Nutrients, Vol. 18, Pages 358: Microbiota-Derived Metabolites Associated with Oats and Bran Attenuate Inflammation and Oxidative Stress via the Keap1-Nrf2 Pathway in Zebrafish
Nutrients doi: 10.3390/nu18020358
Authors:
Wen Duan
Tong Li
Yuyu Zhang
Baoguo Sun
Rui Hai Liu
Background/Objectives: Oats and oat bran are rich in polyphenols and soluble fiber, which are metabolized by gut microbiota into bioactive compounds. Previous studies identified ursodeoxycholic acid (UDCA), 3-(3-hydroxyphenyl)propionic acid (3-HPP), and avenanthramide C (AVC) as key microbial metabolites with protective effects against colitis. Methods: This study aimed to elucidate their antioxidant and anti-inflammatory activities and underlying mechanisms using LPS-induced RAW 264.7 macrophages and AAPH-induced oxidative stress in zebrafish embryos. All three metabolites significantly reduced intracellular reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and pro-inflammatory cytokines (IL-6, TNF-α). They also restored mitochondrial membrane potential and enhanced superoxide dismutase (SOD) activity. Results:In vivo, treatment improved zebrafish survival, normalized SOD activity to 76–89% of control levels, and decreased ROS and MDA by 2.4 to 3.8 fold, with UDCA showing the greatest efficacy. Molecular docking revealed strong binding affinities to Keap1, particularly UDCA, which interacted with residues Met577, Ala440, Val532, and Val486. qRT-PCR further demonstrated downregulation of Keap1 and upregulation of Nrf2 and SOD, indicating activation of the Keap1-Nrf2 pathway. Conclusions: Collectively, these findings show that oats and bran-derived microbial metabolites exert potent antioxidant and anti-inflammatory effects via modulation of the Keap1-Nrf2 axis. Among the metabolites, UDCA exhibited the strongest biological activity at equivalent concentrations. This study provides mechanistic insight into how microbiota-derived oat metabolites contribute to redox balance and immune regulation, supporting their potential as functional components in dietary strategies for managing oxidative stress-related inflammatory diseases.
Background/Objectives: Oats and oat bran are rich in polyphenols and soluble fiber, which are metabolized by gut microbiota into bioactive compounds. Previous studies identified ursodeoxycholic acid (UDCA), 3-(3-hydroxyphenyl)propionic acid (3-HPP), and avenanthramide C (AVC) as key microbial metabolites with protective effects against colitis. Methods: This study aimed to elucidate their antioxidant and anti-inflammatory activities and underlying mechanisms using LPS-induced RAW 264.7 macrophages and AAPH-induced oxidative stress in zebrafish embryos. All three metabolites significantly reduced intracellular reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA), and pro-inflammatory cytokines (IL-6, TNF-α). They also restored mitochondrial membrane potential and enhanced superoxide dismutase (SOD) activity. Results:In vivo, treatment improved zebrafish survival, normalized SOD activity to 76–89% of control levels, and decreased ROS and MDA by 2.4 to 3.8 fold, with UDCA showing the greatest efficacy. Molecular docking revealed strong binding affinities to Keap1, particularly UDCA, which interacted with residues Met577, Ala440, Val532, and Val486. qRT-PCR further demonstrated downregulation of Keap1 and upregulation of Nrf2 and SOD, indicating activation of the Keap1-Nrf2 pathway. Conclusions: Collectively, these findings show that oats and bran-derived microbial metabolites exert potent antioxidant and anti-inflammatory effects via modulation of the Keap1-Nrf2 axis. Among the metabolites, UDCA exhibited the strongest biological activity at equivalent concentrations. This study provides mechanistic insight into how microbiota-derived oat metabolites contribute to redox balance and immune regulation, supporting their potential as functional components in dietary strategies for managing oxidative stress-related inflammatory diseases. Read More