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      An immune-modulating formula comprising whey peptides and fermented milk improves inflammation-related remote organ injuries in diet-induced acute pancreatitis in mice

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          Abstract

          It has been demonstrated that an immune-modulating enteral formula enriched with whey peptides and fermented milk (IMF) had anti-inflammatory effects in some experimental models when it was administered before the induction of inflammation. Here, we investigated the anti-inflammatory effects of the IMF administration after the onset of systemic inflammation and investigated whether the IMF could improve the remote organ injuries in an acute pancreatitis (AP) model. Mice were fasted for 12 hours and then fed a choline-deficient and ethionine-supplemented diet (CDE diet) for 24 hours to induce pancreatitis. In experiment 1, the diet was replaced with a control enteral formula, and mice were sacrificed at 24-hour intervals for 96 hours. In experiment 2, mice were randomized into control and IMF groups and received the control formula or the IMF respectively for 72 hr or 96 hr. In experiment 1, pancreatitis was induced by the CDE diet, and inflammatory mediators were elevated for several days. Remote organ injuries such as splenomegaly, hepatomegaly, and elevation of the hepatic enzymes developed. A significant strong positive correlation was observed between plasma MCP-1 and hepatic enzymes. In experiment 2, the IMF significantly improved splenomegaly, hepatomegaly, and the elevation of hepatic enzymes. Plasma MCP-1 levels were significantly lower in the IMF group than in the control group. Nutrition management with the IMF may be useful for alleviating remote organ injuries after AP.

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          Altered gut flora and environment in patients with severe SIRS.

          The gut is considered an important target organ of injury after severe insult such as sepsis, trauma, and shock. The impact of bacterial translocation or mesenteric lymph on systemic inflammatory response and multiple organ damage has been investigated in animals, but dynamic changes in the gut flora and environment have not been fully clarified in critically ill patients. In the present study, we quantitatively evaluated changes in the gut microflora and environment in patients with severe systemic inflammatory response syndrome (SIRS). Twenty-five patients with severe SIRS, who fulfilled the criteria for SIRS, had a serum CRP level >10 mg/dL, and were treated in the intensive care unit for more than 2 days, were included in our study. SIRS was a result of sepsis in 18 patients, trauma in 6, and burn in 1. A fecal sample was used for quantitative evaluation of microflora (bacterial counts of 10 key groups including Bifidobacterium and Lactobacillus) by plate or tube technique and of the gut environment (pH and 9 organic acids by high speed liquid chromatography). Data obtained from patients were compared with corresponding data from healthy volunteers. Analysis of fecal flora confirmed that patients with severe SIRS had significantly lower total anaerobic bacterial counts (especially 2-4 log fewer "beneficial" Bifidobacterium and Lactobacillus) and 2 log higher "pathogenic" Staphylococcus and Pseudomonas group counts than those of healthy volunteers. Concentrations of total organic acids (especially "beneficial" short-chain fatty acids such as acetic acid, propionic acid, and butyric acid) in the feces were significantly decreased in the patients, whereas pH was markedly increased. The gut flora and environment are significantly altered in patients with severe SIRS. Abnormal gut flora and environment may affect systemic inflammatory response after severe insult.
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            Lactic acid bacteria secrete metabolites retaining anti-inflammatory properties after intestinal transport.

            Probiotic bacteria have a beneficial effect on intestinal inflammation. In this study, we have examined the effect of lactic acid and commensal Gram positive (+) bacteria conditioned media (CM) on tumour necrosis factor alpha (TNF-alpha) release and the mechanisms involved. Lipopolysaccharide (LPS) induced TNF-alpha secretion by peripheral blood mononuclear cells or the THP-1 cell line was monitored in the presence or absence of bacteria CM obtained from two probiotic strains, Bifidobacterium breve (Bb) and Streptococcus thermophilus (St), and three commensal bacterial strains (Bifidobacterium bifidum, Ruminococcus gnavus, and unidentified Streptococcus). Bb and St bacteria CM were allowed to cross filter grown intestinal epithelial cell monolayers (HT29-19A) to assess intestinal transport of active bacterial products. These products were characterised and their effect on LPS binding to THP-1 cells and nuclear factor kappa B (NF kappa B) activation assessed. Dose dependent inhibition of LPS induced TNF-alpha secretion was noted for both probiotic bacteria CM (64% and 71% inhibition for Bb and St, respectively) and to a lesser extent commensal bacteria CM (21-32% inhibition). Active products from Bb and St were resistant to digestive enzymes and had a molecular mass <3000 Da. Their inhibitory effect was preserved after transepithelial transport across intestinal cell monolayers, mainly in inflammatory conditions. LPS-FITC binding to THP-1 cells and NF kappa B activation were significantly inhibited by Bb and St CM. B breve and S thermophilus release metabolites exerting an anti-TNF-alpha effect capable of crossing the intestinal barrier. Commensal bacteria also display a TNF-alpha inhibitory capacity but to a lesser extent. These results underline the beneficial effect of commensal bacteria in intestinal homeostasis and may explain the role of some probiotic bacteria in alleviating digestive inflammation.
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              POST-INJURY MULTIPLE ORGAN FAILURE: THE ROLE OF THE GUT

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                Author and article information

                Journal
                Biosci Microbiota Food Health
                Biosci Microbiota Food Health
                BMFH
                Bioscience of Microbiota, Food and Health
                BMFH Press
                2186-6953
                2186-3342
                25 August 2017
                2018
                : 37
                : 1
                : 1-8
                Affiliations
                [1 ]Nutrition Research Department, Food Science & Technology Research Laboratories, Meiji Co., Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan
                [2 ]Surgical Center, The University of Tokyo, Tokyo, Japan
                Author notes
                *Corresponding author. Kentaro Nakamura (E-mail: kentarou.nakamura@ 123456meiji.com )
                Article
                17-011
                10.12938/bmfh.17-011
                5787410
                c93d4482-2be7-47eb-bef2-0be2593b90df
                ©2018 BMFH Press

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)

                History
                : 31 May 2017
                : 30 July 2017
                Categories
                Full Paper

                immune-modulating formula,acute pancreatitis,inflammation,remote organ injury

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