The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics

Kelly S Swanson, Glenn R Gibson, Robert Hutkins, Raylene A Reimer, Gregor Reid, Kristin Verbeke, Karen P Scott, Hannah D Holscher, Meghan B Azad, Nathalie M Delzenne, Mary Ellen Sanders, Kelly S Swanson, Glenn R Gibson, Robert Hutkins, Raylene A Reimer, Gregor Reid, Kristin Verbeke, Karen P Scott, Hannah D Holscher, Meghan B Azad, Nathalie M Delzenne, Mary Ellen Sanders

Abstract

In May 2019, the International Scientific Association for Probiotics and Prebiotics (ISAPP) convened a panel of nutritionists, physiologists and microbiologists to review the definition and scope of synbiotics. The panel updated the definition of a synbiotic to "a mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host". The panel concluded that defining synbiotics as simply a mixture of probiotics and prebiotics could suppress the innovation of synbiotics that are designed to function cooperatively. Requiring that each component must meet the evidence and dose requirements for probiotics and prebiotics individually could also present an obstacle. Rather, the panel clarified that a complementary synbiotic, which has not been designed so that its component parts function cooperatively, must be composed of a probiotic plus a prebiotic, whereas a synergistic synbiotic does not need to be so. A synergistic synbiotic is a synbiotic for which the substrate is designed to be selectively utilized by the co-administered microorganisms. This Consensus Statement further explores the levels of evidence (existing and required), safety, effects upon targets and implications for stakeholders of the synbiotic concept.

Conflict of interest statement

K.S.S. has received funding from Ingredion, Beneo GmbH and Gnubiotics Sciences. G.R.G. currently receives research funding from GlaxoSmithKline, Pukka Herbs, and consulted for Clasado and Pepsico. G.R. has consulted for Seed, KGK Science, Acerus Pharmaceuticals, Danone, Chris Hansen, Altmann, Kimberly Clark and Metagenics. R.H. has received grants or honoraria from Mead Johnson Nutrition, Pharmavite, Danone, Beachbody, and PepsiCo and is a co-owner of Synbiotic Health. R.A.R. has received presentation honoraria from Beneo and research funding from General Mills and Sensus. K.V. received presentation honoraria from Beneo and Yakult, consultancy fees from Comet Bio and research funding from Nestlé. K.P.S. currently receives research funding from Probi and has received presentation honoraria from Yakult. H.D.H. has received presentation honoraria from Kellogg’s, PepsiCo and Nutricia North America. M.B.A. has received grants and presentation honoraria from Prolacta Biosciences and presentation honoraria from Medela. M.E.S. has been compensated for consulting, serving on advisory boards or for speaking engagements from California Dairy Research Foundation, Church & Dwight, Clorox, Danone North America, Danone Research, General Mills, Georgetown, GlaxoSmithKline, International Scientific Association for Probiotics and Prebiotics, JHeimbach LLC, Kellogg, Kerry, Mead Johnson, PepsiCo, Probi, Trouw, Visalia Dairy Company, Winclove, Yakult and Yakult Foundation of India. N.M.D. declares no competing interests.

Figures

Fig. 1. Synbiotic categories.
Fig. 1. Synbiotic categories.
Synbiotics can be formulated using two approaches. A complementary synbiotic comprises a probiotic plus a prebiotic (more than one of each can be used), working independently to achieve one or more health benefits. Probiotic and prebiotic components of the complementary synbiotic must meet the minimum criteria, as stipulated previously,. A synergistic synbiotic is composed of a live microorganism and a selectively utilized substrate but neither needs to meet the minimum criteria stipulated previously for probiotics and prebiotics. Instead, these components are designed to work together, with the substrate being selectively utilized by the co-administered microorganism. The panel considered whether all synbiotics should be synergistic. However, the absence of such substances today speaks to the difficulty of achieving the required evidence. The panel judged that it was more important for the definition to be useful rather than hypothetical.
Fig. 2. Design and mechanisms of action…
Fig. 2. Design and mechanisms of action of complementary and synergistic synbiotics.
Two approaches to designing synbiotics are represented here. The complementary approach combines a prebiotic and a probiotic that work independently to elicit one or more health benefits. The prebiotic and probiotic must each meet applicable criteria (Table 3). The prebiotic functions by modulating the resident microbiota in a manner associated with an improved health outcome. The synergistic approach selects a substrate that is utilized by the co-administered live microorganism, enhancing its functionality. Synergistic synbiotics work together (not independently) to bring about the resulting health benefits.

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