Probiotics have not been shown to be safe and effective for most gastrointestinal conditions, according to new publications from the American Gastroenterological Association (AGA). "Aside from offering probiotics to premature newborns, there is no good evidence to support their use in any situation," Dr. Alexander Khoruts of the University of Minnesota, in Minneapolis, told Reuters Health by email. Dr. Khoruts and colleagues review historical, scientific and regulatory aspects of probiotics use in a new report appearing in Gastroenterology along with an AGA Clinical Practice Guideline and a technical review supporting it. Early studies in animals showed that probiotics modulate the immune system, provide resistance to invasion by pathogens, improve intestinal barrier function, lower the pH of the gut and modulate intestinal motility and pain perception, the authors note. These findings have yet to be translated into clear evidence of efficacy in humans, despite claims that the products alleviate everything from autism to osteoporosis. One hurdle has been the lack of recognition that many functions of bacteria are specific to the strain, not the species. For example, while one E. coli strain (Nissle 1917) is a currently accepted probiotic bacterium, several other strains (shiga-toxin producing E. coli, enterotoxigenic E. coli, and others) are clearly pathogenic. The common claim that probiotics balance the intestinal microbial composition is almost certainly wrong. Most probiotic strains available today are not adapted to survive in the environment of the human intestine, which is one reason they are generally considered to be safe. Moreover, even if these probiotics survived, their effects would likely be influenced by the indigenous microbiome, which is itself highly heterogeneous among individuals, the authors explain. Probiotics are currently regulated as foods or dietary supplements and, as such, are not required to specify on their product labels the strains or the number of live microbes of each strain that the product delivers through the end of its shelf life. Manufacturers wanting to claim that their probiotic can be used to diagnose, treat, mitigate, cure, or prevent disease will have their products treated as drugs or biologics whose benefits must be demonstrated in clinical trials in human subjects, a costly process that can take more than a decade to complete. It's no surprise, then, that no probiotic strain on the market today has been approved by the US Food and Drug Administration to treat a disease, the authors note. The new AGA Clinical Practice Guideline (CPG) on the role of probiotics in the management of gastrointestinal disorders, based on a technical review, concludes that probiotics containing different strains of Lactobacillus and Bifidobacterium genera are beneficial in preventing necrotizing enterocolitis, the most frequent and devastating gastrointestinal disease in preterm, low-birth-weight newborns. For most other conditions (C. difficile infection, Crohn disease, ulcerative colitis, and irritable bowel syndrome), the AGA recommends the use of probiotics only in the context of a clinical trial. The guideline recommends against the use of probiotics in children with acute infectious gastroenteritis. "Physicians are not educated in microbiome science and many are just as susceptible to seductive marketing as the lay public," Dr. Khoruts said. "The microbiome science is increasingly important in medicine and more education is needed. Also, the methodology for evaluating clinical evidence has advanced over the last decade and the physicians should really understand this process. It is important that physicians are better versed in both of these elements." Co-author Dr. Robert A. Britton of Baylor College of Medicine, in Houston, TX, told Reuters Health by email, "Right now, there really isn't much good clinical evidence for probiotics in most cases as the technical report highlights quite well. Moving forward there will hopefully be a regulatory agency or private organization that will take the lead on assembling a system to allow physicians and consumers to know which probiotics are backed by science and clinical trials and which are simply dietary supplements with no reason to believe they impact human health." Dr. Eran Elinav of Weizmann Institute of Science, in Rehovot, Israel, who recently reviewed the pros and cons of probiotics, told Reuters Health by email, "Currently, no probiotics are considered the standard or primary care for any medical condition. In many cases, it is difficult to establish unequivocal efficacy for probiotics in preventing or treating disease. If the patient is not part of a population at risk, then, considering current knowledge, probiotics can be considered safe, and the physician and the patient need to weigh the potential benefit vs the cost." "Large-scale bias-free randomized controlled trials, coupled with careful scrutiny and attention to heterogeneity between trials in meta-analyses, could facilitate identification of probiotic strains that are efficient in a given indication," said Dr. Elinav, who had no part in the new reports. Dr. Thad Wilkins of the Medical College of Georgia, in Augusta, who earlier summarized the evidence regarding probiotics for gastrointestinal conditions for family physicians, said, "In general, probiotics are safe and effective for most patients for some conditions. There are risks associated with probiotics, and the selection of the most effective (and safe) probiotic for a specified condition is difficult and time-consuming." "New technology will allow for the scientific basis for probiotic selection, which will need to be studied for safety and efficacy in well-designed and powered randomized clinical trials," Dr. Wilkins, who also was not involved in the new reports, told Reuters Health by email. "Regulatory agencies need to regulate the industry to protect patients from serious harm from probiotics." —Will Boggs MD Source
