Researchers at Washington University have been working to unravel the role of the microbiome in malnutrition (Blanton et al. 2016). Toward this end, they coined the term “microbiota-directed foods” (MDFs). This has led them into the quagmire of the narrow FDA approach to foods and drugs (Green et al. 2017). Whereas the scientific mind discovers and imagines without constraint, the regulatory mind determines into what boxes these developments must be constrained. This wouldn’t be such a problematic process except that regulatory limitations can make or break the ability to translate scientific discovery into real life products.
Would MDFs be regulated as foods or drugs? The FDA views ‘substances’ in large part based on what they are intended to do. Something might look, taste and satisfy hunger just like a yogurt, but if it’s represented as a product that can, for example, help manage symptoms of antibiotics associated diarrhea, in the FDA’s eyes, it’s a drug. In short, the FDA considers that foods are intended for taste, aroma or nutritive value*. Taste and aroma are not what’s at play here. Researchers’ challenge is to figure out how MDFs will fit into the FDA concept of nutritive value. FDA defines nutritive value as “a value in sustaining human existence by such processes as promoting growth, replacing loss of essential nutrients, or providing energy.”
Green et al. define MDFs as foods designed to alter properties of a microbiota, presumably for health. In the context of battling malnutrition, such foods would be designed to permanently correct a faulty microbiota – and the associated dysfunctional gut – by introducing missing microbes or substances ‘eaten’ by key microbes. The restructured microbiota would promote normal health and growth by enabling the child’s gut to function properly with regard to keeping pathogens at bay and performing microbe-mediated nutritional functions.
Of particular interest is that the resulting microbiota would have long lasting implications for growth, nutritional status and health of the child. Therefore, it seems that although very different from the classical view of foods, which provide macro and micronutrients, these foods would provide live microbes and other constituents designed to restructure a malnourished child’s microbiota. But the outcome could easily be described as nutritive.
It appears that these foods will help expand how scientists – and hopefully regulators – view nutritive value. As the authors state, “New understanding of how our gut microbial communities (microbiota) transform dietary ingredients into metabolic products that affect human biology is altering our definitions of the nutritional value of foods.” Will these developments lead to expansion of the definition of “essential nutrient” to include products of microbial metabolism?
Research is clearly needed to refine the concept of MDFs. Perhaps most importantly, controlled trials proving causality are needed. Which microbes? How many different ones and what amounts of each are needed? What microbe substrates? Do unique formulations need to be developed for specific population members? Also important, safety assessments must be conducted. A permanently shifted microbiota has potential for long term health consequences. Unlike what is implied in Green et al. GRAS assessment is NOT a lower safety standard compared to drugs or food additives. GRAS is as rigorous as food additive approval. And unlike drugs, GRAS does not allow for a risk/benefit assessment.
It is possible that the FDA will view MDFs as drugs. Drugs are defined as substances that cure, treat, prevent, or mitigate disease, or affect the structure and function of the body. (Foods can also have this latter effect.) Such a determination by regulators could slow the development process.
*U.S. law also allows for foods to be characterized in relationship to a disease or health-related condition, but only with some form of approval: either by FDA review or sanction by an authoritative body, such as the National Academy of Medicine. Approved health claims are here.
Green JM, Barratt MJ, Kinch M, Gordon JI. Food and microbiota in the FDA regulatory framework.Science. 2017 Jul 7;357(6346):39-40.
Blanton LV, Barratt MJ, Charbonneau MR, Ahmed T, Gordon JI. Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics. Science. 2016 Jun 24;352(6293):1533.