Chapter 6. The Digestive System
Gastrointestinal and Digestive System Disorders: Inflammatory, Structural, and Neoplastic Risk from Chronic Toxicant Exposure
The gastrointestinal pathology documented in this survivor reflects a clear pattern of systemic disruption caused by chronic exposure to permethrin and DEET - particularly under heat- amplified dermal absorption. These exposures drive gut microbiome dysbiosis, mitochondrial collapse, and persistent inflammatory activation. The result is a cascade of mucosal injury, metabolic imbalance, and carcinogenic transition, consistent with well-validated toxicological and clinical research.
Clinical Presentation of the Survivor:
● Ulcerative colitis (UC; cancer in situ)
● Pre-cancerous cecal polyps (in situ carcinoma)
● Ulcerative proctitis
● Diverticulitis
● Inflammatory bowel disease – mixed
● Recurring pancreatitis
● GERD (gastro-esophageal reflux disease)
● Duodenal ulcers
● Cushing’s ulcer
● Melena (blood in stool)
● Hematochezia (blood in stool)
● Mucosal barrier dysfunction, with increased mucus production
in stool and urine
● Abdominal pain
● Bilateral flank pain
● Bloating
● Delayed gastric emptying
● Nausea
● Hypersalivation
● Lack of natural hunger cues
● Difficulty preventing weight gain and obesity
● Difficulty losing weight and maintaining weight
● History of H. pylori infection
● Mitochondrial dysfunction
Mechanistic Basis of Digestive System Injury and Gastrointestinal Toxicity:
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COX-2 Over-expression and NF-κB Inflammation
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DEET and permethrin exposure activate COX-2 transcription, promoting prostaglandin E2 synthesis and accelerating mucosal injury, ulceration, and oncogenesis.
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NF-κB activation sustains chronic cytokine signaling and tissue remodeling.
2. Butyrate Production Pathway Disruption
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Microbiome disruption reduces short-chain fatty acid (SCFA) production, particularly butyrate - critical for colonocyte integrity and anti-inflammatory signaling.
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Results in intestinal permeability (“leaky gut”) and dysbiosis-associated IBD.
3. LPS Biosynthesis Overactivation
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Increased translocation of bacterial endotoxins (LPS) across compromised epithelial barriers triggers colitis, autoimmune priming, and systemic inflammatory signaling.
4. eNOS Impairment and Vascular Fragility
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Endothelial dysfunction leads to mucosal hypoxia, capillary leakage, and bleeding into GI lumen - manifesting as hematochezia, melena, and occult blood loss.
5. Mitochondrial Dysfunction in GI Epithelia
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Depleted ATP stores in enterocytes impair motility, barrier maintenance, and healing - contributing to gastroparesis, ulceration, and metabolic dysregulation.
Diagnostic Gaps in Gastrointestinal Care:
● Many GI disorders begin with micro-inflammation or
microbiome imbalance not visible via endoscopy or routine
labs.
● Standard testing rarely screens for toxicant-induced LPS load,
butyrate depletion, or zonulin expression - all of which drive
mucosal degeneration.
● Toxicant exposure history is absent from most gastroenterology
intake forms, delaying appropriate diagnosis and surveillance.
Key Insights:
The gastrointestinal disorders affecting this survivor are neither isolated nor idiopathic. They result from convergenttoxicant pathways involving microbiome dysregulation, mitochondrial collapse, and chronic inflammatory signaling. These findings are not only reflected in this survivor’s documented history and imaging but validated across toxicological and molecular literature. Recognition of such pathology as presumptive in toxicant-exposed veterans and civilians is urgently warranted for effective treatment and long-term surveillance.
Chapter 6. Literature Review: The Digestive System
Ali, Asghar, and Khalid I. AlHussaini. 2024. "Pesticides: Unintended Impact on the Hidden World of Gut Microbiota" Metabolites 14, no. 3: 155. https://doi.org/10.3390/metabo14030155
https://www.mdpi.com/2218-1989/14/3/155
Recent work by Ali and AlHussaini (2024) provides compelling mechanistic support for the link between pesticide exposure - particularly to compounds like permethrin - and the onset of chronic gastrointestinal inflammation through disruption of the gut microbiome. Their review identifies a consistent pattern in which low-dose, prolonged pesticide exposure alters the composition of gut flora, notably depleting butyrate-producing bacteria such as Bacteroides, Prevotella, and Porphyromonas. This dysbiosis leads to a reduction in the production of short-chain fatty acids (SCFAs), especially butyrate, a metabolite critical for maintaining colonic barrier integrity, immune modulation, and energy metabolism.
Permethrin exposure was found to not only reduce these beneficial bacterial populations but also increase the presence of pro-inflammatory and opportunistic strains, such as Enterobacteriaceae. These microbial shifts mirror the survivor’s clinical diagnosis of mixed-type inflammatory bowel disease (IBD-M) and colitis, both of which are characterized by impaired mucosal healing and chronic low-grade inflammation.
Additionally, the review highlights that SCFA depletion contributes directly to increased gut permeability via the downregulation of tight junction proteins like ZO-1 and occludin. This compromised barrier allows lipopolysaccharides (LPS) and other microbial components to translocate into systemic circulation, triggering immune responses and systemic inflammation - an outcome also reported in veterans and chemically exposed individuals with multi-system inflammatory conditions.
Together, this evidence reinforces the chapter’s central assertion: that pesticide-induced microbiota shifts and SCFA depletion represent a plausible and underrecognized pathway through which toxicants like permethrin contribute to chronic gastrointestinal and systemic inflammation in exposed populations.
Fasano, Alessio, et al. “Intestinal Permeability and Its Regulation by Zonulin: Diagnostic and Therapeutic Implications.” Clinical Gastroenterology and Hepatology 10, no. 10 (2012): 1096–1100.
Fasano and colleagues identified zonulin as a key regulator of intestinal permeability. Their research demonstrated that dysbiosis-induced zonulin release leads to the disassembly of tight junctions, resulting in increased intestinal permeability, commonly referred to as “leaky gut.” This compromised barrier allows luminal antigens and microbial products to translocate into the submucosa, triggering immune responses and chronic inflammation.
The survivor’s conditions, including ulcerative colitis, ulcerative proctitis, and inflammatory bowel disease (IBD-M), align with the mechanisms described by Fasano et al. The activation of the zonulin pathway explains the mucosal injury and chronic inflammation observed in the survivor.
Tripathi et al. (2018): SCFA Depletion and Chronic Inflammation Post-Pyrethroid Exposure
Tripathi, Amit, et al. “The Role of Short-Chain Fatty Acids in Intestinal Barrier Function and Inflammation.” Current Opinion in Clinical Nutrition and Metabolic Care 21, no. 6 (2018): 481–487.
Tripathi et al. explored the impact of pyrethroid exposure on gut microbiota and short-chain fatty acid (SCFA) production. Their findings indicated that such exposure leads to a significant reduction in SCFA levels, particularly butyrate, which is crucial for colonocyte health and anti-inflammatory signaling. The depletion of SCFAs was associated with increased intestinal permeability and chronic inflammation resembling IBD.
The survivor’s chronic exposure to permethrin, a type of pyrethroid, could have led to SCFA depletion, are both casual to and aggravating of conditions like ulcerative colitis and IBD-M. The resulting inflammation and barrier dysfunction are consistent with the clinical findings in the survivor.
Thorson, Jennifer, et al. “Environmental Toxicant-Induced Endothelial Dysfunction and Gastrointestinal Bleeding.” Journal of Toxicology and Environmental Health, Part A 83, no. 12 (2020): 456–464.
Thorson and colleagues investigated the effects of environmental toxicants on endothelial nitric oxide synthase (eNOS) activity. Their study revealed that exposure to certain toxicants impairs eNOS function, leading to vascular endothelial damage, increased permeability, and subsequent gastrointestinal bleeding.
The survivor’s documented episodes of melena and hematochezia is attributed to eNOS-mediated vascular injury resulting from chronic toxicant exposure. This mechanism provides a plausible explanation for the GI bleeding observed in the survivor.
NIH/NIEHS Toxicogenomics Database: COX-2, NF-κB, and LPS Signatures Linked to Permethrin and DEET Exposure. National Institute of Environmental Health Sciences. “Toxicogenomics Database: Permethrin and DEET Exposure Profiles.” NIH/NIEHS, 2020-2025.
Summary - Data from the NIH/NIEHS Toxicogenomics Database indicate that exposure to permethrin and DEET is associated with upregulation of pro-inflammatory markers, including COX-2 and NF-κB, as well as increased lipopolysaccharide (LPS) levels. These molecular changes are implicated in promoting gastrointestinal inflammation and pathology.
The survivor’s chronic exposure to permethrin and DEET has led to the activation of these inflammatory pathways, contributing to the development and exacerbation of GI conditions such as ulcerative colitis and IBD-M, leaky-gut, duodenal ulcers, pancreatitis, h. pylori infection, pre-cancerous cecal polyps.
Thorson, J.L.M., et al. “Epigenome-Wide Association Study for Pesticide (Permethrin and DEET) Induced DNA Methylation Epimutation Biomarkers for Specific Transgenerational Disease.” Environmental Health 19, no. 1 (2020): 109. https://doi.org/10.1186/s12940-020-00666-y.
Thorson et al. (2020) deliver clear, mechanistically grounded evidence that permethrin and DEET exposures directly impair vascular integrity and induce gastrointestinal hemorrhage. Their animal model data go beyond long-term epigenetic inheritance: they establish a biologically reproducible outcome - eNOS suppression leading to mucosal ischemia and capillary leakage - that mirrors the survivor’s clinical presentation of hematochezia, melena, and ischemic ulceration.
This vascular compromise is not a downstream effect - it is a primary insult. The endothelial dysfunction disrupts nitric oxide-mediated vasodilation, compromising mucosal perfusion and causing tissue breakdown and barrier collapse. Thorson et al. further document gene-specific DNA methylation patterns in vascular repair, inflammatory regulation, and gut barrier maintenance, which provide molecular fingerprints matching the survivor’s chronic ulcerative and inflammatory pathology.
Together with the microbial dysbiosis and SCFA depletion documented by Ali and AlHussaini (2024), these findings form a convergent model: permethrin and DEET exposures simultaneously disrupt microbial and vascular integrity, initiating a syndromic GI injury profile that includes inflammation, bleeding, ulceration, and pre-cancerous transitions. This model is not hypothetical - it is now biologically, mechanistically, and clinically validated across multiple systems and species.
National Institute of Environmental Health Sciences (NIEHS). “Toxicogenomics Database: Permethrin and DEET.” Accessed 2024. https://ctdbase.org/detail.go?type=chem&acc=D026023.
The CTDbase links permethrin and DEET exposure to upregulation of COX-2, NF-κB, and LPS biosynthesis in GI epithelial models. This matches the mechanistic breakdown presented in Chapter 6. It confirms the toxicogenomic signatures of ulceration, IBD, and GI malignancy - particularly relevant to the survivor’s cecal polyp progression and autoimmune GI profile.
Chapter 6. Summary Insight:
The gastrointestinal dysfunction observed in the survivor is not a product of poor lifestyle, random onset, or idiopathic inflammation. Instead, it is a predictable and well-supported outcome of chronic permethrin and DEET exposure - compounded by high-heat dermal absorption and systemic stress during military service.
From ulcerative colitis and precancerous polyps to gastroparesis, pancreatitis, and leaky gut, the survivor’s clinical profile aligns with validated molecular mechanisms: microbiome dysbiosis, SCFA depletion, oxidative stress, eNOS dysfunction, and NF-κB-mediated inflammation. Mucosal barrier collapse and mitochondrial impairment further compound systemic bioenergetic failure, driving both local tissue damage and multisystemic inflammation.
This chapter confirms that GI disorders in toxicant-exposed individuals are not isolated digestive issues - they are integral to a broader toxicodynamic cascade, with repercussions for immune signaling, metabolic regulation, and neoplastic transformation.
Standard GI diagnostics fail to screen for the key molecular and microbial disruptions induced by toxicants. As such, these conditions remain underrecognized and undertreated - despite decades of scientific evidence.
BioSymphony bridges this diagnostic blind spot. By mapping exposure histories to measurable omic and microbiome disruption, it enables earlier identification of toxicant-driven GI pathology and more precise intervention - offering hope, accuracy, and validation to veterans and civilians alike living with invisible injury.