AhR Plasma Agonist Activity following Plant-Based versus Western Omnivorous Diets in Healthy Individuals

Abstract

Human plasma includes a variety of Aryl-Hydrocarbon-Receptor (AhR) ligands sourced from dietary intake and intestinal microbial activity. The presence and levels of these ligands can be influenced by dietary changes. Plant-based or vegan diets could positively influence immune responses and intestinal homeostasis in various inflammatory diseases, potentially by modulating the AhR activity. We hypothesized that a plant-based diet would alter gut microbiome composition and reduce AhR plasma agonist activity in contrast to effects of an unhealthy Western diet, as explored in our "Targeting AhR-dependent Inflammation for Organ Protection" consortium (TAhRget-Study, Identifier DRKS00031965). In addition, we hypothesized that the effects on AhR activity and microbiome composition promote a protective immune profile. We randomized 12 healthy female and male participants to follow contrasting dietary interventions for 3 days in a highly controlled inpatient environment at the DLR :envihab facility: either a whole food plant-based diet, or a Western diet (3 men and 3 women in each group). The plant-based diet was isocaloric, rich in anti- omega-3 fatty acids, contained low levels of saturated fats, cholesterol, and Omega-6 fatty acids, and a high fiber content. In contrast, the Western diet was hypercaloric, rich in salt, saturated fats, cholesterol, and pro-inflammatory n-6 fatty acids, with an unfavorable Omega-3 to Omega-6 ratio and a low fiber content. Throughout the study, we assessed physiological readouts and collected blood, urine, stool, and peripheral blood mononuclear cells (PBMCs) for deep phenotyping focusing on gut microbiome, immunity, and AhR activation markers. Using a cell based AhR luciferase reporter assay, we observed a longitudinal incremental reduction in AhR activity by 15±10% (repeated measurement two-way ANOVA time x diet, p=0.002) attributed to the whole food plant-based diet. These results were supported by a reduction in AhR target gene expression. Ongoing analyses include gut microbiome composition and function, immune phenotypes as well as AhR ligand profiles. Thereby we aim to identify dietary components that impact AhR-mediated inflammatory risk in health-to-disease transition.