Pharmacology, Toxicology and Environmental Health Commons^™

Gut Dna Virome Diversity And Its Association With Host Bacteria Regulate Inflammatory Phenotype And Neuronal Immunotoxicity In Experimental Gulf War Illness, Ratanesh K. Seth, Rabia Maqsood, Ayan Mondal, Dipro Bose, Diana Kimono, Larinda A. Holland, Patricia Janulewicz Lloyd, Nancy Klimas, Ronnie Horner, Kimberly Sullivan, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

Gulf War illness (GWI) is characterized by the persistence of inflammatory bowel disease, chronic fatigue, neuroinflammation, headache, cognitive impairment, and other medically unexplained conditions. Results using a murine model show that enteric viral populations especially bacteriophages were altered in GWI. The increased viral richness and alpha diversity correlated positively with gut bacterial dysbiosis and proinflammatory cytokines. Altered virome signature in GWI mice also had a concomitant weakening of intestinal epithelial tight junctions with a significant increase in Claudin-2 protein expression and decrease in ZO1 and Occludin mRNA expression. The altered virome signature in GWI, decreased tight junction protein level was …

The Gut-Microbiome In Gulf War Veterans: A Preliminary Report, Patricia A. Janulewicz, Ratanesh K. Seth, Jeffrey M. Carlson, Joy Ajama, Emily Quinn, Timothy Heeren, Nancy Klimas, Steven M. Lasley, Ronnie Horner, Kimberly Sullivan, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting the central nervous system (CNS), immune and gastrointestinal (GI) systems of Gulf War veterans (GWV). We assessed the relationships between GWI, GI symptoms, gut microbiome and inflammatory markers in GWV from the Boston Gulf War Illness Consortium (GWIC). Three groups of GWIC veterans were recruited in this pilot study; GWV without GWI and no gastrointestinal symptoms (controls), GWV with GWI and no gastrointestinal symptoms (GWI-GI), GWV with GWI who reported gastrointestinal symptoms (GW+GI). Here we report on a subset of the first thirteen stool samples analyzed. Results showed significantly different …

Environmental Microcystin Targets The Microbiome And Increases The Risk Of Intestinal Inflammatory Pathology Via Nox2 In Underlying Murine Model Of Nonalcoholic Fatty Liver Disease, Sutapa Sarkar, Diana Kimono, Muayad Albadrani, Ratanesh K. Seth, Philip Busbee, Hasan Alghetaa, Dwayne E. Porter, Geoff I. Scott, Bryan Brooks, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

With increased climate change pressures likely to influence harmful algal blooms, exposure to microcystin, a known hepatotoxin and a byproduct of cyanobacterial blooms can be a risk factor for NAFLD associated comorbidities. Using both in vivo and in vitro experiments we show that microcystin exposure in NAFLD mice cause rapid alteration of gut microbiome, rise in bacterial genus known for mediating gut inflammation and lactate production. Changes in the microbiome were strongly associated with inflammatory pathology in the intestine, gut leaching, tight junction protein alterations and increased oxidative tyrosyl radicals. Increased lactate producing bacteria from the altered microbiome was associated …

Rationale, Design And Methods Of "Set The Rules": A Tailored Peer-To-Peer Health Information Intervention, Jennifer R. Warren, Brandi M. White

Health and Clinical Sciences Faculty Publications

Ensuring equitable access to health information is one strategy to promote health equity for underserved communities, especially for low-income African Americans (AAs). Childcare centers are one viable site to deliver health information to address this disparity. This paper describes the methods used in a community-based participatory research project with a childcare facility that aimed to reduce environmental tobacco smoke (ETS) exposure among low-income AA children. Through collaboration and multiple data collection methods, partners identified communication strategies to overcome informational barriers. These initial findings indicated a peer-to-peer health information intervention, entitled “Set the Rules”, as the best strategy to increase awareness. …

Hmgb1-Rage Pathway Drives Peroxynitrite Signaling-Induced Ibd-Like Inflammation In Murine Nonalcoholic Fatty Liver Disease, Varun Chandrashekaran, Ratanesh K. Seth, Diptadip Dattaroy, Firas Alhasson, Jacek Ziolenka, James Carson, Franklin G. Berger, Balaraman Kalyanaraman, Anna Mae Diehl, Saurabh Chatterjee

Faculty Publications

Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD)-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD) yet the mechanisms remain unknown. The present study identifies high mobility group box 1 (HMGB1) as a key mediator of intestinal inflammation in NAFLD and outlines a detailed redox signaling mechanism for such a pathway. NAFLD mice showed liver damage and release of elevated HMGB1 in systemic circulation and increased intestinal tyrosine nitration that was dependent on NADPH oxidase. Intestines from NAFLD mice showed higher Toll like receptor 4 (TLR4) activation and proinflammatory cytokine release, an outcome strongly …

Altered Gut Microbiome In A Mouse Model Of Gulf War Illness Causes Neuroinflammation And Intestinal Injury Via Leaky Gut And Tlr4 Activation, Firas Alhasson, Suvarthi Das, Ratanesh K. Seth, Diptadip Dattaroy, Varun Chandrashekaran, Caitlin N. Ryan, Luisa S. Chan, Traci Testerman, James Burch, Lorne J. Hofseth, Ronnie Horner, Mitzi Nagarkatti, Prakash Nagarkatti, Stephen M. Lasley, Saurabh Chatterjee

Faculty Publications

Many of the symptoms of Gulf War Illness (GWI) that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease …

Prepubertal Organochlorine Pesticide Concentrations And Age Of Pubertal Onset Among Russian Boys, Thuy Lam, Paige Williams, Mary Lee, Susan Korrick, Linda Birnbaum, Jane Burns, Oleg Sergeyev, Boris Revich, Larisa Altshul, Donald Patterson, Wayman Turner, Russ Hauser

Mary M. Lee

BACKGROUND: In animal studies, organochlorine pesticide (OCP) exposure alters pubertal development; however, epidemiological data are limited and inconsistent. OBJECTIVE: To evaluate the associations of serum OCP concentrations [hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE)] with male pubertal onset. METHODS: In Chapaevsk, Russia, a town environmentally contaminated with OCPs, 350 8-9 year old boys with measured OCPs were enrolled during 2003-2005 and were followed annually for eight years. We evaluated three measures of pubertal onset: testicular volume (TV) > 3 mL in either testis, or stage 2 or greater for genitalia (G2+), or pubic hair (P2+). We used multivariable interval-censored models to …

Accommodations For Patients With Disabilities In Primary Care: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr

Environmental & Occupational Health Faculty Publications

Structural barriers that limit access to health care services for people with disabilities have been identified through qualitative studies; however, little is known about how patients with disabilities are accommodated in the clinical setting when a structural barrier is encountered. The purpose of this study was to identify how primary care medical practices in the United States accommodated people with disabilities when a barrier to service is encountered. Primary care practice administrators from the medical management organization were identified through the organization’s website. Sixty-three administrators from across the US participated in this study. Practice administrators reported that patients were examined …

Predicting Barriers To Primary Care For Patients With Disabilities: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr, Michelle Chino

Environmental & Occupational Health Faculty Publications

Background. People with disabilities continue to be identified as a group who experience disparate health/health care. They are less likely to engage in some health care services. Structural barriers are often identified as one of the reasons for the underutilization of some health care services by people with disabilities. However, to date no study has been conducted to understand why structural barriers persist twenty years after the Americans with Disabilities Act (ADA) became law.

Objectives. We examined the relationship between primary care practice administrators’ knowledge of the ADA and the number of accessibility barriers that patients with mobility disabilities might …

Health Disparities Experienced By People With Disabilities In The Us: A Behavioral Risk Factor Surveillance System Study, Jennifer Renee Pharr, Timothy J. Bungum

Environmental & Occupational Health Faculty Publications

The Americans with Disabilities Act became law in 1990; since then research has shown that people with disabilities continue to experience barriers to health care. The purpose of this study was to compare utilization of preventive services, chronic disease rates, and engagement in health risk behaviors of participants with differing severities of disabilities to those without disabilities. This study was a secondary analysis of 2010 data collected in the Behavioral Risk Factor Surveillance System national survey in the United States. Rao Chi square test and logistic regression were employed. Participants with disabilities had significantly higher adjusted odds ratios for all …