EXPERT ANALYSIS FROM AAP 2017

CHICAGO (FRONTLINE MEDICAL NEWS) When prescribing probiotics in a primary care setting, evidence in the literature supports the efficacy of specific probiotic strains for specific indications. Outside of that, things are less clear.

“In terms of diarrhea, the evidence is positive, but probiotics only provide about 25 hours of benefit. And treatment of antibiotic-associated diarrhea is really dependent on patient adherence,” said Michael D. Cabana, MD. When it comes to treating colic, there is a particular probiotic that looks promising, he added, but the research so far demonstrating effectiveness is limited to breastfed babies. Also, the probiotic therapy appears to work best when started relatively early.

In contrast, when families ask about eczema, inform them that studies in the literature generally do not support treatment with probiotics. “In terms of prevention, the results are mixed. But once a child has eczema, it generally doesn’t help,” Dr. Cabana said at the annual meeting of the American Academy of Pediatrics.

You are very likely to be asked your take on probiotics for a wide range of conditions, Dr. Cabana said, Overall, however, skepticism is warranted. Advise patients and families to be aware of advertising that promotes many different products as “probiotic,” especially around claims of improved “gut health” or “balanced microbiota.” He emphasized: “Make sure what your patients are using has some evidence behind it.”

Knowing the particular probiotic strain is essential to researching the evidence around its use, said Dr. Cabana, professor of pediatrics at the University of California, San Francisco. “I used the Canis familiaris example. All dogs are C. familiaris. But there are different breeds. You want to make sure you match the right breed to the task. If you were in an avalanche in the Swiss Alps, you would want a St. Bernard to rescue you, not a Chihuahua,” he said. “Similarly, when you are using probiotics you want to make sure you have the right strain, not just the genus and species.” For example, if a product label states it contains Bifidobacterium breve C50, the “C50” is the strain.

Another tip is to look for labeling that lists probiotic concentrations in colony-forming units or CFUs, Dr. Cabana said. He’s seen concentrations listed in mg, a red flag that a product is not legitimate.

Families also might ask if it’s better to take a probiotic supplement or choose food that contains probiotics. “Food products offer additional nutritional benefits, but you can give a relatively higher dose with supplements with a much lower volume ingested,” Dr. Cabana said. “And supplements theoretically provide a more consistent dose.” Speaking of dose, it’s difficult to counsel patients on dosing and frequency in general because probiotics really vary by the indication and formulation.

“As a pediatrician, I also get this question: Should kids get a lower dose of probiotic?” Dr. Cabana said. There are no known reports of toxicity associated with probiotic use in either adults or children, he said. “Unless a dose modification has been documented in a clinical trial, it is not clear that this is necessary. You’re just giving less of the probiotic.”

Treating diarrhea and antibiotic-associated diarrhea

When it comes to probiotics for treating acute diarrhea in children, “the literature is actually fairly good here,” Dr. Cabana said. More than 60 studies with an excess of 8,000 participants, the majority with rotavirus infection, suggests probiotics are not associated with any adverse effects and generally shorten duration of diarrhea.

In fact, Dr. Cabana added, multiple meta-analyses support a shorter course of diarrhea. He added, “Look at the units here – it’s hours, not days. You can treat, but on average it’s only 25 hours.” He added that a day less of diarrhea can be significant for patients and parents, however.

In another meta-analysis probiotics, particularly Lactobacillus strains, were analyzed for prevention of antibiotic-associated diarrhea ( JAMA. 2012 May 9;307[18]:1959-69 ). Researchers assessed 63 randomized controlled trials with nearly 12,000 participants. The pooled results showed a statistically significant positive reduction in antibiotic-associated diarrhea (relative risk, 0.58; P less than .001). “Note the number needed to treat to see the effect is 13, so it won’t work in every patient,” Dr. Cabana said.

“So prevention of antibiotic-associated diarrhea is well documented. However, it’s also highly dependent on patent adherence,” he emphasized.

The clinical evidence on colic

For treating babies with colic, the best evidence is behind use of Lactobacilus reuteri DSM 17938, Dr. Cabana said. It tends to work best in breastfed infants, babies not on any gastrointestinal meds, and babies that start therapy early in the course of symptoms. “Use in formula-fed infants is unknown, because there are not enough data so far,” he said.

In some cases, during a prenatal visit, soon-to-be-parents will ask if they should start a probiotic to prevent colic. Dr. Cabana has seen only one prophylaxis study for this indication ( JAMA Pediatr. 2014 Mar;168[3]:228-33 ). In the study, 589 infants were randomly allocated to take L. reuteri DSM 17938 or placebo daily for 90 days. At 3 months of age, the researchers discovered a significantly shorter mean duration of daily crying in the probiotic group (38 vs. 71 minutes; P less than .01).

What’s known about efficacy for eczema

The evidence for treating a child who presents with eczema with probiotics does not support efficacy in general, Dr. Cabana said. And the evidence on prevention of atopic eczema is mixed.

For example, in a randomized, controlled study from Finland, investigators randomized mothers to receive Lactobacillus GG or placebo during the prenatal period ( Lancet. 2001;357:1076-9 ). Of 132 of the children, 35% were later diagnosed with atopic eczema, and the rate in the probiotic group, 23%, was half the 46% rate in the placebo group.

In contrast, researchers found no benefit regarding prevention of atopic dermatitis when 105 pregnant women were randomized to Lactobacillus GG or placebo. At the age of 2 years, atopic dermatitis was diagnosed in 28% of the 50 children in the probiotic group and 27.3% of the 44 in the placebo group ( Pediatrics. 2008;121:e850-6 ).

The region of Germany where the study was conducted was rural/agricultural, so the diet could be different, Dr. Cabana said. Also, the median duration of breastfeeding differed between the Finnish and German study population, 6.8 months versus 9.2 months, respectively. “So that could potentially explain it, or there are just differences that cannot be explained.”

For more information, Dr. Cabana recommended information provided by the International Scientific Association of Prebiotics & Probiotics (https://isappscience.org/infographics/). The association’s website has easy to understand infographics including: What are probiotics and what can they do for you?; What’s so special about fermented foods?; and How do you read a probiotic label?

Dr. Cabana reported he receives research support from the National Institutes of Health, Wyeth Nutrition, and Nestle; is on the speakers bureau for Merck; owns stocks or bonds in Abbot and AbbVie; and is a consultant for Mead Johnson, Abbott, Genentech, Biogaia, General Mills, and Nestle.

pdnews@frontlinemedcom.com

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