Variability in interkingdom gut microbiomes between different commercial vendors shapes fat gain in response to diet
Authors: Mims Tahliyah S. , Al Abdallah Qusai , Watts Sydney , White Catrina , Han Joan , Willis Kent A. , Pierre Joseph Francis 
Published: April 2020

The source of commercial research animals can influence biomedical research findings, despite controlled experimental conditions. Metabolism is intricately influenced by diet, host genetics, environment, and the microbiome. Since commercial vendors supply specific pathogen free mice on equivalent genetic backgrounds derived in unique facilities, thus likely containing unique microbiomes, we utilized this natural experiment to examine the interkingdom communities of each vendor upon weight gain, body fat %, liver histology, and serum biochemistries in response to dietary challenge. Male and female C57BL/6 mice were purchased from Charles River (CR), Envigo (Env), Taconic (Tac), and Jackson Labs (Jax) for baseline assessment or randomized to 8 weeks of purified high fat (HF), low fat (LF), or chow with biweekly MRI. Mice were maintained in microisolators to prevent cross contamination. At baseline, Jax mice contained high levels of the bacteria Allobaculum, S247, Akkermansia and fungi Thermomyces and Penicillium, while other vendors contained the bacteria Clostridiales and the fungi Cladosporium, which were nearly undetectable in Jax. Tac contained extremely high levels of Lactobacillus and high levels of the Fungi Wallemia. Env and CR contained the fungi Fusariumand the bacteria Candidatus Arthromitus (segmented filamentous bacteria), which was not present in Tac or Jax. Sex specific responses were observed following 8‐weeks of dietary intervention, so sexes were analyzed independently. CR and Env males gained the most body fat on purified HF and LF while Tac and Jax gained the least. Assessment of liver adiposity by histology and serum triglyceride found high lipid levels in Env males on HF, while Jax males were the lowest. Following HF, Env males displayed elevated Lactococcus, CR displayed Lactobacillus, Jax displayed Allobaculum, and Tac displayed S247, Ruminococcus, and Desulfovibrio. CR males displayed 7 unique fungi on HF, while Env and Jax exhibited Aspergillus. Under LF, CR males were dominated by the bacteria Lactococcus while Jax and Tac males displayed elevated Allobaculum. Env males displayed high levels of the fungi Trichothecium on LF. Female mice from CR and Jax gained the most fat on HF, while Tac and Env gained the least. CR females displayed high Lactobacillus on HF, while Env, Jac and Tac displayed S247. CR females on LF also exhibited high levels of Lactobacillus, while Env and Tac contained elevated Clostridiales. Our findings demonstrate the source of commercially available animals result in variable metabolic outcomes in response to diet. By surveying intestinal microorganism membership against host metabolic responses to diet, we identified microbial taxa associated with fat gain, including Lactococcus spp and Lactobacillus, and taxa associated with protection against fat gain, such as Allobaculum. This study demonstrates the significance of gut microbial membership in shaping metabolic outcomes under genetic and environmentally controlled conditions and may lead to the identification of key microbial regulators of fat homeostasis under varying dietary intakes.