January 2010 Issue

Probiotics in Pediatrics — Using Friendly Bacteria to Treat Health Conditions
By Christen C. Cooper, MS, RD
Today’s Dietitian
Vol. 12 No. 1 P. 24

Although currently limited, research suggests that these microorganisms may help prevent and manage gastrointestinal troubles in youngsters.

It’s not the stuff of horror movies but a fact of nature: Your gut is crawling with bugs.

But don’t despair. These bugs are small and if you’re healthy, most of them are friendly. The bugs we’re talking about are the millions of bacteria that colonize the human gastrointestinal (GI) tract beginning with an infant’s journey down the birth canal. This collection of microflora, comprised of a number of bacterial strains, changes over the life span due to alterations in diet, exposure to pathogens, and age-related changes in GI functioning.

The number and strength of beneficial bacteria vs. potentially harmful bacteria can impact many aspects of human health. Significant evidence indicates that a preponderance of friendly microflora plays an important role in nutrition, digestion, and immunity. A healthy bacterial balance may help ward off a number of conditions that manifest in the intestines and some conditions that affect distant organs.

Studies have shown that probiotics may benefit not only adults but also infants and children. By analyzing the available evidence, dietitians can provide parents with appropriate guidance on probiotic use in children. For most conditions, probiotic research is limited. However, research on probiotics is expanding at a rapid pace, and many preventive and therapeutic uses will likely emerge over the next several years.

What Are Probiotics?
According to the National Center for Complementary and Alternative Medicine, probiotics are live microorganisms—usually bacteria, but they can also be microbes such as yeasts—that people can ingest to bolster the population of desirable bacteria in the gut. Probiotics exist naturally in some foods and are also available as dietary supplements in powder, capsule, and tablet forms. The World Health Organization and the Food and Agriculture Organization of the United Nations call probiotics the “live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host.”

Most probiotic bacteria are similar to the beneficial bacteria that occur naturally in the gut, including those of the Lactobacillus species (eg, L. acidophilus). Infants acquire other bacteria during their first months, mainly those of the Bifidobacterium and Enterobacter species. Bifidobacterium species dominate in the gut of breast-fed infants, whereas Enterobacter microbes dominate in bottle-fed infants. This difference in species, which has been identified as key to breast-fed infants’ superior immunity to many infections, has spurred much of the medical and pediatric communities’ interest in probiotics. Infant formula manufacturers have also taken interest. In 2002, the industry secured FDA designation of specific strains of B. lactis and Streptococcus thermophilus as substances generally recognized as safe (GRAS) in milk-based formulas for infants aged 4 months and older.1

Common foods containing probiotics include fermented and unfermented milk, miso, tempeh, and some juices, smoothies, nutrition bars, and soy drinks. The most common strains found in yogurt are L. bulgaricus and S. thermophilus. Yogurts labeled as having “live active cultures” must have 100 million live active bacteria per gram.

The American Dietetic Association classifies probiotics as functional foods because they appear to confer benefits beyond nutrition.2

How They Work
How do probiotics protect the body against disease? The favorable bacteria in the gut constantly defend the body against foreign microbes that, when left unchecked, may lead to illness. Current evidence suggests that helping the gut’s fleet of good bacteria grow and thrive by ingesting probiotics can help humans defend their health in a number of ways, not all of which are fully understood.

According to a recent report in the Journal of Pediatric Health Care, effective probiotics are microorganisms that can survive the acidic environment of the upper GI tract, adhere to the colon, and begin to colonize and confer benefits to the host. Probiotic researchers stress that no two bacterial strains have the same effects in the body, and the mechanisms by which they fight disease also vary. Individuals may also respond differently to probiotics, which makes predicting their precise effects difficult.3

Some probiotics strengthen the gut’s mucosal barrier so that pathogens cannot adhere to it. Some also deter disease-causing bacteria by lowering the pH of the lower intestine, creating an unfavorable environment for pathogens. Lactobacillus species work by producing bacteriocins, hydrogen peroxide, and biosurfactants, which help keep pathogens at bay.3 Still others protect the colon by enhancing the immune response of molecules such as immunoglobulin A and T1 helper cells.1,3 Other probiotics help enhance allergy-mediated responses by inhibiting immunoglobulin E antibody production.4

Probiotics in Pediatrics
For years, parents have independently administered probiotics, especially yogurt, to their children to prevent and treat mild conditions such as diarrhea. In recent years, the alternative and mainstream medical communities have become increasingly interested in and supportive of particular probiotics and some prebiotics to prevent and treat a number of other, often more complex conditions.

Since 2005, Martin Floch, MD, of Yale School of Medicine has led periodic academic workshops that bring together the world’s top GI physicians and probiotic researchers to update and generate high-level recommendations based on primary literature. Many of the studies cited herein reflect the findings of this group.5

Also reflected are studies highlighted by Beth Wallace, RD, CNSC, LDN, of the Children’s Hospital of Philadelphia in her review on the clinical use of probiotics in children in the February/March 2009 issue of Nutrition in Clinical Practice. Her paper analyzes the latest findings on probiotics and the diseases for which they seem to have veritable impact, including irritable bowel syndrome (IBS), Crohn’s disease, pediatric diarrheas, short-bowel syndrome, HIV, and food allergies.1

Antibiotic-Associated Diarrhea
Antibiotics can upset the gut’s bacterial balance by eliminating both undesirable and desirable bacteria, which lowers the body’s defenses against other types of invaders, including bacteria, yeasts, fungi, and parasites. Some physicians and dietitians recommend probiotics for children on antibiotic therapy to help replace beneficial bacteria and reduce the risk of antibiotic-associated diarrhea, which occurs in 40% of children on antibiotics.1

The scientific literature supports probiotic use to prevent antibiotic-associated diarrhea, which can occur anytime up to two months after antibiotic use. The Yale physicians’ conference on probiotics cited a recent meta-analysis of 10 randomized, controlled trials on probiotics and antibiotic-associated diarrhea that appeared in the Journal of Clinical Gastroenterology in 2008. The study “confirms the efficacy of Lactobacillus rhamnosus (LGG) and S. boulardii in children.”6 They cited a 2007 Cochrane Database of Systemic Reviews that demonstrated the efficacy of a drink containing a combination of L. bulgaricus and S. thermophilus administered twice per day. The group’s overall rating for the use of probiotics to prevent antibiotic-associated diarrhea was strong.5

Wallace’s review cautions against recommending probiotics for antibiotic-associated diarrhea until scientists better research the effects of this treatment on people of different ages, the effects of single-strain usage, and the effects of specific dosages.1

Clostridium Difficile-Associated Diarrhea
Treatment for Clostridium difficile-associated diarrhea is similar to that for antibiotic-associated diarrhea; thus, the literature often discusses the two conditions together. However, probiotic use to treat C. difficile-associated diarrhea received a “B” from the Yale workshop participants due to lingering debate on its effectiveness. Still, there are a number of studies that support the effectiveness of LGG or S. boulardii for treating C. difficile-associated diarrhea.6

Infectious Diarrhea
Bacteria, viruses, or parasites in contaminated water or in an environment of poor sanitation often cause infectious diarrhea. And unfortunately, this condition spreads easily among children. Probiotics received a “B” for the prevention of sporadic childhood infectious diarrhea, mainly because the research on children in a day care setting showed that the effects of using probiotics to prevent diarrhea were only “modest” and statistically significant for certain strains.5

However, a battery of studies conducted worldwide suggests that probiotics such as S. boulardii and L. rhamnosus strain GG (LGG) can reduce the duration of diarrhea in infants and children. A 2003 Cochrane Review, for example, analyzed data from 23 studies that together included data for 1,499 children and 918 adults. Twenty-one of the studies used strains of lactic acid bacilli and two used S. boulardii. Nearly all of the studies showed significant reductions in diarrhea duration among participants treated with probiotics. In 15 of the studies, probiotics reduced the mean duration of diarrhea by 29.2 hours.1

Allergies
Infants who are exclusively breast-fed have a lower risk of developing atopic disease. Studies on probiotics to promote bowel wall maturation and help prevent allergies represent a significant area of research. The Yale group gave probiotic use for this purpose an “A,” although allergies were discussed for the first time at the 2008 conference. The “A” applies to the use of specific probiotics, especially LGG strains and B. lactis, for the treatment of allergies that affect the intestine, such as eczema from cow’s milk, in infants and children.5

A 2008 meta-analysis published in the Journal of Allergy and Clinical Immunology analyzed six trials on probiotics and pediatric atopic dermatitis prevention and treatment. Participants treated with probiotics experienced a 61% risk reduction during the first two years of life. In addition, the response was greatest among children who were the most allergen sensitive.1

IBS
Individuals with IBS, which includes a collection of symptoms such as diarrhea, constipation, bloating, abdominal distention, and an urgency to defecate, tend to have a decrease in microbial colonies as compared with healthy individuals. A few good-quality studies have bolstered the evidence in favor of using probiotics to treat IBS. However, given the lack of consistent research outcomes, the Yale group gave probiotics a “B to C” rating.5

One randomized, placebo-controlled trial published in The Journal of Pediatrics in 2005 looked at 50 children with IBS. The children were randomized to a treatment group that received LGG in a concentration of 10 billion CFU/day and a control group that received a placebo. After the six-week study period, there were no significant differences in the severity of abdominal pain, diarrhea, constipation, or indigestion between the groups.1

A randomized, controlled trial published in Alimentary Pharmacology & Therapeutics in 2007 looked at LGG use for kids with IBS. Thirty-two participants had IBS and 72 did not, but the group of 104 children was evenly split into a treatment and a control group. All of the children consumed an LGG oral supplement or a placebo twice daily for four weeks. The LGG-treated group experienced 33% success (defined as “no pain”) while the control group experienced 5% success. The researchers found no significant differences between the groups in terms of other measured outcomes, such as school absenteeism.1

Crohn’s Disease and Short-Bowel Syndrome
Few data exist on the use of probiotics to treat Crohn’s disease in children, although using LGG and other strains in conjunction with conventional pharmacologic therapy shows some promise in studies on adults. The Yale doctors gave the evidence on the effectiveness of probiotic use for treating Crohn’s disease a quality rating of “C.”5
Research is also limited in terms of using probiotics in pediatric cases of short-bowel syndrome, which involves an inability to maintain macronutrient, electrolyte, and micronutrient balance with a conventional diet due to intestinal resection or loss of absorption. The use of probiotics for preventing necrotizing enterocolitis and short gut in neonates has been well researched and is one of the more accepted types of alternative treatments.1

HIV
There is limited research on probiotics in treating HIV-associated immune deficiencies and diarrhea. These two conditions are interrelated in patients with HIV, since the disease damages immune cells, rendering the body more susceptible to diarrhea and other conditions. Diarrhea in patients with HIV then hinders the absorption of HIV medications and decreases nutrient absorption. The body ends up weakened by the combination of these problems.5

A study published in 2008 in the Journal of Tropical Pediatrics looked at the use of probiotics to boost intestinal flora and thereby increase immune cell counts and decrease diarrhea in patients with HIV. The study involved 77 children aged 2 to 12. The control group participants received cow’s milk or standard cow’s milk-based infant formula. The treatment group received milk or standard formula fortified with Bifidobacterium and S. thermophilus daily for two months. The treatment group experienced increased immune cell counts and a slight improvement in stool consistency. The control group experienced a slight decrease in immune cell counts and did not have improvements in stool consistency.1

Conclusions
The use of probiotics in pediatrics has tripled in the past five years.1 Clearly there is a demand for affordable, accessible alternatives to traditional pharmaceuticals for a number of pediatric conditions. However, the effects of most probiotics and some prebiotics have not been thoroughly studied in children. Using probiotics and prebiotics, creating what are called synbiotics, is another potential therapy since the prebiotics nourish and fortify the probiotics to survive the upper GI tract. However, there is also little evidence on the safety and effectiveness of this type of combined use in clinical practice.

For safety reasons, dietitians and other health practitioners should caution patients who self-treat with probiotics in supplement form that extended use or unsupervised use may not be entirely safe. Individuals should divulge use of probiotics, like use of other types of complementary and alternative medicines, to their physician.

Overall, probiotics seem to have a bright future in dietetics and in general medicine, as research in this area continues at a quick and enthusiastic pace. The number of conditions that may respond to probiotics is expanding. Conditions under study include vaginitis and vaginosis, periodontal disease, respiratory and skin infections, growth problems, genetic mutation, and even obesity.

An example of a study in another key area of pediatrics is the Trial of Infant Probiotic Supplementation currently under way at the University of California, San Francisco. The study, which began in 2006, seeks to determine whether probiotics can help prevent and treat pediatric asthma. There are hundreds of other small and large studies aiming to test probiotics as treatment, and especially as prevention, for myriad childhood diseases.6
Given the wide range of potential therapeutic and preventive possibilities, discoveries in probiotics and prebiotics will offer dietitians, physicians, and individuals a number of new options for curbing GI conditions and perhaps ways to preserve the health of organs throughout the body.

— Christen C. Cooper, MS, RD, is a Pleasantville, N.Y.-based freelance health and nutrition writer. She has worked in healthcare consulting in Latin America and the United States and holds a master’s degree in nutrition education from Teachers College, Columbia University.

References
1. Wallace B. Clinical use of probiotics in the pediatric population. Nutr Clin Pract. 2009;24(1):50-59.

2. Hasler CM, Brown AC; American Dietetic Association. Position of the American Dietetic Association: Functional foods. J Am Diet Assoc. 2009;109(4):735-746.

3. Young RJ, Huffman S. Probiotic use in children. J Pediatr Health Care. 2003;17(6):277-283.

4. Roberfroid MB. Prebiotics and probiotics: Are they functional foods? Am J Clin Nutr. 2000;71(6 Suppl):1682S-1687S.

5. Floch MH, Walker WA, Guandalini S, et al. Recommendations for probiotic use—2008. J Clin Gastroenterol. 2008;42 Suppl 2:S104-S108.

6. Douaud C. Probiotics play increasing role in pediatric research. May 25, 2007. Available at: http://www.nutraingredients-usa.com/content/view/print/180150. Last accessed October 29, 2009.

Pediatric Conditions Under Study for Treatment With Probiotics1,3
Condition                                                                                Evidence
Antibiotic-associated diarrhea                                                 Strong

Infectious childhood diarrhea                                                  Strong

Allergies                                                                                  Strong

Clostridium difficile-associated diarrhea                                   Moderate

HIV                                                                                          Moderate

Irritable bowel syndrome                                                        Limited

Crohn’s disease                                                                      Limited

Short-bowl syndrome                                                              Limited