Multiple Sclerosis
Multiple sclerosis (MS) is the most common disabling neurological disease in young adults, with symptoms generally appearing between the ages of 20 and 40 years. MS impacts the central nervous system, which is comprised of the brain, spinal cord and optic nerves and controls everything we do (2). The term “multiple sclerosis” refers to distinctive areas of scar tissue (sclerosis—also called plaques or lesions) that result from the immune system attacking myelin, the protective layer that insulates and allows efficient transmission of signals along the wire-like nerve fibers. Worldwide, 2.8 million people have MS, of which nearly 1 million reside in the U.S. Several governmental organizations, nonprofit organizations, health centers, and companies in the US are actively working to address MS (1–8); however, no cure for the disease yet exists.
The exact cause of MS is unknown, but it is established that “something” triggers the immune system to attack the central nervous system. The resulting damage to myelin disrupts signals to and from the brain, causing idiosyncratic and variable symptoms such as numbness, tingling, mood changes, memory problems, pain, fatigue, blindness and/or paralysis. These losses may be temporary or enduring. The particular symptoms experienced depend on the severity of the inflammatory reaction, plaque extent, and plaque location, which can include the brainstem, cerebellum, spinal cord, optic nerves, and white matter around the brain ventricles. No two people have exactly the same symptoms; one might experience only one or two of the possible symptoms, while another may experience several. In addition, each person’s symptoms can change or fluctuate over time. The more common symptoms are fatigue, MS hug, gait difficulties, numbness or tingling, spasticity, weakness, vision problems, vertigo and dizziness, sexual problems, bladder problems, bowel problems and pain and itching (1–2).
At present, there are no symptoms, physical findings or laboratory tests available that can determine if a person has MS. Healthcare providers use several strategies to determine if a person meets the long-established criteria for the diagnosis and to rule out other possible causes of the symptoms being experienced. These strategies include a careful medical history, a neurologic exam and various tests, including magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis and blood tests.
Currently, multiple sclerosis is classified into four types according to disease course (7):
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Clinically isolated syndrome (CIS) - The first episode of MS.
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Relapsing-remitting MS (RRMS) - A course of flare-ups (relapse or exacerbation) of new or worsening symptoms followed by periods of remission (when symptoms stabilize or go away); the most common form of MS.
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Primary progressive MS (PPMS) - Symptoms slowly and gradually worsen without any periods of relapse or remission.
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Secondary progressive MS (SPMS) - A diagnosis of RRMS that progresses to SPMS; patients may still experience some relapses or flares, but no longer have periods of remission.
The exact cause of multiple sclerosis is not known, and its pathogenesis is attributed to a combination of factors triggering the disease (2). Studies support the idea that MS can occur when people with the right combination of genes are exposed to “some trigger” in the environment. This raises the question: what is that “something”? Research suggests that ethnicity and geography play a role. Exposure to certain viruses or bacteria (such as Epstein–Barr virus), where one lives, how the immune system functions, and the genetic variants one carries have all been implicated as contributors to MS pathogenesis. Fully elucidating what causes MS will speed the process of finding more effective ways to treat and cure it. Ideally, we will find a way to prevent MS from developing in the first place.
Current treatments for MS focus on managing symptoms, reducing relapses and slowing disease progression. A comprehensive treatment plan may include the following (7):
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Disease-modifying therapies (DMTs): Several medications have FDA approval for long-term MS treatment. These drugs help reduce relapses, slow disease progression, and can prevent new lesions from forming on the brain and spinal cord.
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Relapse management medications: For severe attacks, neurologists may recommend a high dose of corticosteroids, which can quickly reduce inflammation and slow damage to the myelin sheath surrounding nerve cells.
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Physical rehabilitation: Multiple sclerosis can affect physical function. Staying physically fit and strong will help maintain mobility.
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Mental health counseling: Coping with a chronic condition can be emotionally challenging; moreover, MS can sometimes affect mood and memory. Working with a neuropsychologist or receiving other emotional support is an essential part of managing the disease.
Role of Probiotics in Patients with Multiple Sclerosis
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the areas in which probiotics have been investigated during the past decade is neurodegenerative disorders and diseases, reviewed below.
Several studies have investigated the gut-brain axis, defined by Dziedzic and Saluk (10) as the multifactorial interactions between the intestinal microflora and the nervous, immune, and endocrine systems that connect brain activity and gut functions. Yadav et al. (9) conducted a comprehensive review of the role of the gut-brain axis (GBA) in regulating neurodegenerative diseases and observed disturbance of microbiota, termed dysbiosis, to contribute to conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis; the authors also noted potential possibilities for targeting the gut microbiome to improve neurological health. Alterations in the GBA have been identified in people with MS, suggesting the GBA to have a potential role in disease pathogenesis and therefore promise as a therapeutic target.
Farshbafnadi et al. (20) reviewed studies that examined the relationship of gut microbiota composition to MS and its possible underlying mechanisms. Most such studies agreed that patients with MS suffer from dysbiosis. In addition, altered proportions of certain bacterial phyla were detected in the digestive tracts of these patients compared to healthy individuals. Altieri et al. (13) further described the main changes that occur in the gut microbiota of MS patients, focusing not only on the microbiota and its implications for health and disease, but also the variables that influence it. The authors additionally studied the role of the microbiota as a triggering factor for innate and adaptive immune responses, both in the intestine and in the brain.
Wang et al. (16) reviewed potential mechanisms of gut microbiota involvement in MS pathogenesis, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting blood‒brain barrier integrity, and contributing to chronic inflammation. Zoledziewska (22) reviewed the gut microbiota perspective for interventions in MS and reported the observed impact of the gut microbiome on MS pathophysiology to involve both quantitative and functional changes in composition, metabolism, gut permeability, homeostasis and modulation of the immune system. Ullah et al. (17) likewise reviewed the link between gut dysbiosis and MS development/progression, along with modulation of the gut microbiota as an emerging approach in for prevention and treatment. Shahi et al. (18) extensively studied the role of the gut microbiome in multiple sclerosis, from etiology to therapeutics, and reported it to support diverse physiologic functions, including development and maintenance of the host immune system. Kumar et al. (11) indicated that any change in the gut might increase inflammatory cytokines and affect the quantity of short-chain fatty acids and other metabolites that cause neuroinflammation and demyelination; therefore, alteration of gut microbial composition via probiotic intake may serve as a preventive and treatment strategy. They concluded that it will be easier to develop new therapeutic approaches, particularly probiotic-based supplements, for treating MS if we understand the link between the gut and CNS.
Hashemi et al. (12) reviewed a number of studies using probiotic interventions and determined that probiotics could improve immune cell populations and inflammatory cytokines in patients with MS, potentially contributing to disease management and control. Moravejolahkami et al. (14) conducted a single-center, single-blind randomized clinical trial exploring the effects of an anti-inflammatory, antioxidant-rich diet and supplemented synbiotic intervention in patients with progressive forms of MS. The results indicated this diet and supplementation to reduce intestinal inflammation and improve clinical manifestations. Jiang et al. (15) performed a systematic review of preclinical trials and a meta-analysis of randomized controlled trials involving MS patients receiving probiotics, for a total of 173 patients They determined probiotic supplementation to have significant beneficial effects on mental health, and furthermore that it may have beneficial effects on the prevention and treatment of MS. Mirashrafi et al. (19) likewise conducted a systematic review and meta-analysis of clinical trials exploring the effect of probiotic supplementation on disease progression, depression, general health, and anthropometric measurements in relapsing-remitting MS patients. They concluded that probiotic supplementation can improve disease progression and suppress depression and general health in MS patients. Rahimlou et al. (21) conducted a randomized, double-blind, placebo-controlled trial on the effects of long-term administration of multi-strain probiotics on circulating levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and interleukin 6 (IL-6) and mental health in patients with multiple sclerosis and found that probiotic supplementation, compared to placebo, was associated with significant improvements in the general health questionnaire, Beck Depression Inventory-II, Fatigue Severity Scale and Pain Rating Index. However, they did not find any significant difference between the two groups in terms of other factors. Overall, they concluded that six months of probiotic supplementation resulted in improvement of mental health parameters.
Finally, Dunalska et al. (23) conducted a systematic review of current evidence confirming the role of the gut microbiome in the pathophysiology of MS and related disorders, such as neuromyelitis optica spectrum disorder (NMO-SD). The authors reported the most relevant bacteria for MS pathophysiology to be Pseudomonas, Mycoplasma, Haemophilus, Blautia, Dorea, Faecalibacterium, Methanobrevibacter, Akkermansia and Desulfovibrionaceae, while Clostridium perfringens and Streptococcus have been demonstrated to play roles in the pathophysiology of NMO-SD.