Positive Health Outcomes Associated with Live Microbe Intake from Foods, Including Fermented Foods, Assessed using the NHANES Database.

BACKGROUND: Live dietary microbes have been hypothesized to contribute to human health but direct evidence is lacking. OBJECTIVES: This study aimed to determine whether the dietary consumption of live microbes is linked to improved health outcomes. METHODS: Data from the NHANES 2001-2018 were used to assess microbial intake and their adjusted associations with selected physiological parameters (e.g., blood pressure, anthropometric measures, and biomarkers) among adults aged 19 y and older. Regression models were constructed to assess the microbial intake with each physiological parameter and adjusted for demographics and other covariates. Microbial intake was assessed as both a continuous variable and a 3-level categorical variable. Fermented foods were assessed in a separate model. RESULTS: In continuous models, an additional 100-g intake of microbe-containing foods was associated with a lower systolic blood pressure (regression coefficient: -0.331; 95% CI: -0.447, -0.215 mm Hg), C-reactive protein (-0.013; 95% CI: -0.019, -0.008 mg/dL), plasma glucose -0.347; 95% CI: -0.570, -0.124 mg/dL), plasma insulin (-0.201; 95% CI: -0.304, -0.099 µU/mL), triglyceride (-1.389; 95% CI: -2.672, -0.106 mg/dL), waist circumference (-0.554; 95% CI: -0.679, -0.428 cm), and BMI -0.217; 95% CI: -0.273, -0.160 kg/m2) levels and a higher level of high density lipoprotein cholesterols (0.432; 95% CI: 0.289, 0.574 mg/dL). Patterns were broadly similar when microbial intake was assessed categorically and when fermented foods were assessed separately. CONCLUSIONS: To our knowledge, this study is the first to quantify, in a nationally representative data set of American adults and using stable sets of covariates in the regression models, the adjusted associations of dietary intakes of live microbes with a variety of outcomes, such as anthropometric measures, biomarkers, and blood pressure levels. Our findings suggest that foods with higher microbial concentrations are associated with modest health improvements across a range of outcomes.

A Classification System for Defining and Estimating Dietary Intake of Live Microbes in US Adults and Children.

BACKGROUND: Consuming live microbes in foods may benefit human health. Live microbe estimates have not previously been associated with individual foods in dietary databases. OBJECTIVES: 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). METHODS: Using cross-sectional data from the NHANES (2001-2018), experts assigned foods an estimated level of live microbes per gram [low (Lo), <104 CFU/g; medium (Med), 104-107 CFU/g; or high (Hi), >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. RESULTS: 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). CONCLUSIONS: 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.

Should There Be a Recommended Daily Intake of Microbes?

The collective findings from human microbiome research, randomized controlled trials on specific microbes (i.e., probiotics), and associative studies of fermented dairy consumption provide evidence for the beneficial effects of the regular consumption of safe live microbes. To test the hypothesis that the inclusion of safe, live microbes in the diet supports and improves health, we propose assessment of the types and evidentiary quality of the data available on microbe intake, including the assembly and evaluation of evidence available from dietary databases. Such an analysis would help to identify gaps in the evidence needed to test this hypothesis, which can then be used to formulate and direct initiatives focused on prospective and randomized controlled trials on live microbe consumption. Outcomes will establish whether or not the evidence exists, or can be generated, to support the establishment of dietary recommendations for live microbes.

Is There Evidence to Support Probiotic Use for Healthy People?

Probiotics are typically marketed as foods and dietary supplements, categories for products intended to maintain health in generally healthy populations and which, unlike drugs, cannot claim to treat or cure disease. This review addresses the existing evidence that probiotics are beneficial to healthy people. Our approach was to perform a descriptive review of efficacy evidence that probiotics can prevent urinary, vaginal, gastrointestinal, and respiratory infections, and improve risk factors associated with cardiovascular health or reduce antibiotic use. Other endpoints such as mental, dental, or immune health were not specifically addressed. We concluded that there is sufficient evidence of efficacy and safety for clinicians and consumers to consider using specific probiotics for some indications - such as the use of probiotics to support gut function during antibiotic use or to reduce the risk of respiratory tract infections - for certain people. However, we did not find a sufficiently high level of evidence to support unconditional, population-wide recommendations for other preventive endpoints we reviewed for healthy people. Although evidence for some indications is suggestive of the preventive benefits of probiotics, additional research is needed.

Frequently asked questions about the ISAPP postbiotic definition.

The term postbiotic was defined by the International Scientific Association of Probiotics and Prebiotics (ISAPP) as "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host." Although the ISAPP definition is widely cited, some concerns were aired after publication, and alternative definitions of postbiotic, as well as different terms for inactivated microbes, have been previously suggested. This paper addresses questions about the ISAPP definition that have been raised in different forums, including scientific meetings, social media commentary and personal communications. We focus on the rationale, scope, wording, composition and commercial implementation, as well as what is expected of postbiotics regarding safety, efficacy, quantification and mechanisms of action. We hope that exploring these questions will further clarify the definition and its scope and support a common understanding of the concept of postbiotics.

Postbiotics in the medical field under the perspective of the ISAPP definition: scientific, regulatory, and marketing considerations.

Diverse terms have been used in the literature to refer to the health benefits obtained from the administration of non-viable microorganisms or their cell fragments and metabolites. In an effort to provide continuity to this emerging field, the International Scientific Association of Probiotics and Prebiotics (ISAPP) convened a panel of experts to consider this category of substances and adopted the term postbiotic, which they defined as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host." This definition does not stipulate any specific health benefit, finished product, target population or regulatory status. In this perspective article, we focused on postbiotics developed for pharmaceutical uses, including medicinal products and medical devices. We address how this field is regulated for products based on inanimate microorganisms, marketing considerations and existing examples of postbiotics products developed as cosmetics for the skin, for vaginal health, and as orally consumed products. We focus on the European Union for regulatory aspects, but also give examples from other geographical areas.

Emerging issues in probiotic safety: 2023 perspectives.

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.

The Concept of Postbiotics.

The scientific community has proposed terms such as non-viable probiotics, paraprobiotics, ghostbiotics, heat-inactivated probiotics or, most commonly, postbiotics, to refer to inanimate microorganisms and/or their components that confer health benefits. This article addresses the various characteristics of different definitions of 'postbiotics' that have emerged over past years. In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined a postbiotic as "a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". This definition of postbiotic requires that the whole or components of inactivated microbes be present, with or without metabolic end products. The definition proposed by ISAPP is comprehensive enough to allow the development of postbiotics from different microorganisms, to be applied in different body sites, encouraging innovation in a promising area for any regulatory category and for companion or production animals, and plant or human health. From a technological perspective, probiotic products may contain inanimate microorganisms, which have the potential to impart a health benefit. However, their contribution to health in most cases has not been established, even if at least one probiotic has been shown to confer the same health benefit by live or inanimate cells.