Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related to probiotic use. The importance of whole genome sequencing, which enables determination of virulence, toxin, and antibiotic resistance genes, as well as clear assignment of species and strain identity, is emphasized. We present recommendations to guide the scientific and medical community on judging probiotic safety. What is the context? Probiotics, available to healthy consumers as both dietary supplements and foods, are also used by some patient populations. The goal of this paper is to determine if any new factors have emerged that would impact current views about probiotic safety for both these populations. What is new? The authors conclude that established practices are sensibly addressing factors important to the safety of traditional probiotics used by the general population. They also make recommendations regarding emerging safety considerations. Probiotics targeted for patient populations should undergo stringent testing to meet quality standards appropriate for that population, preferably verified by an independent third party. The safety of probiotics derived from species without a history of safe use must be considered on a case-by-case basis. Research is needed to address some gaps, for example which best animal models to use for safety assessment of live microbes, the possibility of antibiotic resistance gene transfer via transformation, and potential impact of probiotic-induced changes in microbiomes, interactions with drugs, and probiotic colonization. What is the impact? Probiotics of sufficient quality for patient populations are being developed and should be used accordingly. Long-term safety assessments for probiotics should be consistent with, and not more stringent than, current regulatory requirements for biologic drugs, including fecal microbial transplants. Rigor in collecting and reporting data on adverse events is needed. The authors confirm the need for understanding the entire genetic makeup of a probiotic as a cornerstone for assessing its safety.

Consuming live microbes in foods may benefit human health. Live microbe estimates have not previously been associated with individual foods in dietary databases. We aimed to estimate intake of live microbes in US children (aged 2–18 y) and adults (≥19 y) (n = 74,466; 51.2% female). Using cross-sectional data from the NHANES (2001–2018), experts assigned foods an estimated level of live microbes per gram [low (Lo), 10⁷ CFU/g]. Probiotic dietary supplements were also assessed. The mean intake of each live microbe category and the percentages of subjects who ate from each live microbe category were determined. Nutrients from foods with live microbes were also determined using the population ratio method. Because the Hi category comprised primarily fermented dairy foods, we also looked at aggregated data for Med or Hi (MedHi), which included an expanded range of live microbe–containing foods, including fruits and vegetables. Our analysis showed that 52%, 20%, and 59% of children/adolescents, and 61%, 26%, and 67% of adults, consumed Med, Hi, or MedHi foods, respectively. Per capita intake of Med, Hi, and MedHi foods was 69, 16, and 85 g/d for children/adolescents, and 106, 21, and 127 g/d for adults, respectively. The proportion of subjects who consumed live microbes and overall per capita intake increased significantly over the 9 cycles/18-y study period (0.9–3.1 g/d per cycle in children across categories and 1.4 g/d per cycle in adults for the Med category). This study indicated that children, adolescents, and adults in the United States steadily increased their consumption of foods with live microbes between the earliest (2001–2002) and latest (2017–2018) survey cycles. Additional research is needed to determine the relations between exposure to live microbes in foods and specific health outcomes or biomarkers.

To evaluate whether a fermented dairy drink containing the probiotic strain Lactobacillus casei DN-114 001 could reduce the incidence of common infectious diseases (CIDs) and the change of behavior because of illness in children. We conducted a double-blinded, randomized, placebo-controlled allocation concealment clinical trial in the Washington, DC metropolitan area. Participants were 638 children 3–6 years old in daycare/schools. The intervention was a fermented dairy drink containing a specific probiotic strain or matching placebo with no live cultures for 90 consecutive days. Two primary outcomes were assessed: incidence of CIDs and change of behavior because of illness (both assessed by parental report). The rate of change of behavior because of illness was similar among active and control groups. However, the incidence rate for CIDs in the active group (0.0782) is 19% lower than that of the control group (0.0986) (incidence rate ratio=0.81, 95% CI: 0.65, 099) P=0.046. Daily intake of a fermented dairy drink containing the probiotic strain L. casei DN-114 001 showed some promise in reducing overall incidence of illness, but was primarily driven by gastrointestinal infections and there were no differences in change of behavior.

Research from JAMA Pediatrics — The Trial of Infant Response to Diphenhydramine — The TIRED Study—A Randomized, Controlled, Patient-Oriented Trial

Background: Depression, a disabling mental disorder, adversely affects work, sleeping and eating habits, and family. Research does not exist on depression among athletes who have recently graduated from college and retired from their sport after exhausting their collegiate eligibility. Hypothesis: Changes in lifestyle and loss of personal identity, which follow college athletics, would put former college athletes at an increased risk for depression. Methods: A survey was sent to former (n = 163) and current (n = 117) college athletes to correlate depression and retirement from athletics. Results: Depression levels were significantly higher (P = 0.03) in current college athletes (16.77%, n = 27) compared with former, graduated college athletes (8.03%, n = 9). Conclusion: Completion of college sports may not increase levels of depression. There is a need for increased awareness, education, screening, and intervention for depression in college athletes. Clinical Relevance: This study suggests that student athletes’ depression levels should be monitored during their participation in college sports.

Objective. Medicine is shifting from a doctor-centered approach to a model entailing more shared decision-making. Many organizations now recommend a shared-decision approach to treating children with acute otitis media (AOM). Our primary objectives in this study were to assess (1) which style of decision-making on the physician's part would most effectively reduce parents' proclivity to use antibiotics for treatment of their child's AOM and (2) parental satisfaction with different doctor-patient decision-making styles.