The CIRS Protocol: A Sequential, Evidence-Based Treatment for Biotoxin-Associated Chronic Inflammatory Response Syndrome Human Health Part C
Main Article Content
Abstract
Chronic Inflammatory Response Syndrome (CIRS) is a complex, multisystem illness driven by sustained innate immune activation following exposure to biotoxins such as mold, mycotoxins, Actinobacteria, and bacterial endotoxins in water-damaged buildings (WDB), as well as tick-borne and marine toxins. The CIRS Protocol is a sequential 12-step therapeutic framework designed to diagnose and resolve CIRS through a combination of environmental, pharmacologic, and biochemical interventions.
This paper outlines the clinical application of the protocol, beginning with Step 1—complete removal from biotoxin exposure—which requires advanced environmental assessment using qPCR, LAL assays, and other validated building clearance criteria. Step 2 involves removal of internal biotoxin reservoirs using bile acid sequestrants (cholestyramine/Welchol), following immune system priming with high-dose EPA/DHA fish oil. Subsequent steps address eradication of Multiple Antibiotic Resistant Coagulase Negative Staphylococci (MARCoNS,) correction of gliadin antibodies, and restoration of depleted androgens—particularly dehydroepiandrosterone (DHEA) often suppressed in CIRS due to Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation.
The protocol progresses to targeted correction of disrupted biomarkers including Antidiuretic Hormone (ADH)/osmolality, Matrix Metalloproteinase-9 (MMP-9), Vascular Endothelial Growth Factor (VEGF), Complement 3a (C3a), Complement 4a (C4a), and Transforming Growth Factor beta-1 (TGFβ-1), each linked to specific symptoms and tissue-level dysfunction. Evidence-based use of adjunctive agents such as fish oil, losartan, and vasoactive intestinal peptide (VIP) is discussed in depth, with rationale grounded in peer-reviewed clinical and mechanistic data.
When implemented in the prescribed sequence with precision, the CIRS Protocol results in measurable biomarker normalization and clinical resolution in most compliant patients, restoring neuroendocrine-immune homeostasis and function.
Despite evidence from peer-reviewed studies and human clinical trials, the CIRS Protocol remains outside of mainstream medical practice, while unvalidated treatments proliferate—leading to poor outcomes and resource exhaustion for patients. This review aims to provide a clear, detailed, and referenced guide to the CIRS Protocol to support provider education and address the growing need for competent care in biotoxin-related illness.
Keywords:
Chronic Inflammatory Response Syndrome, Biotoxins, Water-Damaged Buildings, CIRS Protocol, Multiple Antibiotic Resistant Coagulase Negative Staphylococci (MARCoNS), Biomarkers, Neuroendocrine-immune homeostasis, Treatment protocol
Article Details
How to Cite
DORNINGER, Eric.
The CIRS Protocol: A Sequential, Evidence-Based Treatment for Biotoxin-Associated Chronic Inflammatory Response Syndrome.
Medical Research Archives, [S.l.], v. 13, n. 8, sep. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6770>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i8.6770.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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4. Hudnell HK. Chronic biotoxin-associated illness: multiple-system symptoms, a vision deficit, and effective treatment. Neurotoxicol Teratol. 2005; 27(5):733-743.
5. Shoemaker RC, House DE. A time-series study of sick building syndrome: chronic, biotoxin-associated illness from exposure to water-damaged buildings. Neurotoxicol Teratol. 2005;27(1):29-46.
6. Sekine T, Cha S, Endou H. The Mult specific organic anion transporter (OAT) family. Eur J Physiol. 2000;440:337-350.
7. Yu Z, You G. Recent advances in the regulations of organic anion transporters. Pharmaceutics. 2024; 16(11):1355.
8. Anzai N, Kanai Y, Endou H. Organic anion transporter family: current knowledge. J Pharmacol Sci. 2006;100(5):411-414.
9. Ticho AL, Malhotra P, Dudeja PK, Gill RK, Alrefai WA. Bile acid receptors and gastrointestinal functions. Liver Res. 2019;3(1):31-39
10. Kim YS, Kim JW, Ha NY, Kim J, Ryu HS. Herbal therapies in functional gastrointestinal disorders: a narrative review and clinical implication. Front Psychiatry. 2020;11:601.
11. Cheema HS, Singh MP. The use of medicinal plants in digestive system related disorders: a systematic review. J Ayurvedic Herb Med. 2021:182–187.
12. Fifi AC, Axelrod CH, Chakraborty P, Saps M. Herbs and spices in the treatment of functional gastrointestinal disorders: a review of clinical trials. Nutrients. 2018;10(11):1715.
13. Ford AC, Talley NJ, Spiegel BM, et al. Effect of fiber, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ. 2008;337
14. Khanna R, MacDonald JK, Levesque BG. Peppermint oil for the treatment of irritable bowel syndrome: a systematic review and meta-analysis. J Clin Gastroenterol. 2014;48(6):505-512.
15. Wegener T, Wagner H. The active components and the pharmacological multi-target principle of STW 5 (Iberogast). Phytomedicine. 2006;13 Suppl 5:20-35.
16. Cho MS, Park JW, Kim J, Ko SJ. The influence of herbal medicine on serum motilin and its effect on human and animal model: a systematic review. Front Pharmacol. 2023;14:1286333.
17. Poggioli R, Hirani K, Jogani VG, Ricordi C. Modulation of inflammation and immunity by omega-3 fatty acids: a possible role for prevention and to halt disease progression in autoimmune, viral, and age-related disorders. Eur Rev Med Pharmacol Sci. 2023;27(15):7380-7400.
18. Gutiérrez S, Svahn SL, Johansson ME. Effects of omega-3 fatty acids on immune cells. Int J Mol Sci. 2019;20(20):5028.
19. Mendivil CO. Dietary fish, fish nutrients, and immune function: a review. Front Nutr. 2021;7:617652.
20. Damsgaard CT, Lauritzen L, Kjær TMR, et al. Fish oil supplementation modulates immune function in healthy infants. J Nutr. 2007 ;137(4) :1031-1036.
21. Gallai V, Sarchielli P, Trequattrini A, et al. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol. 1995;56(2):143-153.
22. Marciani L, Cox E, Hoad C, et al. Effects of various food ingredients on gall bladder emptying. Eur J Clin Nutr. 2013;67:1182–1187.
23. Salman A, Zaheer M, Mallick I, Hassan M. Choleretic and cholagogic effects of anti-cholelithiatic plants. J Pharmacogn Phytochem. 2021;10:1-7.
24. Polymeros D, Beintaris I, Gaglia A, et al. Partially hydrolyzed guar gum accelerates colonic transit time and improves symptoms in adults with chronic constipation. Dig Dis Sci. 2014;59(9):2207-2214.
25. Arnaud MJ. Mild dehydration: a risk factor of constipation? Eur J Clin Nutr. 2003 ;57 Suppl 2 : S88-95.
26. Anti M, Pignataro G, Armuzzi A, et al. Water supplementation enhances the effect of high-fiber diet on stool frequency and laxative consumption in adult patients with functional constipation. Hepatogastroenterology. 1998;45(21):727-732.
27. Song BK, Kim YS, Kim HS, et al. Combined exercise improves gastrointestinal motility in psychiatric inpatients. World J Clin Cases. 2018;6(8):207-213.
28. Kim YS, Song BK, Oh JS, Woo SS. Aerobic exercise improves gastrointestinal motility in psychiatric inpatients. World J Gastroenterol. 2014; 20(30):10577-10584.
29. Bi L, Triadafilopoulos G. Exercise and gastrointestinal function and disease: an evidence-based review of risks and benefits. Clin Gastroenterol Hepatol. 2003;1(5):345-355.
30. Shafer RB, Prentiss RA, Bond JH. Gastrointestinal transit in thyroid disease. Gastroenterology. 1984; 86(5 Pt 1):852-855.
31. Harvey RF, Read AE. Effects of oral magnesium sulphate on colonic motility in patients with the irritable bowel syndrome. Gut. 1973;14(12):983-987.
32. Bueno L, Fioramonti J, Geux E, Raissiguier Y. Gastrointestinal hypomotility in magnesium-deficient sheep. Can J Anim Sci. 2011;60(2):293-301.
33. Stacewicz-Sapuntzakis M, Bowen PE, Hussain EA, et al. Chemical composition and potential health effects of prunes: a functional food? Crit Rev Food Sci Nutr. 2001;41(4):251-286.
34. Wilkinson-Smith V, Dellschaft N, Ansell J, et al. Mechanisms underlying effects of kiwifruit on intestinal function shown by MRI in healthy volunteers. Aliment Pharmacol Ther. 2019;49(6):759-768.
35. Shoemaker R, Hudnell K, House D, Domenico P. Association of nasal carriage of methicillin and multiple antibiotic resistant coagulase negative staphylococci species with deficiency of alpha melanocyte stimulating hormone in chronic fatigue syndrome: implication for expanded treatment options. American Society of Microbiology. 2003.
36. Becker K, Heilmann C, Peters G. Coagulase-negative staphylococci. Clin Microbiol Rev. 2014; 27(4):870-926.
37. Heilmann C, et al. Are coagulase-negative staphylococci virulent? Clin Microbiol Infect. 2019; 25(9):1071-1080.
38. Le KY, Park MD, Otto M. Immune evasion mechanisms of Staphylococcus epidermidis biofilm infection. Front Microbiol. 2018 ;9 :359.
39. Qin L, Da F, Fisher EL, et al. Toxin mediates sepsis caused by methicillin-resistant Staphylococcus epidermidis. PLoS Pathog. 2017;13(2):e1006153.
40. Coagulase-negative staphylococcus, nosocomial infections. Infectious Disease Advisor. February 16, 2024. Accessed July 29, 2025. https://www.infectiousdiseaseadvisor.com/ddi/coagulase-negative-staphylococcus/
41. Vuong C, Otto M. Staphylococcus epidermidis infections. Microbes Infect. 2002;4(4):481-489.
42. Marincola G, Liong O, Schoen C, et al. Antimicrobial resistance profiles of coagulase-negative staphylococci in community-based healthy individuals in Germany. Front Public Health. 2021;9:684456.
43. Asante J, Hetsa BA, Amoako DG, et al. Multidrug-resistant coagulase-negative staphylococci isolated from bloodstream in the uMgungundlovu District of KwaZulu-Natal Province in South Africa: emerging pathogens. Antibiotics (Basel). 2021;10(2):198.
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