Microbiome Initiative 2019 – Funded Projects – UC Irvine Microbiome Initiative

Check out our Pilot Project Proposal page for selection criteria and award details.

Connections between Psychological Stress, Social-Bonds and Gut Microbial Composition in the Parent-Child Dyad
Desiree Chase
Advisor: Jessica Borelli, Ph.D.
Dept. of Psychological Sciences

Project Summary

Researchers initially believed that the composition of the gut microbiome solely impacted physical health; however, recent discoveries regarding the gut-brain-microbiome connection have transformed the way psychobiologists conceptualize this system. Specifically, psychological stress and the microbiome are thought to have reciprocal links, thus we will explore whether these connections are present and how the parent-child bond may alter the nature of the stress-microbiome connection. Further, this project will analyze microbial composition in human parents and their children with the goal of discovering commonalities and differences in the microbiome within families. By analyzing the gut microbiota of 100 parent-child dyads, this project may inform understanding of the development of the personalized microbiome as it corresponds to age, health status, social relationships, and psychological stress. Thus, this work will cross a new frontier at the interface of multiple disciplines–exploring the multifaceted connections between psychological health and microbial composition across generations.

Phyllosphere community composition and contribution to biogenic volatile organic compound emissions from Salvia mellifera
Celia Faiola, Ph.D.
Dept. of Ecology and Evolutionary Biology

Project Summary

An immense assortment of volatiles is emitted by terrestrial ecosystems into the atmosphere where they play an important role in determining the atmospheric constituents, including ozone and aerosols, that control air quality and climate. There is widespread recognition that accurate volatile emission estimates are needed as quantitative inputs to numerical air quality and climate models and yet simulations of these emissions remain highly uncertain. The presence of phyllosphere microbes on foliage has the potential to exert substantial control over these volatile emissions and yet their role has been completely ignored in these models. Our proposed pilot program will be the first step in demonstrating the contribution of leaf microbes to volatile emissions into the atmosphere. The results could transform our current view of the dominant processes controlling air quality and climate and establish the need for interdisciplinary research requiring collaborative investigations with microbial, plant physiology, and atmospheric chemistry expertise.

Understanding the role of the gut microbiota in environmental copper exposure and Alzheimer’s disease
Janielle Vidal
Advisor: Masashi Kitazawa, Ph.D.
Dept. of Medicine, Environmental Health Sciences

Project Summary

Recent emerging evidence supports that changes in diversity of the gut microbiota substantially modulate the host’s inflammatory homeostasis and brain health. We have recently demonstrated that exposure to copper, a suspected environmental risk factor for Alzheimer’s disease (AD), through drinking water results in perturbation of inflammatory activation and accelerated buildup of AD-like neuropathology in animal models. Since copper is a known natural antimicrobial agent, its exposure through oral route is predicted to alter diversity of the gut microbiota. We hypothesize that copper-induced inflammatory dyshomeostasis and subsequent buildup of AD neuropathology is in part mediated by persistent change in the gut microbiota caused by copper exposure. In this pilot study, we propose to evaluate the effect of copper on the gut microbiota in mouse models and predict how copper-mediated changes in diversity may impact on the host’s inflammatory status in the brain, providing possible mechanisms linking environmental factors, inflammation, and AD.

Gut-Brain Axis Interactions in Opioid Use
Shahrdad Lotfipour, Ph.D.
Dept. of Emergency Medicine, Pharmaceutical Sciences

Project Summary

The United States is currently facing an opioid addiction epidemic. Emerging data illustrate that components of the gut microbiome, i.e. bacteria, are significant contributors to drug reward. Whether such effects could directly influence opioid intake is unknown. The central hypothesis of this project is that the gut microbiome is an important regulator of reward, emotion and motivation brain circuitry. The overall objective for this application is to investigate how gut bacteria perpetuate opioid use. Overall, the project aims to provide a causal role of gut bacteria influencing opioid use. Such studies could lead to the development of novel therapeutics in order to sustain a healthy homeostasis within the gut microbiome, thus leading to better treatment efficacy and reduced abuse. Our findings would have a significant impact in the scientific and public health communities given our current opioid addiction epidemic.

Influence of Water Soluble Vitamins on the Gut Microbiome
Jonathan Skupsky, M.D., Ph.D.
Dept. of Medicine, Gastroenterology

Project Summary

Water-soluble vitamins like Biotin and Thiamine play an important role in human health and disease and deficiencies have been associated with diseases like Inflammatory Bowel Disease, Alcoholism, Sepsis and increased gut epithelial permeability. The vitamins can be acquired through diet, but are also produced by the gut microbiome. The causal relationship between changes in the microbiome, vitamin status and colitis remains unknown. To begin to answer this question, we have generated mice with deficiencies in the biotin transporter which develop colitis, and the thiamine transporter which has been identified as an Ulcerative Colitis susceptibility gene. We believe that vitamin deficiency leads to changes in the diversity of the gut microbiome and both of these cause colitis. We will perform a series of experiments using mice with vitamin deficiencies and those receiving supplementation to challenge our hypothesis.

The urogenital microbiome in Alzheimer’s disease
Zhiqun Tan, M.D., Ph.D.
UC Irvine MIND

Project Summary

Growing evidence has shown a critical role of the gut microbiome in the development of Alzheimer’s disease (AD), but it is unknown whether the urogenital microbiome also impacts the penetrance and expressivity of AD and other degenerative brain diseases. We hypothesize that the urogenital microbiome is associated with the pathogenesis of AD, while perturbation of the microbiota in the urogenital tract accelerates and exacerbates the development of AD. This will be tested through two specific aims: (1) to characterize the vaginal microbiome in female mice at different ages from a hAb-knockin mouse model of AD, and (2) to examine effects of experimentally induced urogenital tract infections on AD development in the mouse. Elucidation of the urogenital microbiome contributions to AD will facilitate our understanding of this lethal disease and may provide an alternative approach to manipulating it therapeutically for prevention and treatments.

Comparison of gut microbiome in wild type mice and Alzheimer’s disease mouse models with those containing a deletion of the complement recognition component C1q or of a complement activation fragment proinflammatory receptor, C5aR1.
Andrea Tenner, Ph.D.
Dept. of Molecular Biology and Biochemistry

Project Summary

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder resulting in cognitive impairment, currently afflicting over 5 million people in the US (http://www.alz.org/facts/overview.asp). Our goal is to develop a highly specific therapeutic treatment of human AD, without inhibiting the protective immune system. Our focus is on an ubiquitous component of immunity, the complement system. This group of proteins plays a role in triggering and enhancing inflammation, which, if excessive, is damaging to neurons and thus cognitive processes. Our laboratory has demonstrated that in mouse models of AD loss of neuronal structure and of cognition can be prevented by either pharmacological inhibition or genetic ablation of a single receptor for a peptide generated as the result of complement activation (amyloid plaques in brain are known to activate the complement system in brain in vivo). We have also shown that genetic deletion of another immune molecule critical for the activation of the complement pathway also slows AD-like pathology in mice. Since these molecules also play a role in responding to infection, the goal here is to determine if eliminating either of these molecules alters the gut microbiome. If so, follow up experiments will be important to determine if the altered microbiome has a positive effect on cognition, and if so, whether this change in gut microbiome (and thus metabolites that are produced) provide a major effect of the genetic deletion on pathology and behavior performance. The ultimate goal is to identify and development preventative treatments for AD.