Is the Microbial Status an Extrinsic, Intrinsic, or Intermediate Influence on Experimental Animals?

Living entities, inlcuding laboratory animals, are composed of the host and its associated microbial communities and defined as holobionts. The host genotype and its microbiome drive together as a metagenome, the holobiont phenotype, with the microbiome itself as a well-recognized source of phenotypic variation. Multiple environmental (diet, light/dark cycles, etc.) as well as host-related factors (genotype, maternal effect, etc.) not only influence the animal experimental phenotype but also contribute to the shaping of the microbiome, raising the question of whether the microbiome of experimental animals represents an extrinsic, intrinsic, or intermediate influence. Currently, there is sufficient evidence that microbial communities at different body sites are shaped by distinct endogenous and exogenous factors, indicating that the host does not leave its microbial status to chance but instead actively modulates it through host-specific mechanisms, despite extrinsic influences. This leads to a microbiome that reflects a 'fingerprint' of its own endogenous and exogenous influences. This suggests that the microbiome of experimental animals is an intermediate factor with both intrinsic and extrinsic components and underscores the importance of refining the selection of the appropriate metagenome for each specific rodent experiment.