Reluctant to prescribe probiotics? Gut health, safety and ethics

“First, do no harm.” I can think of no more important principle as I examine a tiny, fragile newborn in the neonatal intensive care unit (NICU). This baby entered the world several months ahead of schedule. As a neonatal gastroenterologist, I primarily treat complications of prematurity, including a devastating inflammatory disease of the bowel called necrotizing enterocolitis (NEC). Around 7% of babies who are born weighing less than 3 pounds are diagnosed with NEC in the NICU. Some need surgery to remove a portion of bowel and require months of intravenous nutrition before they’re able to feed by mouth. NEC can be fatal; survivors often have life-long consequences, including impaired brain development. The cause of NEC is unclear, but we think it may be related to a lack of beneficial bacteria in the gut. Giving beneficial bacteria to preterm newborns may reduce the risk of NEC, but this treatment is highly controversial.

Probiotics are live microbes that confer a health benefit. A few years ago, we published a systematic review of all clinical trials that tested probiotics in premature newborns. We found 63 studies that enrolled nearly 16,000 preterm infants – a substantial body of evidence. Our meta-analysis revealed that several probiotic formulations dramatically reduce the risk of NEC (by more than 50%) and death. Despite this compelling evidence, some medical professionals are reluctant to prescribe probiotics because of unanswered questions regarding their safety.

We recently published a comprehensive review of potential risks associated with probiotic use. We found that probiotics have a strong safety record based on published trials and a long history of safe use as dietary supplements. But not all uses of probiotics are equally safe. We identified risks related to three key differences between probiotics and pharmaceutical drugs.

First, probiotics are living. They could migrate from the gut into the bloodstream to cause sepsis and invasive infections. Although rare, infections caused by probiotics have been reported. Furthermore, new evidence suggests that some probiotics can break down certain medications and supplements. The impact of these interactions is still unclear. Also, some probiotics carry genes that confer resistance to antibiotics, and these genes could be passed from one microbe to another in the gut, leading to antibiotic-resistant pathogens. The likelihood of this theoretical scenario is not yet clear.

Second, unlike drugs, probiotics have the potential to persist in the gut. When a prescription medication is no longer needed, it can be discontinued and is rapidly eliminated from the body. But probiotics may colonize an individual’s gut and reproduce indefinitely. If a probiotic is no longer wanted, it might be difficult to eradicate. Probiotics can re-shape the community of microbes that inhabit one’s intestine and this might have consequences yet to be determined. Few studies document the long-term safety of probiotics months or years after they were given.

Third, probiotics are not regulated by the U.S. Food and Drug Administration. This lack of oversight means there is an increased risk for contamination of a probiotic product in the manufacturing process. For generally healthy people, a small amount of unwanted yeasts or bacteria likely won’t cause problems. But for vulnerable patients, including preterm neonates, a contaminated probiotic could have life-threatening consequences. This is the safety concern that is most often cited by clinicians who oppose probiotic use in the hospital.

In a new publication in JAMA Pediatrics, we provide a roadmap that would allow our patients to benefit from probiotics despite the lack of pharmaceutical-grade formulations. We outline simple action items to help hospitals select products that are safer than those sold in grocery stores or online that are meant for healthy people. Chief among these action items is a set of transparent and stringent testing standards to detect contaminants especially harmful to vulnerable patients. We recommend that the manufacturing process is overseen by an independent third party. Clinicians should be aware of the availability of more stringent testing standards, protocols must be implemented to reduce the risk of contamination during administration and adverse events must be reported. This framework won’t eliminate all risks associated with probiotics, but it will lower the risk of prescribing a contaminated product that may harm vulnerable patients, including preterm infants in the NICU who are at risk of NEC.

With every intervention, there are benefits and risks. This is part of the art of medicine. Probiotics have the potential to reduce some of the devastating consequences of prematurity, but first, we must take some simple steps to increase the odds that we “First, do no harm.”

By Dr. Geoffrey A. Preidis, assistant professor of pediatrics – gastroenterology, hepatology & nutrition; associate director, Medical Scientist Training Program, Baylor College of Medicine, Texas Children’s Hospital