementary results [9]. They took the gut biome from human Multiple sclerosis sufferers and transplanted it into mice with a genetic susceptibility to an MS-like condition. Their paper reports that the Multiple sclerosis gut flora made the mice more likely to develop the condition than mice with a healthy gut biome.

Future steps

These findings are very new, and our understanding of the gut biome in general is in its infancy. We don’t yet know whether the gut biome changes before Multiple sclerosis develops, or if in some way it is a result of the disease or something used to treat patients. We certainly don’t know whether altering the gut biome in human patients could alter the course of Multiple sclerosis, slow frequency or reduce severity of attacks, or even stop the disease in its tracks. We don’t know whether it would be possible to ‘reset’ the gut biome of patients either by using medication, or even reproducing the method used by these researchers and ‘transplanting’ the gut biome from a healthy individual into an Multiple sclerosis patient. Even before any of this, an improved understanding of how inflammation affects the progress of MS, and how inflammation is influenced by gut flora would help enormously.

It is clear that a huge amount of work remains to be done, but there is no doubt that this is a fascinating area of research which holds real potential for the future. It is intriguing to think that gut bacteria really could hold the key to helping patients with Multiple sclerosis.

References:

[1] Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades. Grytten N, Torkildsen Ø, Myhr KM. Acta Neurol Scand. 2015;132(199):29-36.

https://doi.org/10.1111/ane.12428

[2] Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Belbasis L, Bellou V, Evangelou E, Ioannidis JP, Tzoulaki I. Lancet Neurol. 2015 Mar;14(3):263-73.

https://doi.org/10.1016/S1474-4422(14)70267-4

[3] Treatment of progressive multiple sclerosis: what works, what does not, and what is needed. Feinstein A, Freeman J, Lo AC. Lancet Neurol. 2015 Feb;14(2):194-207.

https://doi.org/10.1016/S1474-4422(14)70231-5

[4] Role of the normal gut microbiota. Jandhyala SM, Talukdar R, Subramanyam C, et al. World J Gastroenterol. 2015 Aug 7;21(29):8787-803.

https://doi.org/10.3748/wjg.v21.i29.8787

[5] Systemic effects of gut microbiota and its relationship with disease and modulation. Ho JT, Chan GC, Li JC. BMC Immunol. 2015 Mar 26;16:21.

https://doi.org/10.1186/s12865-015-0083-2

[6] Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls. Chen J, Chia N, Kalari KR, et al. Sci Rep. 2016 Jun 27;6:28484.

https://doi.org/10.1038/srep28484

[7] Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. Miyake S, Kim S, Suda W, et al. PLoS One. 2015 Sep 14;10(9):e0137429.

https://doi.org/10.1371/journal.pone.0137429

[8] Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Cekanaviciute E, Yoo BB, Runia TF, et al. Proc Natl Acad Sci U S A. 2017 Sep 11. pii: 201711235.

https://doi.org/10.1073/pnas.1711235114

[9] Gut microbiota in multiple sclerosis: possible influence of immunomodulators. Cantarel BL, Waubant, Chehoud C, et al. J Investig Med. 2015 Jun;63(5):729-34.

https://doi.org/10.1097/JIM.0000000000000192

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