March 2016 Issue

Probiotics: Treating Pediatric GI Disorders
By Sherry Coleman Collins, MS, RDN, LD
Today's Dietitian
Vol. 18 No. 3 P. 14

Research shows specific strains can help alleviate colic, diarrhea, and other conditions in infants.

As many dietitians know, probiotics are microbes that when consumed in the proper dose confer a benefit to the host.1 While the adult body is colonized with billions of microbes, an infant's gut is sterile at birth. Colonization begins almost immediately when the mother's bacteria are passed on to the baby during vaginal delivery and breast-feeding.1

The type of delivery (vaginal vs cesarean), diet (breast milk vs formula, or early solid foods), and antibiotic administration impact the development of the infant microbiome. A diverse microbiome has been associated with better health, while reduced diversity has been linked to overweight, allergic disease, and poorer health. Researchers have been studying how probiotics may improve or alter gut microbiota to treat many conditions and have been met with varying success.

Probiotic use in the pediatric population isn't new. Like adults, children have been consuming fermented and cultured foods for thousands of years. Research on the therapeutic uses of probiotics began in the early 1900s, but interest has increased exponentially over the past 20 years as well as the frequency in which probiotics are used strategically to treat specific conditions in pediatric patients.

This article will review some of the latest research supporting probiotic use in the treatment of common pediatric gastrointestinal illnesses, including infantile colic, acute gastroenteritis, and diarrhea, as well as necrotizing enterocolitis (NEC) and allergic disease.

Infantile Colic
Infantile colic is an issue for young infants and new parents. It causes significant stress on both the baby and caregivers and reduces the likelihood of ongoing breast-feeding success. Evidence continues to show that the bacterial strain Lactobacillus reuteri 17938 can improve colic symptoms in infants and reduce pain as evidenced by decreased crying spells and less use of pain-relieving medications. In one study, researchers randomized 105 infants diagnosed with colic to receive either L reuteri 17938 (100 million colony forming units [CFU]) with vitamin D3 supplements or vitamin D3 supplements alone. Results showed a significant reduction in pain-relieving medication use and less crying among the group receiving probiotics and vitamin D3 supplementation.2 In another study, researchers compared 52 breast-fed infants diagnosed with infantile colic who were randomized to receive either L reuteri 17938 (100 million CFU) or placebo. Parents recorded symptoms of colic in structured journals and reported their findings via questionnaires.3 Researchers found a significant decrease in the time spent crying and fussing (colic symptoms) among infants who received the probiotic. Indrio and colleagues studied 589 infants randomized to receive either L reuteri 17938 or placebo for 90 days. After the study period, researchers assessed crying time, regurgitation, and constipation and found that every symptom improved significantly in infants who received the supplement.4

Acute Gastroenteritis and Diarrhea
According to a position paper by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition on the use of probiotics for the management of pediatric gastroenteritis, there are two probiotic strains with compelling indications (in spite of low-level evidence) for use: Lactobacillus rhamnosus GG and Saccharomyces boulardii.5 In a study of 124 children who received L rhamnosus GG or placebo for either rotavirus or cryptosporidal diarrhea, researchers observed a reduction in repeated diarrheal episodes and improved immune markers in those with rotavirus, and decreased intestinal permeability in those with cryptosporidal diarrhea.6 In a systematic review published in Pediatrics in July 2014, Feizizadeh and colleagues reviewed 22 studies to determine that S boulardii is both effective and safe. Per their review, administration of S boulardii at approximately 250 mg/day to 750 mg/day found a significant reduction in symptoms. However, more research is needed to determine optimal dosing for S boulardii.

In addition to probiotic supplementation, yogurt also has been shown to have a positive impact on gut health in children. In fact, probiotics in yogurt are a potential treatment for antibiotic-associated diarrhea. In one study, researchers randomized 70 children taking antibiotics to receive either 200 g/day of yogurt containing L rhamnosus GG, Bifidobacterium lactis, and Lactobacillus acidophilus or a placebo during their antibiotic treatment. Researchers recorded stool frequency and consistency throughout treatment plus one week. Only one of the children who ate the probiotic-containing yogurt developed diarrhea, compared with 27 children out of 36 in the placebo group.7

Emerging Applications
In addition to using probiotics to treat infant colic, acute gastroenteritis, and diarrhea, important emerging research suggests probiotics also may help in the treatment of NEC in premature and very low-birthweight newborns, and allergic disease prevention. According to Ann Ming Yeh, MD, FAAP, DABMA, of Stanford Children's Health Pediatric Gastroenterology, Hepatology, and Nutrition, in Palo Alto, California, "Better detection and identification methods [of microbes] are making it possible to determine the impact of specific strains of bacteria on health," yet the sheer numbers of microbes in the gut and human body make the identification process painstakingly slow. Yeh emphasizes that the most important part of current research is being able to accurately characterize the microbiota as well as the dietary and environmental influences.

NEC
Because NEC is a potentially deadly condition for premature newborns, preventing and treating it is essential in neonatal care centers. A November 2015 systematic review and meta-analysis of 26 studies suggested that probiotic use was beneficial in reducing the prevalence of NEC in preterm infants.8 However, there was significant heterogeneity among studies in terms of dosage and types of probiotics used, both of which are essential to properly prescribe probiotics for therapeutic use. While using probiotics to treat NEC appears promising, the researchers indicated there isn't enough evidence to recommend specific bacterial strains or develop protocols for treating the highest at-risk infants such as extremely low-birthweight newborns that weigh less than 1,000 g. The researchers called for more rigorous research before they can develop general guidelines for probiotics use in NEC prevention and treatment.

Allergy Prevention
With regard to allergic disease, research shows probiotics may help. While there are many risk factors for allergic disease, including food allergy, eczema is a primary one. In fact, scientists believe that if eczema were preventable other allergic diseases would be as well. In a 2015 review in the journal Allergy, Zuccotti and colleagues stated that probiotic supplementation in pregnancy and early infancy prevents infantile eczema, suggesting a new potential indication.9 However, this review included the use of a variety of doses and types of probiotics. Study protocols included women taking the probiotics in the third trimester and giving their infants probiotic supplements for at least the first three months of life. In a 2014 Norwegian population-based study, probiotic milk consumption during pregnancy and throughout early infancy resulted in lower rates of allergic disease, including eczema, rhinoconjunctivitis, and asthma.10 However, further study is needed to determine which probiotic strain at what dose is most effective for prevention. The position statement of the World Allergy Organization says that although the evidence doesn't support the use of probiotics in the prevention of allergy per se, they may provide a "net benefit" since they may help prevent eczema.11

Safety Considerations
Nevertheless, not everyone believes probiotics are ready for broad use in the pediatric population. Lingtak-Neander Chan, PharmD, an associate professor and interim chair of the department of pharmacy and interdisciplinary faculty in nutritional sciences at the University of Washington's School of Pharmacy, says that despite increased probiotic use over the past five years, the lack of regulation and oversight remains a concern. Unlike pharmaceutical companies, manufacturers of dietary supplements aren't required to provide studies demonstrating safety and efficacy or the purity and consistency of their products. Chan expressed concerns about probiotic use in neonates, a particularly sensitive and at-risk population, due to their fragility associated with premature birth complications. While studies generally report no serious adverse effects, some case studies have shown the potential for serious infections in pediatric patients who have indwelling catheters or seriously compromised immune systems, such as bacteremia and fungal infections. Therefore, many experts don't recommend their use with these patients.1

Health care professionals also should use caution when recommending probiotic supplements for people with food allergies. Some of these supplements may contain traces of milk proteins, gluten, and fish oils due to cross contact in the factories of manufacturers. Moreover, a ConsumerLab.com study found that many products, though not adulterated with dangerous contaminants or pathogens, don't contain the amount of good bacteria advertised on the label.12 Per a representative of the United Pharmacopeia Symbol (USP), unfortunately there are no probiotic supplements currently on the market that carry the USP designation guaranteeing independent verification.

Practical Applications
Despite these safety concerns, clinical trials have shown there are several specific probiotics (mostly bacteria and yeast) that are efficacious in treating pediatric health conditions. So choosing the right probiotic is the key to efficacy. "You wouldn't just give any antibiotic to treat a condition, and the same is true for probiotics," Yeh says. "You must match the specific probiotic to the condition it's been proven to treat." The following guidelines can help nutrition professionals when recommending probiotics for pediatric patients:

• Choose food first, such as yogurt, kefir, and other cultured products, especially for pediatric patients who are generally healthy, and when there's inconclusive evidence on specific strains and dosing recommendations for probiotic supplements for certain conditions.

• Be cautious when working with the most sensitive populations such as neonates, pediatric patients with significantly compromised immune systems, or those who have indwelling catheters. Consider risk vs potential benefit and work closely with a multidisciplinary health care team for patients with a central line or who are significantly immunocompromised.

• Know exactly what strain at what dose may elicit benefit before suggesting probiotics to treat disease.

• Confirm that the product contains what it says on the package per the recommended dose by contacting the manufacturer to confirm proof of independent verification or obtaining such proof via a testing agency such as ConsumerLab.com.

— Sherry Coleman Collins, MS, RDN, LD, is a private practitioner in Atlanta specializing in food allergies and sensitivities, digestive disorders, and nutrition communications.

[Sidebar]

AVAILABLE PRODUCTS
A variety of probiotic products are marketed to the pediatric population from drinkable yogurt and kefir to powders and chewable tablets. Dietitians should first recommend food, such as yogurt, kefir, and other cultured products, to patients who don't have specific gastrointestinal issues, as there's no evidence that probiotic supplements are effective in improving health among those who are well. For those conditions indicated, RDs may suggest the following products:
• Florastor Kids: Contains Saccharomyces boulardii lyo; 250 mg (includes lactose).
• Culturelle Kids (chewable tablet or packet): Contains Lactobacillus rhamnosus GG (5 billion colony-forming units [CFU]).
• Align Bifantis: Recommended for children over age 12. Contains Bifidobacterium infantis 35624 and 1 billion live bacteria/CFU when manufactured.
• Pedia-Lax Probiotic Yums: Contains Lactobacillus reuteri 17938 (100 million CFU).

— SCC

References
1. Barnes D, Yeh AM. Bugs and guts: practical applications of probiotics for gastrointestinal disorders in children. Nutr Clin Pract. 2015;30(6):747-759.

2. Savino F, Ceratto S, Poggi E, Cartosio ME, Cordero di Montezemolo L, Giannattasio A. Preventing effects of oral probiotic on infantile colic: a prospective, randomised, blinded, controlled trial using Lactobacillus reuteri DSM 17938. Benef Microbes. 2015;6(3):245-251.

3. Chau K, Lau E, Greenberg S, et al. Probiotics for infantile colic: a randomized, double-blind, placebo-controlled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr. 2015;166(1):74-78.

4. Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014;168(3):228-233.

5. Szajewska H, Guarino A, Hojsak I, et al. Use of probiotics for management of acute gastroenteritis: a position paper by the ESPGHAN Working Group for Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014;58(4):531-539.

6. Sindhu KN, Sowmyanarayanan TV, Paul A, et al. Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2014;58(8):1107-1115.

7. Fox MJ, Ahuja KD, Robertson IK, Ball MD, Eri RJ. Can probiotic yogurt prevent diarrhoea in children on antibiotics? A double-blind, randomised, placebo-controlled study. BMJ Open. 2015;5(1):e006474.

8. Aceti A, Gori D, Barone G, et al. Probiotics for prevention of necrotizing enterocolitis in preterm infants: systematic review and meta-analysis. Ital J Pediatr. 2015;41(1):89.

9. Zuccotti G, Meneghin F, Aceti A, et al. Probiotics for the prevention of atopic diseases in infants: systematic review and meta-analysis. Allergy. 2015;70(11):1356-1371.

10. Bertelsen RJ, Brantsaeter AL, Magnus MC, et al. Probiotic milk consumption in pregnancy and infancy and subsequent childhood allergic diseases. J Allergy Clin Immunol. 2014;133(1):165-171.e1-8.

11. Fiocchi A, Pawankar R, Cuello-Garcia C, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Probiotics. World Allergy Organ J. 2015;8(1):4.

12. ConsumerLab.com finds many probiotics don't deliver listed ingredients. ConsumerLab.com website. https://www.consumerlab.com/news/Review_of_Probiotic_Supplements_2009/11_16_2009/. Published November 16, 2009. Accessed January 13, 2016.