A Microbial Endocrinology-Designed Discovery Platform to Identify Histamine-Degrading Probiotics: Proof of Concept in Poultry

Histamine is a biogenic amine found across the phylogenetic spectrum, from plants to fish to animals. In farm animal production, the host's production of histamine within the intestinal tract serves as a neurotransmitter, facilitating communication from the gut to the brain. Histamine functions additionally as a "bridging" chemical between the immune and nervous systems as it facilitates nervous system modulation of host immune response, thereby playing a critical role in host defense within the gut. Increased histamine levels within the gut, whether originating from food-borne sources or produced in situ, can lead to immune dysregulation and consequent physiological harm. As such, control of histamine within the gut can improve overall gut health across a broad range of species. In the present study, we utilized a Microbial Endocrinology-based approach as a platform technology to enable the discovery of unique histamine-degrading bacteria within the gut microbiota. Broiler chickens were fed, or not, a low or high histamine-supplemented diet from one day of age to up to 42 days in order to encourage the increased abundance of putative histamine-degrading bacteria. Intestinal contents were employed in a discovery protocol that involved repeated isolation rounds utilizing a histamine-supplemented minimal medium. We herein report the discovery that the genus <i>Brevibacterium</i> are capable of up to 100% degradation of histamine in vitro. Feeding experiments utilizing one of the identified <i>Brevibacterium</i> spp., a <i>B. sediminis</i> isolate, demonstrated that it reduced the amount of histamine in the gut of broilers fed a histamine-containing diet and enabled an improvement in growth as compared to non-<i>B. sediminis</i>-supplemented animals. As such, this study demonstrates the usefulness of a Microbial Endocrinology-based approach for the discovery of bacteria that may serve as potential probiotic candidates for the control of neurochemical-mediated interactions within the host, thereby improving host health.