2020 Pilot Awards

Investigating the Association Between the Gut Microbial Composition and the Transgenerational Obesity Phenotype in Mice Ancestrally Exposed to Tributyltin 
Bruce Blumberg, Ph.D.
Department of Developmental and Cell Biology, Pharmaceutical Sciences

Obesity is often ascribed to an imbalance between energy intake and expenditure. Despite its importance, energy balance does not fully explain why 39.8% of U.S. adults are obese and at risk for numerous comorbidities. Obesogens are chemicals that can predispose exposed individuals to obesity and may contribute to the rapid increase in obesity rates worldwide. We showed that male offspring of mice exposed to the obesogen tributyltin (TBT) during pregnancy became obese and that this phenotype could be transmitted through the F4 generation without additional exposure. The gut microbiome was shown to be important in the development of obesity but its contribution to the obesity observed in our experiments is unknown. The goals of this study are to elucidate the effects of TBT exposure on composition of the gut microbiome and to investigate the role of these changes in the obesity phenotype observed with ancestral TBT exposure.

Skin microbiome changes in atopic dermatitis patients after treatment with crisaborole ointment
Dr. Margit Juhasz, MD, MSc
Dr. Natasha Mesinkovska, MD, Ph.D.
Department of Dermatology

Atopic dermatitis (AD) is an inflammatory disease of the skin affecting a large proportion of the pediatric and adult population. Chronic pruritus and eczematous lesions lead to a high burden of disease and associated patient morbidity with increased infection rates, emotional stress and associated psychological disease. The microbiome community contributes to human health through host defense mechanisms, inflammatory modulation and homeostasis maintenance. Current research suggests that derangements in the resident microbiota may lead to inflammatory bowel disease, allergy, and metabolic syndromes. Specific to dermatology, new literature has demonstrated that changes in the microbiome may play a role in the development of AD. With this proposal, we hope to characterize the baseline AD skin microbiome and longitudinally monitor the evolution of the skin microbiome during and after treatment with anti-inflammatory topical medications, specifically the Food and Drug Administration (FDA)-approved phosphodiesterase inhibitor, crisaborole ointment 2% (Eucrisa).

 

Intraspecific variation in plankton microbiomes across large environmental gradients
Emma Moffett, Ph.D.
Advisor: Celia Symons, Ph.D.

With climate change, lakes are receiving increasing amounts of low-quality organic carbon from the surrounding terrestrial environment. Will this low-quality terrestrial carbon reduce the growth rate of lake organisms? Or, do organisms’ gut microbiota adjust to extract resources from the low-quality food? Using a natural food quality gradient among lakes in the Sierra Nevada we will determine how plankton microbiomes are associated with food quality. We will examine intraspecific variation in gut microbiomes from two plankton species (Daphnia pulicaria and Leptodiaptomus signicauda) from lakes with terrestrial- to aquatic-based food webs. This work will link variation in the environment to variation in microbiomes and lay the groundwork for future laboratory experiments manipulating microbiomes and plankton responses to food quality. These data will help us to begin understanding the role of microbes in maintaining an important ecosystem function – the transfer efficiency of energy to higher trophic levels such as fish.

 

Role of the gut mycobiome in the dynamics of diarrheal disease
Nicholas Rhoades
Advisor: Ilhem Messaoudi

Diarrheal disease results in approximately 2 million deaths each year including 760,000 children under the age of 5, largely in the developing world. It is unclear why individuals with similar pathogen exposure can have differential susceptibility to disease, although the commensal microbiome is hypothesized to play a role. While recent work has begun to address the role of the gut bacterial microbiome in the development and severity of diarrheal disease, the contribution of the commensal fungal community (mycobiome) to diarrheal disease susceptibility remains unknown. With our collaborators at the Oregon National Primate Research Center, we have developed an infant macaque model of environmentally acquired diarrhea disease. In this proposal we will use ITS sequencing of longitudinally collected fecal samples from infant macaques that develop diarrhea and healthy controls to elucidate the role of the mycobiome in diarrheal disease susceptibility and severity.

 

Genitourinary, vaginal and fecal microbiomes in women with recurrent UTI
Sarah Jeney, MD
Felicia Lane, MD, MS
Department of Obstetrics and Gynecology

Recurrent urinary tract infections (UTI) are a significant medical burden that contribute to and are complicated by worsening bacterial antibiotic resistance patterns. We aim to characterize a ‘healthy’ genitourinary microbiome and to understand microbiome derangements in the disease mechanism of recurrent UTI. To do this, we will evaluate the urinary, vaginal, and fecal microbiomes in women with recurrent UTI and compare these findings to age-matched women without recurrent UTI (our control population). We aim to (1) characterize the urinary, vaginal, and fecal microbiomes of women with recurrent UTI at weekly intervals over a 1 month period, (2) examine differences in species richness and in relative abundance of bacteria between women with recurrent UTI and controls, and (3) examine changes in the microbiome at 4 time points (1 week intervals). This study will help guide therapeutic intervention for women with recurrent UTI.

 

Reducing coastal disease outbreaks through natural filtration of waterborne pathogens by commercially important marine bivalves
Joleah Lamb, Ph.D.
Dept. of Ecology and Evolutionary Biology

With an estimated 1 billion people projected to reside in coastal zones by 2060, strategies for reducing outbreak risks in marine environments will be vital for improving human and ecosystem health both locally and worldwide. Our group recently demonstrated that seagrass meadows can be used as a natural system for pathogen removal—when seagrass meadows are present, there was a 50% reduction in the relative abundance of potential bacterial pathogens in ambient seawater capable of causing disease in humans and marine organisms. This pilot study will test whether commercially valuable bivalve industries can be used both solely and alongside seagrass meadows in order to remove waterborne pathogens for future research and use at a global scale.

 

Elucidating dynamics of microbiota – host interactions using gut-specific ketohexokinase-C knockout mice
Cholsoon Jang, Ph.D.
Department of Biological Chemistry

Driven by the pleasurable experience of sweet taste, over the past two centuries, per capita consumption of dietary fructose has increased 100-fold. Excessive fructose consumption contributes to metabolic diseases, including obesity, diabetes and fatty liver disease. Unlike glucose, high-dose fructose is not fully absorbed by the small intestine and excess fructose spills over to the colon, feeding gut microbiota. Remarkably, antibiotics treatment in rodents prevents fructose-induced pathologies, indicating key roles of microbiota in the disease development. In this study, we will determine how chronic fructose feeding progressively alters microbiota, host metabolism and immune system, contributing to fatty liver disease. We will perform metabolomics, metagenome sequencing and physiological analysis in our new genetic mouse model that shows increased fructose spillover to the colon and worsened fatty liver upon fructose feeding. The study will reveal the causal relationship between microbiota and fructose-elicited pathologies, thereby elucidating the underlying mechanisms of the disease.

 

Effects of mouth rinses for treating gingival and periodontal disease on the microbiome of the oral cavity and GI tract
Petra Wilder-Smith, DDS, Ph.D.
Beckman Laser Institute

Goal of this project is to identify the effects of two OTC mouthwashes on the microbiome of the mouth and GI tract. Periodontal disease is associated with a progressive shift in the levels of specific bacteria (periodontopathogens) in the oral cavity, and also with increased prevalence of oral and colon cancer. Typically, antibacterial mouth rinses are used to treat periodontal disease. However, the short and long-term effects of these mouthwashes on the microbiome of the mouth and GI tract remain unknown. In this study we will compare effects on these microbiomes of a broad spectrum antibacterial mouthwash (ListerineR, Johnson & Johnson Consumer Healthcare Products, Skillman, New Jersey) vs those of a mouthwash which targets the harmful products of periodontopathogens without bactericidal effects (Lumineux Oral Essentials Clean and Fresh  MouthwashR, Los Angeles CA).