Lactobacillus Acidophilus to Prevent Traveler’s Diarrhea
May 1999; Volume 2: 53-55
By Jay Udani, MD
Traveler’s diarrhea is the most common medical condition affecting travelers to Latin America, Asia, and Africa. Between 20-50% of all travelers to these areas are affected.1
Pathogenesis
Eighty percent of these travelers’ diarrheal illnesses are caused by bacterial enteropathogens, especially Escherichia coli.1 Toxin-producing strains of E. coli are the single largest pathogen responsible for traveler’s diarrhea.2 The most common sources of infection are contaminated food and water.
Usual Prophylaxis
There are many options for the prophylaxis of traveler’s diarrhea, none of which is ideal. Antibiotics such as doxycycline and trimethoprim-sulfa have prophylactic abilities, but also carry the risk of side effects ranging from rashes and photosensitization to Stevens-Johnson syndrome and anaphylaxis. Bismuth subsalicylate has some antimicrobial properties, but must be taken four times a day to be effective. Ciprofloxacin is also used, but this indication is off-label; the drug is expensive; and it may have untoward adverse effects. Prophylactic therapy may also give travelers a false sense of security and may decrease their vigilance in making food selections.1
Some patients are more likely to benefit from prophylaxis than others. On the one hand there are persons in poor health or at higher risk for serious medical problems (immunocompromised, frail elderly, patients with chronic diseases).1 On the other hand, healthy patients may be loath to take any substance as daily prophylaxis.3
Overview
The World Health Organization has included bacterial interference or "Microbial Interference Treatment" (MIT) as part of its program to combat increasing resistance to antibiotics.4 The ability of MIT to combat gram-negative bacteria may make it a useful alternative to antibiotic therapy in selected cases.
Of the more than 400 species of microflora in the human GI tract,5 the most important "friendly" or "probiotic" bacteria are Lactobacilli.
Lactobacilli appear to be a convenient, safe alternative for the prophylaxis of traveler’s diarrhea. In addition, Lactobacilli have been reported to decrease the incidence of colon cancer; restore equilibrium to gut flora after the use of antibiotics; treat candidal vaginal infections; lower serum cholesterol and triglyceride levels; prevent relapses of C. difficile infections; stimulate the immune system; and prevent radiotherapy associated diarrhea.6
Mechanism of Action
Lactobacillus acidophilus, an anaerobic gram-positive bacterium, is the most stable intestinal lactobacillus. It is found throughout the GI tract and requires folic acid, riboflavin, and other B vitamins and amino acids for growth.6
L. acidophilus competes for the same intestinal wall environment as gram-negative bacteria such as E. coli, salmonella, clostridium, shigella, and staphylococcus. Competitive inhibition of intestinal wall attachment sites by L. acidophilus may prevent colonization by these bacteria.6
L. acidophilus also has the ability to hydrolyze lactose rapidly and produce lactic acid.6 This lowers the intraluminal pH and creates a hostile environment for other bacterial species. Lastly, L. acidophilus can produce bacterocins, which are reported to be proteins with antibiotic-like bactericidal properties.6 These bacterocins appear to have specific activity against proteus, staphylococcus, streptococcus, escherichia, and bacillus.
Clinical Trials
The literature was searched using MEDLINE, PUBMED, the Alternative Medicine Literature CD-ROM, and bibliographies. Protection rates were calculated using the formula in Figure 1. Lower protection rates confer a higher rate of protection against diarrhea.
The earliest RCT involving Lactobacilli for traveler’s diarrhea was conducted in 1978 and involved 50 American tourists traveling to Mexico.7 Twenty-six subjects received Lactobacillus and 24 subjects received placebo preparations. The preparations were given for one week, and the incidence of diarrhea was recorded for four weeks. The two groups were similar in incidence of diarrhea for the one week of active treatment and the three weeks following treatment. No information was available on the exact strain used in the treatment or the freeze-drying or preparation process.
A 1990 Finnish study described 820 tourists traveling to Turkey; 418 were randomized to receive placebo and 402 were randomized to receive Lactobacillus GG powder containing 2 billion Lactobacilli.2 The intervention began two days prior to departure. Only 756 patients completed the study, however, and an intent to treat analysis was not performed. Data were obtained from a questionnaire completed on the return flight. A total of 178 patients (46.5%) experienced traveler’s diarrhea in the placebo group, and 153 (41.0%) in the Lactobacilli group. The overall protection rate was 11.8%. Analysis of variance showed no impact of gender, but travel destination did show significant differences. Of the two resort destinations in Turkey, subjects staying in Alanya showed significant protection (P = 0.02), and those staying in Marmaris showed no significant protection.
In 1995, British soldiers deployed to Belize were randomized to receive L. acidophilus or placebo for three weeks.8 Among 282 subjects, no significant difference was seen in the incidence of diarrhea episodes either during the three weeks of treatment or during the one week after treatment was discontinued. Subjects with greater than 90% compliance, whether on placebo or Lactobacilli, were found to have a significant (P < 0.001) decrease in diarrhea (15.4% for compliant, 52.9% for non-compliant). This suggests that good compliance may be associated with other risk-minimizing behavior.
In 1997, a trial was conducted of 245 American patients (126 on Lactobacillus GG and 119 on placebo) who were traveling to developing countries for one to three weeks.3 Patients were instructed to drink only bottled water and to avoid salads, fruits, and fresh vegetables. The risk of having diarrhea on any given travel day was 7.4% for placebo and 3.9% for Lactobacillus GG patients (P = 0.05). The relative risk of diarrhea for patients on Lactobacillus GG was 53% with a protection rate of 47%. Age and gender did not impact the incidence of diarrhea as tested by analysis of variance. The protective effect was amplified (42%) in a subset of patients who had a prior history of traveler’s diarrhea. In these patients, the risk of diarrhea was 29% for placebo and 16.7% for the group who had received Lactobacillus GG.
Lactobacilli have not been tested against standard treatments, noted above.
Adverse Effects and Allergy
To date, there have not been any serious side effects associated with the ingestion of L. acidophilus. Two patients receiving Lactobacillus GG in one of the RCTs3 reported abdominal cramping, but did not stop taking the preparation. It is suggested to limit dosage to fewer than 10 billion viable L. acidophilus daily to decrease the risk of possible mild gastrointestinal disturbance.6
Lactobacillus GG has shown no invasive properties. Trials of over 2,000 healthy normal adult volunteers have shown no harmful effects of Lactobacillus GG.9 Although it has been suggested that Lactobacilli may aggregate platelets, a 1996 study showed that Lactobacillus GG does not increase the risk of spontaneous or physiologically-induced platelet aggregation in vitro.10 No reports of allergic reactions to L. acidophilus were found in the literature reviewed, but L. acidophilus preparations often contain lactose and milk proteins and these substances have an allergic potential in some people.6
Drug Interactions
L. acidophilus should be taken two to three hours after an antibiotic’s dose to prevent killing the L. acidophilus. L. acidophilus has also been found to interfere with the metabolism of sulfasalazine, chloramphenicol, and palmitate by degrading them in the stomach if taken concurrently.6 Lactobacilli are also negatively affected by alcohol, which should not be taken concurrently.5
Preparation
Aside from freeze-dried powder, there are many dietary sources of Lactobacillus. These include fermented milk products such as kefir, yogurt, and cheese, as well as miso and tempeh.5 The pasteurization process kills Lactobacillus.6 When buying milk products for their probiotic (such as L. acidophilus) content, make sure the probiotic bacteria were added after the pasteurization process.
A particular strain of L. acidophilus, the Lactobacillus GG strain, has been isolated from healthy humans because of its ability to resist acid and bile and adhere to human ileal cells.3 The Lactobacillus GG strain has consistent adhesive properties that are independent of the freeze-drying process.4 This strain is often used as the standard in traveler’s diarrhea treatment.
Formulation and Dosage
When dosing L. acidophilus, the preferred species is Lactobacillus GG, which is supplied as a freeze-dried powder. The bacteria should be packaged moisture and contamination free.6 The bottle should be stored and transported at temperatures no greater than 60° F (15° C) or the bacteria will die.6 In other words, it should be refrigerated at all times. Oxygen, moisture, and light are potentially harmful, and thus L. acidophilus should be stored in dark bottles.6
The minimum colony forming units (cfu) per weight in grams (g) should be 2 billion cfu/g.6 Prophylaxis should begin on the day the person leaves the country and should continue for one to two days after returning. Lactobacilli are ingested by mouth in either freeze-dried powder form mixed with water or in capsules containing the freeze-dried form. There are no data to show that continued use beyond three weeks is detrimental, but it is not recommended.1 L. acidophilus counts have been found to remain elevated for up to four weeks after the discontinuation of supplementation.6
Conclusion
The issue of prophylaxis for traveler’s diarrhea is not clear cut, regardless of which drug or bug is used. The most effective prophylaxis for traveler’s diarrhea still remains careful selection of food and beverage while traveling. Of the other choices available, L. acidophilus has the best side effect profile and the easiest dosing regimen, but highly challenging environmental conditions. Patients with a previous history of traveler’s diarrhea may receive greater protection from Lactobacillus GG than do others. The literature on probiotics for the prevention of traveler’s diarrhea is not conclusive, but the more recent and rigorous articles lean toward L. acidophilus as useful in preventing traveler’s diarrhea.
Recommendation
Travelers at high risk for traveler’s diarrhea, travelers whose health may be at risk if they contract traveler’s diarrhea, and travelers who cannot take the time necessary to recover should they become ill with traveler’s diarrhea should consider taking Lactobacillus GG in a dose of 2-10 billion cfu/g per day starting one day before departure and continuing up to two days after their return.
Dr. Udani is a Fellow in Integrative Medicine and Health Services Research at Cedars-Sinai Medical Center in Los Angeles.
References
1. DuPont HL, Ericsson CD. Prevention and treatment of traveler’s diarrhea. N Engl J Med 1993;328:1821-1827.
2. Oksanen PJ, et al. Prevention of traveller’s diarrhoea by Lactobacillus GG. Ann Med 1990;22:53-56.
3. Hilton E, et al. Efficacy of Lactobacillus GG as a diarrheal preventive in travelers. J Travel Med 1997;4: 41-43.
4. Bengmark S. Ecological control of the gastrointestinal tract. The role of probiotic flora. Gut 1998;42:2-7.
5. Murray M. Probiotics: Acidophilus, bifidobacter, and FOS. Am J Nat Med 1996;3:14-19.
6. Anonymous. Lactobacillus Acidophilus 96 Description. HealthPlus CDROM. The JAG Group, 1998.
7. de dios Pozo-Olano J, et al. Effect of a lactobacilli preparation on traveler’s diarrhea. A randomized, double blind clinical trial. Gastroenterology 1978;74: 829-830.
8. Katelaris PH, et al. Lactobacilli to prevent traveler’s diarrhea? N Engl J Med 1995;333:1360-1361.
9. Salminen S, Donohue D. Safety assessment of Lactobacillus strain GG. Nutr Today 1996;31:12s-15s.
10. Moilanen E, et al. Effect of Lactobacillus GG on platelet aggregation. Nutr Today 1996;31:43s-44s.
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