Pharmacology, Toxicology and Environmental Health | Open Access Articles

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 …

Go to article

Obesity Worsens Gulf War Illness Symptom Persistence Pathology By Linking Altered Gut Microbiome Species To Long-Term Gastrointestinal, Hepatic, And Neuronal Inflammation In A Mouse Model, Dipro Bose, Punnag Saha, Ayan Mondal, Brian Fanelli, Ratanesh K. Seth, Patricia Janulewicz, Kimberly Sullivan, Stephen Lasley, Ronnie Horner, Rita R. Colwell, Ashok K. Shetty, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese …

Go to article

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 …

Go to article

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 …

Go to article

Dysbiosis-Associated Enteric Glial Cell Immune-Activation And Redox Imbalance Modulate Tight Junction Protein Expression In Gulf War Illness Pathology, Diana Kimono, Sutapa Sarkar, Muayad Albadrani, Ratanesh K. Seth, Dipro Bose, Ayan Mondal, Yuxi Li, Amar N. Kar, Mitzi Nagarkatti, Prakash Nagarkatti, Kimberly Sullivan, Patricia Janulewicz, Stephen Lasley, Ronnie Horner, Nancy Klimas, Saurabh Chatterjee

Faculty Publications

About 14% of veterans who suffer from Gulf war illness (GWI) complain of some form of gastrointestinal disorder but with no significant markers of clinical pathology. Our previous studies have shown that exposure to GW chemicals resulted in altered microbiome which was associated with damage associated molecular pattern (DAMP) release followed by neuro and gastrointestinal inflammation with loss of gut barrier integrity. Enteric glial cells (EGC) are emerging as important regulators of the gastrointestinal tract and have been observed to change to a reactive phenotype in several functional gastrointestinal disorders such as IBS and IBD. This study is aimed at …

Go to article

Pharmacology, Toxicology and Environmental Health Commons^™

Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Faculty Publications

Faculty Publications

Faculty Publications

Faculty Publications

Faculty Publications