Pharmacist's Letter/Prescriber's Letter ;22(7):220704.

Probiotics are live, "friendly" organisms that live in the intestine. They help decrease "unfriendly" bacteria and viruses that cause diseases such as diarrhea. Examples of probiotics include Lactobacillus, Bifidobacteria, and Saccharomyces boulardii.

For what conditions are probiotics effective?

Certain probiotics have been shown to be beneficial for preventing and treating some types of diarrhea, including diarrhea caused by antibiotics. Probiotics also seem to help some bowel diseases such as ulcerative colitis and irritable bowel syndrome.

Some yogurts that contain the probiotic Lactobacillus might also help women who get frequent vaginal yeast infections. However, eating yogurt doesn't seem useful for preventing vaginal yeast infections caused by antibiotics.

What probiotic products are available, and how do I choose one?

Not all probiotic products are the same. Some do not contain what they say on the label. Others do not contain enough live organisms to be effective. And some probiotics work better for certain conditions than others. Clearly, product selection is important.

To prevent diarrhea caused by antibiotics, choose Culturelle (Lactobacillus GG) or Florastor (Saccharomyces boulardii). You can also try these products for prevention of traveler's diarrhea. Start taking them a few days before travel, and continue them for the duration of your trip.

Yogurt is a source of probiotics, but not all yogurts contain the right kinds of organisms. Choose a product with the National Yogurt Association's "Live and Active Cultures" seal on the label (e.g., Dannon, Yoplait). You will need to eat about 8 oz twice daily to prevent antibiotic-associated diarrhea. To prevent frequent vaginal yeast infections, try 6 oz daily of a yogurt containing Lactobacillus acidophilus.

VSL#3 is a probiotic mixture used for certain bowel conditions such as ulcerative colitis and irritable bowel syndrome. It may help reduce stomach pain and bloating if you have irritable bowel syndrome.

What are the side effects of probiotics?

In some people, probiotics can cause stomach and intestinal upset, including gas and bloating. These usually improve with time.

Are there any drug interactions with probiotics?

Antibiotics are used to reduce harmful bacteria in the body. They can also reduce friendly bacteria like Lactobacillus and Bifidobacteria. If you are using these probiotics or yogurt, you should take them at least two hours before or after the antibiotic.

The calcium in yogurt can also decrease the effectiveness of some antibiotics. You may need to allow more than two hours between eating your yogurt and taking your antibiotic. Check with your pharmacist for the best way to avoid this interaction.

Saccharomyces boulardii is a fungus. Medications for fungal infections help reduce fungus in and on the body. Taking Saccharomyces boulardii with medications for fungal infections can reduce its effectiveness. Some medications for fungal infections include Diflucan, Lamisil, Sporanox, and others.

Who should not take probiotics?

For healthy people, routine use of probiotics to maintain bowel health is unnecessary. There is a small risk of infection with probiotics. If you have a weakened immune system you should not take probiotics unless you've checked with your healthcare professional. If you are pregnant or breastfeeding, you should get approval from your healthcare professional before taking any probiotic other than yogurt.

Comparison of Common Probiotic Products

Helpful Notes:

a.        Brand used in studies

b.        Also referred to as Bifidus Regularis (U.S. product) or B. lactis (Canadian product).

c.        Possibly Effective: Reputable references suggest that the product might work for the given indication based on one or more clinical trials giving positive results for clinically relevant end-points.

d.        Likely Effective: Reputable references generally agree that the product is effective for the given indication, based on two or more randomized, controlled, clinical trials involving several hundred to several thousand patients, giving positive results for clinically relevant end-points and published in established, refereed journals.

e.        Separate from antibiotics by two hours. Antibiotic may kill bacterial probiotics.

f.         Study used Perenterol, a similar product not readily available in North America.

g.        Possibly Ineffective: Reputable references suggest that the product might not work for the given indication based on one human study giving negative results for clinically relevant end-points.

h.        Insufficient Evidence: There is not enough reliable scientific evidence to provide an Effectiveness Rating.

Information for Health Professionals:

Probiotics

Probiotics, Beneficial Microbes

Probiotics are live organisms that are ingested to provide therapeutic or preventative benefit for the host. The most commonly used are the lactic acid-producing bacteria: bifidobacteria and lactobacilli. Probiotics also include the yeast Saccharomyces boulardii.

Beneficial microbes such as bifidobacteria live in the intestinal ecosystem with potentially pathogenic bacteria. Beneficial microbes prevent the overgrowth of "bad bacteria" by producing antimicrobial agents. Additionally, beneficial microbes competitively limit pathogenic bacterial overgrowth by occupying receptor sites and vying for space and nutrients. Beneficial microbes may also increase intestinal production of mucin, which stimulates the production of mucus, forming a protective barrier on the intestinal lining.^1-3

Diarrhea can result from an imbalance between beneficial and pathogenic microbes. Antibiotics and illness can tip the balance favoring pathogenic bacteria. Probiotics are given to recolonize the intestine with beneficial microbes.^1-3

In order to be effective, probiotics must be able to withstand a wide range of pH variation. Many microbes cannot withstand the protective acid barrier of the stomach and the effects of bile. An effective probiotic also must be able to colonize the gut and be able to attach to the intestinal epithelium. Additionally, the probiotic should not disturb healthy intestinal microbes.¹

Probiotic Bacteria and Yeasts

Bifidobacteria are anaerobic, rod-shaped, gram-positive bacteria. Bifidobacteria are the most prominent beneficial microbes in the colon. Bifidobacteria produce antimicrobial substances that have a broad spectrum of antimicrobial activity.^4,5

Bifidobacteria that are commonly used as probiotics include Bifidobacterium longum, B. breve, B. infantis, B. bifidum, B. lactis, and B. adolescentis.⁵ Bifidobacteria supplements are most commonly combined with other probiotics.

Lactobacilli are a group of gram-positive rods that are obligate and facultative anaerobes. Lactobacilli are in the colon in much lower numbers than bifidobacteria. Lactobacilli also produce a range of antimicrobial agents. Lactobacilli that are commonly used as probiotics are Lactobacillus rhamnosus, L. acidophilus, L. casei, L. reuteri, and L. bulgaricus.⁵ Lactobacilli supplements are used alone or in combination with other probiotics.

Other bacteria sometimes used as probiotics include Streptococcus thermophilus and Enterococcus faecium.⁵ The yeasts Saccharomyces boulardii and S. cerevisiae are also used.

Probiotics for Diarrhea

Probiotics may be useful as adjunctive treatment of adults and children with infectious diarrhea. Several species of Lactobacillus seem to reduce the duration of diarrhea, particularly in rotaviral infections.^6,7 Typically 10,000 to 100,000 million colony forming units (cfu) are given twice daily.⁶

For antibiotic-associated diarrhea, Lactobacillus rhamnosus GG, S. boulardii, and probiotic mixtures appear to be effective prophylactic agents.^8,9 Given along with antibiotics, these probiotics can reduce the incidence of diarrhea by about 60% to 65%.⁸ The effectiveness of probiotics on treatment of antibiotic-associated diarrhea is less clear. S. Boulardii as an adjunct might be useful for recurrent Clostridium difficile-associated diarrhea.^9,10

Probiotics may reduce diarrhea during Helicobacter pylori eradication treatment.¹¹ But they don't seem to be effective alone or with standard therapy for eradicating H. pylori.¹²

Results of studies looking at probiotics for traveler's diarrhea have been mixed. Studies using Lactobacillus species have shown very modest or no effect. Combination treatment with L. acidophilus, L. bulgaricus, B. bifidum, and S. thermophilus may be better for reducing the frequency of diarrhea, but there have been no head-to-head comparisons with single agents. S. boulardii also may modestly reduce traveler's diarrhea.^1,2,12

Preliminary clinical research suggests that probiotics might also be useful for radiation-induced diarrhea and diarrhea associated with tube-feedings.^1,2,12 HIV-associated diarrhea may also benefit.⁷

Other Probiotic Uses

B. infantis may benefit abdominal discomfort, bloating, and difficult bowel movements in irritable bowel syndrome.^7,13 There is contradictory evidence about effectiveness of Lactobacillus for irritable bowel.

Activia yogurt containing Bifidobacterium animalis (labeled as Bifidus Regularis [U.S.] and B. lactis [Canada]) is marketed to regulate the digestive system. This product has been shown to speed gut transit time.^14-16 However, its efficacy for constipation, irritable bowel, or any gastrointestinal disease or symptom has not been studied. People who like yogurt can try Activia to see if it helps with bloating or difficulty passing stool. Suggest one to three servings daily for at least ten to 14 days.^14-16 Effects on gut transit time last at least two weeks after consumption.^15,16

Pouchitis is a complication of surgery for ulcerative colitis. Continuous treatment with Lactobacillus, Bifidobacterium, and Streptococcus (VSL#3) for one year may maintain remission in 85% of patients.⁷ VSL#3 has also shown efficacy for achieving and maintaining remission in ulcerative colitis.^7,17,18 Data for probiotic benefit in Crohn's is conflicting.⁷

Atopic diseases such as atopic dermatitis (eczema), allergic rhinitis, and asthma might benefit from probiotics. Probiotics may enhance the breakdown of antigens and improve intestinal barrier function. They may also suppress proinflammatory immune responses. Clinical trials for atopic dermatitis are encouraging.^7,19,20 L. fermentum, Lactobacillus CG, and B. lactis may help reduce symptoms in children.^7,21 Probiotics given to infants at risk for atopic dermatitis seem to prevent development of allergic symptoms up to four years after treatment.²²

Neither oral nor vaginal probiotics seem to prevent vaginal yeast infections caused by antibiotics.^7,23 Some yogurts are possibly effective (taken orally) for prevention of recurrent vaginal candidiasis.⁷ The efficacy of probiotics for treatment of bacterial vaginosis and prevention of urinary tract infections is unclear.^7,24

Probiotic Sources

Probiotics are available in a variety of forms. Yogurt is often suggested as a probiotic source, but the two probiotics used in the fermentation of milk to yogurt, L. bulgaricus and S. thermophilus, may not survive transit through the gut to the colon, eliminating their probiotic effects. Other more acid-resistant bacteria such as L. acidophilus are sometimes added to yogurt to give it probiotic effects.²⁵ Most Bifidobacterium animalis ingested survives transit through the gastrointestinal tract and is recovered in the stool.²⁶ The National Yogurt Association's criteria for "live and active culture yogurt" require that the product contain 100 million organisms per gram that remain active throughout the stated shelf life.²⁵

Bacteria such L. casei, L. acidophilus, and L. reuteri are found in some probiotic drinks. Fermented dairy drinks such as DanActive in the U.S. and Bio-K Plus in Canada that are marketed for their probiotic content are beginning to become available. Yogurt smoothies that contain probiotics (Stonyfield Farm Yogurt Smoothie) are also available. Probiotic drinks are more widely used in Europe where probiotic fortified fruit juices are available.²⁷

Probiotics in capsule, tablet, and powder form abound. These contain a wide variety of probiotic bacteria and yeast. Culturelle capsules contain the patented bacterium Lactobacillus GG, which is a subspecies of L. rhamnosus. Florastor capsules contain S. boulardii. Many products contain a combination of probiotics, usually L. acidophilus plus varying numbers of other probiotics. There is no conclusive evidence that fresh preparations are more effective than freeze-dried products.

Safety

Infections caused by lactobacilli, bifidobacteria, and Saccharomyces are extremely rare in humans. There are two reported cases of infections with L. rhamnosus. Thirty cases of Saccharomyces fungemia have been reported, all in very ill intensive care unit (ICU) patients with indwelling catheters. Most infections occurred when packets of Saccharomyces were used or Saccharomyces capsules were opened at bedside.^28,29

The risk of infection caused by probiotics appears to be minimal, including consumption by people with compromised immune function.^27,28

The Bottom Line

For healthy people, routine intake of probiotics "to maintain a healthy digestive system" is unnecessary. For specific indications, such as to prevent antibiotic-associated diarrhea, a short course of probiotics may be useful.

Probiotics appear to be useful as adjunctive treatment of adults and children with infectious diarrhea. [Evidence level A; High-quality meta-analysis (quantitative systematic review)].⁶

Probiotics also appear to prevent antibiotic-associated diarrhea. [Evidence level A; High-quality meta-analysis (quantitative systematic review)].⁸ The probiotic S. boulardii appears to be useful for adjunctive treatment of recurrent Clostridium difficile infections. [Evidence level A; High-quality randomized controlled trial (RCT); meta-analysis].^9,10

Research on the use of probiotics for other types of diarrhea is less conclusive.

Probiotics are regulated as dietary supplements and foods, which raises concerns about quality. Culturelle and Florastor (250 mg, Biocodex) are the best studied.

Expiration dates are particularly important for probiotic products. Some probiotic products have short shelf-lives.²⁷ Questions about the numbers of viable bacteria after manufacture are a concern. Theoretically, refrigeration might extend viability.

Remind patients that probiotics only temporarily colonize the intestine. For chronic conditions, it is likely that probiotics must be taken chronically to be effective.⁵

Advise patients who are taking bacterial probiotics (e.g., Lactobacillus, Bifidobacterium) with antibiotics to separate the products by two hours. The yeast Saccharomyces could be rendered ineffective by antifungals (e.g., Diflucan, Sporanox), but no recommendations for dose separation are available.

In very rare cases, probiotics can be pathogenic. Consider benefit versus risk in immunocompromised patients.

Levels of Evidence

In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish.

Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.

Project Leaders in preparation of this Detail-Document: Gayle Nicholas Scott, Pharm.D., BCPS, ELS, Assistant Editor and Melanie Cupp, Pharm.D., BCPS

References

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Cite this Detail-Document as follows: Probiotics. Pharmacist's Letter/Prescriber's Letter 2006;22(7):220704.