Using Data Science to Reveal Host-Microbiota Interactions that Promote Obesity During Early Life (DSI-SRP)
This DSI-SRP fellowship funded Jessica Mo to work in the laboratory of Professor Mariana Byndloss in the Department of Pathology, Microbiology, and Immunology at Vanderbilt University Medical Center during the summer of 2021. Jessica is a senior with majors in Medicine, Health, and Society and minor in Earth and Environmental Sciences.
This project centered around the gut microbiota–the commensal microbes that live in the gastrointestinal tract–and its relationship with childhood obesity. A high-fat diet and exposure to antibiotics have been identified as two environmental risk factors for childhood obesity; exposure to these factors is also thought to perturb the gut microbiota. Perturbations of the gut microbiota may change the landscape of microbiota-derived metabolites available in the gut, which in turn may impact host metabolism in a manner that facilitates weight gain. Consequently, this project revolves around the changes in the composition of the gut microbiota in response to a high-fat diet and/or antibiotics.
The Byndloss lab has developed a mouse model in which young mice are exposed to one of four treatments: low-fat diet (LFD), low-fat diet + low-dose penicillin (LFD + LDP), high-fat diet (HFD), or high-fat diet + low-dose penicillin (HFD + LDP). 16S rRNA gene sequencing was conducted on the contents of the small and large intestine. Jessica used R to analyze the 16S data, following the dada2 pipeline to ultimately assign taxonomy to sequences. Exploratory ordination plots (Fig. 1) and heat maps (Fig. 2) were created with the phyloseq package. DESeq2 was used to identify differentially abundant taxa between the treatment groups. Ordination revealed that changes in community composition appeared to be diet- and antibiotic-driven (Fig. 1). The genus Lactobacillus (highly abundant in the small intestine) is particularly interesting with regards to reduced adiposity given previous data from the lab. In the large intestine, Lactobacillus is depleted in the HFD + LDP group compared to the LFD group. In the small intestine, differential abundance analysis revealed that one Lactobacillus taxon was dramatically reduced in HFD + LDP mice compared to HFD mice. These findings indicate that Lactobacillus may play an important role in reducing childhood weight gain.
In addition to receiving support through a DSI-SRP fellowship, this project was supported and facilitated by the DSI Data Science Team through their regular summer workshops and demo sessions.