[Show abstract][Hide abstract] ABSTRACT: Clinical and preclinical studies have associated gastrointestinal inflammation and infection with altered behavior. We investigated whether chronic gut inflammation alters behavior and brain biochemistry and examined underlying mechanisms.
AKR mice were infected with the noninvasive parasite Trichuris muris and given etanercept, budesonide, or specific probiotics. Subdiaphragmatic vagotomy was performed in a subgroup of mice before infection. Gastrointestinal inflammation was assessed by histology and quantification of myeloperoxidase activity. Serum proteins were measured by proteomic analysis, circulating cytokines were measured by fluorescence activated cell sorting array, and serum tryptophan and kynurenine were measured by liquid chromatography. Behavior was assessed using light/dark preference and step-down tests. In situ hybridization was used to assess brain-derived neurotrophic factor (BDNF) expression in the brain.
T muris caused mild to moderate colonic inflammation and anxiety-like behavior that was associated with decreased hippocampal BDNF messenger RNA (mRNA). Circulating tumor necrosis factor-α and interferon-γ, as well as the kynurenine and kynurenine/tryptophan ratio, were increased. Proteomic analysis showed altered levels of several proteins related to inflammation and neural function. Administration of etanercept, and to a lesser degree of budesonide, normalized behavior, reduced cytokine and kynurenine levels, but did not influence BDNF expression. The probiotic Bifidobacterium longum normalized behavior and BDNF mRNA but did not affect cytokine or kynurenine levels. Anxiety-like behavior was present in infected mice after vagotomy.
Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry, which can be normalized by inflammation-dependent and -independent mechanisms, neither of which requires the integrity of the vagus nerve.
[Show abstract][Hide abstract] ABSTRACT: Carrageenan (CGN) is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN) can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1) to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2) to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM) and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-alpha expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-kappaB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype.
PLoS ONE 01/2010; 5(1):e8666. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn's disease patients, we identified genes that might be biomarkers of Crohn's and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease states.
[Show abstract][Hide abstract] ABSTRACT: The objective of the present study was to determine whether acacia gum (GUM) is a prebiotic fibre and to evaluate its intestinal tolerance in healthy subjects. The effects of increasing doses of GUM were compared to those of sucrose (SUC) on stool output, concentration of the main bacterial populations in stools, and occurrence and severity of intestinal symptoms (flatulence, bloating, abdominal cramps, diarrhoea). Ingestion of GUM 10 and 15 g/day for 10 days increased total lactic acid-producing bacteria and bifidobacteria counts in stools, without affecting total anaerobe and aerobe counts. The magnitude of this selective effect was greater in subjects with a low initial faecal concentration of bifidobacteria. Faecal digestibility of GUM was around 95% and its caloric value was estimated to range between 5.5 and 7.7 kJ/g. In addition, stool weight increased 30% because of greater faecal water content. Digestive tolerance of GUM was high and not statistically different from that of SUC up to a daily dose of 30 g. Above this dose, the main complaint was excessive flatulence. However, the mean degree of severity remained mild (<1), even at doses >50 g/day. Other intestinal events were rarely reported. Thus GUM is a very well tolerated dietary fibre with bifidogenic properties believed to benefit intestinal health.
[Show abstract][Hide abstract] ABSTRACT: Coevolution shapes interorganismal crosstalk leading to profound and diverse cellular and metabolic changes as observed in gut dysbiosis in human diseases. Here, we modulated a simplified gut microbiota using pro-, pre-, and synbiotics to assess the depth of systemic metabolic exchanges in mice, using a multicompartmental modeling approach with metabolic signatures from 10 tissue/fluid compartments. The nutritionally induced microbial changes modulated host lipid, carbohydrate, and amino acid metabolism at a panorganismal scale. Galactosyl-oligosaccharides reduced lipogenesis, triacylglycerol incorporation into lipoproteins and triglyceride concentration in the liver and the kidney. Those changes were not correlated with decreased plasma lipoproteins that were specifically induced by L. rhamnosus supplementation. Additional alteration of transmethylation metabolic pathways (homocysteine-betaine) was observed in the liver and the pancreas following pre- and synbiotic microbial modulation, which may be of interest for control of glucose metabolism and insulin sensitivity. Probiotics also reduced hepatic glycogen and glutamine and adrenal ascorbate with inferred effects on energy homeostasis, antioxidation, and steroidogenesis. These studies show the breadth and the depth of gut microbiome modulations of host biochemistry and reveal that major mammalian metabolic processes are under symbiotic homeostatic control.
Journal of Proteome Research 05/2009; 8(4):2090-105. · 5.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The intestinal mucus layer and endogenous microbiota are strongly intertwined and this contributes to the maintenance of the epithelial barrier and ultimately of gut homeostasis. To understand the molecular foundations of such relationship, we investigated if the nature of the microbiota transcriptionally regulates mucus layer composition in vivo. We found that the expression of mucins 1 to 4 and trefoil factor 3 was down-regulated in the ileum and colon of conventional and reconventionalized mice compared with germ-free animals. Conversely, very limited colon-restricted changes in transmembrane mucins were detected in mice colonized with human adult or baby microbiota. Moreover, by microarray analysis, the murine endogenous microbiota was found to modulate genes putatively involved in mucin secretion. These findings show that a well-established microbial community participates in the regulation of the gut mucus layer and that its composition and adequacy to the host are key factors in this process.
[Show abstract][Hide abstract] ABSTRACT: Fructooligosaccharides (FOS) are considered prebiotics because of their ability to promote growth of specific beneficial gut bacteria, such as bifidobacteria. Some studies reported potential immune-modulating properties. The aim of this study was to investigate the effect of FOS:inulin mix on murine response to Salmonella vaccine and evaluate the relevance toward protection against Salmonella infection. Balb/c mice were fed a diet containing 5% FOS:inulin mix or a control diet 1 wk before oral immunization with a suboptimal dose of live attenuated Salmonella typhimurium vaccine. Four weeks after vaccination, mice were infected with LD100 of virulent S. typhimurium. Specific blood Salmonella immunoglobulin G and fecal immunoglobulin A significantly increased in mice fed the diet containing prebiotics compared with control mice 4 wk postimmunization. Peritoneal macrophage phagocytic activity also significantly increased in FOS:inulin-fed mice at 1 wk postimmunization compared with control mice. No detectable effects were observed on the percentage of lymphoid cell subsets in the spleen. However, production of cytokines, interferon-gamma, interleukin-12, and tumor necrosis factor alpha, was numerically increased in spleen cell cultures stimulated with mitogens from FOS:inulin-fed mice 1 and 4 wk postimmunization. Salmonella translocation to lymphoid organs was not affected by feeding FOS:inulin. However, the improved response to Salmonella vaccine was concomitant with an increase in the survival rate of FOS:inulin-fed mice upon challenge with virulent Salmonella. No detectable effects were observed on the composition or the metabolic activity of the microbiota. Overall, the data suggest that a diet supplemented with FOS:inulin mix stimulates mucosal immunity and seems to improve efficacy of an oral vaccine.
Journal of Nutrition 02/2008; 138(1):123-9. · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gut microbiome-host metabolic interactions affect human health and can be modified by probiotic and prebiotic supplementation. Here, we have assessed the effects of consumption of a combination of probiotics (Lactobacillus paracasei or L. rhamnosus) and two galactosyl-oligosaccharide prebiotics on the symbiotic microbiome-mammalian supersystem using integrative metabolic profiling and modeling of multiple compartments in germ-free mice inoculated with a model of human baby microbiota. We have shown specific impacts of two prebiotics on the microbial populations of HBM mice when co-administered with two probiotics. We observed an increase in the populations of Bifidobacterium longum and B. breve, and a reduction in Clostridium perfringens, which were more marked when combining prebiotics with L. rhamnosus. In turn, these microbial effects were associated with modulation of a range of host metabolic pathways observed via changes in lipid profiles, gluconeogenesis, and amino-acid and methylamine metabolism associated to fermentation of carbohydrates by different bacterial strains. These results provide evidence for the potential use of prebiotics for beneficially modifying the gut microbial balance as well as host energy and lipid homeostasis.
Molecular Systems Biology 01/2008; 4:205. · 11.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the effects of a whey-predominant infant formula and breast milk on the gut microbiota, growth, and tolerance of infants, we conducted an open, prospective, parallel-group study in healthy newborn infants. A total of 60 infants were enrolled, and 55 completed the study. Of the 55 infants, 21 were breast-fed and 34 were fed a whey-predominant study formula that had low phosphate concentration (31 mg/100 kcal), was reduced in protein (1.8 g/100 kcal or 0.43 g/kJ), had lactose as the sole carbohydrate source, and had an amino acid profile and buffering capacity similar to that of human milk. At 30 and 60 days of age, fecal bacterial counts were determined using fluorescence in situ hybridization and culture plating, and growth and digestive tolerance were evaluated. There were no differences in fecal bacterial counts between formula-fed and breast-fed infants at either 30 or 60 days. Fecal counts of bifidobacteria, lactobacilli, clostridia, enterococci, and Enterobacteriacea were similar in the 2 groups using both bacterial enumeration methods. Growth and digestive tolerance were also similar in the 2 groups. Thus, this whey-predominant infant formula is safe and well tolerated, and it affects infants' microbiota in a similar manner as observed with breast milk.
Nutrition Research - NUTR RES. 01/2007; 27(12):735-740.
[Show abstract][Hide abstract] ABSTRACT: Psychological stress during the neonatal period results in intestinal barrier dysfunction and growth alterations later in life. We aimed to restore impaired barrier function and growth rate by a nutritional intervention.
Male rat pups (n = 84) were assigned to 1 of 2 rearing conditions from postnatal day (PND) 2 to PND14: S, separated 3 h/d from their mothers, or H, 15 min/d handled controls. From PND15 to PND35, rats received a control diet or a similar diet adapted to contain arachidonic and docosahexaenoic acids, galacto- and fructo-oligosaccharides and Lactobacillus paracasei NCC2461.
Maternal separation had only a minor impact on the measured gut barrier parameters at PND15, whereas it severely affected them at PND35. At this age, intestinal permeability to macromolecules was higher, mucin content in small intestinal tissues was lower and microbiota composition was altered in S compared with H animals. Feeding the adapted diet normalized the intestinal permeability, although it did not restore intestinal mucin content or microbiota. In addition, the adapted diet improved the growth rate recovery of the S animals after weaning and resulted in increased villus length in small intestine.
Our results suggest that an adapted diet containing specific long-chain polyunsaturated fatty acids, prebiotics and probiotics can revert the negative imprinting of neonatal stress on both intestinal barrier function and growth.
Journal of Pediatric Gastroenterology and Nutrition 08/2006; 43(1):16-24. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Colonic mucosal protection is provided by mucous gel, mainly composed of secreted (Muc2) and membrane-bound (Muc1, Muc3, Muc4) mucins. Our aim was to determine the expression profile of secreted and membrane-bound mucins in experimental dextran sulfate sodium (DSS)-induced colitis. Acute colitis was induced in Balb/C mice by oral administration of 1.0% DSS (5 days) and chronic colitis was maintained by subsequent 0.15% DSS treatment (28 days). Clinical symptoms (mortality, weight gain), stool scores, and MPO activity confirmed the inflammatory state in the two phases of colitis. Muc2 gene expression was not modified by colitis, whereas Muc3 gene expression was increased (x2) only in the cecum and the distal colon of mice after acute colitis. Muc1 and Muc4 mRNA levels were more significantly increased in the cecum (x8-10) than in colonic segments (x4) after acute colitis. TFF3 involved in mucosal repair was up-regulated during colitis induction. These results indicate that Muc and TFF3 genes are regulated early in inflammation and suggest that their mRNA levels could be used as early markers of inflammation.
Digestive Diseases and Sciences 03/2006; 51(2):381-9. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The mucus layer covering the epithelium is one of the main lines of defense of the colonic barrier. Both mucus gel and mucin expressions are altered during colonic inflammation and could be involved in epithelial repair. We postulated that modulating colonic mucus and mucins by probiotic supplementation could contribute to healing inflammatory mucosa. Our aim in this study was to determine whether probiotics could repair dextran-sodium sulfate (DSS)-induced chronic colitis in mice, and whether modifications of the colonic mucins could be involved. For that purpose, the VSL#3 probiotic mixture of 8 lactic acid bacteria probiotic strains was administered daily for 2 wk to mice with a mucosa impaired by a mild DSS treatment, and to mice with a normal mucosa. Probiotic strains survived in the gastrointestinal tract, increased the cecal concentrations of bifidobacteria, and modified cecal microflora metabolic activity in both DSS-treated and healthy mice. However, probiotic supplementation did not reverse the inflammation induced by DSS at either the macroscopic or histological level. Concurrently, probiotics did not modify the colonic mucus barrier, in terms of either mucin gene expression or adherent mucus layer thickness. In conclusion, the modification of microflora by supplementation with the VSL#3 probiotic mixture did not help to repair the colonic barrier breakdown caused by DSS treatment. The potential healing roles of mucins were neither confirmed nor invalidated by this study.
Journal of Nutrition 01/2006; 135(12):2753-61. · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The postnatal maturation of the gut, partially modulated by bacterial colonization, ends up in the establishment of an efficient barrier to luminal antigens and bacteria. The use of broad-spectrum antibiotics in pediatric practices alters the gut bacterial colonization and, consequently, may impair the maturation of the gut barrier function. To test this hypothesis, suckling Sprague-Dawley rats received a daily intragastric gavage of antibiotic (Clamoxyl; an amoxicillin-based commercial preparation) or saline solution from postnatal day 7 (d7) until d17 or d21. Luminal microbiota composition and global gene expression profile were analyzed on samples from small intestine and colon of each group. The treatment with Clamoxyl resulted in the almost-complete eradication of Lactobacillus in the whole intestine and in a drastic reduction of colonic total aerobic and anaerobic bacteria, in particular Enterobacteriacae and Enterococcus. The global gene expression analysis revealed that Clamoxyl affects the maturation process of 249 and 149 Affymetrix probe sets in the proximal and distal small intestine, respectively, and 163 probe sets in the colon. The expression of genes coding for Paneth cell products (defensins, matrilysin, and phospholipase A2) was significantly downregulated by the Clamoxyl treatment. A significant downregulation of major histocompatibility complex (MHC) class Ib and II genes, involved in antigen presentation, was also observed. Conversely, mast cell proteases expression was upregulated. These results suggest that early treatment with a large-spectrum antibiotic deeply affects the gut barrier function at the suckling-weaning interface, a period during which the gut is challenged by an array of novel food-borne antigens.
[Show abstract][Hide abstract] ABSTRACT: To assess the role of lactate as a precursor for butyrate biosynthesis in human colonic microflora.
Three human faecal microfloras were incubated in vitro with media supplemented with 30 mmol l(-1) unenriched or 13C-enriched lactate. Lactate metabolism and short-chain fatty acid (SCFA) production were quantified. Lactate conversion to butyrate was investigated by gas chromatography-mass spectrometry and the pathways involved were identified by 13C nuclear magnetic resonance spectroscopy. All human faecal microfloras rapidly and completely fermented lactate, yielding approx. 19 mmol l(-1) total SCFAs. However, the SCFA composition varied markedly between microfloras. Butyrate was the main end-product for two microfloras but not for the third (60 and 61%vs 27% of the net concentration of SCFA produced respectively). The latter was typified by its ability to produce propionate as a major product (37%), and valerate (3%). 13C-Labelling showed that butyrate was produced through the acetyl-CoA pathway and that the three microfloras possessed significant differences in their metabolic pathways for lactate consumption.
In contrast to the ruminal microflora, the human intestinal microflora can utilize both d- and l-lactate as precursors for butyrate synthesis. Inter-individual variation is found.
This study suggests that the butyrogenic capability of colonic prebiotics could be related to lactate availability. These findings will direct the development of selection strategies for the isolation of new butyrate-producing bacteria among the lactate-utilizing bacteria present in the human intestinal microfloras.
Journal of Applied Microbiology 02/2005; 99(1):201-12. · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Propionibacteria are cheese starters, also studied for their probiotic potential. An interesting feature is the ability of some strains to synthesize nitric oxide (NO) from nitrate reduction. NO production is hypothesized to be the mechanism by which some probiotics improve the mucosal barrier in rats. We therefore investigated the ability of two Propionibacterium acidipropionici strains (TL15 & TL223), which differ in their in vitro production of NO, to improve colitis in rats. Three groups of rats in which colitis was induced by trinitrobenzene sulfonic acid (TNBS), received intracolonic infusions of 9 g·L–1 NaCl (n = 6), or 0.9 × 1010 CFU·d–1 of TL15 (n = 7), or 1.4 × 1010 CFU·d–1 of TL223 (n = 7), for 7 days. Following treatment, animal weight, food consumption, inflammatory score and myeloperoxydase (MPO) activity, together with changes in intestinal bacteria and SCFA concentrations, were investigated. As expected, both TL223 and TL15 supplements induced detectable counts of P. acidipropionici in colonic contents of rats (7.67 ± 0.67 and 7.43 ± 0.50 log eq. CFU·g–1, respectively, as determined by real-time PCR). Food consumption and body weight of rats receiving propionibacteria were overall higher than those of rats with NaCl (P = 0.007 and P = 0.004). Moreover, both propionibacteria infusions similarly and dramatically reduced the gross score for inflammation (P = 0.004) as compared with NaCl (0.6 ± 0.3 and 0.7 ± 0.5 vs. 4.8 ± 1.5). A similar effect was observed for MPO activity (P = 0.056), which reached 2.50 ± 1.37 U·g–1 of mucosal tissue for NaCl vs. 0.05 ± 0.02 and 0.26 ± 0.18 U·g–1 for TL223 and TL15, respectively. This study shows for the first time the potential benefit of propionibacteria in colonic mucosa healing, but the mechanism involved needs to be elucidated. L’administration colique de Propionibacterium acidopropionici atténue la sévérité de la colite induite chez le rat. Les bactéries propioniques, utilisées comme levains fromagers, sont également étudiées pour leurs propriétés probiotiques. Une caractéristique intéressante concerne la capacité de certaines souches à synthétiser du monoxyde d’azote (NO) lors de la réduction des nitrates. La production de NO est évoquée comme mécanisme d’action de certains probiotiques capables de restaurer la muqueuse intestinale chez des rats. Nous avons donc déterminé l’impact de deux souches de Propionibacterium acidipropionici (TL15 & TL223) présentant des capacités de synthèse de NO différentes in vitro, sur des colites induites chez le rat. Trois groupes de rats à colite induite par le trinitrobenzene sulfonic acid (TNBS) ont reçu pendant 7 j des infusions intracoliques de solution saline (9 g·L–1 NaCl), ou de suspensions de TL15 (0,9 × 1010 UFC·j–1) ou de TL223 (1,4 × 1010 UFC·j–1). Les effets des traitements sur le poids des animaux, leur consommation alimentaire, le score inflammatoire, l’activité myéloperoxydase (MPO) et sur les concentrations intestinales en bactéries et en acides gras à chaîne courte ont été recherchés. Comme attendu, les infusions de TL223 et de TL15 ont induit des niveaux de population détectables de P. acidipropionici dans les contenus coliques des rats (respectivement 7,67 ± 0,67 et 7,43 ± 0,50 log éq. UFC·g–1, déterminés par PCR quantitative). La consommation alimentaire et le poids des animaux recevant les propionibactéries étaient globalement supérieurs à ceux des animaux recevant le NaCl (P = 0,007 et P = 0,004). Le score macroscopique inflammatoire observé en présence de NaCl (4,8 ± 1,5) était très nettement (P = 0,004) diminué par la supplémentation en propionibactéries, sans différence entre les 2 souches (0,6 ± 0,3 et 0,7 ± 0,5 pour TL223 et TL15). Un résultat similaire a été obtenu pour l’activité MPO (P = 0,056), qui atteignait 2,50 ± 1,37 U·g–1 de tissu mucosal pour NaCl alors qu’elle n’était que de 0,05 ± 0,02 et 0,26 ± 0,18 U·g–1 pour TL223 et TL15, respectivement. Cette étude démontre pour la première fois le bénéfice potentiel des propionibactéries pour la cicatrisation de la muqueuse colique, mais le mécanisme mis en jeu reste à déterminer.
[Show abstract][Hide abstract] ABSTRACT: The mucus layer covering the gastrointestinal mucosa is considered the first line of defense against aggressions arising from the luminal content. It is mainly composed of high molecular weight glycoproteins called mucins. Butyrate, a short-chain fatty acid produced during carbohydrate fermentation, has been shown to increase mucin secretion. The aim of this study was to test 1) whether butyrate regulates the expression of various MUC genes, which are coding for protein backbones of mucins, and 2) whether this effect depends on butyrate status as the major energy source of colonocytes. Butyrate was provided at the apical side of human polarized colonic goblet cell line HT29-Cl.16E in glucose-rich or glucose-deprived medium. In glucose-rich medium, butyrate significantly increased MUC3 and MUC5B expression (1.6-fold basal level for both genes), tended to decrease MUC5AC expression, and had no effect on MUC2 expression. In glucose-deprived medium, i.e., when butyrate was the only energy source available, MUC3 and MUC5B increase persisted, whereas MUC5AC expression was significantly enhanced (3.7-fold basal level) and MUC2 expression was strikingly increased (23-fold basal level). Together, our findings show that butyrate is able to upregulate colonic mucins at the transcriptional level and even better when it is the major energy source of the cells. Thus the metabolism of butyrate in colonocytes is closely linked to some of its gene-regulating effects. The distinct effects of butyrate according to the different MUC genes could influence the composition and properties of the mucus gel and thus its protective function.
[Show abstract][Hide abstract] ABSTRACT: Chronic nutritional disorders such as protein malnutrition are associated with delayed gastric emptying and increased postprandial cholecystokinin (CCK) levels. This study investigated the mechanisms involved in gastric emptying adaptation to low-protein diet. Two groups of 12 rats were adapted to a low-protein (LPD) or standard diet (SD) for 3 weeks. As compared to rats fed a SD, in rats adapted to a LPD gastric emptying was delayed, whereas postprandial CCK levels were increased. LPD enhanced antral muscle contractile response to CCK and cerulein without altering response to acetylcholine. This increased contractility was associated with up-regulation of CCK-A receptor mRNA levels in antral muscle. Our data suggest that modulation of gastric emptying after adaptation to a low-protein diet involves up-regulation of both CCK-A receptors and CCK-induced contraction of antral smooth muscle.
[Show abstract][Hide abstract] ABSTRACT: Leptin, a protein with a cytokine-like structure, is produced predominantly by adipocytes. It appears to play a key role in immune responses by increasing the secretion of Th1 and pro-inflammatory cytokines. As fat-wrapping is a characteristic feature of Crohn's disease (CD), and as increased leptin levels have been reported in animal models of intestinal inflammation, this study investigated whether mesenteric adipose tissue could be a source of leptin in human inflammatory bowel disease (IBD).
To quantify the expression of leptin mRNA in mesenteric adipose tissue of patients with CD or ulcerative colitis (UC).
Specimens were obtained from mesenteric white adipose tissue close to healthy and inflammatory small intestine and/or colon in patients with CD or UC and, for controls, from apparently healthy mesentery of patients operated for carcinoma of the right colon. The expression of leptin mRNA was assessed by reverse transcription-competitive polymerase chain reaction.
Leptin mRNA levels were significantly higher in mesenteric adipose tissue of CD and UC patients than in controls (P<0.05). In CD and UC, concentrations were not significantly different in mesenteric fat specimens, whether contiguous to macroscopically normal or grossly abnormal intestine.
This study provides the first evidence of a novel abnormality of the mesentery of patients with IBD. Overexpression of leptin mRNA in mesenteric adipose tissue may contribute to (a) the inflammatory process, (b) enhancement of mesenteric TNF alpha expression in CD (as recently reported), and/or (c) the anorexia frequently reported during flares of IBD.
Gastroentérologie Clinique et Biologique 12/2003; 27(11):987-91. · 1.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper will summarize the most recent clinical and experimental data on the effects of prebiotics in inflammatory and cancerous diseases of the large intestine.
Animal studies, as well as data obtained in in-vitro cell culture systems, have underlined the potential of certain prebiotics to protect against inflammatory and cancerous processes in the large intestine. Clinical trials are now in progress to assess the relevance of these promising results. The biochemical mechanisms are still incompletely deciphered, but both the promotion of lactic acid-producing bacteria and the production of short-chain fatty acids, particularly butyrate, during the fermentation of prebiotics could be key factors.
Enteric resident bacteria are involved in inflammatory bowel diseases and may contribute to colonic carcinogenesis. Dietary manipulation of the flora may thus represent a useful aid to prevent or to treat these diseases, and this could be a place for prebiotics. Inulin-like prebiotics have shown encouraging results in animal models, but clinical and epidemiological trials are necessary to define their efficacy in humans. In the next few years, important advances are expected in understanding the interactions between prebiotics, intestinal flora and the colonic mucosa in health and diseases, enabling the improvement of therapy as well as better nutritional handling of susceptible individuals.
Current Opinion in Clinical Nutrition and Metabolic Care 10/2003; 6(5):581-6. · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics.
Journal of Clinical Gastroenterology 09/2003; 37(2):105-18. · 3.20 Impact Factor