{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:01:40Z","timestamp":1785391300225,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endotoxin-driven intestinal inflammation represents a major contributor to impaired barrier function, metabolic inefficiency, and immune dysregulation in both human and animal health. Strategies that reduce luminal inflammatory triggers rather than directly suppress host signaling pathways represent an emerging paradigm in functional nutrition. Clinoptilolite zeolite, a naturally occurring aluminosilicate mineral with high adsorption capacity, is widely used as a feed additive; however, its capacity to modulate endotoxin-mediated inflammatory signaling has not been mechanistically defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically evaluated the immunomodulatory potential of feed-grade clinoptilolite\n                      <jats:italic>in vitro<\/jats:italic>\n                      and assessed its subchronic safety\n                      <jats:italic>in vivo<\/jats:italic>\n                      . LPS-induced NF-\u03baB activation was quantified in THP-1 Dual reporter cells, nitric oxide production was measured in RAW264.7 macrophages, and pro-inflammatory cytokine secretion (IL-1\u03b2, IL-6, IL-8, and TNF-\u03b1) was analyzed in Caco-2 intestinal epithelial cells. To determine whether clinoptilolite reduces endotoxin bioactivity, LPS was pre-incubated with the material prior to cellular stimulation. Systemic tolerability was evaluated in Wistar rats receiving daily oral administration (5\u2013500 mg\/kg) followed by comprehensive hematological and histopathological assessments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinoptilolite significantly attenuated LPS-induced NF-\u03baB activation and nitric oxide production in innate immune cells without intrinsic pro-inflammatory activity. Pre-incubation experiments demonstrated a marked reduction in residual LPS bioactivity, supporting an adsorption-mediated mechanism. In intestinal epithelial cells, clinoptilolite selectively reduced LPS-induced IL-6 and IL-8 secretion while preserving IL-1\u03b2 and TNF-\u03b1 responses, indicating pathway-specific modulation rather than global immune suppression. Subchronic oral administration produced no clinically relevant hematological alterations or treatment-related histopathological changes in major organs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings provide integrated mechanistic and safety evidence that clinoptilolite zeolite attenuates endotoxin-driven inflammatory signaling by reducing luminal bioavailability while maintaining systemic tolerability. The data support its development as a functional nutritional material aimed at modulating intestinal inflammatory responses without directly targeting host intracellular pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1818740","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:39:09Z","timestamp":1785389949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adsorption-mediated modulation of lipopolysaccharide bioactivity by clinoptilolite zeolite with in vitro immunomodulatory effects and in vivo safety evaluation"],"prefix":"10.3389","volume":"17","author":[{"given":"Povilas","family":"Kavaliauskas","sequence":"first","affiliation":[{"name":"Department of Animal Nutrition, Lithuanian University of Health Sciences","place":["Kaunas, Lithuania"]},{"name":"Biological Research Center, Lithuanian University of Health Sciences","place":["Kaunas, Lithuania"]},{"name":"Institute of Infectious Diseases and Pathogenic Microbiology","place":["Prienai, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolandas","family":"Stankevicius","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition, Lithuanian University of Health Sciences","place":["Kaunas, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Rakickas","sequence":"additional","affiliation":[{"name":"Public Institution \u0160ilut\u0117 Primary Health Care Center","place":["\u0160ilut\u0117, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alius","family":"Pockevicius","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, Lithuanian University of Health Sciences","place":["Kaunas, 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