Environmental enteric dysfunction (EED) affects 50-90% of children in low-income countries and is likely an important factor in child stunting as it impedes efficient nutrient uptake in the small intestine. EED is suspected to be the result of persistent exposure to enteric pathogens, although it has not been correlated with any specific pathogen. My research explores the interplay of gut microbiota, including enteric pathogens, and the host immune system with a focus on understanding EED so we can rationally design treatments and preventive measures.
Honors & Awards
School of Medicine Dean's Postdoctoral Fellowship, Stanford University (2021)
Stanford Interdisciplinary Graduate Fellowship, Stanford University (2015-2018)
Graduate Research Fellowship, National Science Foundation (2011-2015)
Boards, Advisory Committees, Professional Organizations
Member, Stanford Military-Affiliated Advisory Committee (2019 - Present)
Member, American Society of Tropical Medicine and Hygiene (2014 - Present)
Member, American Society for Microbiology (2009 - Present)
PhD, Stanford University (2019)
MS, Penn State University (2011)
BS, United States Military Academy at West Point (2001)
David Relman, Postdoctoral Research Mentor
Introducing riskCommunicator: An R package to obtain interpretable effect estimates for public health.
2022; 17 (7): e0265368
Common statistical modeling methods do not necessarily produce the most relevant or interpretable effect estimates to communicate risk. Overreliance on the odds ratio and relative effect measures limit the potential impact of epidemiologic and public health research. We created a straightforward R package, called riskCommunicator, to facilitate the presentation of a variety of effect measures, including risk differences and ratios, number needed to treat, incidence rate differences and ratios, and mean differences. The riskCommunicator package uses g-computation with parametric regression models and bootstrapping for confidence intervals to estimate effect measures in time-fixed data. We demonstrate the utility of the package using data from the Framingham Heart Study to estimate the effect of prevalent diabetes on the 24-year risk of cardiovascular disease or death. The package promotes the communication of public-health relevant effects and is accessible to a broad range of epidemiologists and health researchers with little to no expertise in causal inference methods or advanced coding.
View details for DOI 10.1371/journal.pone.0265368
View details for PubMedID 35849588
Advantageous microbial community development and improved performance of pilot-scale field systems treating high-risk acid mine drainage with crab shell.
Journal of hazardous materials
2021; 420: 126665
Microbial communities are crucial to the effectiveness and stability of bioremediation systems treating acid mine drainage (AMD); however, little research has addressed how they correlate to system performance under changing environmental conditions. In this study, 16S rRNA gene sequencing and quantitative PCR (qPCR) were used to characterize microbial communities within different substrate combinations of crab shell (CS) and spent mushroom compost (SMC) and their association with chemical performance in pilot-scale vertical flow ponds (VFPs) treating high risk AMD in central Pennsylvania over 643 days of operation. As compared to a control containing SMC, VFPs containing CS sustained higher alkalinity, higher sulfate-reducing rates, and more thorough metals removal (>90% for Fe and Al, >50% for Mn and Zn). Correspondingly, CS VFPs supported the growth of microorganisms in key functional groups at increasing abundance and diversity over time, especially more diverse sulfate-reducing bacteria. Through changing seasonal and operational conditions over almost two years, the relative abundance of the core phyla shifted in all reactors, but the smallest changes in functional gene copies were observed in VFPs containing CS. These results suggest that the high diversity and stability of microbial communities associated with CS are consistent with effective AMD treatment.
View details for DOI 10.1016/j.jhazmat.2021.126665
View details for PubMedID 34351284
High-throughput low-cost nl-qPCR for enteropathogen detection: A proof-of-concept among hospitalized patients in Bangladesh.
2021; 16 (10): e0257708
BACKGROUND: Diarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients.METHODS: A census-based study was conducted among diarrheal patients admitted at two government hospitals in rural Bangladesh during a diarrheal outbreak period. DNA was extracted from stool samples and assayed by nl-qPCR for common bacterial, protozoan, and helminth enteropathogens as the primary outcome.RESULTS: A total of 961 patients were enrolled; stool samples were collected from 827 patients. Enteropathogens were detected in 69% of patient samples; More than one enteropathogen was detected in 32%. Enteropathogens most commonly detected were enteroaggregative Escherichia coli (26.0%), Shiga toxin-producing E.coli (18.3%), enterotoxigenic E. coli (15.5% heat stable toxin positive, 2.2% heat labile toxin positive), Shigella spp. (14.8%), and Vibrio cholerae (9.0%). Geospatial analysis revealed that the median number of pathogens per patient and the proportion of cases presenting with severe dehydration were greatest amongst patients residing closest to the study hospitals."CONCLUSIONS: This study demonstrates a proof-of-concept for nl-qPCR as a high-throughput low-cost method for enteropathogen detection among hospitalized patients.
View details for DOI 10.1371/journal.pone.0257708
View details for PubMedID 34597302
Effect of water, sanitation, handwashing and nutrition interventions on enteropathogens in children 14 months old: a cluster-randomized controlled trial in rural Bangladesh.
The Journal of infectious diseases
BACKGROUND: We evaluated the impact of low-cost water, sanitation, handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural Bangladesh.METHODS: We analyzed 1411 routine fecal samples from children 14±2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative PCR. Outcomes included the number of co-occurring pathogens; cumulative quantity of four stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat.RESULTS: 326 (99.1%) control children had one or more enteropathogens detected (mean 3.8±1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: -11% [95% confidence interval [CI], -5 to -17%]; sapovirus: -9% [95%CI, -3 to -15%]; and adenovirus 40/41: -9% [95%CI, -2 to - 15%]). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm.CONCLUSIONS: WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age.
View details for DOI 10.1093/infdis/jiaa549
View details for PubMedID 32861214
Gold-standard cholera diagnostics are tarnished by lytic bacteriophage and antibiotics.
Journal of clinical microbiology
A fundamental, clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR for V. cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.
View details for DOI 10.1128/JCM.00412-20
View details for PubMedID 32611794
- Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Environmental Enteric Dysfunction in Young Children: A Cluster-randomized, Controlled Trial in Rural Bangladesh CLINICAL INFECTIOUS DISEASES 2020; 70 (5): 738–47
Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention
View details for DOI 10.1038/s41598-020-58000-y
High-Throughput Multiparallel Enteropathogen Detection via Nano-Liter qPCR.
Frontiers in cellular and infection microbiology
2020; 10: 351
Quantitative molecular diagnostic methods can effectively detect pathogen-specific nucleic acid sequences, but costs associated with multi-pathogen panels hinder their widespread use in research trials. Nano-liter qPCR (nL-qPCR) is a miniaturized tool for quantification of multiple targets in large numbers of samples based on assay parallelization on a single chip, with potentially significant cost-savings due to rapid throughput and reduced reagent volumes. We evaluated a suite of novel and published assays to detect 17 enteric pathogens using a commercially available nL-qPCR technology. Amplification efficiencies ranged from 88 to 98% (mean 91%) and were reproducible across four operators at two separate facilities. When applied to fecal material, assays were sensitive and selective (99.8% of DNA amplified were genes from the target organism). Due to nanofluidic volumes, detection limits were 1-2 orders of magnitude less sensitive for nL-qPCR than an enteric TaqMan Array Card (TAC). However, higher detection limits do not hinder detection of diarrhea-causing pathogen concentrations. Compared to TAC, nL-qPCR displayed 99% (95% CI 0.98, 0.99) negative percent agreement and 62% (95% CI 0.59, 0.65) overall positive percent agreement for presence of pathogens across diarrheal and non-diarrheal fecal samples. Positive percent agreement was 89% among samples with concentrations above the nL-qPCR detection limits. nL-qPCR assays showed an underestimation bias of 0.34 log10 copies/gram of stool [IQR -0.40, -0.28] compared with TAC. With 12 times higher throughput for a sixth of the per-sample cost of the enteric TAC, the nL-qPCR chip is a viable alternative for enteropathogen quantification for studies where other technologies are cost-prohibitive.
View details for DOI 10.3389/fcimb.2020.00351
View details for PubMedID 32766166
View details for PubMedCentralID PMC7381150
Shared bacterial communities between soil, stored drinking water, and hands in rural Bangladeshi households.
Water research X
2020; 9: 100056
Understanding household-level transmission pathways of fecal pathogens can provide insight for developing effective strategies to reduce diarrheal illness in low- and middle-income countries. We applied whole bacterial community analysis to investigate pathways of bacterial transmission in 50 rural Bangladeshi households. SourceTracker was used to quantify the shared microbial community in household reservoirs (stored drinking water, soil, and hands) and estimate the percentage of fecal-associated bacteria from child and mothers' feces in these reservoirs. Among the reservoirs studied, most bacterial transfer occurred between mothers' and children's hands and between mothers' hands and stored water. The relative percentage of human fecal-associated bacteria in all household reservoirs was low. We also quantified the number of identical amplicon sequence variants within and between individual households to assess bacterial community exchange in the domestic environment. Intra-household sharing of bacteria between mothers' and children's hands and between hands and soil was significantly greater than inter-household sharing.
View details for DOI 10.1016/j.wroa.2020.100056
View details for PubMedID 32529181
View details for PubMedCentralID PMC7276488
Effects of water, sanitation, handwashing, and nutritional interventions on environmental enteric dysfunction in young children: a cluster-randomized controlled trial in rural Bangladesh.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
BACKGROUND: We hypothesized that drinking water, sanitation, handwashing (WSH) and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting.METHODS: Within a subsample of a cluster-randomized controlled trial in rural Bangladesh, we enrolled pregnant women in four arms: control, combined WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and combined nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1beta) at median ages 3, 14, and 28 months. Analysis was intention-to-treat.RESULTS: We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L, CI -0.37, -0.05) and N+WSH (-0.20 log nmol/L, CI -0.34, -0.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH (0.23 log ng/ml, CI 0.06, 0.39) and nutrition (0.27 log ng/ml, CI 0.07, 0.47) arms and lactulose was higher in the WSH arm (0.30 log mmol/L, CI 0.07, 0.53).CONCLUSIONS: Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of better understanding the pathophysiology of EED and targeting interventions early in childhood during the critical period when they are likely to have the largest benefit to intestinal health.(ClinicalTrials.gov NCT01590095).
View details for PubMedID 30963177
Identification of widespread antibiotic exposure in cholera patients correlates with clinically relevant microbiota changes.
The Journal of infectious diseases
A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in cholera patients.A priority list for targeted LC/MS was generated from medication vendor surveys in Bangladesh. A study of cholera and non-cholera patients was conducted to collect and analyze paired urine and stool samples.Among 845 patients, 11% (n=90) were Vibrio cholerae positive; at least one antibiotic was detected in 86% and at least two in 52% of cholera stools. Among paired urine and stool (n=44), at least one antibiotic was detected in 98% and at least two in 84%, despite 55% self-reporting medication use. Compared to LC/MS, a low-cost antimicrobial detection bio-assay lacked sufficient negative predictive value (10%; 95% CI 6-16). Detection of guideline-recommended antibiotics in stool did (azithromycin; p=0.040) and did not (ciprofloxacin) correlate with V. cholerae suppression. A non-recommended antibiotic (metronidazole) was associated with decreases in anaerobes (Prevotella; p<0.001).The findings suggest there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.
View details for DOI 10.1093/infdis/jiz299
View details for PubMedID 31192364
- Effects of lipid-based nutrient supplements and infant and young child feeding counseling with or without improved water, sanitation, and hygiene (WASH) on anemia and micronutrient status: results from 2 cluster-randomized trials in Kenya and Bangladesh AMERICAN JOURNAL OF CLINICAL NUTRITION 2019; 109 (1): 148–64
- Remediation of High-Strength Mine-Impacted Water with Mixed Organic Substrates Containing Crab Shell and Spent Mushroom Compost JOURNAL OF ENVIRONMENTAL ENGINEERING 2016; 142 (2)