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.
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.