In our previous blog, we discussed the role of the microbiome in autoimmunity and how you can use comprehensive microbiome testing to inform your approaches to long-term wellness. But the elephant-in-the-room question is: what about probiotics? If the microbiome can contribute to healing or disease in autoimmune conditions, why not take beneficial microbes in a probiotic supplement? The answer, it turns out, is not so straightforward. Read on to learn about the specific probiotics that research shows can help autoimmune conditions, and what to look for in a probiotic supplement!
Probiotic bacteria in autoimmune conditions
Most probiotics on the market today are either from the genus Bifidobacterium or Lactobacillus, with several newer probiotics from Akkermansia and Bacillus. (“Genus” is the name of the grouping in taxonomy that is one level broader than species, and is typically listed before the species in scientific names. For example, human beings are of the genus “Homo” and the species “sapiens.”)
These microbes are natural residents of a healthy gut microbiome, and have been long associated with overall health in observational studies on the general populations.1–3 The role of these probiotic bacteria in autoimmunity is controversial. For instance, some studies have found people with rheumatoid arthritis have decreased levels of Bifidobacterium,4 Lactobacillus,5 and Akkermansia,6 while other studies have found increased levels of these three.6–8 Hashimoto’s has been associated with decreased Lactobacillus,9,10 while lupus is associated with increased levels.11 While several studies have found people with Hashimoto’s have lower Bifidobacterium,9,10,12 the most recent study found higher levels among patients.13
Myths about probiotics
Despite this controversy, Bifidobacterium and Lactobacillus probiotics have the potential to benefit these autoimmune conditions. This is because different strains of these probiotic bacteria do unique things in the gut.14
Myth #1: All Bifidobacteria and Lactobacilli are the same
When it comes to probiotic bacteria, it’s not just the genus (e.g. Lactobacillus) and species (e.g. rhamnosus) that count, but the particular strain (e.g. Lactobacillus rhamnosus GG) that determines its effects. Research has consistently shown that different strains from the same species can have opposite effects, some producing benefits while others cause harm!15 This makes sense if we think about dogs—all dogs are from the same species (Canis familiaris), but you wouldn’t try to use a chihuahua to herd sheep!
Myth #2: The benefit of probiotics is that they passively repopulate the gut
The true, evidence-based benefit of probiotics is that these microbes do things while they pass through your gut.16 They interact with your resident gut microbes in different ways, create various supportive molecules, and influence your immune system and gut lining. Specific strains of Bifidobacterium and Lactobacillus may be able to do beneficial things for autoimmune conditions, even if your gut already has plenty of microbes
Clearly, probiotics are complicated! Just like pharmaceutical medicines, we have to rely on clinical research to show us which probiotics have which effects. This is challenging, because most probiotics on the market today have no research to back them up. Many popular probiotics only list the genus and species without specifying the strain. That’s like selling a dog without knowing whether it’s a pitbull or a greyhound!
Clinical studies show that certain probiotics on the market have a strong potential to benefit specific autoimmune conditions. Let’s take a look at the research on rheumatoid arthritis (RA), systemic lupus erythematosus (lupus), and Hashimoto’s. Let’s take a look:
Rheumatoid Arthritis (RA)
- Lactobacillus rhamnosus GG
Study: randomized, double-blind, placebo-controlled
Population: 21 adults with RA
Intervention: 20 billion CFU (colony forming units) per day for 12 months
Outcomes: This is one of the most well-researched probiotic strains on the market, and it just might benefit some people with RA. Lactobacillus rhamnosus GG reduced disease activity in 71% of participants, while their average number of swollen joints was nearly halved.17 The small size of the study prevented the finding from reaching statistical significance, because 30% of people taking the placebo also had reduced disease activity. Nonetheless, some people likely received a true benefit from the probiotic.
Products: Culturelle (15 billion/capsule), Pure Encapsulations PureGG (25 billion/capsule)
- Bacillus coagulans GBI-30 6086
Study: randomized, double-blind, placebo-controlled
Population: 45 adults with RA
Intervention: 2 billion CFU per day for 60 days
Outcomes: This probiotic strain reduced subjective pain ratings as well as blood levels of CRP—an objective marker of inflammation—while increasing the number of participants able to walk 2 miles.18
Products: Schiff Digestive Advantage (2 billion/capsule)
- Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14
Study: randomized, double-blind, placebo-controlled
Population: 29 adults with stable RA and at least 4 swollen joints
Intervention: 2 billion CFU of equal parts both strains per day for 3 months
Outcomes: This combination of probiotics significantly improved subjective quality of life and functional scores versus placebo, without altering clinical disease activity.19 It is more difficult to change disease activity when the disease is stable, which may have prevented this isolated intervention from making a difference on its own, in addition to the small sample size. Nonetheless, increased ability to move with comfort is nothing to scoff at.
Products: Metagenics Ultraflora Women’s (1 billion/capsule), Jarrow FemDophilus (1 billion/capsule)
- Lactobacillus acidophilus La-14, Lactobacillus casei Lc-11, Lactococcus lactis Ll-23, Bifidobacterium lactis Bl-04 and Bifidobacterium bifidum Bb-06
Study: randomized, double-blind, placebo-controlled
Population: 42 adults with RA
Intervention: 1 billion CFU of each strain per day for 60 days
Outcomes: This five-strain blend reduced white blood cell counts, inflammatory cytokines, and markers of oxidative stress, but did not influence global markers of inflammation such as CRP or ESR, nor disease activity.20 This is likely not a first-line option, though RA patients with high oxidative stress may potentially benefit from this combination.
Products: No product has this exact blend. Xymogen ProBioMax has all five strains plus many more, while Pure Encapsulations Probiotic GI has ⅘ and two additional strains.
Lupus
- Lactobacillus helveticus R0052, Bifidobacterium infantis R0033 20%, Bifidobacterium bifidum R0071
Study: randomized, double-blind, placebo-controlled
Population: 46 adults with lupus
Intervention: 3 billion CFU, 60% Lactobacillus helveticus R0052, for 60 days
Outcomes: These probiotics prevented an increase in hsCRP seen in the placebo group, while lowering levels of the inflammatory cytokine IL-6 as well as lowering disease activity measured by the validated SLEDAI score.21 The primary species Lactobacillus helveticus R0052 has also been found in other recent studies to possibly reduce symptoms of depression.
Products: No product contains all three strains. Xymogen Lacidofil or Life Extension FLORASSIST Mood have just Lactobacillus helveticus R0052.
Hashimoto’s
- Visbiome (proprietary blend of strains formerly called VSL#3)
Study: randomized, single-blind, placebo-controlled
Population: 80 adults with hypothyroidism
Intervention: 1 sachet Visbiome per day for 60 days
Outcomes: This study found that Visbiome reduced the frequency of levothyroxine dose adjustments, suggesting the probiotic may help to stabilize thyroid hormone function and hormone replacement doses.22
Products: These strains are only available as the product Visbiome. The product now called VSL#3 does not have the same strains.
Future perspectives – Fecal Microbiota Transplant?
The story is far from over on how modulating the microbiome can influence autoimmune diseases. While new probiotics and new uses for them will continue to be discovered, research is rapidly expanding on fecal microbiota transplants (FMT)—a whole new category of microbiome therapy that may prove even more powerful. FMT entails giving a patient a complete microbiome sample from the stool of a healthy donor in order to shift their microbiome into a healthy balance, and potentially treat the disease. FMT is currently being explored for people with lupus,23, and has been used successfully in a single case of RA.24 FMT is still new and caution is warranted—dangerous latent infections can also be transferred from seemingly-healthy donors. However, watch this space! The microbiome holds great promise for the future of personalized medicine.
References:
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2. O’Callaghan J, O’Toole PW. Lactobacillus: host-microbe relationships. Curr Top Microbiol Immunol. 2013;358:119-154. doi:10.1007/82_2011_187
3. Zhang T, Li Q, Cheng L, Buch H, Zhang F. Akkermansia muciniphila is a promising probiotic. Microb Biotechnol. 2019;12(6):1109-1125. doi:10.1111/1751-7915.13410
4. Chiang HI, Li JR, Liu CC, et al. An Association of Gut Microbiota with Different Phenotypes in Chinese Patients with Rheumatoid Arthritis. J Clin Med. 2019;8(11):1770. doi:10.3390/jcm8111770
5. Sun Y, Chen Q, Lin P, et al. Characteristics of Gut Microbiota in Patients With Rheumatoid Arthritis in Shanghai, China. Front Cell Infect Microbiol. 2019;9:369. doi:10.3389/fcimb.2019.00369
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7. Li Y, Zhang SX, Yin XF, et al. The Gut Microbiota and Its Relevance to Peripheral Lymphocyte Subpopulations and Cytokines in Patients with Rheumatoid Arthritis. J Immunol Res. 2021;2021:6665563. doi:10.1155/2021/6665563
8. Ruiz-Limón P, Mena-Vázquez N, Moreno-Indias I, et al. Collinsella is associated with cumulative inflammatory burden in an established rheumatoid arthritis cohort. Biomed Pharmacother Biomedecine Pharmacother. 2022;153:113518. doi:10.1016/j.biopha.2022.113518
9. El-Zawawy HT, Ahmed SM, El-Attar EA, Ahmed AA, Roshdy YS, Header DA. Study of gut microbiome in Egyptian patients with autoimmune thyroid diseases. Int J Clin Pract. 2021;75(5):e14038. doi:10.1111/ijcp.14038
10. Gong B, Wang C, Meng F, et al. Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis. Front Endocrinol. 2021;12:774362. doi:10.3389/fendo.2021.774362
11. Vieira JRP, Rezende AT de O, Fernandes MR, da Silva NA. Intestinal microbiota and active systemic lupus erythematosus: a systematic review. Adv Rheumatol Lond Engl. 2021;61(1):42. doi:10.1186/s42358-021-00201-8
12. Cayres LC de F, de Salis LVV, Rodrigues GSP, et al. Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis. Front Immunol. 2021;12:579140. doi:10.3389/fimmu.2021.579140
13. Liu J, Qin X, Lin B, et al. Analysis of gut microbiota diversity in Hashimoto’s thyroiditis patients. BMC Microbiol. 2022;22(1):318. doi:10.1186/s12866-022-02739-z
14. McFarland LV, Evans CT, Goldstein EJC. Strain-Specificity and Disease-Specificity of Probiotic Efficacy: A Systematic Review and Meta-Analysis. Front Med. 2018;5:124. doi:10.3389/fmed.2018.00124
15. Ligaarden SC, Axelsson L, Naterstad K, Lydersen S, Farup PG. A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomised controlled trial. BMC Gastroenterol. 2010;10:16. doi:10.1186/1471-230X-10-16
16. Wieërs G, Belkhir L, Enaud R, et al. How Probiotics Affect the Microbiota. Front Cell Infect Microbiol. 2019;9:454. doi:10.3389/fcimb.2019.00454
17. Hatakka K, Martio J, Korpela M, et al. Effects of probiotic therapy on the activity and activation of mild rheumatoid arthritis–a pilot study. Scand J Rheumatol. 2003;32(4):211-215. doi:10.1080/03009740310003695
18. Mandel DR, Eichas K, Holmes J. Bacillus coagulans: a viable adjunct therapy for relieving symptoms of rheumatoid arthritis according to a randomized, controlled trial. BMC Complement Altern Med. 2010;10:1. doi:10.1186/1472-6882-10-1
19. Pineda M de LA, Thompson SF, Summers K, de Leon F, Pope J, Reid G. A randomized, double-blinded, placebo-controlled pilot study of probiotics in active rheumatoid arthritis. Med Sci Monit Int Med J Exp Clin Res. 2011;17(6):CR347-354. doi:10.12659/msm.881808
20. Cannarella LAT, Mari NL, Alcântara CC, et al. Mixture of probiotics reduces inflammatory biomarkers and improves the oxidative/nitrosative profile in people with rheumatoid arthritis. Nutr Burbank Los Angel Cty Calif. 2021;89:111282. doi:10.1016/j.nut.2021.111282
21. Widhani A, Djauzi S, Suyatna FD, Dewi BE. Changes in Gut Microbiota and Systemic Inflammation after Synbiotic Supplementation in Patients with Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Trial. Cells. 2022;11(21):3419. doi:10.3390/cells11213419
22. Spaggiari G, Brigante G, De Vincentis S, et al. Probiotics Ingestion Does Not Directly Affect Thyroid Hormonal Parameters in Hypothyroid Patients on Levothyroxine Treatment. Front Endocrinol. 2017;8:316. doi:10.3389/fendo.2017.00316
23. Huang C, Yi P, Zhu M, et al. Safety and efficacy of fecal microbiota transplantation for treatment of systemic lupus erythematosus: An EXPLORER trial. J Autoimmun. 2022;130:102844. doi:10.1016/j.jaut.2022.102844
24. Zeng J, Peng L, Zheng W, et al. Fecal microbiota transplantation for rheumatoid arthritis: A case report. Clin Case Rep. 2021;9(2):906-909. doi:10.1002/ccr3.3677