VSL#3 probiotics provide protection against acute intestinal ischaemia/reperfusion injury.
Acute intestinal ischaemia/reperfusion injury (AII/R) is an adaptive physiologic response during critical illness, involving mesenteric vasoconstriction and hypoperfusion. Prevention of AII/R in high risk patient populations would have a significant impact on morbidity and mortality. The purpose of this study was to investigate the protective effects of VSL#3 probiotic treatment in a murine model of AII/R. Adult 129/SvEv mice were subjected to an experimental AII/R model using superior mesenteric artery occlusion. Animals were pre-treated with either three days or two weeks of VSL#3 probiotics. Local tissue injury markers were assessed by levels of myeloperoxidase and activation of nuclear factor kappa B (NFкB). Systemic and local cytokines, including interleukin (IL)-1β, IL- 10, TNFα, and interferon gamma were measured by ELISA and multiplex fluorescent detection. VSL#3 probiotics reduced local tissue inflammation and injury due to AII/R. A two-week course of VSL#3 was more effective than a shorter three-day course. The reduction in local inflammation from the two-week course of VSL#3 is correlated to a significant reduction in levels of active IL-1β, and tissue levels of myeloperoxidase. Levels of active NFкB were significantly elevated in the vehicle-fed AII/R mice, corroborating with tissue inflammation, which were attenuated by VSL#3 administrations. VSL#3 did not cause any systemic inflammation or lung injury. VSL#3 probiotics are effective in reducing local tissue injury from AII/R by down-regulating pro-inflammatory mediators and immune cell recruitment. This study highlights a potential role for VSL#3 in management of patients at high risk for AII/R.
Department of Surgery, University of Alberta, 2D WMC, 8440-112 St NW, Edmonton, AB T6G 2B7, Canada.|Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada.
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Salim
Department of Surgery, University of Alberta, 2D WMC, 8440-112 St NW, Edmonton, AB T6G 2B7, Canada.
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Young
Department of Surgery, University of Alberta, 2D WMC, 8440-112 St NW, Edmonton, AB T6G 2B7, Canada.
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Lukowski
Department of Medicine, University of Alberta, Edmonton, AB T6G 2E1, Canada.
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Madsen
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2B7, Canada.
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Sis
Department of Surgery, University of Alberta, 2D WMC, 8440-112 St NW, Edmonton, AB T6G 2B7, Canada.
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Churchill
Department of Surgery, University of Alberta, 2D WMC, 8440-112 St NW, Edmonton, AB T6G 2B7, Canada.|Division of Critical Care Medicine, University of Alberta, Edmonton, AB T6G 2B7, Canada.
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Khadaroo
D000818:Animals; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D007410:Intestinal Diseases / Q000517:prevention & control*; D007511:Ischemia / Q000150:complications*; D051379:Mice; D016328:NF-kappa B / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D019936:Probiotics / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome
D016207:Cytokines; D016328:NF-kappa B; D009195:Peroxidase
IL-1β; NFкB; inflammation; myeloperoxidase; small intestine