Research in the Carey Laboratory uses hibernating mammals as models for adaptation to extreme changes in physiology and nutrition that occur on a seasonal basis, with a focus on the gastrointestinal tract and liver. Current studies in the laboratory are examining the symbiotic relationship between mammalian hibernators and their gut microbes.

Our laboratory also uses hibernators as models for identifying natural mechanisms for protection against stress and trauma conditions, including liver cold ischemia (e.g., during organ storage) and warm ischemia/reperfusion injury in gut and liver. These projects are designed to translate basic insights gained from the hibernation phenotype to improvements in human and animal biomedicine.

The Gut Microbial Community in Mammalian Hibernation

Hibernating mammals provide a unique perspective and novel experimental opportunities to study the evolution of host-gut microbe symbioses because of their natural annual cycles of extreme dietary change. Many hibernating mammals cease food intake during winter, relying solely on stored lipids to fuel metabolism. Winter fasting in these species eliminates a major source of degradable substrates to support the growth of gut microbes, which may affect microbial community structure and host-microbial interactions. Our recent studies explored the effect of the annual hibernation cycle on gut microbiotas using deep sequencing of 16S rRNA genes from ground squirrel cecal contents. Squirrel cecal microbiotas are dominated by members of the phyla Bacteroidetes, Firmicutes and Verrucomicrobia. UniFrac analysis showed that microbiotas cluster strongly by season, and maternal influences, diet history, host age and host body temperature having minimal effects. Phylogenetic diversity is lowest in late winter, after 4-5 months of fasting, and highest in the spring after a 2-week period of refeeding. Hibernation increase relative abundance of the phyla Bacteroidetes and Verrucomicrobia, both of which contain species capable of surviving on host-derived substrates such as mucins, and reduced relative abundance of Firmicutes, many of which prefer dietary polysaccharides. The results showed that the ground squirrel microbiota is restructured each year in a manner that reflects differences in microbial preferences for dietary versus host-derived substrates, and thus the competitive abilities of different taxa to survive in the altered environment in the hibernator gut.
Our continuing studies are examining the effect of the hibernation cycle on the mucosal microbiota, a separate population that resides close to the epithelium in the mucus layer, and has more intimate contact and interactions with host tissue than the luminal microbiota. These studies will build on our previous work that demonstrated a dramatic restructuring of the intestinal immune system during the hibernation season (Carey et al. 2013), which likely reflects alterations in host-microbe communication during winter fasting when intestinal permeability increases. Our long-term goal is to understand how the annual hibernation cycle in mammals affects the structure and function of the gut microbial community, and how the microbiota influences the hibernation phenotype.