Courtney J. Smith

Courtney J. Smith

MD/PhD Student in Genetics at Stanford University | Lab of Jonathan Pritchard

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publications

Short-Term Dairy Product Elimination and Reintroduction Minimally Perturbs the Gut Microbiota in Self-Reported Lactose-Intolerant Adults Permalink

Published in American Society for Microbiology, 2022

An outstanding question regarding the human gut microbiota is whether and how microbiota-directed interventions influence host phenotypic traits. Here, we employed a dietary intervention to probe this question in the context of lactose intolerance. Lactose intolerance is a gastrointestinal disorder diagnosed with a lactose hydrogen breath test. Lifestyle changes such as diet interventions can impact the gut microbiome; however, the role of the microbiome in lactose intolerance is unclear. Our study assessed the effects of a 12-week dietary dairy product elimination and (re)introduction on the microbiome and clinical lactose intolerance status in 12 adult self-reported lactose-intolerant individuals. We found each subject’s gut microbiome remained highly individualized and largely stable in the face of this diet manipulation. We also report that none of the subjects showed change in a clinically defined measure of lactose tolerance.

Link to the code for the paper here.
Read the full paper here.

Recommended citation: Smith, Courtney J et al. (2022). "Short-Term Dairy Product Elimination and Reintroduction Minimally Perturbs the Gut Microbiota in Self-Reported Lactose-Intolerant Adults." mBio vol.13,3:e0105122. doi:10.1128/mbio.01051-22.

Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation Permalink

Published in eLife, 2022

This paper explores the use of the extensive amount of known biology of metabolites and the biochemical pathways involved in their formation and breakdown to investigate the molecular basis of pleiotropy and genetic correlation. To do this, we first performed GWAS of 16 NMR metabolites in ~100,000 UK Biobank individuals, including those invovled in glycolysis, ketone formation and breakdown, and amino acid metabolism. This resulted in 213 independent signals across the genome significantly associated with a change in levels in at least one of the metabolites. From there, we worked backwards from the known biochemistry to annotate these variants, the majority of which were in noncoding regions. We found 68 variants were likely affecting genes encoding pathway relevant enzymes, 40 affecting transporter genes, and 30 TFs. The substantial enrichment for biologically interpretable variants reinforced the use of metabolites as model traits for examining the molecular mechanisms underlying pleiotropy.

See detailed tutorial of the paper with annotations of key figures at my Twitter tutorial here.
Link to code for the paper here.
Read the full paper here.

Recommended citation: Courtney J Smith, Nasa Sinnott-Armstrong, Anna Cichońska, Heli Julkunen, Eric B Fauman, Peter Würtz, Jonathan K Pritchard (2022). "Integrative analysis of metabolite GWAS illuminates the molecular basis of pleiotropy and genetic correlation" eLife 11:e79348. https://doi.org/10.7554/eLife.79348.

Factors of Transurethral Incision Effectiveness for Ureteroceles in Pediatric Patients: A 28-year, Single-Institution Retrospective Review Permalink

Published in Journal of Pediatric Urology, 2023

As a congenital anomaly, ureteroceles occur in 1 in 4000 children, and are usually diagnosed prenatally. Initial management typically includes early transurethral incision (TUI) of ureterocele, or observation with the option for lower urinary tract reconstruction once the patient is older. There is currently no consensus on best practices for the decision between initial TUI and conservative management. An important advantage of TUI is that it is less invasive and can be performed on patients soon after birth. However, many physicians delay treatment until the patients are older and able to undergo alternative options such as lower urinary tract reconstruction. Thus, identification of factors that accurately predict TUI success in pediatric ureterocele patients will enable more informed management decisions, earlier treatment, better patient outcomes, and decreased financial burden related to additional surgeries. Here, we leverage our institutional database records from 1993 to 2021 to evaluate the effectiveness of initial TUI ureterocele in 75 pediatric patients and identify pre- and post-operative factors that correlated with TUI effectiveness. We find initial TUI was an effective procedure for the majority of our pediatric ureterocele patients, a higher success rate compared to other cohorts. Patients with a simplex system were more likely to have an effective first TUI than patients with duplex systems, as were patients without preoperative reflux. Although not statistically significant, our data suggest prior UTI, prenatal diagnosis, higher preoperative hydronephrosis grade, and the use of electrocautery may be associated with having additional surgeries.

Link to the code for the paper here.
Link to the full paper here.

Recommended citation: Smith, Brian R* and Smith, Courtney J* et al. (2023). "Factors of transurethral incision effectiveness for ureteroceles in pediatric patients: A 28-year, single-institution retrospective review." Journal of Pediatric Urology S1477-5131(23)00070-0. doi:10.1016/j.jpurol.2023.02.020.
*These authors contributed equally