Microbial modulation of host body composition and plasma metabolic profile

Authors: HUDA, NAZMUL - University Of California, Davis; WINNIKE, JASON - David H Murdock Research Institute; CROWELL, JOCELYN - University Of California, Davis; O'CONNOR, ANNA - University Of North Carolina; Bennett, Brian

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/26/2020
Publication Date: 4/16/2020
Citation: Huda, N.M., Winnike, J., Crowell, J., O'Connor, A., Bennett, B.J. 2020. Microbial modulation of host body composition and plasma metabolic profile. Scientific Reports. 10. https://doi.org/10.1038/s41598-020-63214-1.
DOI: https://doi.org/10.1038/s41598-020-63214-1

Interpretive Summary: The gastrointestinal tract is heavily colonized with bacteria, often referred to as the gut microbiota, which provides surface energy, and nutrients that benefit microbial growth and the health of the host. Alterations in the microbiome are thought to affect risk of obesity and chronic disease. One proposed treatment for obesity is fecal microbiome transplants (FMT). We test the effects of FMT on obesity, plasma glucose and the metabolome. For these studies we collected microbiota from 2 inbred strains of mice that differ in adiposity and glucose tolerance, C57Bl/6J and WSB/EiJ. We observe novel but unexpected interactions where FMT leads to increased adiposity but decreased plasma glucose. These results indicate that complex host-microbiota interactions exist that cannot be simply predicted by examining the phenotype of the fecal donor.

Technical Abstract: The gut microbiota is a critical mediator of nutrition and disease risk. Similar to most complex traits, the microbiome is under genetic regulation and differs between inbred strains of mice. We test the effect of fecal microbiome transplants (FMT) on obesity, and plasma glucose. For these studies we collected microbiota from 2 inbred strains of mice that differ in adiposity and glucose tolerance, C57Bl/6J and WSB/EiJ. 18 C57BL/6J mice were first treated with antibiotics for 4 weeks to ablate the microbiota. Following ablation the recipients of FMT were transplanted with either microbiota from C57Bl/6J or WSB/EiJ and the mice were assessed at 2 and 4 weeks post transplant. Unexpectedly the mice receiving WSB/EiJ microbiota had increased adiposity while having reduced plasma glucose. Metabolomic and 16S microbiota profiling indicate broad metabolic changes occurring during and after FMT. Detailed analysis of these interactions demonstrate specific microbiota:host metabolite interactions which alter disease susceptibility.