Probiotics for Diarrhea or Eczema: Updates
By David Kiefer, MD, Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; Adjunct Faculty, Bastyr University, Seattle. Dr. Kiefer reports no financial relationships relevant to this field of study.
Introduction
Evidence for the use of probiotics in a variety of medical conditions continues to accumulate. Defined as live, nonpathogenic microorganisms that benefit the host (humans, in this case) when provided in adequate amounts,1-3 probiotics comprise a variety of species of bacteria and one yeast, and are found in mixed or single species preparations, recommended in a variety of dosages. This review will update two prior issues of Alternative Medicine Alert that addressed probiotic therapy,4,5 focusing on the use of probiotics in gastrointestinal and atopic disease. The previous article in this issue reviews data regarding the use of probiotics in gynecologic conditions.
Physiology
Both in vitro and in vivo research have demonstrated that probiotic species outcompete pathogenic bacteria for binding sites in the gastrointestinal tract and help to strengthen the gastrointestinal epithelial barrier.1-3 Probiotics also, predictably, modify the gastrointestinal flora, and can lead to systemic and local changes in immune system function.1,2 Relevant to childhood atopy, probiotics may help temper excessive immune system and inflammatory responses to foreign antigens through changes in various cytokines, decrease exposure to dietary antigens by gastrointestinal macromolecule alterations, and improve serum immunoglobulin A responses.2,6,7
Probiotic species with known beneficial physiological effects include numerous species of Lactobacillus (acidophilus, rhamnosus, bulgaricus, reuteri, and casei), Bifidobacterium species, Streptococcus species, Enterococcus faecium, and the yeast, Saccharomyces boulardii.2,8
Clinical Trials
Diarrhea. There are numerous clinical studies describing the effects of probiotics on the prevention or treatment diarrhea of varying etiologies and in different demographics. Of note, due to variations in study design, probiotics strains used, doses administered, and formulation, the results of the different studies are difficult to compare. Nonetheless, one meta-analysis of 34 studies found that probiotics significantly reduced the risk of acute diarrhea of diverse causes by 34% (confidence interval [CI] 8-53%, P = 0.013).9 The effect was similar across probiotic species, including L. rhamnosus, L. acidophilus, L. bulgaricus, and S. boulardii, though the overall effect seemed to be higher in children than for adults. Another systematic review of probiotics for the prevention of childhood diarrhea supported a positive preventive effect, primarily in the dose range of 5-40 billion colony forming units (cfu) daily of either L. rhamnosus or S. boulardii.10
In addition to this preventive role, probiotics may function in the treatment of acute infectious diarrhea in both children and adults. A systematic review found that the duration of symptoms may be shortened by about 30 hours when using probiotics for acute diarrhea.11 An example of a specific intervention examined in this context is a three times daily dosage of 1 billion cfu of E. faecium for adults with acute diarrhea.12 In addition, clinical trials have shown that different probiotic strains, including Lactobacillus species (reuteri, rhamnosus, or casei) and S. boulardii are useful in reducing the severity and duration of acute infectious diarrhea in children; the oral administration of probiotics shortens the duration of acute diarrheal illness in children by approximately 1 day.13 The evidence from studies on viral gastroenteritis (e.g., rotavirus) is more convincing than the evidence for bacterial or parasitic infections.13
The coadministration of some probiotic strains may prevent antibiotic-associated diarrhea (AAD).14 The same meta-analysis that addressed children's infectious diarrhea found that children receiving Lactobacillus species, Streptococcus species, or S. boulardii plus antibiotics had a 30% reduced incidence of AAD when compared to placebo groups.13 In adults, Lactobacillus species and S. boulardii seem to significantly reduce the incidence of AAD.15 Both of these reviews were corroborated by a meta-analysis finding a 52% reduction of AAD in both children and adults taking probiotics (CI 35-65%, P < 0.001).9
For other types of diarrhea, there is less research. A meta-analysis of clinical trials for probiotics in traveler's diarrhea showed that S. boulardii and a mixture of L. acidophilus and Bifidibacterium bifidum prevented traveler's diarrhea, but there was a large variation in methodology between the trials, making it difficult to draw firm conclusions.16 Another meta-analysis failed to find benefits for probiotics in the prevention of traveler's diarrhea.9 Interestingly, probiotics may be useful in the treatment of stress-induced diarrhea,17 as well as the prevention of diarrhea from Clostridium difficile after antibiotic treatment.18
Atopic Dermatitis. Prior issues of Alternative Medicine Alert1,2 detailed clinical trials and conclusions based on the probiotic-eczema medical literature through 2008. At that time, the primary conclusions were that probiotic supplementation in pregnant or breastfeeding women, or for their newborn helps to decrease the incidence and severity of newborn atopic dermatitis, especially if there is a history of atopy in the family.19,20 Common dosing in this context was 5-10 billion cfu, using a variety of single or multiple probiotic species.
Since that time, further clarification about the use of probiotics to prevent or treat atopic disease, either in the perinatal period or after delivery, has surfaced in clinical trials. One recent randomized clinical trial replicated the common methodology for a probiotic intervention for atopy, namely that pregnant women with a family history of atopic disease (n = 112) were randomized to receive probiotics (a blend of species, 4.8 billion cfu daily) from 2 months before delivery to 3 months afterward.21 The prevalence of eczema in the newborn was found to be less in the probiotic group vs placebo at 1 year of age (18.2% vs 40.0%, P = 0.048). This positive effect has not always been replicated in clinical trials, prompting researchers to search for reasons to explain the disparities. For example, it is possible, though not definitively proven, that probiotic supplementation more adequately prevents atopic dermatitis in children who are IgE sensitized, that is, those children who have a positive skin prick test and/or elevated serum IgE levels.22 This conclusion would dovetail with in vitro research documenting cytokine and immune system effects.
With respect to treatment of childhood eczema, a recent meta-analysis of 12 clinical trials did not find any probiotic benefit on symptoms or investigator rating of eczema severity.23 There was, as with other reviews of this topic, a significant heterogeneity of study quality and methodology (including dosing, from 1-100 billion cfu daily, and probiotic species used) that could compromise the final conclusion. Lacking in this review article, and, in fact, the other reviews also mentioned in this article, is a subgroup analysis by dose or species that would help to statistically clarify the relationship of these two important variables to clinical outcome.
Other Conditions
Advances in clinical research have shown, to varying extents, effects of probiotics on numerous different clinical conditions (see Table). It is beyond the scope of this article to fully review the relevant literature but researchers have found some evidence that probiotics may maintain remission from pouchitis in inflammatory bowel disease,24 induce remisison in Crohn's disease,25 help relieve symptoms of allergic rhinitis or asthma,22 and help to prevent the development of acute upper respiratory tract infections from infancy onward.26,27 In addition, probiotic supplementation may improve some, but not all, of the symptoms associated with irritable bowel syndrome.28-29 Not all clinical trials have found benefit; probiotic supplementation for childhood constipation has had mixed results1,30,31 and probiotics do not seem to decrease colonization with vancomycin-resistant E. faecium (a variety of the same species that is part of our normal flora and a constituent of some probiotic supplements) nor help clinical or laboratory findings in hepatic encephalopathy.1
Dosing
It is not possible to suggest a general dosage for probiotics. The dose needed depends greatly on the species, product, and indication. Most of the products employed in research trials contain between 100 million and 10 billion cfu/dose, and used up to 20 billion cfu daily, though higher doses are sometimes recommended for acute indications.2 As a general rule, extrapolating from clinical trials, dosing on the higher end of the dose range (5 billion cfu daily for children and 10 billion cfu daily for adults) would be more likely to yield a positive clinical effect for prevention or treatment of gastrointestinal conditions or atopic dermatitis.2,4
Adverse Effects
Probiotics are considered safe, with a low risk of adverse effects, in healthy individuals.7 Some clinical trials have documented a range of adverse effects, though often similar in incidence to side effects documented in members of placebo groups.23 Mild adverse effects in children may include rash, nausea, gas, flatulence, vomiting, increased phlegm, chest pain, constipation, taste disturbance, and poor appetite, with no serious adverse effects in otherwise healthy children.10,32 In other populations, self-limiting and mild gastrointestinal discomfort or flatulence have been reported.2
There have been case reports of bowel ischemia and sepsis in children, for which some authors believe that probiotics should be relatively contraindicated in certain populations, such as preterm infants, children with short-gut syndrome, immunocompromised children and adults, or in people with "chronic disease," the latter presumably due to decreased immune system function.2,22,23,32
Conclusion
Probiotics comprise a range of species, including bacteria such as Lactobacillus and Bifidobacterium species, and the yeast S. boulardii. The physiological effects of orally administered probiotics, as demonstrated in both in vitro and in vivo research, comprise not only local gastrointestinal effects, such as displacement of pathogenic bacteria and improvement of inter-intestinal cell tight junctions, but systemic improvements in cytokine profiles and immune system function. Clinical trials exist that have explored the use of probiotics for numerous conditions, including diarrhea and atopic dermatitis. The data are convincing for the use of probiotics to prevent both acute infectious diarrhea and antibiotic-associated diarrhea, as well as to treat viral gastroenteritis, helping children (more than adults) to recover approximately one day faster, when used in an average dose of 10 billion cfu daily (5 billion cfu for children). Probiotics seem less likely to help prevent traveler's diarrhea. For atopic dermatitis, there is little doubt that probiotics, begun during pregnancy and continued through the first year of life, help to decrease the prevalence and severity of eczema in newborns born into so-called "atopic families." It is possible that positive probiotic effects are more likely to occur in newborns who are IgE sensitized, but this needs to be further clarified with more clinical trials. The medical literature is mixed on whether probiotics are a useful adjunct in the treatment of already-existing eczema. Adverse effects of probiotics are generally rare and mild, though caution is warranted in select individuals, such as those who are immunocompromised.
Recommendation
Probiotics composed of a mixture of species and dosed at a minimum of 5 billion cfu daily for children and 10 billion cfu daily for adults should be given to anyone on antibiotics, except in the context of severe illness or chronic disease, or in preterm infants, infants with short-gut syndrome, or anyone with a compromised immune system. In addition, children who are at risk of acute diarrheal illness, such as those who attend day care, should ingest daily probiotics, either from food or supplements. Finally, in families with a high prevalence of atopic disease, probiotic supplementation should be considered for inclusion as a part of a pregnant woman's regimen and continued through the early months of a healthy newborn's life, in order to help prevent the development of atopic dermatitis. Convincing clinical trials and physiologic mechanistic work show that probiotic therapy is a generally safe and important therapeutic tool for enhancing gastrointestinal and immune system function.
References
1. Deshpande G, et al. Progress in the field of probiotics: Year 2011. Curr Opin Gastroenterol 2011;27:13-18.
2. Kligler B, Cohrssen A. Probiotics. Am Fam Physician 2008;79:1073-1078.
3. Lomax AR, Calder PC. Probiotics, immune function, infection and inflammation: A review of the evidence from studies conducted in humans. Curr Pharm Design 2009;15:1428-1518.
4. Kiefer D. Yogurt and you? Probiotics and infant atopic dermatitis. Altern Med Alert 2009;12:5-9.
5. Kiefer D. Probiotics to treat childhood eczema: Another useful Lactobacillus strain. Alt Med Alert 2010:13:100-102.
6. Boyle RJ, et al. Probiotics for treating eczema. Cochrane Database Syst Rev 2008;(4):CD006135.
7. Isolauri E, et al. Probiotics in the management of atopic eczema. Clin Exp Allergy 2000;30:1604-1610.
8. Thomas DW, Greer FR and Committee on Nutrition; Section on Gastroenterology, Probiotics and Prebiotics in Pediatrics. Hepatology and nutrition. Pediatrics 2010;126;1217.
9. Sazawal S, et al. Efficacy of probiotics in prevention of acute diarrhoea: A meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis 2006;6:374-382.
10. Johnston BC, et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev 2011;11:CD004827.
11. Allen SJ, et al. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2004;(2)CD003048.
12. Allen SJ, et al. Probiotics for treating acute infectious diarrhoea. Sao Paulo Med J 2011;129:185.
13. Chen CC, Walker WA.Clinical applications of probiotics in gastrointestinal disorders in children. Nat Med J India 2011;24:153-160.
14. Hidding I, Koning C. Probiotics in the prevention and treatment of antibiotic associated diarrhoea. Agro Food Industry Hi-Tech 2005;16:18-20.
15. Verna EC, Lucak S. Use of probiotics in gastrointestinal disorders: What to recommend? Ther Adv Gastroenterol 2010;3:307-319.
16. McFarland LF. Meta-analysis of probiotics for the prevention of travelers diarrhea. Travel Med Inf Dis 2007;5:97-105.
17. Lutgendorff F, et al. The role of microbiota and probiotics in stress-induced gastrointestinal damage. Curr Mol Med 2008;8:282-298.
18. Surawicz CM. Probiotics, antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in humans. Best Pract Res Clin Gastroenterol 2003;17:775-783.
19. Kalliomaki, M, et al. Probiotics during the first 7 years of life: A cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol 2007;119:1019-1021.
20. Boyle RJ, et al. Probiotics for treating eczema. Cochrane Database Syst Rev 2008,(4):CD006135.
21. Kim JY, et al. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: A double-blind, randomized, placebo-controlled trial. Pediatr Allergy Immunol 2010;21(2 Pt 2):e386-e393.
22. Ozdemir O. Various effects of different probiotic strains in allergic disorders: An update from laboratory and clinical data. Clin Exp Immunol 2010;160:295-304.
23. Boyle RJ, et al. Probiotics for the treatment of eczema: A systematic review. Clin Exp Allergy 2009;39:1117-1127.
24 Wall GC, et al. Pharmacotherapy for acute pouchitis. Ann Pharmacother 2011;45:1127-1137.
25. Butterworth, AD, et al. Probiotics for induction of remission in Crohn's disease. Cochrane Database Syst Rev 2008(3):CD006634.
26. Hao Q, et al. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev 2011;9:CD006895.
27. Rautava S, et al. Specific probiotics in reducing the risk of acute infections in infancy a randiomsed, double-blind, placebo-controlled study. Br J Nutr 2009;101:1722-1726.
28. Malone MA. Irritable bowel syndrome. Prim Care 2011;38:433-447.
29. Brenner DM, et al. The utility of probiotics in the treatment of irritable bowel syndrome: A systematic review. Am J Gastroenterol 2009;104:1033-1049.
30. Tabbers MM, et al. Nonpharmacologic treatments for childhood constipation: Systematic review. Pediatrics 2011;128:753-761.
31. Guerra PV, et al. Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: A crossover, double-blind, controlled trial. World J Gastroenterol 2011;17:3916-3921.
32. Boyle RJ, et al. Probiotic use in clinical practice: What are the risks? Am J Clin Nutr 2006:83:1256-1264.
Evidence for the use of probiotics in a variety of medical conditions continues to accumulate.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content