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A review of probiotics in gastrointestinal health.

Introduction

This evidence-based review of research in probiotics provides a comprehensive look at peer-reviewed, published research in humans that focuses primarily on supplemental probiotics for health promotion and disease prevention.

The concept of probiotics dates back to the 19th century to research at the Pasteur Institute in Paris, but the term probiotics was not introduced until 1960. In 1989, the idea of their beneficial impact on the host was introduced. (1)

In October 2001, the Food and Agriculture Organization of the United Nations and the World Health Organization (FAO/WHO) cosponsored an important conference on nutrition and health. The conference, termed an expert consultation, focused on the evaluation of available scientific evidence of the properties, functionality, benefits, safety, and nutritional features of probiotic foods. From that meeting came the now widely accepted definition of probiotics as "live microorganisms which when administered in adequate amounts confer a health benefit on the host." (1) This accepted definition remains in use today, as there is no legal definition for the term probiotic in the US.' The FAO/WHO meeting in 2001 also determined that there is potential for probiotic foods to provide health benefits and that specific strains are safe for human use.'

Probiotics are now commonly understood to be beneficial bacteria that are a crucial part of the exceedingly complex ecosystem of a healthy adult intestinal tract. It is estimated that the healthy adult gut harbors between 500 and 1125 different bacterial species. (3), (4) Some of these species are considered potentially harmful, as they can produce toxins, invade the mucosa, and activate carcinogens and inflammatory responses; therefore, in order for a bacterial strain to be classified as probiotic, there are additional requirements. Probiotics must be safe for human use, identified to the strain level, and shown to have some benefit on human health. Though not required, they should also be stable in acid and bile and proliferate in or adhere to the intestinal mucosa. (1-3) The most frequently used genera fulfilling these criteria are Lactobacillus and Bifidobacterium.

The Gastrointestinal Interface

The gastrointestinal tract is both an entryway into and a protective interface for the internal environment of the body. Along with nutrients, humans regularly ingest chemicals and microorganisms in their food and beverages that can be harmful, especially through the activation of inflammatory responses. In fact, environmental factors, particularly those associated with intestinal inflammation, may alter the normal immune regulation in the gut to the point of creating both local and systemic inflammation. (5) Among these factors are antibiotics, medications, food sensitivities, surgery, chemotherapy, and irradiation.

Even without these stressors, many people today have a less than optimal intestinal environment. With the advent of modern food processing and a Western diet that includes few fresh nutritional components with living microbes, much of what we ingest is quite sterile. On the surface, this seems beneficial; but when we don't ingest enough bacteria, we deprive the immune system of its ability to build tolerance and keep the healthy bacteria plentiful. Indeed, research has shown that the secondary lymphoid organs; that is, the spleen and lymph nodes, are poorly developed in germ-free animals because of the lack of antigenic stimulation in the gut. (6) When a poorly developed gut encounters infectious and inflammatory conditions, the balance of its microecology is altered; the number of potentially pathogenic bacteria grows and the healthy interaction between the host and microbes is further disturbed.

Probiotic therapy is based on the concept of a healthy bacterial balance in the intestinal system. Probiotics have been shown to help stabilize the gut environment and the intestine's permeability barrier and to enhance systemic and mucosal responses, thereby promoting a strong immunologic barrier into the internal environment. Consumption of sufficient quantities of probiotics holds great promise for the support of good health and nutrition status, as well as the prevention and treatment of clinical conditions associated with impaired gut barrier functions and sustained inflammatory responses. (7)

Probiotic Use in Clinical Care

Probiotics are routinely prescribed by holistic practitioners, naturopaths, chiropractors, and nutritionists. They are less commonly prescribed by allopathic physicians whose medical school training does not usually include their use. However, physician interest in probiotics is rapidly increasing, in large part due to surging levels of multidrug resistance and antibiotic failure and the rapidly growing amount of scientific evidence demonstrating effectiveness of certain probiotic strains. (8)

Added to this is the growing number of older adults willing to take an active part in their health care through self-education. An increasing portion of the public is demanding natural substitutes for expensive synthetic drugs. In clinical care, two general groups of patients are likely candidates for probiotic treatment: those with specific health concerns for which evidence of the efficacy of probiotics is available, and generally informed individuals interested in doing all that they can to keep themselves healthy.

Of particular interest are ongoing studies of probiotic treatment in premature infants and those delivered by cesarean section who frequently struggle with rotavirus diarrhea and antibiotic-related diarrhea. (8) Other studies are showing positive treatment of H. pylori infection and its complications, inflammatory bowel diseases and syndromes, and women's reproductive and bladder health, as well as reductions in postsurgical infections. (8)

Published scientific literature has reported the following effects of probiotics (2):

* enhanced immune response to pathogens

* downregulation of autoimmune and inflammatory responses

* reduced absences or illness in workplace and day-care center settings

* enhanced gastrointestinal tolerance to antibiotic therapy

* control of symptoms associated with lactose intolerance

* reduced severity of or incidence of respiratory infections

* reduced incidence and improvement of symptoms of some allergic diseases

* improved outcomes in cases of bacterial vaginosis

* improved symptoms in those with irritable bowel syndrome

* decreased incidence of dental caries

* reduction of Clostridium difficile toxin in individuals taking antibiotics

* prolonged remission in patients with pouchitis

* shorter duration of infectious diarrhea in infants

Mechanisms of Action

Current evidence, as reviewed by Sherman et al., indicates that different probiotic strains have different effects that depend on dosage as well as the route and frequency of delivery. (9) Some probiotics create a direct line of defense by exerting a direct antimicrobial effect, such as inhibition of the growth and virulence of enteric bacterial pathogens. Lactic-acid-producing probiotics may reduce the local pH of the microenvironment of the gut lumen.

Some probiotics affect the lumen. Others interact with epithelial cells lining the GI tract to prevent pathogens from binding and moving downstream. Some may also compete for a specific and limited niche in the large bowel, thereby taking up space that could be invaded by replicating pathogens.

Other probiotics affect the mucosa. For example, they may enhance the mucosal layer, creating an antibacterial shield that prevents pathogens, such as enteropathogenic E. coli, from binding to surfaces, helping the body clear them from the GI tract. (10) Some probiotics enhance release of defensins from intestinal epithelia, reducing the effects of infection. (11) Still others appear to strengthen the integrity of the intestinal junctions.

Some probiotics have submucosal effects. Through bacterial-epithelial cell "cross-talk," some strains can promote the differentiation of B cells into plasma cells and increase the production of secretory immunoglobulin A, which then sticks to the mucus layer and binds to pathogenic microorganisms. (12) Some act by preventing inflammatory processes and impacting certain T cell immune responses, reducing inflammation. (13)

Probiotics have also been shown to be capable of signaling to the host beyond the gut; that is, to the liver, the systemic immune system (e.g., lymph), and other potential organs, such as the brain. (14) In one novel study, compelling evidence indicated the capacity of some probiotics to activate opioid and cannabinoid receptors in the gut, suggesting a promising use of probiotic treatment for conditions that manifest in visceral pain, such as irritable bowel syndrome (IBS). (15)

Demonstrated Safety

A review of 143 human clinical trials of probiotics that had been conducted over a 39-year period concluded that there were no adverse events reported with probiotic use in the 7526 people who had participated in the studies. (16) The most likely side effects experienced with probiotic therapy are transient flatulence and bloating. (17)

In general, high doses of probiotics are well tolerated. A randomized, placebo-controlled, double-blind, parallel dose-response study on probiotics and blood lipids was completed in 71 healthy young adults (46 women, 25 men, age range 1840). (18) They were randomly assigned to five groups and received either placebo or a mixture of Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in concentrations of 108, 109, 1010, or 1011 CFU/day in a 2-week run-in period, a 3-week intervention, and a 2-week washout. Although no dose-response effect on blood lipids was found and there was a change in stool consistency (looser stools) with increasing dose, the high doses of probiotics were well tolerated and a dose-related recovery of BB-12 from feces was observed.

Probiotics do not appear to pose any safety concerns for pregnant and lactating women. Systemic absorption is rare when probiotics are used by healthy individuals, and the current literature does not indicate an increase in adverse pregnancy outcomes. (19), (20) In addition, probiotics administered orally to combat urogenital infections are not systemically absorbed but rather reach the site of action by passing through the gastrointestinal system and ascending into the urogenital tract. (19)

Review of Human Research Studies Using Probiotic Supplementation

Bowel Health

Not surprisingly, probiotics are currently being studied in a wide variety of digestive disorders, from constipation to prevention and treatment of antibiotic-associated diarrhea to chronic diseases such as IBS. Although their exact causes are not yet fully understood, disturbances of the naturally occurring intestinal microflora and the stimulation of pro-inflammatory immunological mechanisms seem to play a role in a number of inflammatory diseases of the intestine. Increasing evidence shows that gut microflora play an important part in the initiation and maintenance of the mucosal inflammatory response in these disorders. Microflora in these patients become aberrant with normal microflora decreased, such as bifidobacterium and lactobacillus, and pathogenic or potential harmful bacteria increased. Supplementation with probiotics appears to balance the indigenous microflora in patients with some GI disorders. (21)

General Intestinal Health

* In a study of 100 middle-aged adults (64% women) with functional GI symptoms (e.g., constipation, flatulence, abdominal pain, regurgitation, nausea), Waller et al. found that daily doses of B. lactis HNO19 (17.2 x [10.sup.9] CFU or 1.8 x [10.sup.9] CFU) for 14 days had a significant dose-response effect on reducing whole gut transit time. In addition, patients in both treatment groups experienced decreases in functional GI symptoms compared with placebo. (22) Time to excretion was significantly shorter in both treatment groups vs. placebo.

* A double-blind, placebo-controlled clinical trial using the probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis B-LBi07 twice a day ([10.sup.11] CFU) vs. placebo over 8 weeks in 60 patients who had abdominal bloating (mostly white women, mean age 37 years) found significant improvements with probiotic treatment. (23)

Evacuation disorders and hard stools occur in an estimated 12% to 17% of the otherwise healthy adult population of any age in industrialized nations. (24)

* In a randomized, double-blind, placebo-controlled study of 300 healthy male and female volunteers (aged 24-71 years) with evacuation disorders and hard stools, Del Piano et al. evaluated the effectiveness of two different probiotic blends, either mixed Lactobacillus plantarum LP01 and Bifidobacterium breve BRO3 (2.5 x [10.sup.9] CFU/ day) or Bifidobacterium animalis subsp lactis BS01 (5 x [10.sup.9] CFU/day).24 After 30 days, the number of weekly bowel movements significantly improved, as did consistency of feces and ease of expulsion in both probiotic groups. Furthermore, symptoms of intestinal discomfort such as abdominal bloating, anal itching, burning, or pain were also eased.

Probiotic supplementation has been investigated in adults with constipation or symptoms of constipation.

* In a study of 209 frail elderly nursing home residents in Finland, a randomized controlled trial using Bifidobacterium longum ([10.sup.9] CFU/day) or Bifidobacterium lactis ([10.sup.9] CFU/day) vs. placebo for 7 months reported normalized bowel functions and reduced incidence of diarrhea and constipation in both probiotic groups. (25)

* In a randomized, double-blind, placebo-controlled study of 70 adults with chronic constipation, Koebnick et al. found that 65 mL/day of a probiotics beverage containing at least 6.5 x [10.sup.9] L. casei Shirota resulted in a significant improvement in self-reported severity of constipation and stool consistency. (26) No adverse reactions were reported. Interestingly, all patients noted relief beginning in the second week, suggesting colonization effects.

Studies have shown benefits of using probiotics in children with constipation.

* In a 4-week pilot study, Tabbers et al. found that treatment with a daily dose of Bifidobacterium breve ([10.sup.8]-[10.sup.10] CFU) significantly increased stool frequency in 20 children (mostly boys, aged 3-16 years) with functional constipation. (27) In addition to improving stool frequency, daily use of the probiotics also improved stool consistency, decreased episodes of fecal incontinence, and reduced abdominal pain.

* A double-blind, placebo-controlled, randomized study of 45 children under age 10 years with chronic constipation was completed by Bu et al. They compared the effectiveness of Lactobacillus casei rhamnosus (Lcr35; (8 x [10.sup.8] CFU/day), magnesium oxide (MgO; 50 mg/kg/day), or placebo. The children who received probiotics or MgO had significantly greater frequency of defecation, fewer hard stools, less need for glycerin enema, and a higher rate of treatment success than the placebo group. There was no significant difference between MgO and probiotic groups, although abdominal pain occurred less frequently in the probiotic group than in both the MgO and the placebo groups (p = 0.03). No adverse effect was noted in the probiotic and placebo groups, and one patient in the MgO group suffered from mild diarrhea.

* In a pilot study, 20 children aged 4 through 16 years with constipation were treated daily with a probiotic mixture containing 4 x [10.sup.9] CFU of Bifidobacterium (B.) bifidum, B. infantis, B. longum, Lactobacillus (L.) casei, L. plantarum, and L. rhamnosus for four weeks. (29) Bekkali et al. found that the frequency of bowel movements increased significantly, while abdominal pain and episodes of fecal incontinence decreased significantly. Stool consistency also improved and no side effects were reported.

The use of probiotics for the alleviation of constipation secondary to diseases such as Parkinson's disease was recently investigated.

* In a randomized controlled trial, 40 persons suffering from Parkinson's disease and constipation were treated daily with a 65 mL fermented milk drink containing Lactobacillus casei Shirota (6.5 x [10.sup.9] CFU). After probiotic supplementation, Cassani et al. measured statistically significant improvements in stool consistency, bloating, and abdominal pain. (30)

Diarrhea and C. Difficile

Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic treatment, most likely because beneficial bacterial microbes in the gut are outnumbered: for example, a factor of 100 pathogenic cells to 10 protective cells. Antibiotics can increase this ratio in favor of the pathogenic organisms, further impairing the gut's immune system. The disturbance of normal GI flora, especially after antibiotic use, is thought to predispose patients to issues related to pathogenic bacterial colonization, including Clostridium difficile-associated diarrhea (CDAD). (31) The idea that probiotics could replace missing components of the GI normal flora to prevent CDAD has been explored by clinical investigators for nearly 20 years. Probiotics show promise in the treatment of these diseases. (32)

* A meta-analysis of 35 randomized, controlled trials supported the efficacy of probiotics in the prevention of AAD but not necessarily CDAD. (33) A total of 2810 patients with AAD were included: 64% of the studies consisted of adults and 36% children; all received antibiotics. There was variability in the individual probiotic strains and mixtures, duration of treatment, and dosing. Significant efficacy for probiotics was seen in 44% of adult studies and 67% of the trials involving children. It was concluded that S. boulardii, LGG, and probiotic mixtures showed the most potential for a protective effect from AAD. In 6 trials involving 354 adult patients with CDAD, only S. boulardii achieved a significant reduction in the recurrence of C. difficile infection in patients who were concurrently receiving high-dose oral vancomycin.

* In a double-blind, placebo-controlled study in Shanghai, China, Gao et al. randomized 255 adult inpatients into three groups receiving 5 x [10.sup.10] CFU of a probiotic mixture (Lactobacillus acidophilus CL1285 + Lactobacillus casei LBC8OR Bio-K + CL1285) or 2.5 x [10.sup.10] CFU of the same mixture or placebo daily for 5 days following last antibiotic use. (34) Both probiotic groups had significantly lower incidence of AAD and CDAD than the placebo group. Of interest to note, participants who consumed 5 x [10.sup.10] CFU had a lower incidence of AAD (15.5% in the 5 x [10.sup.10] CFU group, 28.2% in the 2.5 x [10.sup.10] CFU group, and 44% in the placebo group) as well as a shorter duration of symptoms if they acquired AAD (2.8 days in the 5 x [10.sup.10] CFU group, 4.1 days in the 2.5 x [10.sup.10] CFU group, and 6.4 days in the placebo group). Hence, a beneficial effect from a higher dose of probiotics was demonstrated.

* In a review of research, Marteau et al. noted two randomized controlled studies of 581 participants that showed a significant therapeutic effect of S. boulardii in treatment of AAD and CDAD. (35) The first study results indicated that the rate of AAD was 4.5% in the probiotic group vs. 17.5% in the placebo group. In the second trial, AAD occurrence was 7.2% in the probiotic group vs. 14.6% in the placebo group. Although not effective against initial occurrences of CDAD infections, S. boulardii decreased the recurrence of subsequent infections.

* A meta-analysis by D'Souza et al. reviewed 9 studies and concluded that probiotics can be used to prevent AAD and that S. boulardii and Lactobacilli strains have the strongest potential to be useful in this situation. (36)

* A meta-analysis of acute infectious diarrhea in children treated with Lactobacillus found that diarrhea duration and frequency were both significantly reduced in the treatment group compared with the placebo. None of the studies indicated safety concerns. (37)

Other Gastrointestinal Disorders

* In a review of studies of inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticulitis, necrotizing enterocolitis, or inflammation of an ileal pouch after colectomy), de Vrese and Marteau found that patients showed a positive response to probiotics such as LGG, E. coli Nissle 1917, or a mixed culture preparation containing 4 strains of Lactobacilli, 3 strains of Bifidobacteria, and Streptococcus thermophilus (known as VS L#3). (38) Beneficial effects were a decreased expression of inflammatory markers ex vivo, increased immune response, improvement of gut barrier function, maintenance of remission, and lower drug consumption. Overall, researchers observed both fewer symptoms and a higher quality of life in the children and adult patients.

* A randomized, double-blind, controlled, parallel group study of 34 patients with irritable bowel syndrome found that daily treatment with fermented milk containing 1.25 x [10.sup.9] CFU of B. lactis DN-173 significantly reduced abdominal distension and constipation compared with the placebo group. (39)

* In a randomized clinical trial of a multistrain probiotics preparation composed of 2 strains of Lactobacillus acidophilus CU [60 and CUL21, Bifidobacterium lactis CU L34, and Bifidobacterium bifidum CUL20, 52 adults with IBS received a total of 2.5 x [10.sup.10] CFU/capsule or a placebo daily for 8 weeks. (40) The treatment group self-reported significantly greater improvement both during treatment and 2 weeks after cessation when compared with the placebo group.

* A randomized controlled study of 141 children (aged 5-14 years) with functional abdominal pain were given probiotics (LGG 3 x [10.sup.9] CFU) or placebo twice daily for 8 weeks of treatment, followed by 8 weeks of follow-up without intervention. (41) The treatment group had a significant reduction in frequency and severity of abdominal pain; they also showed a significant decrease in intestinal permeability. These differences were still significant at the end of the follow-up period.

Further Resources

The website probiotic-research.com maintains a library of original abstracts of published peer-reviewed human research, presented by category, for health professionals and the research community.

The International Probiotics Association (IPA) is an international organization with equal membership from industry and academia. Its goal is to provide a unique forum for the exchange of research and the latest breakthroughs in probiotic technology and new product development. The organization maintains a website and library at internationalprobiotics.org.
Clinician's Reference Information

Probiotic Nomenclature
Category    Example
Group       Bifidobacterium bacteria
Genus       Bifidobacterium
Species     Bifidobacterium lactis
Strain      B. lactis HNO19

Adapted from the International
Probiotics Association, 2012.

Conversion Values
[10.sup.6]                1,000,000  1 million
[10.sup.9]             1000,000,000  1 billion
2.5 x [10.sup.9]      2,500,000,000  2.5 billion
[10.sup.10]          10,000,000,000  10 billion
3 x [10.sup.10]      30,000,000,000  30 billion
5 x [10.sup.10]      50,000,000,000  50 billion
[10.sup.11]         100,000,000,000  100 billion


Disclaimer: This informative review is provided as a service by Advanced Naturals for educational purposes only. Current and peer-reviewed research is cited. It is not intended as medical advice of any kind. The educational information in this document is not intended to diagnose, treat, or cure any disease nor has this document been reviewed or approved by the FDA.

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Notes

(1.) Food and Agriculture Organization of the United Nations and the World Health Organization. Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Expert consultation, Cordoba, Argentina. October 1-4, 2001.

(2.) Douglas LC, Sanders ME. Probiotics and probiotics in dietetics practice. J Am Diet Assn 2008; 108: 510-521.

(3.) Williams NT. Probiotics. Am J Health-Syst Pharm 2010; 67: 449-458.

(4.) Lee J-H, O'Sullivan DJ. Genomic insights into bifidobacteria. Microbiol Molecular Biol Rev 2010; 74 (3): 378-416.

(5.) Fargeas MJ, et al. Boosted systemic immune and local responsiveness after intestinal inflammation in orally sensitized guinea pigs. Gastroenterology 1995; 109: 53-62.

(6.) Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol 1996; 4: 430-435.

(7.) Isolauri E. Probiotics in human disease. Am J Clin Nutr 2001; 73: 11425-1146S.

(8.) Reid G, et al. Potential uses of probiotics in clinical practice. Clin Micro Rev 2003; 16 (4): 658-672.

(9.)Sherman PM, et al. Unraveling mechanisms of action of probiotics. Nutr Clin Prac 2009; 24 (1): 10-14.

(10.) Mack OR, et al. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut 2003; 52: 827-833.

(11.) Schlee M, et al. Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin Exp Immunol 2008; 151: 4528-4535.

(12.) Corthesy B, et al. Cross-talk between probiotics bacteria and the host immune system. J Nutr 2007; 137: 781S-790S.

(13.) Di Giacinto C, et al. Probiotics ameliorates recurrent Th1-mediated murine colitis by inducing 11-10 and 11-10-dependent TGF-alpha-bearing regulatorycens. J Immunol 2005; 174: 3237-3246.

(14.) Rijkers GT, et al. Guidance for substantiating the evidence for beneficial effects of probiotics: Current status and recommendations for future research. J Nutr 2010; 140: 671S-676S.

(15.) Rousseaux C, et at. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinioid receptors. Nat Med 2007; 13: 35-37.

(16.) Madsen KL. The use of probiotics in gastrointestinal disease. Can I Gastroenterol 2001; 15 (8): 17-22.

(17.) The Medical Letter. Probiotics. 2007; 49: 66-68.

(18.) Larsen CN, et at. Dose-response study of probiotic bacteria Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in healthy young adults. Eur J Clin Nutr 2006; 60 (11): 1284-1293.

(19.) Elias J, et al. Are probiotics safe for use during pregnancy and lactation? Canadian Family Physician 2011; 57: 299/301.

(20.) Allen SJ, et al. Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy. J Nutr 2010; 140 (3): 483-488.

(21.) Bai A-P, Ouyang Q. Probiotics and inflammatory bowel diseases. Postgrad Med J 2006;82:376-382.

(22.) Waller PA, et al. Dose-response effect of Bifidobacterium lactis HNO19 on whole gut transit time and functional gastrointestinal symptoms in adults. Scan Gastroenterol 2011; 46: 1057-1064.

(23.) Ringel-Kulka T, et at. Probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 versus placebo for the symptoms of bloating in patients with functional bowel disorders: A double-blind study. J Clin Gastroenterol 2011; 45: 518-525.

(24.) Del Piano M, et at. The use of probiotics in healthy volunteers with evacuation disorders and hard stools: A double-blind, randomized, placebo-controlled study. J Clin Gastroenterol 2010; 44 (1): 530-S34.

(25.) Pitkala KH, et al. Fermented cereal with specific bifidobacteria normalizes bowel movements in elderly nursing home residents: A randomized, controlled trial. J Nutr Health Aging 2007; 11: 305-311.

(26.) Koebnick C, et at. Probiotic beverage containing Lactobacillus casei Shirota improves gastrointestinal symptoms in patients with chronic constipation. Can J Gastroenterol 2003; 17 (11): 655-659.

(27.) Tabbers MM, et al. Is Bifidobacterium breve effective in the treatment of childhood constipation? Results from a pilot study. Nutr J 2011; 10: 19.

(28.) Bu IN, et al. Lactobacillus casei rhamnosus Lcr35 in children with chronic constipation. Pediatr Int 2007; 49: 485-490.

(29.) Bekkali NIH, et al. The role of a probiotics mixture in the treatment of childhood constipation: A pilot study. Nutr J 2007; 6: 17.

(30.) Cassani E, et al. Use of probiotics for the treatment of constipation in Parkinson's disease patients. Minerva Gastroenterol Diem, 2011; 57 (2): 117-121.

(31.) Rohde CL, et al. The use of probiotics in the prevention and treatment of antibiotic-associated diarrhea with special interest in Clostridium difficile-associated diarrhea. Nutr Clin Prac 2009; 24 (1): 33-40.

(32.) Imhoff A, et al. Is there a future for probiotics in preventing Clostridium difficile-associated disease and treatment of recurrent episodes? Nutr Clin Prac 2009; 24 (1): 15-32.

(33.) McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006; 101: 812-822.

(34.) Gao XW, et at. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC8OR for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol 2010; 105 (7): 1636-1641.

(35.) Marteau PR et at. Protection from gastrointestinal diseases with the use of probiotics. Am J Clin Nutr 2001; 73 (suppl): 430S-4365.

(36.) D'Souza AL, et at. Probiotics in prevention of antibiotic-associated diarrhoea: Meta-analysis. BMJ 2002; 324(7350): 1361. Review.

(37.) van Niel CW, et at. Lactobacillus therapy for acute infectious diarrhea in children: A meta-analysis. Pediatrics 2002; 109 (4): 678-684.

(38.) De Vrese M, Marteau PR. Probiotics and prebiotics: Effects on diarrhea. J Nutr 2007; 137: 8035-811s.

(39.) Agrawal A, et al. Clinical trial: The effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2008; 29: 104-114.

(40.) Williams EA, et al. Clinical trial: A multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study. Aliment Pharmacol Ther 2009; 29: 97-103.

(41.) Francavilla R, et al. A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain. 2010; 126: e1445-el 452.

by Leonard Smith, MD

[ILLUSTRATION OMITTED]

Dr. Leonard Smith is a prominent board-certified, general, gastrointestinal, and vascular surgeon who had a successful private practice for 25 years. In addition to his active surgery practice, he also incorporated lifestyle, diet, supplementation, exercise, detoxification, and stress management into many of the therapies that he would prescribe. Many of his patients with cancer, cardiovascular disease, and other serious illnesses did so well under his treatment regimes that he began to devote most of his career to foundational health care and preventive medicine.
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