ChiroACCESS Article



The Use of Probiotics in the Treatment and Prevention of Disease



This information is provided to you for use in conjunction with your clinical judgment and the specific needs of the patient.

Dwain M. Daniel, D.C.

  

ChiroACCESS



Published on

May 6, 2010

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Probiotics, a term coined in 1965 by two veterinarians (1), has emerged as a major player in the prevention and treatment of many different disease states.  It is defined by the World Health Organization as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” (2).  Original interest and the majority of research are related to pathology of the intestinal tract.  More recent and occasionally lower quality research has expanded its role to a variety of conditions to include dental caries (3), gingivitis (4), allergy (5), prevention of atopic dermatitis (6), respiratory tract infections (7), cardiovascular disease (8) and control of inflammation and infection (9).  Unlike many lesser known alternative therapies, probiotics have a remarkable amount of information available in the scientific literature.  Searching PubMed with restrictions to major topic headings and using the terms “probiotics AND therapeutic use” yields 2145 articles which includes 542 clinical trials, all published since 1997.

bacteria close-upBefore exploring the value of probiotics it would be wise to discuss shortcomings of the available research.  A recurring refrain in the literature is the wide variety of organisms categorized as probiotics and the lack of consistency in many studies in the use of specific organisms.  Just a few of the many varieties that have been studied are Lactobacillus (L. acidophilus, L. rhamnous, L. bulgaricus, L. reuteri. L. casei), Bifidobacterium and Saccharomyces boulardii (10).  It should also be mentioned over 500 organisms have been identified but  the vast majority of gastro-intestinal organisms cannot be cultured and remain unknown (11).   In addition to the confusion created by many species, a lack of consistency in dosage is also of concern.  Dosages of 1 to 450 billion colony-forming units (CFU) have been examined.  Higher dosages generally provide the most benefit (10).  Additional research matching specific organisms to specific conditions in the proper dosage are needed.

Another disturbing finding among many brands of probiotics is the poor quality control during the manufacturing and distribution process.  McFarland, in an evidence based review published in 2008, reported one study of 14 U.S. probiotic products and found only 7% contained the bacteria listed on the bottle.  A second study of 58 probiotic products found 30% did not contain the labeled organism.  Those which contained the labeled organism, 60% contained less than the specified amount (12).  In a 2010 report, Consumer Lab found 9 of 27 tested probiotic products failed the testing protocol (13).

Lastly, concerns have been expressed relating to safety.  It is now well established that the use of probiotics in severe acute pancreatitis and immunocompromised  patients should be done so with caution (14).  Other than these considerations probiotics are generally considered safe.  A meta-analysis of 14 randomized controlled trials (RCT) with 1225 participants found the most common side effects to be dyspepsia, headache and nausea with no difference in occurrence from the control groups (15).  A second meta-analysis of probiotics in the treatment of ulcerative colitis concluded “compared with many pharmaceutical agents, serious adverse effects from probiotics rarely occur because they are well tolerated and safe” (16).

Clinical Application and Evidence Level


Gastro-intestinal conditions:   A systematic review of 9 RCT’s reported 2 trials that had significantly higher remission rates for ulcerative colitis, 2 trending toward significance and 5 with no difference when compared to control groups.  The organism which seemed to be most effective in these trials was Bifidobacteria.  Five of the 9 trials compared probiotics directly to anti-inflammatory drugs.  In these studies only 1 showed a trend favoring probiotics and 4 showed no difference (16).  A second review reported on a clinical trial of 32 patients using VSL#3 (Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, Streptococcus thermophilus).  The  response or remission rate for these patients was 77% after 6 weeks of treatment (17). Since these reviews were published other RCT’s have been conducted.  One RCT of 95 patients was divided into three groups.  The first group used Bifidobacterium longum 20 billion CFU daily, the second 8.0 g of the prebiotic psylliun and the third symbiotics (combination of pre- and pro- biotics).  All groups continued with their normal medications of aminosalicylates and prednisolone.  At the conclusion of the 4 week trial the combination group had significant improvement in quality of life, sustained remission and reduced C reactive protein (18).  Another RCT of 147 patients compared VSL#3 to a placebo.  Dosage was 450 billion CFU per day for 12 weeks.  Statistically significant improvements in remissions (42.9% v 15.7%) and quality of life were found in the VSL#3 group (19).   Clostridium difficile infections, a potentially deadly condition,  are present in up to 21% of hospitalized patients with 37% developing diarrhea (20).  A meta-analysis by McFarland demonstrated benefit using Saccharomyces boulardii (21) but a Cochrane review found insufficient evidence to support the use of probiotics (22).  Several RCT’s and reviews have reported the effectiveness of probiotics in the prevention and treatment of antibiotic associated diarrhea (AAD) (21;23-25).   Canani et al reported only specific strains were effective.  These included Lactobacillus GG (2 billion CFU) and a formula which contained Streptococcus thermophilus (2 billion CFU) and Bifidobacterium bifidum (1 billion CFU) (25).  Irritable bowel syndrome (IBS) effects between 3% and 15% of the population (26).  A meta-analysis of 20 RCT’s concludes “probiotics offer promise for the treatment of IBS”. Lactobacillus plantarum and streptococcus faecalis appeared to be the most effective strains (27).  A systematic review stated “probiotics may have a role” in treating IBS.  In this review Lactobacillus GG,Lactobacillus plantarum and Streptococcus faecium demonstrated the most improvement (15).  Limited evidence is available for the use of probiotics in the treatment of functional constipation (28) and traveler’s diarrhea (17).  The effectiveness of probiotics in the treatment of Crohn’s disease has not been as encouraging as in other areas.  A 2008 Cochrane review could find only 1 qualifying RCT of 11 patients which did not demonstrate effectiveness (29).  A meta-analysis of 8 RCT’s reached the same conclusion (30).

Respiratory tract infections:   Several RCT’s have explored the effectiveness of probiotics in the treatment of respiratory tract infections (RTI).  Two of these studies were pediatric studies.  Hatakka et al found in a study of 571 children over 30 weeks that Lactobacillus rhamnous GG reduced respiratory infections by 17%, prescriptions for antibiotics by 19%, days absent from school by 15% and occurrence of otitis media by 21% (31) .  A second RCT of 326 children treated for 6 months with Lactobacillus acidophilus or L acidophilus in combination with Bifidobacterium animalis subsp lactis had even better resultsCompared to a placebo the two probiotic groups had statistically significant reductions in fever incidence (53.0% and 72.7%), coughing incidence (41.4% and 62.1%) and rhinorrhea incidence (28.2% and 58.8%).  Overall antibiotic use incidence was also reduced (68.4% and 84.2%) (32).  When using adult populations the results are not as dramatic.  A 2009 systematic review concluded that probiotics reduced the severity and duration of RTI but did not reduce the incidence (7).

AllergiesAllergy:  A systematic review published in 2008 examined 12 RCT’s.  Nine of the studies showed improved outcomes with the use of probiotics.  Lactobacillus casei, L acidophilus, L paracasei and L rhamnous were the most commonly used.  Dosages ranged from 1 to 9 billion CFU (33).  An interesting RCT that examined the effect of L. acidophilus and Bifidobacterium lactis (combined 5 billion CFU) on 47 children with birch pollen allergy was published in 2009.  Statistically significant lower levels of eosinophils in the nasal mucosa and fecal IgA were noted in the probiotic group which translated to a trend for reduced nasal symptoms (p=0.01) (5).  A review by Kalliomaki et al stated the consensus for the use of probiotics is stronger for prevention of atopic disease than for atopic eczema and further research is needed (34).

Oral healthThe argument for the use of probiotics in maintaining oral health is based on a handful of studies with outcomes based primarily on lab values, not patient oriented outcomes.  Two RCT’s have examined the effect of probiotics on dental caries.  The first study of 594 children aged 1 to 6 used L rhamnosus GG fortified milk as the treatment group.  They found a 44% reduction in caries over 7 months compared to the placebo group (35).  A second study of 248 children was divided into a placebo group and a group receiving milk fortified with L rhamnosus LB21 (10 million CFU) plus 2.5 mg of fluoride daily for 21 months.  The authors reported the probiotics prevented 75% of dental caries.  The study also reported 60% fewer days on antibiotics and 50% less days with otitis media in the treatment group (3).  Two studies were found that explored the role of probiotics and gingivitis.  Both were small and one was unblinded.  The first study used L casei for 8 weeks and found statistically significant decreases in myeloperoxidase activity and presence of Streptococus mutans and salivary yeasts (4).  The second study was an RCT of 59 patients which compared Lactobacillus reuteri (200 million CFU) over a period of 14 days.  The authors reported probiotics were effective in reducing gingivitis and plaque (36).  Lastly a small preliminary study concluded that Streptococcus salivarius may be beneficial in reducing halitosis (37).

Cardiovascular disease:  Although the evidence is far from complete, the role of probiotics in reducing risk factors in cardiovascular disease is intriguing.  A randomized cross-over study of 36 patients with mild hypercholesterolemia using soy plus a probiotic yogurt containing L acidophilus, B bifidus and Lactobacillus GG (100 million CFU each) was compared to a soy plus a prebiotic yogurt (resistant starch bread) and a soy control over 14 weeks.  At the completion of the study the probiotic group demonstrated statistically significant lowering of total cholesterol of 4.7% while the prebiotic group lowered total cholesterol 5.5% and low-density lipoprotein by 7.3% (38).  Another study of 50 patients using a RCT design compared three probiotic containing yogurts and a placebo.  One group used a yogurt containing L acidophilus and Streptococcus thermophilis (StLa) another contained S thermophilus and L rhamnosus (StLr) and the third contained Enterococcus faecium and S thermophilus (G). At the completion of 8 weeks the G group reduced LDL cholesterol by 8.4% in overweight patients.  Statistically significant reductions in systolic blood pressure were also found in the StLa (4.4 mm Hg) and G groups (8.0 mm Hg) (8).  Another RCT of 80 high normal or mildly hypertensive patients compared the probiotic L helveticus to a placebo.  After 4 weeks the high normal group reduced diastolic blood pressure by 5.0 mmHg and in the mildly hypertensive group systolic blood pressure by 11.2 mm Hg.  Other measurements of blood pressure were also lower in the probiotic group but did not reach statistical significance (39).

Immune functionA very interesting recent review by West et al explores the role of probiotics in systemic immunity.  While acknowledging additional research is necessary, the authors state the mucosal immune system is the body’s first line defense system against invading pathogens and probiotics may play a significant role in maintaining homeostasis of that system.  According to West et al the evidence demonstrates that probiotics increase the number and levels of activity of granulocytes and lymphocytes, increase phagocytosis, increase the number of natural killer cells, increase serum IgG, improves cytokine response and may have an anti-viral capacity (11).

OtherA pilot study of 45 adult patients with rheumatoid arthritis using Bacillus coagulans GBI-30, 6086 LAB (dosage not specified) reported a statistically significant improvement in pain after 60 days (40).  Although the evidence is very limited, two authors speculate that probiotics may play a role in the treatment of liver disease (41;42).

In conclusion, there is a significant evidence base supporting the value of probiotics in the treatment of many conditions.  In order to maximize effectiveness of probiotics more evidence is needed to determine which specific strains of bacteria are best used with  specific conditions.  Additional research is needed to determine most effective dosing.  Lastly, the quality control of manufacturers needs to improve in order to provide the physician with confidence in recommending a specific treatment regimen.
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