Safety assessment of probiotics for human use

The safety of probiotics is tied to their intended use, which includes consideration of potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are alive when administered, and unlike other food or drug ingredients, possess the potential for infectivity or in situ toxin production. Since numerous types of microbes are used as probiotics, safety is also intricately tied to the nature of the specific microbe being used. The presence of transferable antibiotic resistance genes, which comprises a theoretical risk of transfer to a less innocuous member of the gut microbial community, must also be considered. Genetic stability of the probiotic over time, deleterious metabolic activities, and the potential for pathogenicity or toxicogenicity must be assessed depending on the characteristics of the genus and species of the microbe being used. Immunological effects must be considered, especially in certain vulnerable populations, including infants with undeveloped immune function. A few reports about negative probiotic effects have surfaced, the significance of which would be better understood with more complete understanding of the mechanisms of probiotic interaction with the host and colonizing microbes. Use of readily available and low cost genomic sequencing technologies to assure the absence of genes of concern is advisable for candidate probiotic strains. The field of probiotic safety is characterized by the scarcity of studies specifically designed to assess safety contrasted with the long history of safe use of many of these microbes in foods

Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-bein

Gérénétion de cellules T CD4+CD25+ suppressives, induite par des lymphocytes T CD8+CD28- au cours de réactions leucocytaires mixtes autologues

La réaction mixte lymphocytaire autologue (aMLR) permet l'étude des circuits de régulation du système immunitaire et correspond à la prolifération des lymphocytes T CD4+ suite à une stimulation par des cellules dendritiques autologues (aMLRs déficientes dans: maladie de Hodgkin, syndrome de Down, lupus érythémateux systématique, arthrite rhumatoïde, cirrhose biliaire primitive, etc). Les lymphocytes T CD8+CD28- sont des cellules régulatrices capables de suppression directe de l'allo- et la xéno-réactivité de lymphocytes T CD4+ et de rendre tolérogènes des cellules dentritiques. L'objectif de notre étude est de développer un système de co-culture in vitro permettant l'étude des rôles suppresseurs des lymphocytes T CD8+CD28-. Ce sont les MLR autologues de 5 jours: (Mo-DCs . cellules T CD4+ . cellules T CD8+CD28-). Les résultats montrent une forte réponse proliférative des cellules T CD4+, qui est inhibée par des anticorps monoclonaux dirigés contre HLA DR, CD2, CD11a, CD54 et CD86 et s'accompagne d'une sécrétion d'IFN-g et d'IL-12, reflétant une réponse de typeTh1. De plus, on observe l'émergence d'une population cellulaire de phénotype CD4+ CD25+ CTLA4+ (expression intracellulaire et membranaire) CD45RA- 45RO+ au cours de l'aMLR : ces cellules, dotées par ailleurs de faibles capacités prolifératives, sont capables de supprimer par contact cellulaire la réactivité de lymphocytes T CD4+ vis-à-vis d'auto- et d'allo-antigènes présentés par des DCs matures. Notre étude montre que cette population cellulaire T CD8+CD28- pourraitégalement exercer des fonctions régulatrices indirectes en générant une population de lymphocytes T aux fonctions suppressives. Nous montrons donc qu'il est possible de générer in vitro, et dans un modèle syngénique, des lymphocytes T régulatrices CD4+CD25+. S'agit-il ici de lymhocytes générés de novo? Ou alors la MLR autologue a-t-elle permis d'amplifier une population régulatrice existante et quiescente? Ce système pourrait refléter un mécanisme intervenant dans le maintien de la tolérance périphérique, par génération de cellules T régulatrices.LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-being