Move Over, Standard Drugs: Probiotics Are Coming!

Jeannette Y. Wick, RPh, MBA, FASCP
Published Online: Monday, July 11, 2011

These trendy microorganisms are marketed heavily to patients, but are they safe and effective for gastrointestinal health? 


Probiotics—live, nonpathogenic, microbial supplements—have been used since 1908, when the Russian biologist Ilya Metchnikov proposed that fermented milk products and their resulting fermenting bacilli gave Bulgarian peasants excellent health and long life. Although his specific theory was later disproved, it started a movement that has recently crescendoed. 1 Today, some researchers believe that probiotics, via carbohydrate fermentation that creates digestible end products, can ameliorate gastrointestinal (GI) distress, influence mood, compete with pathogens, improve energy, and possibly tweak cognition. 2

Market demand has escalated, and many people seek functional foods— foods that are augmented for health— containing probiotics. Traditional uses have been in immune modulation and gastric upset. Increasingly, clinical studies are allowing us to describe probiotic use as “evidence-based.” 3

The most common probiotics used today include lactobacilli, bifidobacteria, and yeast strains (Table). 4Probiotic Microorganisms

Human intestinal microbiota do 2 things: (1) they adhere to host proteins; and (2) they ferment carbohydrates. In doing so, they provide a first line of defense against pathogens, normalize the mucosal barrier, produce short chain fatty acids needed for nutrient absorption and metabolism, extract vitamins, improve immune response, and promote enzyme production.

Each individual’s normal gut microbiota have a fingerprint-like profile—their pattern is unique to the individual, but potentially altered by acute or chronic illness. 3,5 Probiotics are commensals— they live on or within another organism, deriving benefit without causing injury. 3 From the many definitions for probiotics, let’s use this one: probiotics are microorganisms primarily of human origin that when administered in sufficient amounts bestow health benefits on the host and help prevent or improve some diseases. 4 Probiotics live transiently in the gut, and must be consumed every day. 5 Theoretically, probiotics work by producing bacteriocidins like normal gut microbiota do.

Safety

Intuitively, it seems that administering live bacteria or yeast could be dangerous, but all probiotics are subject to safety examinations. Numerous studies have been conducted in critically ill patients— those with ventilator-associated pneumonia, Clostridium difficile prevention, and multiorgan failure, in whom introduction of live bacteria could have the largest adverse impact—but most studies have found either no clinical effect or a positive response with no adverse effects. 5 Few studies have assessed probiotic safety; experts generally agree that studies are needed that evaluate patient vulnerability, specific probiotic dose and duration, and the type and frequency of administration. 6

Common and Growing Uses

Intestinal immune response. Specific probiotic strains can influence intestinal immune function in various ways. They stabilize the intestinal lumen. They may also inhibit inflammatory response, inhibit natural killer cell activity, and influence cytokine production. 2 Based on these findings, they are currently under investigation to treat chemotherapy-induced nucositis, 7,8 diverticular disease, 9 and irritable bowel syndrome. 10,11

Pediatric intestinal disease. From the moment of birth, children are challenged with exposure to bacteria, both pathogenic and nonpathogenic, that they never “saw” in utero. Infants who are breast-fed are predominantly colonized with Escherichia coli and Streptococci bifidobacteria. Those who are formula-fed, however, are predominantly colonized with bifidobacteria, bacteroidi, clostridia, and enterobacteria. For this reason, some formula is now supplemented with probiotics to encourage microbiota that resemble natural colonization more closely. 2

Infectious gastroenteritis. Probiotics use can reduce stool frequency and episode duration in infectious diarrhea. Treatment should begin at symptom onset and continue for at least 5 days, with concurrent aggressive rehydration. 12-14

Antibiotic-associated diarrhea. Antibiotic-associated diarrhea (AAD) is a serious concern, because up to 30% of patients may experience this adverse effect. 2 Several studies have found that probiotics can prevent AAD, but the specific probiotic strain is important. 2,15 Saccharomyces boulardii has been proved helpful in AAD in general and in preventing C difficile%u2500related diarrhea recurrence. Data confirm that Lactobacillus GG (LGG) is also helpful in preventing AAD in children and adults. 15-17 Doses of 5 to 40 billion CFU/day of LGG or S boulardii seem to be most effective in AAD. 18,19

Necrotizing enterocolitis. Necrotizing enterocolitis (NEC), an acquired GI disorder affecting preterm infants, causes mortality and serious morbidity at rates inversely proportional to gestational age and weight at birth. 20 Some studies have shown that preterm infants treated with probiotics have lower risk of NEC and death. Researchers believe that probiotics prevent bacterial migration across the GI mucosa, competitively excluding pathogenic bacteria and enhancing infants’ immune responses. 21 Further study is needed to determine which probiotics produce the best result.

Allergic and atopic diseases. Probiotics can activate a mucosal immune response that extends to sites distant from the intestine, including the respiratory tract. 22 Human studies suggest selected probiotics may reduce some allergic parameters, but the scope of their effects is undefined. The most positive results seem to be in neonates. 23

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in infancy, and is increasing in incidence in industrialized countries. Usually treated symptomatically with moisturizers, corticosteroids, and calcineurin inhibitors, AD’s dry skin, intractable itching, and chronic course of relapses distresses children and their families. AD’s etiology may be related to no or low exposure to microbes in early childhood. Additionally, AD patients also have elevated superantigen-secreting Staphylococcus aureus colonization that has been linked to immunosuppressive activity of regulatory T cells. Certain probiotic strains can modify antigen-presenting cells and regulatory T cell activity. Response to probiotics in AD appears variable, and may depend on the probiotic strain used. 2,24

Respiratory infections. Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb-12 may reduce the risk of early acute otitis media and reduce antibiotic use for recurrent respiratory infections by up to 65% in children younger than 5 years. 25,26 Studies in adults using various Lactobacillus strains, combinations of Lactobacillus and Bifidobacterium strains, a Bifidobacterium strain alone, or a nonpathogenic Enterococcus faecalis strain have found that those who take probiotic supplements generally have as many colds as others do—but their symptom severity and cold duration is generally shorter. 27

Today’s Probiotic Products

Many of today’s products contain probiotic strain mixtures, although there is no evidence that this is beneficial. They are manufactured by treating sucrose, lactose, or plant materials, or are fermented in dairy products. 4 Administered in ways that allow the probiotics to pass through the gastric and ileal environments, they reproduce in the large intestine. In most indications, it is still unclear how much live bacteria or yeast is needed to be most effective, as dose-response studies have not usually been conducted. 2

Conclusion

Pharmacists should be familiar with different types of probiotics. When patients need advice, pharmacists should refer to each product’s labeling and the growing body of clinical literature that supports specific indications. PT

 

Table 2. Dose and Dosage Forms for Probiotic Strains

Probiotic

Available Dose and Dosage form

 

Lactobacillus acidophilus

·        20 million units oral wafers

·        25 million unitscapsules

·        100 million units capsules

·        200 million units soy-basedtablets

·        500 million units capsules

·        >1 billion CFU capsules

·        2 billion strain DDS-1 per g oral powder ≥6 billion CFUcapsules

 
 
 
 

Saccharomyces boulardii lyo

·        250-mg capsules

 

Lactobacillus GG

·        10 billion live cells capsules

·        1 billion live cells oral powder

 

Ganeden BC30

·        2 billion cells capsules

 

Bifidobacterium infantis

·        4-mg capsules

 

Saccharomyces boulardii lyo

·        250-mg oral powder

 

Lactobacillus reuteriProtectis

·        100 million per 5 drops concentrated solution

 

 

Combination Products

·        2 billion CFU Lactobacillus acidophilus, 2 billion CFU Lactobacillus salivarius, 2 billion CFU Lactobacillus plantarum, 2 billion CFU Lactobacillus casei, 2 billion CFU Bifidobacterium lactis capsules

·        4.5 billion CFU Bifidobacterium longum, Lactobacillus rhamnosus A, L plantarum, Saccharomyces boulardii capsules

·        Lyophilized lactic acid ≥ 225 billion units. Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, L plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii capsules

·        1 million CFU L acidophilus and Lactobacillus bulgaricuschewable tablets

·        Lactobacillusand Bifidobacterium 150-mg chewable tablets

·        Mixed culture of L acidophilus and L bulgaricus oral granules

·        1 billion units L acidophilus and Lactobacillus bifidus oral wafers

·        Lyophilized lactic acid ≥900 billion units. S thermophilus, Bbreve, B longum, B infantis, L acidophilus, L plantarum, L paracasei, L delbrueckii oral powder

·        Lyophilized lactic acid ≥450 billion units. S thermophilus, B breve, B longum, Bifidobacterium infantis, L acidophilus, Lactobacillus phantarum, L paracasei, L delbrueckii oral powder

 

CFU = colony forming units

Adapted from reference 28.


Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 


References

1. Dobrogosz WJ, Peacock TJ, Hassan HM. Evolution of the probiotic concept from conception to validation and acceptance in medical science. Adv Appl Microbiol. 2010;72:1-41.

2. Aureli P, Capurso L, Castellazzi AM, et al. Probiotics and health: An evidence-based review. Pharmacol Res. 2011;63:366-376.

3. Hill C. Probiotics and pharmabiotics: Alternative medicine or an evidence-based alternative? Bioeng Bugs. 2010;1:79-84.

4. Figueroa-González I, Quijano G, Ramírez G, Cruz-Guerrero A. Probiotics and prebiotics-perspectives and challenges. J Sci Food Agric [published online ahead of print March 28, 2011]. doi: 10.1002/jsfa.4367.

5. Jacobi CA, Schulz C, Malfertheiner P. Treating critically ill patients with probiotics: beneficial or dangerous? Gut Pathog. 2011;3:2.

6. Sanders ME, Akkermans LM, Haller D, et al. Safety assessment of probiotics for human use. Gut Microbes. 2010;1:164-185.

7. Prisciandaro LD, Geier MS, Butler RN, Cummins AG, Howarth GS. Evidence supporting the use of probiotics for the prevention and treatment of chemotherapy-induced intestinal mucositis. Crit Rev Food Sci Nutr. 2011;51:239-247.

8. Whitford EJ, Cummins AG, Butler RN, et al. Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU). Cancer Biol Ther [published online ahead of print August 2009].

9. Hall J, Hammerich K, Roberts P. New paradigms in the management of diverticular disease. Curr Probl Surg. 2010;47:680-735.

10. Wu JC. Complementary and alternative medicine modalities for the treatment of irritable bowel syndrome: facts or myths? Gastroenterol Hepatol (NY). 2010;6:705-711.

11. Ringel Y, Ringel-Kulka T, Maier D, et al. Probiotic bacteria: probiotic bacteria lactobacillus acidophilus NCFM and bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in

patients with functional bowel disorders-a double-blind study. J Clin Gastroenterol [published online ahead of print 2011].

12. Davidson GP, Butler RN. Probiotics in pediatric gastrointestinal disorders. Curr Opin Pediatr. 2000;12:477-481.

13. Guandalini S. Probiotics for children: use in diarrhea. J Clin Gastroenterol. 2006;40:244-248.

14. Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev. 2010;10(11):CD003048.

15. Song HJ, Kim JY, Jung SA, et al. Effect of probiotic Lactobacillus (Lacidofil® cap) for the prevention of

antibiotic-associated diarrhea: a prospective, randomized, double-blind, multicenter study. J Korean Med Sci. 2010;25:1784-1791.

16. McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010;16:2202-2222.

17. Jones K. Probiotics: preventing antibiotic-associated diarrhea.J Spec Pediatr Nurs. 2010;15:160-162.

18. Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr. 2006;83:1256-1264.

19. Johnston BC, Supina AL, Ospina M, Vohra S. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2007;(2):CD004827.

20. Morgan JA, Young L, McGuire W. Pathogenesis and prevention of necrotizing enterocolitis. Curr Opin Infect Dis. 2011;24:183-189.

21. Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. 2011;3:CD005496.

22. Forsythe P. Probiotics and lung diseases.Chest. 2011;139:901-908.

23. Gourbeyre P, Denery S, Bodinier M. Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions. J Leukoc Biol [published online ahead of print January 13, 2011].

24. Fölster-Holst R. Probiotics in the treatment and prevention of atopic dermatitis. Ann Nutr Metab. 2010;57(suppl)16-9 [published online ahead of print September 8, 2010].

25. Leyer GJ, Li S, Mubasher ME, Reifer C, Ouwehand AC. Probiotic effects on cold and influenza-like symptom incidence and duration in children. Pediatrics. 2009;124:e172-e179.

26. Rautava S, Salminen S, Isolauri E. Specific probiotics in reducing the risk of acute infections in infancy--a randomised, double-blind, placebo-controlled study. Br J Nutr. 2009;101:1722-1726.

27. Vouloumanou EK, Makris GC, Karageorgopoulos DE, Falagas ME. Probiotics for the prevention of respiratory tract infections: a systematic review. Int J Antimicrob Agents. 2009;34:197.e1-e10.

28. eFacts. Probiotics. http://tinyurl.com/63e2ydj. Published 2011. Accessed May 6, 2011.



Related Articles
Latest Issues
$auto_registration$