Dietary supplementation with Bifidobacterium lactis NCC2818 from weaning reduces local immunoglobulin production in lymphoid-associated tissues but increases systemic antibodies in healthy neonates

Weaning is associated with a major shift in the microbial community of the intestine, and this instability may make it more acquiescent than the adult microbiota to long-term changes. Modulation achieved through dietary interventions may have potentially beneficial effects on the developing immune system, which is driven primarily by the microbiota. The specific aim of the present study was to determine whether immune development could be modified by dietary supplementation with the human probiotic Bifidobacterium lactis NCC2818 in a tractable model of weaning in infants. Piglets were reared by their mothers before being weaned onto a solid diet supplemented with B. lactis NCC2818, while sibling controls did not receive supplementation. Probiotic supplementation resulted in a reduction in IgA (P0·05). Probiotic-supplemented pigs had more mast cells than unsupplemented littermates (P<0·0001), although numbers in both groups were low. In addition, the supplemented piglets made stronger serum IgG responses to fed and injected antigens (P<0·05). The present findings are consistent with B. lactis NCC2818 reducing intestinal permeability induced by weaning, and suggest that the piglet is a valuable intermediate between rodent models and human infants. The results also strongly suggest that measures of the effect of probiotic supplementation on the immune system need to be interpreted carefully as proxy measures of health benefit. However, they are useful in developing an understanding of the mechanism of action of probiotic strains, an important factor in predicting favourable health outcomes of nutritional interventio

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.</p> <p>Methods</p> <p>Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.</p> <p>Results</p> <p>14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).</p> <p>Conclusion</p> <p>The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN92101486</p

Nigella sativa (Black Cumin) Seed Extract Alleviates Symptoms of Allergic Diarrhea in Mice, Involving Opioid Receptors

The incidence of food hypersensitivity and food allergies is on the rise and new treatment approaches are needed. We investigated whether N. sativa, one of its components, thymoquinone, or synthetic opioid receptor (OR)-agonists can alleviate food allergy. Hence, ovalbumin (OVA) -sensitized BALB/c-mice were pre-treated either with a hexanic N. sativa seed extract, thymoquinone, kappa- (U50'4889) or mu-OR-agonists (DAMGO) and subsequently challenged intra-gastrically with OVA. All 4 treatments significantly decreased clinical scores of OVA-induced diarrhea. N. sativa seed extract, thymoquinone, and U50'488 also decreased intestinal mast cell numbers and plasma mouse mast cell protease-1 (MMCP-1). DAMGO, in contrast, had no effect on mast cell parameters but decreased IFNγ, IL-4, IL-5, and IL-10 concentration after ex vivo re-stimulation of mesenteric lymphocytes. The effects on allergy symptoms were reversible by OR-antagonist pre-treatment, whereas most of the effects on immunological parameter were not. We demonstrate that N. sativa seed extract significantly improves symptoms and immune parameters in murine OVA-induced allergic diarrhea; this effect is at least partially mediated by thymoquinone. ORs may also be involved and could be a new target for intestinal allergy symptom alleviation. N. sativa seed extract seems to be a promising candidate for nutritional interventions in humans with food allergy

<i>In vitro</i> opioid receptor-displacement assay.

<p>(Abbr.: CHO = Chinese hamster Ovary, HEK = Human embryonic kidney, DOP = delta opioid; KOP = kappa opioid, MOP = mu opioid, recomb. = recombinant).</p

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study-0

<p><b>Copyright information:</b></p><p>Taken from "Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study"</p><p>http://www.biomedcentral.com/1471-230X/7/36</p><p>BMC Gastroenterology 2007;7():36-36.</p><p>Published online 4 Sep 2007</p><p>PMCID:PMC1995200.</p><p></p> different study during study period (1)

<i>N. sativa</i> seed extract decreases clinical macroscopic scores and immune parameters in OVA-allergic mice.

<p>OVA-sensitized mice were challenged with saline (Saline), OVA (OVA), or with OVA after intragastric administration of <i>N. sativa</i> seed extract (Ns) with the OR antagonist naloxone-methiodide pre-treatment at the dose indicated (Ns N-M), or with naloxone-methiodide alone (N-M). Panels <b>A</b> and <b>B</b> represent the median of clinical macroscopic scores at sacrifice. Panels <b>C</b> and <b>D</b> show the plasma concentration of MMCP-1 (<b>C</b>) and the numbers of mast cells per intestinal villus (<b>D</b>) at sacrifice. Each dot represents the corresponding value for one animal and the bars represent the median with interquartile range, * = <i>p</i><0.05; n = 5–19.</p

<i>In vitro</i> ligand displacement by thymoquinone.

a)<p>20–50% = moderate displacement (Abbr.: MOR = μ-opioid receptor, KOR = ê-opioid receptor, DOR = δ-opioid receptor).</p

KOR-agonist (U50'488) and MOR-agonist (DAMGO) alleviate allergy related immune markers in OVA-allergic mice.

<p>OVA-sensitized mice were challenged with saline (Saline) or OVA (OVA) with or without pre-treatment. The graph shows the concentration of total plasma MMCP-1 (<b>A</b>) at sacrifice after subcutaneous treatment with 5 mg/kgBW KOR-agonist U50'488 (U50'488), with 20 mg/kgBW NorBNI (U50'488+NorBNI), or with NorBNI alone (NorBNI), and the concentration of plasma IL-4 (<b>B</b>) and IFN-gamma (<b>C</b>) after subcutaneous treatment with 5 mg/kgBW MOR-agonist (DAMGO) and naloxone-methiodide (DAMGO+N-M 1 mg), or naloxone-methiodide alone (N-M 1 mg). MMCP-1 levels were unchanged with MOR-agonist and IL-4 and IFN-gamma levels were unchanged with KOR-agonist respectively (data not shown). Each dot represents the corresponding value for one animal and the bars represent the median and interquartile range, * <i>p</i><0.05; n = 5–10.</p

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study-1

<p><b>Copyright information:</b></p><p>Taken from "Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study"</p><p>http://www.biomedcentral.com/1471-230X/7/36</p><p>BMC Gastroenterology 2007;7():36-36.</p><p>Published online 4 Sep 2007</p><p>PMCID:PMC1995200.</p><p></p> different study during study period (1)

Thymoquinone decreases clinical symptoms, plasma MMCP-1 levels, and mast cell numbers in OVA-allergic mice.

<p>OVA-sensitized mice were challenged with saline (Saline), OVA (OVA), or with OVA after intragastric treatment with 13 mg/kgBW thymoquinone (Thq) and with thymoquinone after 30 mg/kgBW naloxone-methiodide pre-treatment (Thq N-M). Panel <b>A</b> represent the median of clinical macroscopic scores at sacrifice. Panel <b>B</b> shows the plasma concentrations of MMCP-1 and Panel <b>C</b> the numbers of mast cells per intestinal villus at sacrifice. The dots correspond to results from individual animals and the bars represent the median with interquartile range, * = p<0.05, panels show the results from two pooled experiments, n = 10–20. Panel <b>D–G</b> are representative histological pictures of mast cells in the jejunum of OVA-sensitized mice challenged with saline (<b>D</b>), OVA (<b>E</b>), or with OVA after intragastric treatment with 13 mg/kgBW thymoquinone (<b>F</b>) and with thymoquinone after 30 mg/kgBW naloxone-methiodide pre-treatment (<b>G</b>). Mast cells appear in bright red.</p