Metabonomic Identification of Two Distinct Phenotypes in Sprague-Dawley (Crl:CD(SD)) Rats

Abstract

Genetic drift in animal populations has been a recognized concern for many years. Less understood is the potential for phenotypic "drift" or variation that is not related to any genetic change. Recently, stock Sprague-Dawley (Crl:CD(SD)) rats obtained from the Charles River Raleigh facility demonstrated a distinct endogenous urinary metabonomic profile that differed from historical control SD urine spectral profiles obtained over the past several years in our laboratory. In follow-up studies, the origin of the variant phenotype was narrowed down to animals of both sexes that were housed in one specific room (Room 9) in the Raleigh facility. It is likely that the two phenotypes are related to distinct populations of gut flora that particularly impact the metabolism of aromatic molecules. The most pronounced difference between the two phenotypes is the relative amounts of hippuric acid versus other aromatic acid metabolites of chlorogenic acid. Though both molecular species are present in either phenotype, the marked variation in levels of these molecules between the two phenotypes has led to the designation of high hippuric acid (HIP) and high chlorogenic acid metabolites (CA) phenotypes. Specific urinary components that distinguish the phenotypes have been thoroughly characterized by NMR spectroscopy with additional, limited characterization by LC-MS (high performance liquid chromatography coupled with mass spectrometry). Co-habitation of rats from the two phenotypes rapidly facilitated a switch of the CA phenotype to the historical Sprague-Dawley phenotype (HIP). The impact of these variant phenotypes on drug metabolism and long-term safety assessment studies (e.g., carcinogenicity bioassays) is unknown.

The immediate environment during postnatal development has long-term impact on gut community structure in pigs

“…The resultant individuality of gut communities has the potential to influence the health and well being of the host. In adult rats or mice, differences between the microbiota of individuals have been predicted or identified as a contributing factor in metabolic and physiological variations between individuals, such as metabolite profiles (Robosky et al, 2005), obesity (Ley et al, 2005;Turnbaugh et al, 2006) and drug response (Clayton et al, 2006). However, in these examples, the phenotypes are inferred to reflect comparatively stable interindividual differences of mature gut microbiotas.…”

“…As a consequence, investigations of the significance of community composition to an individual's health must focus on fine-scale diversity at the species and strain level (in rRNA terms, this approximates 97% and 99% identity, respectively). At this scale of resolution, there is evidence that community structure is a source of variation in host outcomes (Backhed et al, 2004;Robosky et al, 2005). This has given rise to the concept that diseases of relevance to humans, or growth performance issues relevant to animal production, can be linked to the quality of an individual's intestinal microbiota.…”

Standard reporting requirements for biological samples in metabolomics experiments: mammalian/in vivo experiments

“…Indeed, differentiation of various stages of the estrus cycle has been attributed to alterations in numerous components of the tricarboxylic acid cycle in urine, as well as creatine, creatinine and glucose excretion rates. Diet has far reaching influences on the metabolome, including influencing the composition of the gut microflora present within the animals (Phipps et al 1998;Robosky et al 2005). There have also been studies demonstrating that diurnal light/dark cycles have a profound influence on the metabolome of both biofluids and tissue.…”

Gut microflora may facilitate adaptation to anthropic habitat: A comparative study in Rattus

“…The diversity and composition of intestinal microbiota have been linked to several host physiological functions such as nutrient processing (Hooper, Midtvedt, & Gordon, 2002), structure and function of the digestive system (Robosky et al., 2005), as well as in regulating the immune systems of the host (Hooper, 2001). Recent advances in the field of culture‐independent techniques have brought to light several hidden interactions between hosts and their intestinal microflora.…”