Probiotics
Lactobacillus spp. (eg, L. acidophilus , L. casei , L. rhamnosus , L. bulgaricus , L. plantarum , L. helveticus ), Bifidobacterium spp. (eg, B. bifidum , B. longum , B. breve , B. infantis ), Sacchromyces boulardii , Streptococcus salvarius , Enterococcus faecium
Yogurt, sour milk, VSL-3, Indian yogurt, various commercial preparations
 
Clinical Overview
Uses
Common uses include treatment of acute/infectious diarrhea, antibiotic-associated diarrhea, immunity/allergy, respiratory and urinary tract infections, and vaginosis. Each agent or preparation may have unique actions. Despite the widespread availability of probiotic products, few commercially available preparations are supported by placebo-controlled, double-blind studies, and the results of in vitro studies cannot be extrapolated to in vivo situations.

Dosing
Daily intake of oral probiotic preparations usually is recommended, although some trials have used twice-weekly dosing. Preparation strength commonly is described per million/billion colony-forming units/capsule.

Contraindications
The use of probiotics is not advised in patients at risk for opportunistic infections and in those with badly damaged GI tracts.

Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Trials investigating probiotics in the form of vaginal douches have been conducted in pregnant women.

Interactions
None well documented.

Adverse Reactions
Probiotics are considered relatively safe. There are isolated reports linking probiotics to adverse reactions.

Toxicology
No data.

 
History
A long history exists for the use of probiotic preparations. Abraham's longevity was attributed to drinking sour milk in the Old Testament of the Bible, and Roman history (76 BC) describes fermented milk as a remedy for gastroenteritis. In 1916, experiments were conducted to implant Escherichia coli as a means of fighting pathogenic intestinal flora. 1
In 1965, the term probiotic was first used when describing “substances secreted by one microorganism which stimulates the growth of another.” 1,  Revised versions of the definition have appeared in literature to accommodate mechanisms of action and components other than bacteria. 1,  , 2,  An all-encompassing version has been proposed as follows: “A preparation of or a product containing viable, defined microorganisms in sufficient numbers, which alter the microflora (by implantation or colonization) in a compartment of the host, and by that exert beneficial health effects in this host.” 1,  Concepts of prebiotics and synbiotics also have been discussed by researchers. 1
 
Uses and Pharmacology
Reports describe the following multiple mechanisms by which probiotics may exert their action: production of pathogen-inhibitory substances, inhibition of pathogen attachment, inhibition of the action of microbial toxins, stimulation of immunoglobulin A, trophic effects on intestinal mucosa.
Each agent or preparation may have unique actions. 2,  Despite the widespread availability of probiotic products, few commercially available preparations are supported by placebo-controlled, double-blind studies, and the results of in vitro and animal experiments cannot be extrapolated to in vivo situations. 2,  , 3,  , 4
GI conditions   Studies examining the effect of probiotics on the healthy adult GI tract, in contrast to the diseased state, have generally found no effect or only minor effects with no residual activity. 5,  , 6,  , 7,  , 8
Helicobacter pylori eradication   Clinical trials to date have not convincingly shown probiotics to be effective in eradicating H. pylori , with only a trend toward increased eradication when used in conjunction with antibiotic therapy.
L. casei and Bifidobacterium lactis have shown in vitro activity against H. pylori . However, evidence for activity of L. acidophilus is conflicting. 9,  , 10,  , 11
A reduction in the incidence of adverse reactions from triple and quadruple H. pylori treatment regimens, and consequently improved compliance, has been demonstrated with preparations containing Bifidobacterium 12 and L. casei . 13
GI inflammatory diseases   Clinical trials vary in quality and results are conflicting.
Trials examining the preparation VSL-3 (containing 4 lactobacilli strains, 3 bifidobacilli strains, and S. salvarius ) in pouchitis and acute mild/moderate ulcerative colitis have shown positive effects. Relapse rates were reduced in pouchitis, and time to relapse and percentage of patients achieving remission were better in study patients versus placebo. 14,  , 15 In another long-term trial, clinical symptoms were improved in patients with mild/moderate ulcerative colitis who took a preparation of B. bifidum , B. breve , and L. acidophilus for 1 year compared with placebo. 16
A case-control study showed improved symptoms in patients with irritable bowel syndrome taking L. acidophilus , L. helevticus , and Bifidobacterium spp. after 12 weeks. 17
Studies of probiotics in patients with Crohn disease have largely shown no effect. L. casei var. rhaminosus ( Lactobacillus GG) for 6 months to 1 year, as well as B. longum , were used. 18,  , 19,  , 20
Antibiotic-induced diarrhea   A review and a meta-analysis of published trials investigating the effect of probiotics in preventing antibiotic-associated diarrhea have been released. 2,  , 21 Both found positive results for treatment with probiotics compared with placebo. Organisms studied include S. boulardii , L. acidophilus , L. bulgaricus , L. rhamnosus , and B. longum .
A more recent double-blind, placebo-controlled trial in patients receiving antibiotic therapy favored the use of probiotics in preventing disruption of the intestinal microflora, 22 but another study found inconclusive results for L. acidophilus and B. lactis . 23 E. faecium SF68 (not available in the United States) also is reportedly effective, but widespread use is not advised because of the potential for resistance to develop. 2
Results of trials investigating the effect of probiotics on Clostridium difficile are conflicting. Some trials suggest a positive effect (using S. boulardii or L. acidophilus with B. bifidum ), 2,  , 24 and others show no effect (with L. acidophilus and B. lactis ) 23 or a trend toward an effect (with L. rhamnosus ). 2
Acute/infectious diarrhea   A Cochrane review found probiotics to be useful adjuncts to rehydration therapy in acute diarrhea by reducing the duration of diarrhea. 25 Preparations with L. acidophilus and B. bifidis appeared to be most effective (and most commonly studied), while Streptococcus thermophilus and L. bulgaricus were less effective. Another trial found yogurt containing S. thermophilus and L. bulgaricus effective in reducing the duration of diarrhea in infants compared with placebo, but not better in achieving resolution of diarrhea or weight gain. 26 Other probiotics reported to be effective in decreasing the duration of diarrhea are Lactobacillus reuteri , S. boulardii , L. lactis , L. casei , and Leuconostoc mesenteroides cremoris . 2,  , 27
Most studies examining the role of probiotics in preventing acute/infectious diarrhea have found no effect. No effect has been shown for S. boulardii , L. casei , or other Lactobacillus spp., 2,  , 28 and results for L. rhamnosus are conflicting. 2 B. bifidum and S. thermophilus showed a protective effect in decreasing the incidence of diarrhea in hospitalized infants in 1 study. 2
Other GI conditions   In very low birth weight infants, the use of oral probiotics ( L. acidophilus and B. infantis ) reduced the incidence and severity of necrotizing enterocolitis. The study was too small to detect adverse effects, and cautious use of probiotics in this population is advised. 29,  , 30,  , 31
Probiotics increased fecal Bifidobacterium counts, reduced fecal blood and pH ( Bifidobacterium , L. acidophilus , and Enterococcus ), and decreased the incidence of fecal Clostridium ( Bacillus subtilis and E. faecium ) in patients with liver cirrhosis. 32
L. acidophilus reduced the length of hospital stay and the need for surgery in patients with partial adhesive small bowel obstruction. 33
Despite altering the intestinal flora in critically ill patients, the use of probiotics L. acidophilus and L. bulgaricus , B. lactis , and S. thermophilus failed to show any difference in clinical outcomes, 34,  and no measurable effects were found for probiotics in patients undergoing elective abdominal surgery. 35
Urogenital conditions   Bacterial vaginosis has been associated with a reduction in vaginal lactobacilli (and an overgrowth of Gardnerella vaginalis and anaerobes) and an unfavorable alkaline environment. 2 L. acidophilus , commonly used in probiotic preparations and most commonly investigated, is not efficient at adhering to vaginal epithelial cells and is not considered the predominant species in the anal-vaginal ecosystem. 36 Lactobacillus crispatus and Lactobacillus jensenii are suggested to be the most common forms of vaginal lactobacilli and are able to restore the acidic vaginal pH via hydrogen peroxide production. 36,  The basis for oral probiotic use is that lactobacilli, which have survived GI transit, will migrate from the anus to the vaginal introitus. 2,  , 3,  , 36
Bacterial vaginosis   Trials examining the effect of vaginal tablets, suppositories, or douches have shown positive results for bacterial vaginosis. In these trials, higher cure rates were found for hydrogen peroxide-producing L. acidophilus strains than for placebo, and clinical and laboratory eradication of bacterial vaginitis was demonstrated. 2,  , 36 Oral administration of L. acidophilus showed a reduced rate of bacterial vaginosis at 1 month, but high attrition over 6 months limited the quality of the study. 2
Candidiasis   Long-term trials investigating the effect of oral hydrogen peroxide-producing L. acidophilus in preventing candidiasis have shown positive and negative results following long-term use (6 months) but were limited in the high loss to follow-up of trial participants. 2,  , 36 A large, randomized, placebo-controlled, double-blind trial of oral or vaginal L. rhamnosus and B. longum over 10 days showed no effect in treating postantibiotic candidiasis compared with placebo. 37 In another placebo-controlled, double-blind trial, daily oral intake of L. rhamnosus and Lactobacillus fermentum modified the vaginal flora and decreased the amount of yeast and coliforms. 3
Urinary tract infections   There are few quality trials published on the effect of probiotics in preventing recurrent or chronic urinary tract infections. Some trials have been able to demonstrate efficacy comparable with that of antimicrobials, 2,  , 38,  while others have failed to show any therapeutic effect. 2
Other uses
Immunity/Allergy   Dietary consumption of probiotics ( B. lactis and L. rhamnosus ) has enhanced some aspects of cellular immunity in elderly and stressed patients. 38,  , 39,  , 40,  , 41,  , 42,  Probiotics also have diminished exaggerated reactions, such as allergy and inflammation, and offered a possible alternative in managing atopic allergy/dermatitis and inflammatory bowel disease. 38,  , 40,  , 43,  Probiotics administered to pregnant women reportedly reduced the incidence of atopic dermatitis in their babies. 4
Respiratory tract infections/Otitis media   Studies among healthy adults and children using the oral probiotics L. reuteri , L. casei , and L. rhamnosus have shown a reduction in missed work/school days because of respiratory illness. The need for antibiotic intervention also was reduced. 44,  , 45,  , 46,  Probiotics ingested for 3 weeks reduced nasal colonization with pathogenic bacteria 47,  and demonstrated efficacy in treating acute otitis media. 48
Nutrition/Lactose intolerance   Milk and yogurts containing L. acidophilus have been studied in patients with lactose intolerance, but controversy regarding its efficacy in lactose digestion remains. 49,  , 50,  The need for adequate, live bacteria, which may account for the variation of results in other studies, has been demonstrated in lactose-intolerant adults. 51
Effect on cholesterol levels   It has been suggested that appropriately selected probiotics may be useful adjuncts in controlling hypercholesterolemia because of the bacteria's ability to assimilate cholesterol and grow well in the presence of bile. 52,  However, conflicting studies exist, 53,  , 54,  , 55,  , 56,  , 57 and a study in which the probiotics L. acidophilus and B. longum were administered in capsule form, rather than in milk/yogurt, failed to show a beneficial effect on lipids. 53
Effect on reproductive hormones   Studies have investigated the effect of L. acidophilus and B. longum on plasma phytoestrogens, but no association has been found in pre- or postmenopausal women. 58,  , 59,  , 60
Cancer   Despite positive in vitro studies showing decreased carcinogenic aflatoxins and beta-glucuronidase, efficacy studies in humans are lacking. 38,  , 61 The combination of L. acidophilus and lactulose appears beneficial in the therapy of radiotherapy-related intestinal side effects. 62
 
Administration & Dosage
Daily intake of oral probiotic preparations usually is recommended, but some trials have used twice-weekly dosing.
Preparation strength is usually described per million/billion colony-forming units/capsule.
 
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking. Trials investigating probiotics in the form of vaginal douches have been conducted in pregnant women. 36
 
Interactions
None well documented.
 
Adverse Reactions
There are isolated reports linking probiotics to adverse reactions. Probiotics are considered relatively safe, but caution is advised for patients at risk for opportunistic infections and in those with badly damaged GI tracts. 2
Endocarditis caused by Lactobacillus species, including L. acidophilus , has been reported. 63 Neurological sequelae from D-lactic acidosis, caused by consumption of acidophilus tablets and yogurt containing L. acidophilus , were observed in a child with short-bowel syndrome. 64 Antibiotic resistance has been reported for some Lactobacillus species found in European probiotic preparations. 65
 
Toxicology
Research reveals little or no information regarding toxicology. No adverse reactions were found in a study examining the safety of B. longum in healthy adults. 66
 
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