286: Bioactivity of Microbial Metabolites Derived From B-Type Proanthocyanidins

Introduction

B-type proanthocyanidins (PACs) are major polyphenol constituents found in grape berries and seeds and are associated with protection against chronic metabolic disease. While parent PAC compounds are poorly absorbed, they undergo biotransformation by gut bacteria into more bioavailable microbial metabolites (MMs), which may contribute to their metabolic health benefits. While most existing research focuses on parent polyphenol compounds, the present work compared the anti-inflammatory effects of PACB2 and PAC-derived MMs in cell culture models.

Methods

To compare the anti-inflammatory activity of PACB2 and PAC-derived MMs, in vitro experiments were conducted using murine ileal organoids and RAW264.7 macrophages. Cells were treated with PACB2 or MMs (0.1-100μM) and challenged with pro-inflammatory mediators (LPS and TNFα). Supernatants were collected to measure nitrite production, and RNA was extracted for real-time quantitative PCR to measure inflammation gene markers.

Results

In ileal organoids, PACB2 and a mixture of seven PAC-derived MMs reduced inflammatory markers in a dose- and target-dependent manner. In RAW264.7 cells, PACB2 and the MM mixture exhibited dose-dependent anti-inflammatory responses. Among the MMs, four significantly suppressed inflammatory markers, while three remaining were inactive individually but may exhibit synergistic effects in combination. Ongoing experiments aim to explore potential synergistic interactions among MMs in RAW264.7 cells and investigate whether PACB2 and/or the MM mixture can stimulate glucagon-like peptide-1 (GLP-1) secretion for glucose regulation in murine ileal organoids.

Significance

The variability in gut microbial species among individuals leads to differences in PAC-derived MM production. Delivering bioactive PAC-derived metabolites directly, rather than parent PACs, may provide a more effective strategy for reducing chronic inflammation. Identifying effective metabolites could lead to novel treatments for individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D) who lack the gut bacterial strains necessary to produce these bioactive compounds.

Authors: Yue Wu, Rocio M. Duran, Diana E. Roopchand