{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T01:53:56Z","timestamp":1775008436756,"version":"3.50.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"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:p>The gastrointestinal tract represents one of the largest body surfaces that is exposed to the outside world. It is the only mucosal surface that is required to simultaneously recognize and defend against pathogens, while allowing nutrients containing foreign antigens to be tolerated and absorbed. It differentiates between these foreign substances through a complex system of pattern recognition receptors expressed on the surface of the intestinal epithelial cells as well as the underlying immune cells. These immune cells actively sample and evaluate microbes and other particles that pass through the lumen of the gut. This local sensing system is part of a broader distributed signaling system that is connected to the rest of the body through the enteric nervous system, the immune system, and the metabolic system. While local tissue homeostasis is maintained by commensal bacteria that colonize the gut, colonization itself may not be required for the activation of distributed signaling networks that can result in modulation of peripheral inflammation. Herein, we describe the ability of a gut-restricted strain of commensal bacteria to drive systemic anti-inflammatory effects in a manner that does not rely upon its ability to colonize the gastrointestinal tract or alter the mucosal microbiome. Orally administered EDP1867, a gamma-irradiated strain of <jats:italic>Veillonella parvula<\/jats:italic>, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora.\u00a0In murine models of inflammatory disease\u00a0including\u00a0delayed-type hypersensitivity (DTH),\u00a0atopic dermatitis,\u00a0psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted\u00a0in significant reduction in inflammation and immunopathology.\u00a0<jats:italic>Ex\u00a0vivo<\/jats:italic>\u00a0cytokine analyses revealed\u00a0that EDP1867 treatment diminished\u00a0production of pro-inflammatory cytokines involved in inflammatory cascades. Furthermore, blockade of lymphocyte migration to the gut-associated lymphoid tissues impaired the ability of EDP1867 to resolve peripheral inflammation, supporting the hypothesis that circulating immune cells are responsible for promulgating the signals from the gut to peripheral tissues. Finally, we show that adoptively transferred T\u00a0cells from EDP1867-treated mice inhibit inflammation induced in recipient mice. These results demonstrate that an orally-delivered, non-viable strain of commensal bacteria can mediate potent anti-inflammatory effects in peripheral tissues through transient occupancy of the gastrointestinal tract, and support the development of non-living bacterial strains for therapeutic applications.<\/jats:p>","DOI":"10.3389\/fimmu.2022.768076","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T05:13:51Z","timestamp":1643778831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Regulation of Peripheral Inflammation by a Non-Viable, Non-Colonizing Strain of Commensal Bacteria"],"prefix":"10.3389","volume":"13","author":[{"given":"Kritika","family":"Ramani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"Cormack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam N. 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