Probiotics
From the hygiene hypothesis have come probiotic strategies, based on consumption of non-pathogenic live microorganisms which may confer a health benefit1,2. Studies in animal models of MS have identified members of the gut microflora that alleviate neuroinflammation.
Outcomes of disease were evaluated in an EAE animal model of MS in response to two commercial multispecies probiotics, 1.6 × 109 CFU of “Lactibiane iki” (Bifidobacterium lactis LA 304, Lactobacillus acidophilus LA 201, and Lactobacillus salivarius LA 302) and 9 × 109 CFU of “Vivomixx” (Lactobacillus acidophilus (DSM 24735), Lactobacillus plantarum (DSM 24730), Lactobacillus paracasei (DSM 24733), Lactobacillus delbrueckii subsp. bulgaricus (DSM 24734), Bifidobacterium longum (DSM 24736), Bifidobacterium breve (DSM 24732), Bifidobacterium infantis (DSM 24737), and Streptococcus thermophilus (DSM 24731)). Lactibiane iki was observed to improve EAE outcome in a dose-dependent manner, decreasing CNS demyelination and inflammation and stimulating immunoregulatory mechanisms. Both probiotic products improved the number and type of dendritic cells3.
In an EAE model evaluating mobility using just Vivomixx, treatment improved motor function, as evidenced by an increase in horizontal and vertical activity, compared to the more limited activity in the control group. Further, the probiotic increased plasma levels of the ketones butyrate and acetate and inhibited pro-inflammatory cytokine production by autoimmune cells4.
In a small pilot study of newly diagnosed, drug-free RRMS patients, 2500 units of an oral helminthic probiotic (Trichuris suis eggs) taken every two weeks for three months was associated with a lower new lesion burden as seen in MRIs, with no significant adverse effects. Additionally, increases in the anti-inflammatory cytokines IL-4 and IL-10 were observed in the majority of subjects5.
In a randomized double-blind placebo-controlled clinical trial in RRMS patients, participants who received a probiotic (containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum at a total dose of 2 x 109 CFU/g) every two weeks for 12 weeks experienced improvements in inflammatory factors6,7, disability, parameters of mental health, markers of insulin resistance, HDL and total cholesterol, and oxidant levels6.
In another randomized controlled clinical study, RRMS patients were compared to healthy controls in their response to an oral probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus twice-daily for two months. Probiotic treatment increased several types of bacteria known to be depleted in MS, such as Lactobacillus and Bifidobacterium, and decreased those associated with dysbiosis in MS, such as Akkermansia and Blautia. It also induced an anti-inflammatory immune response, including decreased inflammatory monocytes and human leukocyte antigen (HLA) on dendritic cells8.
According to the National Library of Medicine (NLM) and the National Institute of Health (NIH), probiotics are likely safe according to current data indicating probiotic supplements to rarely be absorbed into the bloodstream. The chance of contracting a bacterial blood infection from taking Lactobacillus probiotics (common in fermented foods and supplements) is less than 1 per 1 million individuals consuming it, and of a fungal blood infection from Saccharomyces boulardii (also common) is approximately 1 per 5.6 million.
In the limited research on probiotic use during pregnancy, there have been no associations with miscarriages or malformations of any kind. Furthermore, a meta-analysis by Canadian researchers found no association with probiotic use and the incidence of Caesarean section, birth weight, or gestational age10. A later meta-analysis found similar safety11.
The NLM and NIH concluded there does not appear to be any risk of probiotic use for expectant or lactating mothers9.
Fermented foods naturally contain probiotics, and some have probiotics added to them. Good sources include yogurt, kefir, kombucha, sauerkraut, pickles, miso, tempeh, kimchi, sourdough bread and some cheeses12. The plant-based options have the additional advantage of providing prebiotics (nourishment for the bacteria themselves), which can enhance the benefit to humans. Types of prebiotics include inulin, galactooligosaccharides (GOS), fructooligosaccharides (FOS), and transgalactooligosaccharides (TOS), and food sources include almonds, artichoke, asparagus, bananas, beans, blueberries, cabbage, whole corn, eggplant flaxseed, raw garlic, raw leafy greens, jicama, oat, onion, peas, soy, and whole wheat and other grains in the wheat family13.
References
1.Johannsen H, Prescott SL. Practical prebiotics, probiotics and synbiotics for allergists: how useful are they? Clin Exp Allergy. Dec 2009;39(12):1801-14. doi:10.1111/j.1365-2222.2009.03368.x
2.Food and Agriculture Organization and World Health Organization Expert Consultation: Evaluation of health and nutritional properties of powder milk and live lactic acid bacteria. Córdoba: Food and Agriculture Organization of the United Nations and World Health Organization; 2001.
3.Calvo-Barreiro L, Eixarch H, Ponce-Alonso M, et al. A Commercial Probiotic Induces Tolerogenic and Reduces Pathogenic Responses in Experimental Autoimmune Encephalomyelitis. Cells. Apr 7 2020;9(4)doi:10.3390/cells9040906
4.Mestre L, Carrillo-Salinas FJ, Feliu A, et al. How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process. Gut Microbes. Nov 9 2020;12(1):1813532. doi:10.1080/19490976.2020.1813532
5.Fleming JO, Isaak A, Lee JE, et al. Probiotic helminth administration in relapsing-remitting multiple sclerosis: a phase 1 study. Mult Scler. Jun 2011;17(6):743-54. doi:10.1177/1352458511398054
6.Kouchaki E, Tamtaji OR, Salami M, et al. Clinical and metabolic response to probiotic supplementation in patients with multiple sclerosis: A randomized, double-blind, placebo-controlled trial. Clin Nutr. Oct 2017;36(5):1245-1249. doi:10.1016/j.clnu.2016.08.015
7.Tamtaji OR, Kouchaki E, Salami M, et al. The Effects of Probiotic Supplementation on Gene Expression Related to Inflammation, Insulin, and Lipids in Patients With Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial. J Am Coll Nutr. Nov-Dec 2017;36(8):660-665. doi:10.1080/07315724.2017.1347074
8.Tankou SK, Regev K, Healy BC, et al. Investigation of probiotics in multiple sclerosis. Mult Scler. Jan 2018;24(1):58-63. doi:10.1177/1352458517737390
9.Elias J, Bozzo P, Einarson A. Are probiotics safe for use during pregnancy and lactation? Can Fam Physician. Mar 2011;57(3):299-301.
10.Dugoua JJ, Machado M, Zhu X, Chen X, Koren G, Einarson TR. Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. J Obstet Gynaecol Can. Jun 2009;31(6):542-552. doi:10.1016/S1701-2163(16)34218-9
11.Sheyholislami H, Connor KL. Are Probiotics and Prebiotics Safe for Use during Pregnancy and Lactation? A Systematic Review and Meta-Analysis. Nutrients. Jul 13 2021;13(7)doi:10.3390/nu13072382
12.Probiotics. National Institutes of Health. Accessed August 23, 2024, https://ods.od.nih.gov/factsheets/Probiotics-HealthProfessional/
13.Davani-Davari D, Negahdaripour M, Karimzadeh I, et al. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. Mar 9 2019;8(3)doi:10.3390/foods8030092