About

Dr. Saurabh Chatterjee is a human physiologist with specialized training in immunology. He earned his Ph.D. in inflammation biology (Life Sciences) at the Bhabha Atomic Research Center affiliated with the University of Mumbai. Following his doctoral studies, he pursued postdoctoral research at the Laboratory of Pharmacology and Toxicology, National Institute of Environmental Health Sciences, NIH. Subsequently, he continued his specialized research in chronic liver disease at Duke Gastroenterology under the K99 portion of his NIH Pathway to Independence Award. Dr. Chatterjee has made significant contributions to the understanding of host microbiome interactions with redox biology, neuroimmune pathology, and gut-brain interactions in pro-inflammatory disease processes such as Gulf War illness, chronic multi-symptom illnesses, and brain manifestations of liver diseases. His work also extends to drug discovery and gut-brain directed therapeutics. He has been continuously funded by NIH, Department of Defense, and the Veterans Affairs, with total extramural funding exceeding $7.3 million. His research interests include the role of the microbiome, particularly the liver-gut-brain axis, in environment-linked non-alcoholic fatty liver disease (NAFLD) and the impact of climate change stressors such as harmful algal blooms, as well as microbiome alterations related to Gulf War Illness and chronic multi-symptom illness.

Research topics

• Medicine
• Biology
• Internal medicine
• Environmental health
• Endocrinology
• Environmental protection
• Waste management
• Environmental science
• Environmental chemistry
• Ecology
• Chemistry

Selected publications

• Underlying MASLD-induced gut microbiome dysbiosis and intestinal inflammation are key to poor outcomes in vibriosis infections in a preclinical model

  Gut Microbes · 2026-04-13

  articleOpen accessSenior authorCorresponding

  to investigate the pathophysiological outcomes in both control and diet-induced MASLD mouse cohorts. Our results showed that non-cholera vibriosis in mice with underlying MASLD caused increased liver damage, an inflammatory surge, followed by the onset of fibrotic lesions compared to the chow-diet fed control mice, depicting a worsened outcome. Depletion of the gut bacteriome by antibiotic treatment and following fecal microbiota transplantation in these mouse cohorts showed decreased pathophysiology in the livers, indicating that an altered gut microbiome in MASLD could be a key factor in the increased likelihood of non-cholera vibriosis in patients with MASLD.

  PublisherDOI

• Spermidine Attenuates Neuroimmune Dysfunction in Gulf War Illness via Modulation of the Gut- Brain Axis

  Molecular Neurobiology · 2026-01-01

  articleOpen accessSenior authorCorresponding

  Gulf War illness (GWI) affects nearly one-third of US veterans deployed during the 1990-1991 Gulf War (GW) and is characterized by chronic fatigue, neuroinflammation, and gut dysbiosis. Through comprehensive fecal metabolomics sequencing, our lab previously reported the depletion of beneficial metabolites including spermidine in the preclinical GWI mouse model. Spermidine is an endogenously synthesized polyamine known for its anti-inflammatory and mucosal barrier protective effects in various pathological diseases. Given its established role in mitigating intestinal inflammation and maintaining homeostasis, this study investigated the therapeutic potential of spermidine in a persistent (22 weeks) GWI mouse model, with a specific focus on gut-brain axis regulation. Our results demonstrated that spermidine effectively restored both microbial richness and diversity by selectively enriching beneficial bacterial taxa and suppressing growth of opportunistic pathogens, which are otherwise dysregulated following exposure to GW chemicals. Spermidine treatment also improved gut epithelial barrier integrity and reduced epithelial release of high-mobility group box 1 (HMGB1) into systemic circulation. Recent studies on GWI have implicated a critical role of gut-derived damage-associated molecular patterns (DAMPs), particularly HMGB1 in mediating neuroinflammation. Our findings indicate that systemic levels of HMGB1 critically influence the extent of blood-brain barrier (BBB) disruption and subsequent microglial activation. Mechanistically, spermidine activated intestinal aryl hydrocarbon receptor (AhR)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling, which played a role in limiting intestinal HMGB1 release and suppressing downstream receptor for advanced glycation end-product (RAGE)-mediated microglial activation in the brain. In vitro results indicate spermidine promoted AhR/Nrf2 nuclear translocation which reduced LPS-induced HMGB1 release from primary intestinal epithelial cells (IECs), effects abrogated by AhR inhibition. Additionally, we observed that HMGB1 directly induces microglial activation via RAGE receptors in immortalized microglial (IMG) cell lines in a dose-dependent manner. These results demonstrate that spermidine decreases neuroinflammation by modulating gut-brain axis pathophysiology associated with GWI. Together, this study demonstrates the therapeutic role of spermidine in ameliorating systemic and neurological disturbances in GWI.

  PublisherOA PDFDOI

• Novel insights into cyanobacterial (microcystins) neurotoxicity in rats: hepatic encephalopathy

  Archives of Toxicology · 2025-11-06 · 1 citations

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  PublisherDOI

• Increased susceptibility to vibrio vulnificus infection in patients with MASLD, cirrhosis, and chronic liver diseases

  The American Journal of the Medical Sciences · 2025-06-05 · 1 citations

  letter
  PublisherDOI

• Mo1599: ELEVATED SUSCEPTIBILITY TO VIBRIO VULNIFICUS INFECTION IN PATIENTS WITH MASLD, CIRRHOSIS, AND CHRONIC LIVER DISEASES: A NATIONAL CROSS-SECTIONAL STUDY

  Gastroenterology · 2025-05-01

  article
  PublisherDOI

• Underlying metabolic syndrome exacerbates <i>Vibrio vulnificus-</i>induced acute kidney injury via systemic Th17/Treg dysregulation

  American Journal of Physiology-Renal Physiology · 2025-09-24 · 1 citations

  articleOpen accessSenior authorCorresponding

  This study reveals that high-fat diet (HFD)-induced metabolic dysfunction exacerbates Vibrio vulnificus sepsis-associated acute kidney injury (AKI) via TLR4-driven inflammation, oxidative stress, and systemic Th17/Treg imbalance. Novel in vitro findings show that IL-17 and leptin synergistically activate NF-κB signaling in renal epithelial cells, amplifying inflammation, which is mitigated by IL-17 receptor blockade. These results highlight IL-17 signaling as a potential therapeutic target for reducing AKI severity in obese individuals with bacterial sepsis.

  PublisherDOI

• Peroxynitrite is key to Cylindrospermopsin-mediated MASLD to MASH progression via triggering TXNIP binding to NLRP3 and subsequent inflammasome activation

  Toxicology and Applied Pharmacology · 2025-08-21 · 2 citations

  articleOpen accessSenior authorCorresponding

  Harmful algal bloom (HAB) toxins are shown to be associated with Metabolic dysfunction-associated steatohepatitis (MASH) progression. Several studies link the HAB toxin microcystin to hepatic inflammasome activation, but the role of cylindrospermopsin (CYN) in Metabolic dysfunction-associated steatotic liver disease (MASLD) pathology remains unknown. Using a mouse model of MASLD, we show that CYN exposure served as a second hit for MASLD to MASH progression, as shown by histopathology and NAS scoring. The pathology was attenuated by the use of NADPH oxidase 2 (NOX2) inhibitor apocynin and peroxynitrite inhibitor phenylboronic acid. Inhibition of peroxynitrite and other redox signaling processes decreased stellate cell activation and fibronectin protein in the hepatic lobules, thus confirming the involvement of the above nitrosative moiety in early fibrotic remodeling, crucial for MASH progression. Redox inhibitors also decreased the endothelial Nitric Oxide Synthase (eNOS)/inducible Nitric Oxide Synthase (iNOS) protein ratio, thus raising the yield of inducible nitric oxide and facilitating the uncoupling of eNOS. Mechanistically, peroxynitrite inhibitors coupled with attenuation of redox processes prevented Thioredoxin-interacting protein (TXNIP) colocalization with NLRP3 and resulted in the inhibition of NLRP3 inflammasome activation, a crucial mediator of hepatic inflammation in MASH. Hepatocyte-hepatic macrophage crosstalk, crucial for MASH progression, was shown to induce NOX2 activation, the generation of 3-nitrotyrosine in close proximity to iNOS, a predictive nitric oxide source, thus confirming the role of these cells in activating the inflammation cascade. The results show a crucial role of peroxynitrite in TXNIP-NLRP3 induced inflammasome activation and can be a crucial therapeutic target in treating MASH etiology from environmental exposure. Graphical abstract representing the effects of 15 days of oral CYN treatment in diet-induced obese mice, resulting in increased NADPH oxidase 2 (NOX2)-mediated oxidative stress, NLRP3 inflammasome-mediated pyroptosis, and hepatocyte damage (HMGB1 secretion), leading to the onset of MASH-like heightened inflammation and fibrosis. APO, apocynin; CYN, Cylindrospermopsin; DMPO, 5,5-Dimethyl-1-pyrroline N-oxide; HMGB1, high mobility group box 1; iNOS, inducible nitric oxide synthase; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; NLRP3, NLR family pyrin domain containing 3; NOX2, NADPH oxidase 2; PBA, phenylboronic acid; RAGE, receptor for advanced glycation Endproducts; TXNIP, thioredoxin interacting protein. ↑ denotes an increase. Created with a license from biorender.com • Although known to be a potent hepatotoxin, the exact pathophysiological role of the environmental cyanotoxin Cylindrospermopsin in underlying obesity is still unknown. • Cylindrospermopsin-induced peroxynitrite formation is key to the disease progression from so-called ‘benign’ MASLD to more advanced MASH-like conditions with early onset of fibrosis. • Activation of the HMGB1-RAGE-NF-κB signaling pathway is crucial for Cylindrospermiopsin-mediated hepatocyte damage. • Peroxynitrite-mediated NLRP3 inflammasome activation via TXNIP plays a major role in subsequent hepatic pathophysiological outcomes and could serve as a potential target for future therapeutic approaches.

  PublisherDOI

• Role of Spermidine, a Host-bacterial metabolite, in attenuating Persistent Gastrointestinal Mediated Neurotoxicity in Gulf War Illness Mouse model

  Physiology · 2025-05-01

  articleSenior author

  Post three decades of Persian Gulf War, Gulf War (GW) veterans suffers from gut dysbiosis persistently resulting in extreme gastrointestinal (GI) and neuroinflammation resulting in cognitive and behavioral impairments. Through a metabolomics analysis, we identified spermidine, a metabolite produced by host-associated bacteria, as a key mediator of microbiome metabolism within the host. Spermidine is a natural polyamine, synthesized through a metabolic pathway involving the amino acid ornithine and has been reported to exert anti-inflammatory and anti-aging properties. Further, spermidine is reported to produce Kynurenine, an Aryl-Hydrocarbon Receptor (AhR) ligand, thereby initiating AhR activation, leading to ameliorating intestinal barrier integrity. Gut barrier disruption with alterations in tight junction (TJ) proteins is widely reported in Gulf War Illness (GWI), leading to persistent GI inflammation, which in turn drives neuroinflammation through blood-brain barrier (BBB) disruption. Therefore, we decided to investigate the therapeutic role of spermidine in attenuating GI mediated neuroinflammation in persistent GWI mouse model. Wild-type C57BL/6J mice were orally gavaged with Pyridostigmine bromide and Permethrin, for two weeks. A subset of these GWI-induced mice was then treated orally with spermidine for five days per week over five months. Our results indicated that spermidine supplementation mitigated the disrupted intestinal gut barrier integrity by restoring the levels of TJ proteins- Occludin and Claudin-2 and decreased the release of pro-inflammatory cytokines- IL-1β and IL-6. Further, spermidine ameliorated intestinal inflammation by decreasing the release of HMGB1 in systemic circulation from intestinal epithelial lining of the small intestine by the activation of AhR/NRF-2/HO-1 pathway. Certain damage-associated molecular patterns (DAMPs), such as HMGB1, can function in an autocrine manner. In this context, we also investigated spermidine’s effect in mitigating intestinal inflammation by inhibiting HMGB1- RAGE activation and attenuating NFκB signaling through the decreased phosphorylation of the p65 subunit. The reduction in circulating HMGB1 levels results in decreased disruption of the blood-brain barrier (BBB) and a reduction in microglial cell activation, thereby mitigating neuroinflammation. These findings highlight the potential therapeutic efficacy of spermidine in ameliorating the inflammatory manifestations of GWI, offering significant insights into the complex molecular mechanisms underlying its effects. This study was supported by VA Merit Award I01CX001923-01 awarded to Dr. Saurabh Chatterjee This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Identifying differential survival, photolocomotor behavior, and gene expression responses to cylindrospermopsin in Danio rerio and Pimephales promelas

  The Science of The Total Environment · 2025-02-01 · 1 citations

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  PublisherDOI

• Aging and climate change-induced heat stress synergistically increase susceptibility to Vibrio vulnificus infection via an altered gut microbiome-immune axis

  The Science of The Total Environment · 2025-06-13 · 6 citations

  articleOpen accessSenior authorCorresponding

  Climate change is exacerbating heatwaves, significantly increasing public health risks, including heightened vulnerability to Vibrio vulnificus infections, especially among older adults. While heat stress alone impairs immune regulation and compromises gut integrity, the combined effects of aging and climate-induced heat stress on infectious severity remain insufficiently explored. Using young (12-week-old) and aged (24-month-old) mouse models, we examined how aging and periodic heat stress synergistically influence susceptibility to Vibrio vulnificus by assessing gut microbiome alterations, immune responses, and antibiotic resistance gene dynamics. Heat stress markedly impaired intestinal barrier function, induced significant microbiome shifts, elevated systemic inflammation, and promoted enrichment of antibiotic resistance genes particularly those conferring tetracycline resistance with effects significantly amplified in aged mice. Upon Vibrio vulnificus infection, aged heat-stressed mice demonstrated elevated inflammatory responses, severe intestinal damage, and pronounced immune dysregulation compared to younger counterparts. Gut depletion and probiotic recolonization models further validated microbiota involvement, showing that Roseburia intestinalis significantly reduced heat stress-exacerbated CD4 + T-cell immunosenescence in aged mice. Collectively, this study provides robust experimental evidence highlighting the critical interplay between aging and climate-driven heat stress in intensifying infectious disease severity via microbiome–immune axis disruptions, underscoring the need for microbiota-targeted strategies in climate-vulnerable populations. • Aging and heat stress together increase Vibrio vulnificus infection severity in mice. • Periodic heat exposure impairs gut barrier and accelerates T-cell immunosenescence. • Aged mice show heightened systemic inflammation and endotoxemia under dual stress. • Heat stress disrupts microbial diversity and enriches antibiotic resistance genes. • Recolonization with key probiotics restored intestinal health and immune regulation.

  PublisherDOI

Recent grants

• Analytical Core

  NIH · $28.5M · 2022

• NIH Grant R00ES019875

  NIH · $498k · 2017

• Dietary Supplements and Inflammation Phase-2: Isoxanthohumol as a treatment for estrogen-deficient-induced visceral hyperalgesia.

  NIH · $37.0M · 2012–2025

• Effects of selected climate change-affected pathogens and pollutants on Critical Organs, Inflammation and Human disease

  NIH · $9.2M · 2018–2024

• Effects of selected climate change-affected pathogens and pollutants on Critical Organs, Inflammation and Human disease

  NIH · $2.3M · 2018–2023

Frequent coauthors

• Hugo Ten Cate

  Maastricht University

  2569 shared

• Ralf Paschke

  1962 shared

• Christian A. Koch

  University of Stuttgart

  1775 shared

• Alexander K. C. Leung

  1540 shared

• Hülya Ilıksu Gözü

  Marmara University

  1492 shared

• Dieter Häussinger

  1468 shared

• Mallikarjuna Nallegowda

  Loma Linda University Medical Center

  1119 shared

• Alexander K. C. Leung

  1113 shared

Labs

• Chatterjee LabPI

Education

• Ph.D., Environmental Health Sciences

  University of California, Los Angeles

  2005

• M.S., Environmental Health Sciences

  University of California, Los Angeles

  2001

• B.S., Environmental Health Sciences

  University of California, Los Angeles

  1999

Awards & honors

• Society of Toxicology SIG “Outstanding Early Career Toxicolo…
• VA merit Award, 2019
• Investigator Initiated Research Focus Award, Department of D…