Article from Townsend Letter 
Some Thoughts About Using Probiotics
by Alan R. Gaby, MD

 

Some Thoughts About Using Probiotics

Probiotics are bacteria or yeast organisms that may have beneficial effects on human physiology and health. Probiotic organisms are believed to work in part by enhancing digestion and immune function, by competing with pathogenic microorganisms for binding sites on mucosal surfaces, and by producing chemicals that inactivate or kill pathogens or have other desirable effects.

Probiotics appear to be useful for preventing or treating a wide range of health conditions, including constipation, irritable bowel syndrome, inflammatory bowel disease, infantile colic, antibiotic-associated diarrhea, various types of infections, cirrhosis, nonalcoholic fatty liver disease, and vaginitis. This editorial provides some thoughts about how to use probiotics safely and effectively.

Different Strains May Be Preferable for Different Conditions

A wide range of probiotic strains are commercially available, and it cannot be assumed that their effects are the same or even similar. The normal bacterial flora differs substantially in different parts of the body, and the capacity of specific probiotic organisms to exert a beneficial effect may vary at different sites. For example, while Lactobacillus rhamnosus GG has been found to be useful for preventing and treating certain gastrointestinal conditions, it was not effective at colonizing the vaginal mucosa.1 In contrast, L. rhamnosus GR-1 and L. reuteri RC-14 were relatively effective at colonizing the vaginal mucosa, and these organisms have been used successfully for preventing and treating vaginitis2,3 and recurrent urinary tract infections.4

It would seem that the most logical approach when treating a particular condition is to use the specific probiotic preparations that have been found to be effective for that condition. If those strains are not commercially available, a reasonable alternative might be to use a product that has demonstrated efficacy for other conditions in the same body system as the condition being treated (e.g., gastrointestinal, genitourinary, nasopharyngeal, or dermatological).

Same Strain, Different Manufacturer, Different Effects

While it is logical to recommend the same probiotic product that was found to be effective in clinical trials, identifying that product among the commercially available options is not always straightforward. For example, one study found that different commercial sources of the same probiotic strain (L. rhamnosus GG) differed to some extent in their biological properties. These differences may have been due to differences in the manufacturing process.5

  1. rhamnosusGG (also calledL. GG) is one of the most widely used probiotic strains. Numerous studies have found it to be useful for treating acute diarrhea in children, antibiotic-associated diarrhea (including Clostridium difficile), functional abdominal pain, irritable bowel syndrome, gastrointestinal symptoms associated with systemic sclerosis, and nonalcoholic fatty liver disease in children. It was also effective in some studies for preventing dental caries, respiratory tract infections in children attending daycare centers, and pulmonary exacerbations in people with cystic fibrosis. However, not all of the studies have been positive.

It is possible that the conflicting results in different studies were due in part to the use of products from different manufacturers, although that possibility is difficult to investigate because research papers often do not mention the source of the product. I have typically used the Culturelle brand of L. rhamnosus GG, because it is manufactured according to the original production method and it contains the preparation that has been subjected to the most research.6 In contrast, some of the other commercially available L. rhamnosus GG products appear to have been manufactured by a different method.

Another well-studied probiotic is a proprietary product that consists of four strains of lactobacilli, three strains of bifidobacteria, and one strain of Streptococcus salivarius subsp. thermophilus. Originally sold under the name VSL#3, this product has been shown to induce remission and to prevent relapses in patients with ulcerative colitis,7-9 and to prevent hepatic encephalopathy in patients with cirrhosis.10,11

VSL#3 was invented over 25 years ago by Dr. Claudio De Simone and was produced by a United States company, VSL Pharmaceuticals. In 2014, Dr. De Simone left VSL Pharmaceuticals and began working with another US company, ExeGi Pharma, to produce the same product as the original VSL#3 preparation. In 2016, VSL Pharmaceuticals announced that they had moved the production of VSL#3 to Italy and, unlike the original VSL#3 product, they no longer used dairy products in the manufacturing process.

The new product made by ExeGi Pharma is sold under the brand name Visbiome in the US, Vivomixx in Europe, and DeSimone Formulation in Korea. The brand name VSL#3 is now applied to the formulation manufactured in Italy by CSL/Nutrilinea. Like the original VSL#3 product, Visbiome is manufactured using dairy products.

A recent study found significant differences in vitro between the effects of Visbiome (the original VSL#3 product) and the new VSL#3 product made in Italy. Specifically, the production and metabolism of 1,3-dihydroxyacetone differed between products, resulting in a 40-fold higher 1,3-dihydroxyacetone concentration in the Italian product than in Visbiome. In vitro, 1,3-dihydroxyacetone reduced the viability and decreased the rate of repair of rat intestinal epithelial cells.12 In addition, the VSL#3 product produced in Italy had adverse effects in vitro on several measures of epithelial barrier function.

In contrast, Visbiome had either positive effects or no effect on these parameters.13 These differences could conceivably be due to differences in epigenetic modulation of bacterial genes, which could influence the metabolic effects of the organisms. The available evidence suggests that Visbiome (not Italian-made VSL#3) should be used for conditions that have been reported in the medical literature to respond to VSL#3.

Safety Considerations

Probiotic organisms are well tolerated by most people, although individuals with milk protein allergy may experience allergic or anaphylactic reactions to probiotics grown on milk protein.14 An analysis of 11 probiotic products available in Spain revealed that one contained milk protein despite claiming to be milk-free, and two others contained milk protein without providing such information on the label.15 Allergic reactions to Saccharomyces boulardii (a probiotic yeast organism) have also been observed.16

In addition, there have been reports of vaginitis due to S. cerevisiae (brewer’s or baker’s yeast), which presumably resulted from fecal-to-genital migration following oral ingestion of the organism. Saccharomyces vaginitis was clinically indistinguishable from vaginitis due to Candida albicans, and often required prolonged treatment because of reduced sensitivity to common antifungal agents (with outright resistance to fluconazole).17

The most serious adverse effects of probiotics have been Lactobacillus bacteremia (from ingestion of Lactobacillus strains) and fungemia or invasive fungal disease (from ingestion of S. boulardii or S. cerevisiae). In some cases these infections were fatal or appeared to contribute to the patient’s death.

Predisposing factors to probiotic-induced bacteremia or fungemia include critical illness, severe underlying disease, compromised immune function, a damaged gastrointestinal barrier, prosthetic heart valves, indwelling central venous catheter, administration of multiple antibiotics, and prolonged treatment with probiotics or use of excessive dosages. Probiotics should be avoided or used with caution in patients who have these predisposing factors.

References

  1. Gardiner GE, et al. Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but not L. rhamnosus GG in the human vagina as demonstrated by randomly amplified polymorphic DNA.Clin Diagn Lab Immunol. 2002;9:92-6.
  2. Martinez RC, et al. Improved treatment of vulvovaginal candidiasis with fluconazole plus probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14.Lett Appl Microbiol. 2009;48:269-274.
  3. Anukam K, et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial.Microbes Infect. 2006;8:1450-1454.
  4. Beerepoot MA, et al. Lactobacilli vs antibiotics to prevent urinary tract infection. A randomized, double-blind, noninferiority trial in postmenopausal women.Arch Intern Med. 2012;172:704-712.
  5. Grzeskowiak L, et al. Manufacturing process influences properties of probiotic bacteria.Br J Nutr. 2011;105:887-94.
  6. Haldeman M. Product Development, Scientific Affairs, i-Health, Inc. Personal communication, March 5, 2020.
  7. Shen J, et al. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: meta-analysis of randomized controlled trials.Inflamm Bowel Dis. 2014;20:21-35.
  8. Miele E, et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis.Am J Gastroenterol. 2009;104:437-43.
  9. Sood A, et al. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis.Clin Gastroenterol Hepatol. 2009;7:1202-9.
  10. Lunia MK, et al. Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial.Clin Gastroenterol Hepatol. 2014;12:1003-8.e1.
  11. Dhiman RK, et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial.Gastroenterology. 2014;147:1327-37.e3.
  12. Trinchieri V, et al. Efficacy and safety of a multistrain probiotic formulation depends from manufacturing.Front Immunol. 2017;8:1474.
  13. Palumbo P, et al. The epithelial barrier model shows that the properties of VSL#3 depend from where it is manufactured. Endocr Metab Immune Disord Drug Targets 2019;19:199-206.
  14. Moneret-Vautrin DA, et al. Probiotics may be unsafe in infants allergic to cow’s milk.Allergy. 2006;61:507-8.
  15. Martín-Munoz MF, et al. Anaphylactic reaction to probiotics. Cow’s milk and hen’s egg allergens in probiotic compounds.Pediatr Allergy Immunol. 2012;23:778-84.
  16. Hwang JB, et al. Probiotic gastrointestinal allergic reaction caused by Saccharomyces boulardii.Ann Allergy Asthma Immunol. 2009;103:87-8.
  17. Sobel JD, et al. Vaginitis due to Saccharomyces cerevisiae: epidemiology, clinical aspects, and therapy.Clin Infect Dis. 1993;16:93-9.

Author bio

Alan R. Gaby, MD, received his undergraduate degree from Yale University, his M.S. in biochemistry from Emory University, and his M.D. from the University of Maryland. He was in private practice for 19 years, specializing in nutritional medicine.

He is past-president of the American Holistic Medical Association who has given expert testimony to the White House Commission on Complementary and Alternative Medicine on the cost-effectiveness of nutritional supplements. He is the author of Preventing and Reversing Osteoporosis (Prima, 1994), The Doctor’s Guide to Vitamin B6 (Rodale Press, 1984), the co-author of The Patient’s Book of Natural Healing (Prima, 1999). Dr. Gaby has written numerous scientific papers in the field of nutritional medicine. He has been the contributing medical editor for the Townsend Letter for Doctors since 1985, and was contributing editor for Alternative Medicine Review from 1996 to 2010.

Over the past 36 years, Dr. Gaby has developed a computerized database of more than 28,000 individually chosen medical journal articles related to the field of natural medicine. He was professor of nutrition and a member of the clinical faculty at Bastyr University in Kenmore, Washington, from 1995 to 2002. He is Chief Science Editor for Aisle 7 (formerly Healthnotes, Inc.) and has appeared on the CBS Evening News and the Donahue Show. In 2010, Dr. Gaby completed a 30-year project: the textbook Nutritional Medicine. Over the past six years, he has worked on completing the updated second edition of Nutritional Medicine.

Consult your doctor before using any of the treatments mentioned in this article.

Reprinted with permission from the July 2020 Townsend Letter & Townsend e-Letter 11 Feb 2023 and Alan R. Gaby, MD.

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