| 1. |
- Carlsson, Anders, 1980-
(författare)
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Role of mast cells and probiotics in the regulation of intestinal barrier function
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicles. The epithelium covering the Peyer’s patches is called follicle-associated epithelium and is specialized in antigen sampling and uptake. The special epithelium enables presentation of luminal antigen to immune cells in the underlying follicle.Persistent life stress and stressful life events affect the course of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) through largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immune-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis and Crohns disease. Vasoactive intestinal polypeptide (VIP) and corticotropin-releasing factor have been implicated as important mediators of stress-induced abnormalities in intestinal mucosal functions in animal models. Both of these mediators have been reported to regulate bowel ion secretion in humans during stress and uptake of horseradish peroxidase in rodents. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated.The aim of this thesis was to elucidate whether mast cells play an important role in intestinal barrier function during stress and inflammation. Moreover, we wanted to determine whether probiotics can ameliorate the mucosal barrier integrity during stress and inflammation.To study the function of mast cells we conducted in vitro experiments on cell lines and ex vivo experiments in Ussing chambers on mouse, rat and human intestinal tissue. The Ussing chamber technique measures electrophysiological properties of the tissue and also gives the possibility to study transcellular and paracellular passage of markers and bacteria. Immunohistology and confocal microscopy have been used to identify mast cells and receptors of interest.Our results show that stress affects the follicle-associated epithelium barrier by mechanisms involving VIP and mast cells. These findings were corroborated by the localization of VIP receptors on mucosal mast cells. Furthermore, pretreatment with probiotics was effective in protecting the gut against stress-induced intestinal barrier dysfunction and mucosal inflammation. This protection appeared to involve a mast cell and peroxisome proliferatoractivated receptor-γ dependent mechanism.
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| 2. |
- Edwards, M. V., et al.
(författare)
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Spray-dried porcine plasma and yeast derived protein meal influence the adaption to weaning of primiparous and multiparous sow progeny in different ways
- 2013
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Ingår i: Animal Production Science. - 1836-5787. ; 53:1, s. 75-86
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Tidskriftsartikel (refereegranskat)abstract
- Pigs from 154 litters (n = 1132, 19 +/- 3 days of age, 4.9 +/- 1.1 kg of bodyweight) were used in a 3 x 2 factorial design to evaluate two raw materials with nutraceutical properties being used in feeds, spray-dried porcine plasma (SDPP) and a yeast protein meal, and their effects on growth performance, immune parameters and gastrointestinal adaption of piglets to weaning. Factors included dietary treatments being (1) 5% SDPP (PLA), (2) 3.5% yeast protein meal (NUP) and (3) medicated control (TMC) and parity (primiparous versus multiparous). The treatment groups were imposed from Day 19 through to weaning at Day 27. Selected pigs (n = 720, 28 +/- 3 days of age, 7.4 +/- 1.0 kg of bodyweight) were weaned and remained on their respective diets from Day 28 to Day 34. From Day 35 to Day 48 all group-housed pigs were offered a commercial weaner 1 diet, and from Day 49 to Day 68 pigs were offered a commercial weaner 2 diet. Growth performance, survival, and serum immunoglobulinGwere monitored throughout the nursery phase (Day 28 to Day 68). Adaptation of the gastrointestinal tract in the acute post-weaning phase (Day 28 to Day 34) was assessed in 36 individually housed male weaners, with the effects of feed on structural, digestive, microbial and immune parameters along the gastrointestinal tract determined atDay 34. Pre-weaning feed disappearance was greater (P< 0.01) in multiparous litters independent of diet. In the commercial nursery, total removals (mortality and morbidity) were highest (P<0.01) in primiparous sow progeny, with pigs offered NUP having greater (P <= 0.05) total removals. Pigs offered PLA had superior average daily gain, average daily feed intake and feed conversion ratio from Day 28 to Day 34 (P<0.05). Pigs offered NUP tended to (P=0.07) have superior average daily gain from Day 35 to Day 49. Pigs offered NUP had higher (P<0.05) serum immunoglobulinGconcentrations at Day 68 compared with pigs offered TMC, with the effect most pronounced in primiparous sow progeny. Individually housed weaners offered PLA consumed more (P<0.05) feed on Day 30 to Day 31, had shorter relative intestine length (P<0.05), greater villous height in the medial jejunum (P<0.10) and lower immuno-pathology scores along the intestine. Pigs offered PLA also tended (P<0.10) to have increased pancreatic-specific lipase and amylase activity compared with pigs offered NUP. Pigs offered NUP had a higher ratio of E. coli : coliforms in the colon (P<0.01) and more counts of beta-haemolytic bacteria in the medial jejunum (P<0.05) and colon (P<0.10). Diets containing either SDPP or NUP offered pigs benefits beyond nutrition relative to the medicated control diet. The benefits of SDPPwere highly effective but transient, while the yeast derived protein had a successive or accumulative effect which was more pronounced in primiparous sow progeny. Received 3 May 2012, accepted 17 October 2012, published online 29 November 2012
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| 3. |
- Emek, Sinan Cem, et al.
(författare)
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Pigments protect the light harvesting proteins of chloroplast thylakoid membranes against digestion by gastrointestinal proteases
- 2011
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Ingår i: Food Hydrocolloids. - : Elsevier BV. - 0268-005X. ; 25:6, s. 1618-1626
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Tidskriftsartikel (refereegranskat)abstract
- Chloroplast thylakoid membranes inhibit pancreatic lipase/colipase activity in vitro and, when included in food, induce satiety signals. As thylakoid membranes themselves are nutrients, containing lipids and proteins, it is of interest to study the digestion of thylakoids by enzymes of the gastrointestinal tract. Thylakoid membranes were treated with pepsin, trypsin, gastric and pancreatic juice at 37 degrees C and the resulting enzymatic breakdown was analyzed by gel electrophoresis, electron microscopy and mass spectroscopy. In all cases, several of the proteins were degraded within half an hour, while the main parts of the pigment-protein complexes were resistant for hours. Oil emulsified thylakoids were more resistant towards the enzymatic breakdown. Electron microscopy demonstrated that, after treatments, the thylakoids still remained in a membrane vesicular form. The capacity of thylakoid membranes to inhibit the lipase/colipase activity was partly reduced in all cases. About 50% of the inhibition capacity remained after treatment with pancreatic juice when the thylakoids were present in an oil emulsion. Delipidated thylakoids and plasma membranes, which lack the photosynthetic pigments, were degraded rapidly by pancreatic juice. Conclusion: The pigments, closely bound to the trans-membrane helices of thylakoid membrane proteins protect these from digestion by pepsin, trypsin, gastric and pancreatic juice. This supports the notion that a substantial inhibition of lipase/colipase takes place during the first 2 h in the intestine resulting in a retardation and prolongation of lipolysis in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
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| 4. |
- Fåk, Frida, et al.
(författare)
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Effects of a high-fat diet during pregnancy and lactation are modulated by E. coli in rat offspring
- 2012
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 36:5, s. 744-751
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Microbial manipulations in early life can affect gut development and inflammatory status of the neonate. The maternal diet during pregnancy and lactation also influences the health of the offspring, but the impact of maternal high-fat (HF) feeding along with modulations of the gut microbiota on body weight, fat deposition and gut function in the offspring has been poorly studied. Methods: Rat dams were given access to either an HF or a standard low-fat diet during the last 2 weeks of pregnancy and during lactation and effects on body weight and gastrointestinal function were investigated in the 14-day-old offspring. To elucidate whether bacterial administration to the dam could modulate any effects of the diets in the rat pups, another group of dams were given Escherichia coli in their drinking water. Results: Maternal HF feeding resulted in increased body and fat pad weights in the offspring, along with increased levels of the acute-phase protein, haptoglobin and decreased protein content and disaccharidase activities in the small intestine. The addition of E. coli further accentuated these responses in the young rats, which, in addition to higher body weights and increased fat deposition, also showed an increased intestinal permeability and elevated levels of haptoglobin. Conclusions: The present study demonstrates for the first time how bacterial administration to the maternal diet during the neonatal period can affect body weight and fat deposition in the offspring. The results point to a mechanistic link between the gut microbiota, increased intestinal permeability and metabolic endotoxemia, which appear to have led to increased adiposity in the young rats. International Journal of Obesity (2012) 36, 744-751; doi:10.1038/ijo.2011.118; published online 5 July 2011
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| 5. |
- Köhnke, Rickard, et al.
(författare)
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Feeding appetite suppressing thylakoids to pigs alters pancreatic lipase/colipase secretion
- 2010
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Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413. ; 134:1-3, s. 68-71
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Konferensbidrag (refereegranskat)abstract
- The mechanism for a new appetite suppressor named thylakoids (membrane proteins derived from spinach leaves) was examined in vivo in pigs. Thylakoids inhibit the lipase/colipase hydrolysis of triacylglycerols (TG) in vitro and suppress food intake, decrease body weight gain and raise the circulating satiety hormone cholecystokinin (CCK) in rats but its mechanism in vivo remains unclear. We hypothesized that a thylakoid-enriched diet prolongs intestinal digestion of food and therefore promote satiety signaling. Five pigs were surgically prepared with a fistula in the duodenum for collection of digesta and with two catheters, one in v. jugularis and one in v. porta, for blood collection. After 1 week of recovery and an overnight fast the pigs were fed a high-fat diet with and without supplementation with thylakoids. Duodenal content and blood samples were taken before and 15, 30, 60, 120, 240 and 360 min after feeding. Pancreatic lipase and colipase enzymes were measured in duodenal digesta. Blood samples were analyzed for the satiety hormone CCK as well as insulin and glucose. We found that pancreatic lipase/colipase level increased and stayed elevated for a longer time in the duodenum in the pigs receiving thylakoids compared to the control. CCK levels were unchanged. Insulin levels were significantly reduced by the thylakoid treatment without any change in blood glucose. In conclusion, thylakoids increased lipase/colipase secretion. The mechanism for this secretion appears not to be related to CCK and may be an effect of vagal activation. Thylakoids gave reduced insulin levels without any change in glucose levels. (C) 2010 Published by Elsevier B.V.
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| 6. |
- Lavasani, Shahram, et al.
(författare)
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A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells.
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). One potential therapeutic strategy for MS is to induce regulatory cells that mediate immunological tolerance. Probiotics, including lactobacilli, are known to induce immunomodulatory activity with promising effects in inflammatory diseases. We tested the potential of various strains of lactobacilli for suppression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. METHODOLOGY/PRINCIPAL FINDINGS: The preventive effects of five daily-administered strains of lactobacilli were investigated in mice developing EAE. After a primary screening, three Lactobacillus strains, L. paracasei DSM 13434, L. plantarum DSM 15312 and DSM 15313 that reduced inflammation in CNS and autoreactive T cell responses were chosen. L. paracasei and L. plantarum DSM 15312 induced CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) and enhanced production of serum TGF-beta1, while L. plantarum DSM 15313 increased serum IL-27 levels. Further screening of the chosen strains showed that each monostrain probiotic failed to be therapeutic in diseased mice, while a mixture of the three lactobacilli strains suppressed the progression and reversed the clinical and histological signs of EAE. The suppressive activity correlated with attenuation of pro-inflammatory Th1 and Th17 cytokines followed by IL-10 induction in MLNs, spleen and blood. Additional adoptive transfer studies demonstrated that IL-10 producing CD4(+)CD25(+) Tregs are involved in the suppressive effect induced by the lactobacilli mixture. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence showing that the therapeutic effect of the chosen mixture of probiotic lactobacilli was associated with induction of transferable tolerogenic Tregs in MLNs, but also in the periphery and the CNS, mediated through an IL-10-dependent mechanism. Our findings indicate a therapeutic potential of oral administration of a combination of probiotics and provide a more complete understanding of the host-commensal interactions that contribute to beneficial effects in autoimmune diseases.
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| 7. |
- Linninge, Caroline, et al.
(författare)
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Effects on weight gain and gut microbiota in rats given bacterial supplements and a high-energy-dense diet from fetal life through to 6 months of age
- 2011
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 106:6, s. 887-895
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the long-term effects of a high-energy dense diet, supplemented with Lactobacillus plantarum (Lp) or Escherichia coli (Ec) on weight gain, fattening and the gut microbiota in rats. Since the mother’s dietary habits can influence offspring physiology, the dietary regimes started with the dams at pregnancy and through lactation, and continued with the offspring for six months. The weight gain of group Lp was lower than for groups C (control) and Ec (P=0•086). More retroperitoneal adipose tissue (P=0•030) and higher plasma leptin (P=0•035) were seen in group Ec compared to group Lp. The viable count of Enterobacteriaceae was higher in group Ec than in group Lp (P=0•019) and when all animals were compared, Enterobacteriaceae correlated positively with body weight (r=0•428, P=0•029). Bacterial diversity was lower in group Ec than in groups C (P=<0•05) and Lp (P=<0•05). Firmicutes, Bacteroidetes and Verrucomicrobia dominated in all groups, but Bacteroidetes were more prevalent in group C than in groups Lp (P=0•036) and Ec (P=0•056). The same five bacterial families dominated the microbiota of groups Ec and C, and four of these were also present in group Lp. The other five families dominating in group Lp were not found in any of the other groups. Multivariate data analysis pointed in the same directions as the univariate statistics. Our results suggest that supplementation of L. plantarum or E. coli can have long-term effects on the composition of the intestinal microbiota, as well as on weight gain and fattening.
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| 8. |
- Montelius, Caroline, et al.
(författare)
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Chloroplast thylakoids reduce glucose uptake and decrease intestinal macromolecular permeability.
- 2011
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Ingår i: British Journal of Nutrition. - 1475-2662. ; 106:6, s. 836-844
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoid membranes, derived from chloroplasts, have previously been shown to retard fat digestion and lower blood glucose levels after oral intake. The purpose of the present study was to investigate the effect of thylakoid membranes on the passage of methyl-glucose, dextran and ovalbumin over rat intestine in vitro using Ussing chambers. The results show that thylakoids retard the passage of each of the test molecules in a dose-dependent way. The thylakoids appear to be attached on the mucosal surface and a mechanism is suggested that the thylakoids delay the passage of the test molecules by sterical hindrance. The present results indicate that thylakoid membranes may be useful both to control intestinal absorption of glucose and to enhance the barrier function of the intestine.
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| 9. |
- Montelius, Caroline, et al.
(författare)
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Dietary thylakoids suppress blood glucose and modulate appetite-regulating hormones in pigs exposed to oral glucose tolerance test.
- 2014
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 33:6, s. 1122-1126
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Tidskriftsartikel (refereegranskat)abstract
- Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet.
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| 10. |
- Montelius, Caroline, et al.
(författare)
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Feeding spinach thylakoids to rats modulates the gut microbiota, decreases food intake and affects the insulin response
- 2013
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Ingår i: Journal of Nutritional Science. - : Cambridge University Press (CUP). - 2048-6790. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Thylakoid membranes derived from green leaf chloroplasts affect appetite-regulating hormones, suppress food intake, reduce blood lipids and lead to a decreased body weight in animals and human subjects. Thylakoids also decrease the intestinal in vitro uptake of methyl-glucose in the rat. The aim of this study was to investigate the effect of dietary thylakoids on the gut microbiota composition, mainly the taxa of lactobacilli and bifidobacteria, in rats fed either a thylakoid-enriched diet or a control diet for 10 d. At the same time, a glucose-tolerance test in the same rats was also performed. Food intake was significantly decreased in the thylakoid-fed rats compared with the control-fed rats over the 10-d study. An oral glucose tolerance test after 10 d of thylakoid- or control-food intake resulted in significantly reduced plasma insulin levels in the thylakoid-fed rats compared with the control-fed rats, while no difference was observed for blood glucose levels. Analysis of gut bacteria showed a significant increase of lactobacilli on the ileal mucosa, specifically Lactobacillus reuteri, in the rats fed the thylakoid diet compared with rats fed the control diet, while faecal lactobacilli decreased. No difference in bifidobacteria between the thylakoid and control groups was found. Analyses with terminal restriction fragment length polymorphism and principal component analysis of faeces demonstrated different microbial populations in the thylakoid- and control-fed animals. These findings indicate that thylakoids modulate the gut microbial composition, which might be important for the regulation of body weight and energy metabolism.
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