Can glyphosate’s disruption of the gut microbiome and induction of sulfate deficiency
explain the epidemic in gout and associated diseases in the industrialized world?

Seneff, Stephanie; Causton, N.J.; Nigh, G.L.; Koenig, Gerald; Avalon, D

doi:10.4024/04se17a.jbpc.17.02

Cited by 4 publications

(3 citation statements)

References 186 publications

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“…Being high in phenolic compounds, cigarette smoke toxicants serve as substrates for SULTs, and may, therefore, interfere with the metabolism of 17βestradiol and other endogenous compounds that require sulfation, 27 such as VD. Similarly, many drugs, biotoxins, xenobiotic compounds, 27 and environmental toxins (e.g., glyphosate, [232][233][234][235] PCBs, 230 cyanide, 236 and ethylene glycol [237][238][239] ) that either inhibit sulfation or are metabolized through sulfation, will result in impaired sulfation of the GL and other endogenous metabolites 29 (Figure 2). The effect will be more pronounced with cumulative use and if a combination of drugs is taken.…”

Section: Drugs and Toxinsmentioning

confidence: 99%

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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The glycocalyx surrounds every eukaryotic cell and is a complex mesh of proteins and carbohydrates. It consists of proteoglycans with glycosaminoglycan side chains, which are highly sulfated under normal physiological conditions. The degree of sulfation and the position of the sulfate groups mainly determine biological function. The intact highly sulfated glycocalyx of the epithelium may repel severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) through electrostatic forces. However, if the glycocalyx is undersulfated and 3‐O‐sulfotransferase 3B (3OST‐3B) is overexpressed, as is the case during chronic inflammatory conditions, SARS‐CoV‐2 entry may be facilitated by the glycocalyx. The degree of sulfation and position of the sulfate groups will also affect functions such as immune modulation, the inflammatory response, vascular permeability and tone, coagulation, mediation of sheer stress, and protection against oxidative stress. The rate‐limiting factor to sulfation is the availability of inorganic sulfate. Various genetic and epigenetic factors will affect sulfur metabolism and inorganic sulfate availability, such as various dietary factors, and exposure to drugs, environmental toxins, and biotoxins, which will deplete inorganic sulfate. The role that undersulfation plays in the various comorbid conditions that predispose to coronavirus disease 2019 (COVID‐19), is also considered. The undersulfated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a hyperinflammatory response, vascular permeability, and shedding of the glycocalyx components, giving rise to a procoagulant and antifibrinolytic state and eventual multiple organ failure. These symptoms relate to a diagnosis of systemic septic shock seen in almost all COVID‐19 deaths. The focus of prevention and treatment protocols proposed is the preservation of epithelial and endothelial glycocalyx integrity.

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Section: Drugs and Toxinsmentioning

confidence: 99%

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

et al. 2021

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“…It is possible to explain the strong correlations that are seen between the rise in a large number of debilitating chronic diseases and glyphosate usage on core crops through such a mechanism [61,62]. Detailed descriptions of strong glycine dependencies in proteins linked to various diseases have been presented in a sequence of recent papers, relating glyphosate substitution for glycine during protein synthesis as a plausible contributory cause of diabetes, obesity and Alzheimer’s disease [60], amyotrophic lateral sclerosis (ALS) [63], autism, multiple sclerosis and prion diseases [64], anencephaly [65], CKDu [66] and gout [67].…”

Section: Glyphosate As a Glycine Analoguementioning

confidence: 99%

“…Glutathione is composed of glycine, glutamate and cysteine. It is possible that glyphosate disrupts glutathione by directly substituting for its glycine residue, as proposed in Seneff et al, (2017) [67]. Gamma glutamyl transpeptidase (GGT) is an enzyme that breaks glutathione down into its individual amino acids, allegedly so that the components can be distributed in the blood for reuptake and reassembly back into glutathione by another cell.…”

Section: Synergy Between Glyphosate and Other Toxic Elementsmentioning

confidence: 99%

Glyphosate’s Synergistic Toxicity in Combination with Other Factors as a Cause of Chronic Kidney Disease of Unknown Origin

Gunatilake

Seneff

Orlando

2019

IJERPH

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Chronic kidney disease of unknown etiology (CKDu) is a global epidemic. Sri Lanka has experienced a doubling of the disease every 4 or 5 years since it was first identified in the North Central province in the mid-1990s. The disease primarily affects people in agricultural regions who are missing the commonly known risk factors for CKD. Sri Lanka is not alone: health workers have reported prevalence of CKDu in Mexico, Nicaragua, El Salvador, and the state of Andhra Pradesh in India. A global search for the cause of CKDu has not identified a single factor, but rather many factors that may contribute to the etiology of the disease. Some of these factors include heat stroke leading to dehydration, toxic metals such as cadmium and arsenic, fluoride, low selenium, toxigenic cyanobacteria, nutritionally deficient diet and mycotoxins from mold exposure. Furthermore, exposure to agrichemicals, particularly glyphosate and paraquat, are likely compounding factors, and may be the primary factors. Here, we argue that glyphosate in particular is working synergistically with most of the other factors to increase toxic effects. We propose, further, that glyphosate causes insidious harm through its action as an amino acid analogue of glycine, and that this interferes with natural protective mechanisms against other exposures. Glyphosate’s synergistic health effects in combination with exposure to other pollutants, in particular paraquat, and physical labor in the ubiquitous high temperatures of lowland tropical regions, could result in renal damage consistent with CKDu in Sri Lanka.

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Combined effects of MSU crystals injection and high fat-diet feeding on the establishment of a gout model in C57BL/6 mice

et al. 2020

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Objective Gout is characterized by inflammatory arthritis with hyperuricaemia and deposition of monosodium urate (MSU) crystals in the joints. Several animal models have been proposed based on MSU crystals injection or high-fat diet feeding; however, neither hyperuricaemia model nor acute gout model can effectively reflect clinical features of gout. This study aimed to assess the effectiveness of a compound gout model induced by the combination of MSU crystals injection and high-fat diet feeding. Methods The compound gout model was induced by high-fat diet feeding per day and the intraplantar injection of MSU crystals (1 mg) into the footpad of each mouse every 10 days. Serum uric acid, foot swelling and pain analyses were performed at days 22, 32 and 42. Gout inflammation, serum proinflammatory cytokines and gut microbiota analyses were performed only at day 42. Results Compared to hyperuricaemia model or acute gout model, the compound gout model showed little advantages of elevating serum uric acid, causing foot swelling and gout inflammation, while it caused more severe serum inflammation and gut microbiota dysbiosis. Severe serum inflammation in the compound gout model could be reflected by the increased levels of IL-1α, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IFN-γ, KC, MCP-1 and MIP-1β. In addition, the compound gout model induced more alterations in the gut microbiota, including increasing levels of Desulfovibrio and Parasutterella. Conclusion The injection of MSU and feed of high-fat diet have a combined effect on elevating serum inflammation and causing gut microbiota disorders in the process of establishing a gout model.

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Can glyphosate’s disruption of the gut microbiome and induction of sulfate deficiency explain the epidemic in gout and associated diseases in the industrialized world?

Cited by 4 publications

References 186 publications

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Pathogenesis of COVID‐19 described through the lens of an undersulfated and degraded epithelial and endothelial glycocalyx

Glyphosate’s Synergistic Toxicity in Combination with Other Factors as a Cause of Chronic Kidney Disease of Unknown Origin

Combined effects of MSU crystals injection and high fat-diet feeding on the establishment of a gout model in C57BL/6 mice

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