Identification and Biological Characterization of a Novel NRF2 Activator Molecule Released From the Membranes of Heat‐Treated <i>Bifidobacterium breve</i> NCC 2950

Postbiotics are defined as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host". They represent an attractive alternative to probiotics as they could be used in a broader range of applications, where probiotic stability is limiting. To date knowledge on the mechanism of action of inanimate microorganisms is relatively scarce. In this study, we investigated the impact of heat treatment on NRF2 activation by several candidate probiotic strains from the Nestlé Culture Collection (NCC), including species encompassed in the Bifidobacterium genus and the Lactobacillaceae family. We identified an NRF2-activating bioactive molecule, 4-oxo-2-pentenoic acid (OPA), specifically released during heat treatment of Bifidobacterium breve NCC 2950. We explored cellular pathways that can be modulated by OPA, such as antiinflammatory signals and organismal defense against oxidative stress in zebrafish in vivo. We identified a new B. breve NCC 2950-derived postbiotic that, based on the mode of action, may have important applications for nutritional strategies to benefit human health.