Review: Mechanism of herbivores synergistically metabolizing toxic plants through liver and intestinal microbiota

Interspecific interactions are central to ecological research. Plants produce toxic plant secondary metabolites (PSMs) as a defense mechanism against herbivore overgrazing, prompting their gradual adaptation to toxic substances for tolerance or detoxification. P450 enzymes in herbivore livers bind to PSMs, whereas UDP-glucuronosyltransferase and glutathione S-transferase increase the hydrophobicity of the bound PSMs for detoxification. Intestinal microorganisms such as Bacteroidetes metabolize cellulase and other macromolecules to break down toxic components. However, detoxification is an overall response of the animal body, necessitating coordination among various organs to detoxify ingested PSMs. PSMs undergo detoxification metabolism through the liver and gut microbiota, evidenced by increased signaling processes of bile acids, inflammatory signaling molecules, and aromatic hydrocarbon receptors. In this context, we offer a succinct overview of how metabolites from the liver and gut microbiota of herbivores contribute to enhancing metabolic PSMs. We focused mainly on elucidating the molecular communication between the liver and gut microbiota involving endocrine, immune, and metabolic processes in detoxification. We have also discussed the potential for future alterations in the gut of herbivores to enhance the metabolic effects of the liver and boost the detoxification and metabolic abilities of PSMs.