The dynamic gut: the vertebrate gastrointestinal tract and associated microbiome exhibit physiological flexibility...

In this Review, we consider evidence for the adaptive digestion hypothesis (ADH), which proposes that digestive enzyme and transporter levels should usually relate positively to levels of their respective dietary substrates. In this way, energy is not wasted in maintaining the molecular machinery needed to hydrolyze and absorb substrates that are present at low levels. Genomic, transcriptomic and functional studies generally support this notion, as observed from evolutionary transitions to starch-rich diets in avian and mammalian lineages, and comparative studies in mammals, birds and fish specializing on different diets (e.g. plants, flesh, fruit, nectar, insects). Furthermore, studies of vertebrates' microbiomes provide evidence of large-scale shifts in microbial taxonomy and function in accordance with the specialized dietary strategies of hosts across evolutionary time scales. Omnivorous vertebrates commonly exhibit phenotypic matching of digestive enzyme and/or transport activity to changes in major caloric substrates, as predicted by the ADH. The regulation of these activities may involve interactions among various cell types and includes responses on time scales ranging from minutes to days. New evidence outlines molecular and cellular interactions regulating apparently synchronous changes in the transcription of enzymes and transporters in response to higher levels of dietary carbohydrate; however, further research is necessary to determine whether such changes reflect actual or pseudo-coordination. Overall, the study of molecular regulatory mechanisms in both hosts and their microbiomes across animal taxa will shed light on the coordination of digestive adaptation and modulation.