How the gut and liver hibernate

For hibernating mammals, the transition from summer active to winter hibernation seasons come with significant remodeling at cellular, organ and whole organism levels. This review summarizes and synthesizes what is known about hibernation-related remodeling in the gastrointestinal tract of the thirteen-lined ground squirrel, including intestinal and hepatic physiology and the gut microbiota. Hibernation alters intestinal epithelial, immune and cell survival pathways in ways that point to a protective phenotype in the face of prolonged fasting and major fluctuations in nutrient and oxygen delivery during torpor-arousal cycles. The prolonged fasting associated with hibernation alters lipid metabolism and systemic cholesterol dynamics, with both the gut and liver participating in these changes. Fasting also affects the gut microbiota, altering the abundance, composition and diversity of gut microbes and impacting the metabolites they produce in ways that may influence hibernation-related traits in the host. Finally, interventional studies have demonstrated that the hibernation phenotype confers resistance to experimental ischemia-reperfusion injury in both gut and liver, suggesting potential therapeutic roadmaps. We propose that the plasticity inherent to hibernation biology may contribute to this stress tolerance, and in the spirit of August Krogh, makes hibernators particularly valuable for study to identify solutions to certain problems.