Pharmacology, Toxicology and Environmental Health Commons^™

Andrographolide Attenuates Gut-Brain-Axis Associated Pathology In Gulf War Illness By Modulating Bacteriome-Virome Associated Inflammation And Microglia-Neuron Proinflammatory Crosstalk, Punnag Saha, Peter T. Skidmore, Larinda A. Holland, Ayan Mondal, Dipro Bose, Ratanesh K. Seth, Kimberly Sullivan, Patricia A. Janulewicz, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Efrem S. Lim, Saurabh Chatterjee

Faculty Publications

Gulf War Illness (GWI) is a chronic multi-symptomatic illness that is associated with fatigue, pain, cognitive deficits, and gastrointestinal disturbances and presents a significant challenge to treat in clinics. Our previous studies show a role of an altered Gut-Brain axis pathology in disease development and symptom persistence in GWI. The present study utilizes a mouse model of GWI to study the role of a labdane diterpenoid andrographolide (AG) to attenuate the Gut-Brain axis-linked pathology. Results showed that AG treatment in mice (100 mg/kg) via oral gavage restored bacteriome alterations, significantly increased probiotic bacteria , , and , the genera that …

Tlr Antagonism By Sparstolonin B Alters Microbial Signature And Modulates Gastrointestinal And Neuronal Inflammation In Gulf War Illness Preclinical Model, Dipro Bose, Ayan Mondal, Punnag Saha, Diana Kimono, Sutapa Sarkar, Ratanesh K. Seth, Patricia Janulewicz, Kimberly Sullivan, Ronnie Horner, Nancy Klimas, Mitzi Nagarkatti, Prakash Nagarkatti, Saurabh Chatterjee

Faculty Publications

The 1991 Persian Gulf War veterans presented a myriad of symptoms that ranged from chronic pain, fatigue, gastrointestinal disturbances, and cognitive deficits. Currently, no therapeutic regimen exists to treat the plethora of chronic symptoms though newer pharmacological targets such as microbiome have been identified recently. Toll-like receptor 4 (TLR4) antagonism in systemic inflammatory diseases have been tried before with limited success, but strategies with broad-spectrum TLR4 antagonists and their ability to modulate the host-microbiome have been elusive. Using a mouse model of Gulf War Illness, we show that a nutraceutical, derived from a Chinese herb Sparstolonin B (SsnB) presented a …

Microbiome Targeted Therapies In Gulf War Illness, Diana Agnes Kimono

Theses and Dissertations

Gulf war illness (GWI) is a chronic multisymptomatic disorder affecting about 30% of veterans of the 1990-1991 Persian Gulf war. Affected veterans complain of chronic symptoms which begun during or shortly after the war and persist 30 years later. This dissertation is a report of three studies which use a murine model to investigate the microbiome as a therapeutic target in GWI. Mice were exposed to pesticides and the prophylactic drug pyridostigmine bromide (PB) and studied these chemical’s impact on the microbiome in both an acute and persistence model of GWI.

The first study looks at the effect of altered …

Host Abundance Correlates With Gulf War Illness Symptom Persistence Via Nlrp3-Mediated Neuroinflammation And Decreased Brain-Derived Neurotrophic Factor, Diana Kimono, Dipro Bose, Ratanesh K. Seth, Ayan Mondal, Punnag Saha, Patricia Janulewicz, Kimberly Sullivan, Stephen Lasley, Ronnie Horner, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

Neurological disorders are commonly reported among veterans who returned from the Gulf war. Veterans who suffer from Gulf War illness (GWI) complain of continued symptom persistence that includes neurological disorders, muscle weakness, headaches, and memory loss, that developed during or shortly after the war. Our recent research showed that chemical exposure associated microbial dysbiosis accompanied by a leaky gut connected the pathologies in the intestine, liver, and brain. However, the mechanisms that caused the symptoms to persist even 30 years after the war remained elusive to investigators. In this study, we used a rodent model of GWI to investigate the …