The pros, cons, and many unknowns of probiotics

Consumption of over-the-counter probiotics for promotion of health and well-being has increased worldwide in recent years. However, although probiotic use has been greatly popularized among the general public, there are conflicting clinical results for many probiotic strains and formulations. Emerging insights from microbiome research enable an assessment of gut colonization by probiotics, strain-level activity, interactions with the indigenous microbiome, safety and impacts on the host, and allow the association of probiotics with physiological effects and potentially useful medical indications. In this Perspective, we highlight key advances, challenges and limitations in striving toward an unbiased interpretation of the large amount of data regarding over-the-counter probiotics, and propose avenues to improve the quality of evidence, transparency, public awareness and regulation of their use.

The concept of oral consumption of microorganisms as a means of inducing health benefits has intrigued humans for centuries. The term ‘probiotics’ first appeared in this context in 1974 and has conceptually evolved to its current common definition as live microorganisms that confer a health benefit when consumed in adequate amounts, suggested by the Food and Agriculture Organization/World Health Organization in 2002 (ref. ¹). Nowadays, probiotics constitute a constantly growing multi-billion-dollar industry² and are one of the most commonly consumed food supplements worldwide³. Foods such as yogurt, cheese, ice cream, snacks and nutrition bars, breakfast cereals and infant formulas are supplemented with probiotics, as are cosmetic products. Probiotics are also commercialized as lyophilized pills⁴. Probiotic consumption is widely supported by physicians⁵, specifically gastroenterologists⁶.

The popularity of probiotics notwithstanding, data from decades of research on the efficacy of probiotics in the treatment and prevention of disease often point toward opposing conclusions and remain conflicting, debated and confusing in many cases. Moreover, the major medical regulatory authorities, such as the European Food Safety Authority⁷ and the US Food and Drug Administration⁸, have yet to approve any probiotic formulation as a therapeutic modality. As a result, marketing of probiotics as dietary supplements is often driven by properties such as safety, viability in the gastrointestinal (GI) tract and lack of impact on the taste of food, rather than by unequivocal health-promoting effects⁹. This confusing state merits better evidence-based proof of the impacts that probiotics have on humans and their adverse effects¹⁰.

In this Perspective, we will highlight and discuss some of the major prospects and limitations of the current approach to probiotic research, present challenges in the interpretation of available data and suggest possible strategies to clarify these issues and transform investigation of probiotics into a more reproducible and universally accepted measurement-based approach. In our work, the reviewed over-the-counter microbial interventions will be termed probiotics regardless of their benefit and efficacy or lack thereof. Of note, the aim of this Perspective is not to review investigational, non-commercially-available ‘next-generation’ microbial therapy approaches that are being proposed as interventions for various medical indications. These are discussed elsewhere¹¹. We will highlight notable examples to discuss the following: the ‘knowns’ and challenges with respect to the strength of evidence and clinical interpretation of studies assessing the health benefits of probiotics; the suggested probiotic mechanisms of action, relating to the debate of whether these will require gut colonization; interactions of probiotic strains with the gut microbiome; safety; and future directions.