by Melissa Blake, ND
The use of probiotics has grown substantially over the last several years. Propelled by development in sequencing methods and analytical techniques, we are now able to identify and study specific probiotic strains. This had led to a significant increase in the understanding of the importance of a healthy microbiome and the various ways probiotic strains may influence human health.1
With this increase in demand and knowledge of potential benefit, it is important for healthcare practitioners to have a clear understanding of when, why, and which probiotic strains, or combination of probiotic strains, to prescribe to their patients.
This article will review the evidence that shows clearly defined benefits with specific probiotic strains and discuss the differences between multi- vs single-strain probiotics.
A probiotic defined
We’ve been talking about the use of probiotics for over a hundred years,2 but when it comes to probiotic therapy, what do we really know? To first understand how to use probiotics clinically, we need a clear definition. The currently accepted definition of a probiotic states they are “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”3
This definition, updated by the International Scientific Association for Probiotics and Prebiotics (ISAPP) in 2013 is consistent with that of the World Health Organization (WHO) and Food and Agriculture Organization (FAO).4
However, we cannot assume that all bacteria, for example those in fermented foods and commensal microorganisms in the gut, as well as those found in supplements, fit this definition. Basically, for these strains to be called “probiotics,” they have to be researched and adequately characterized for content, stability, and health effects at sufficient amounts.
The vast amount of available information (a PubMed search brings up almost 20,000 articles related to the search term “probiotics + humans”) along with marketing claims and strategies make the clinical application of probiotic therapy difficult to navigate. In order to determine the best approach for patients, clinicians need to refer to the definition and reference the available literature.
A specific strain for specific condition
Convincing evidence of the human health implications of probiotics exists. Hundreds of well-controlled trials, systematic reviews, and meta-analyses have highlighted the clinical use of probiotics and their valuable benefits.
The problem with the research is that data is often presented collectively, drawing conclusions based on various strains, combinations, and doses of probiotics, which can be misleading.5 The challenge with these generalized conclusions is the wide range of proposed methods of action by which probiotics exert their benefits. Probiotics are complex and likely have both unique and overlapping effects depending on the strain. For example, several core benefits, such as supporting barrier function6-8 or producing antimicrobial and beneficial metabolites9-13 are shared by several different strains. To achieve these benefits clinically, a multistrain probiotic may be the best approach. More targeted, disease-specific actions may require a specific strain.
With that in mind, when looking at the evidence, it’s essential to evaluate the specific strain that was used as well as the specific disease state or outcome that was measured. The evidence suggests that probiotic therapy is far from a one-size-fits-all approach. Studies that show clearly defined benefits in specific disease states associated with specific strains of bacteria do exist; however, comparison studies are lacking.
If some are good, are more better?
Until recently, science had not yet found a way to isolate the many bacterial species from the human body and therefore gravely underestimated their abundance and diversity. Researchers at the Human Microbiome Project now calculate that more than 15,000 bacterial species occupy the human ecosystem.14 These bacteria live in a symbiotic relationship not only with us, but also with one another.
The evidence continues to demonstrate the benefits of probiotics are strain-specific; however, knowing the complexity and diversity of bacterial species that live on or within human beings, it may seem too simplistic to assume a single strain of bacteria is all we need to optimize health. If one strain is clinically efficacious, would not multiple strains be even better?
A recent analysis of the clinical studies in the literature concluded that the answer to this question is unknown, and, although both may be effective, it currently cannot be stated whether a multiple-strain formula or a single-strain probiotic is more effective.15 Largely the reason for the inability to determine the answer to this question is the lack of studies directly evaluating a multiple-strain combination versus a single strain in the clinical study design. Studies comparing effectiveness of various doses are also lacking.15
To highlight the point, we can review the literature on the impact of probiotics and the management of ulcerative colitis. Much of the research in this area has evaluated the benefits of an 8-species blend16 (containing Lactobacillus plantarum, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus casei, Lactobacillus acidophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, and Streptococcus salivarius subsp. thermophiles) or the single strain Escherichia coli Nissle 1917.17,18 Although results are promising, the studies do not provide a comparison to each other, and therefore it is unknown which option (single strain or multistrain) offers more clinical benefit.
Similar evidence exists for the prevention of diarrhea with probiotic therapy. Single strains such as L. rhamnosus GG for children’s acute gastroenteritis19 or the probiotic yeast S. boulardii for traveler’s diarrhea20 as well as multiple strain combinations (Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bi-07, and Bifidobacterium lactis Bl-04) for antibiotic-associated diarrhea21 have shown efficacy. The cause of the disease state, in this case diarrhea, varies as does the studied population.
Trials comparing the use of probiotics in specific populations, at consistent doses, with specific strains and/or combinations, and for specific disease states have not been done; therefore, the question of which is best for what cannot yet be answered.
It’s also essential to clinical outcomes that the research reflects strain specificity, as different strains of the same species may confer different results. Lactobacillus species are common in probiotic supplements but are extremely taxonomically complex. The genus, composed of over 170 species, is naturally occurring in the human gastrointestinal tract and vagina with a variety of “ecological niches.”22 The variability within a species requires specificity to the strain level rather than generalizations in the research. For example, L. plantarum MF1298 did not mitigate irritable bowel syndrome (IBS), while L. plantarum 299v was found to provide relief.23,24
Based on the information available as to which is best, multi- or single strain, we don’t currently have comparative study to demonstrate the differences, and a clear conclusion cannot be drawn.
So where does that leave the clinician?
Clinical guidelines, developed and published by the World Gastroenterology Organization25 and AEProbio,26 are available resources to support physician recommendation of probiotics.
An evidence-based approach to probiotic prescribing includes recognizing the importance of specific strains of probiotics, the type of disease, as well as product quality. These factors provide significant clinical relevance when choosing the appropriate probiotic for your patient. It’s not a one-size-fits-all approach.
Choosing the right probiotic requires an evaluation of the patients, their specific needs, and treatment goals. A patient-centered approach may mean being flexible with your probiotic prescribing, occasionally using a multistrain and other times opting for the specificity of a single-strain.
Thankfully, research in the area of the human microbiome and probiotic therapy is ongoing, and we can hope that soon enough the question of multistrain vs single-strain will be answered.
- Ursell L et al. Defining the human microbiome. Nutr Rev. 2012;70(1):S38–S44.
- Gasbarrini G et al. Probiotics history. J Clin Gastroenterol. 2016;50:S116-S119.
- Hill C et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506-514.
- FAO/WHO. http://www.fao.org/3/a-a0512e.pdf. Accessed October 10, 2019
- McFarland LV et al. Strain-specificity and disease-specificity of probiotic efficacy: a systematic review and meta-analysis. Front Med. 2018;5:124.
- Bermudez-Brito M et al. Probiotic mechanisms of action. Ann Nutr Metab. 2012;61(2):160-174.
- Mack DR et al. Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression. Am J Physiol. 1999;276(4):G941-G950.
- Miyauchi E et al. Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius: strain dependence and attenuation by bacteriocin production. Am J Physiol Gastrointest Liver Physiol. 2012;303(9):G1029-G1041.
- Dunne C et al. Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials. Antonie Van Leeuwenhoek. 1999;76(1-4):279-292.
- Corr SC et al. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc Natl Acad Sci U S A. 2007;104(18):7617-7621.
- Jungersen M et al. The science behind the probiotic strain Bifidobacterium animalis lactis BB-12(®). Microorganisms. 2014;2(2):92-110.
- Stenman L. Probiotic with or without fiber controls body fat mass, associated with serum zonulin in overweight and obese adults – randomized controlled trial. 2016;13:190-200.
- Schneider SM et al. Effects of Saccharomyces boulardii on fecal short-chain fatty acids and microflora in patients on long-term total enteral nutrition. World J Gastroenterol. 2005;11(39):6165-6169.
- Agnew B. The human microbiome comes into focus. National Human Genome Research Institute. https://www.genome.gov/news/news-release/As-the-human-microbiome-comes-into-clearer-focus-researchers-look-more-closely-at-its-role-in-health-and-disease. Accessed October 10, 2019.
- Korada SK et al. Single probiotic versus multiple probiotics – a debate on current scenario for alleviating health benefits. Cur Pharm Des. 2018;24(35):4150-4153.
- Tursi A et al. Treatment of relapsing mild‐to‐moderate ulcerative colitis with the probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: a double‐blind, randomized, placebo‐controlled study. Am J Gastroenterol. 2010;105:2218‐2227.
- Kruis W et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. 2004;53(11):1617-1623.
- Rembacken BJ et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomized trial. Lancet. 1999;21(9179):635-639.
- Szajewska H et al. Meta-analysis: Lactobacillus GG for treating acute gastroenteritis in children – updated analysis of randomized controlled trials. Aliment Pharmacol 2013;38(5):467-476.
- Kelesidis T et al. Efficacy and safety of the probiotic Saccharomyces boulardii for the prevention and therapy of gastrointestinal disorders. Therap Adv Gastroenterol. 2012;5(2):111-125.
- Ouwehand AC et al. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study. Vaccine. 2014;32(4):458-463.
- Godlstein EJ et al. Clostridium difficile infection: a review of current and emerging therapies. Clin Inf Dis. 2015;60(2):S98-S107.
- Ligaarden SC et al. A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomized controlled trial. BMC Gastroenterol. 2010;10:16.
- Ducrotte P et al. Clincal trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome. World J Gastroenterol. 2012;18(30):4012-4018.
- http://www.worldgastroenterology.org/guidelines/global-guidelines/probiotics-and-prebiotics. Accessed October 11, 2019.
- Probiotic Chart. http://www.usprobioticguide.com/PBCIntroduction.html?utm_source=intro_pg&utm_medium=civ&utm_campaign=USA_CHART. Accessed October 11, 2019.
Melissa Blake, BSc, ND is the Manager of Curriculum Development at Metagenics. Dr. Blake completed her pre-medical studies at Dalhousie University in Halifax, Nova Scotia and obtained her naturopathic medical training from the Canadian College of Naturopathic Medicine. Dr. Blake has over 10 years of clinical experience, specializing in the integrative and functional management of chronic diseases.