Health and nutrition promotion program for patients with dementia (NutriAlz): cluster randomized trial.

OBJECTIVE: To assess the effectiveness of health and nutrition program (NutriAlz) versus usual care on functional level in elderly people with dementia living at home, as well as on clinical practice related to nutrition and on the caregiver's burden. DESIGN: Cluster randomized multi-centre study with one-year follow-up. SETTING: 11 Alzheimer outpatients and day care centres (Barcelona, Spain). PARTICIPANTS: Nine hundred and forty six home-living Alzheimer patients with identified caregiver were consecutively recruited (intervention group: 6 centres, 448 patients vs control group: 5 centres, 498 patients). INTERVENTION: The intervention was a teaching and training intervention on health and nutrition program, NutriAlz, directed both to physician and main caregiver, as well as persons affected by Alzheimer's disease or other dementias, including a standardised protocol for feeding and nutrition. MAIN OUTCOME MEASURES: The main outcome measure was the reduction in the loss of autonomy (Activities of daily living (ADL/IADL) scales) assessed at 6 and 12 months. Secondary outcomes measures were Improvement in nutritional status (Mini Nutritional Assessment (MNA), BMI, and weight changes), and caregiver burden (Zarit scale). RESULTS: The one-year assessment was completed for 293 patients (65.4%) in the intervention group and 363 patients (72.9%) in the control group (usual care). The annual rate of ADL change was -0.83 vs -0.62 (p=0.984), and the caregiver's subjective burden 0.59 vs 2.36 (p=0.681) in intervention and control group, respectively. MNA, however, showed an improvement (+0.46 vs -0.66, p=0.028), suggesting an effective nutritional behaviour. CONCLUSION: The NutriAlz program had no effect on functional decline in Alzheimer disease patients living at home over one year, but reduced the risk for malnutrition, as recommendations concerning diet and exercise were provided.

Health and nutritional promotion program for patients with dementia (NutriAlz Study): design and baseline data.

BACKGROUND: There is a lack of data on global weight loss prevention programs for patients with dementia or clear evidence about their impact on a functional level, caregiver burden or the use of healthcare and social resources. NutriAlz is a socio-educative and nutritional intervention program to prevent weight loss and loss of function in dementia patients. STUDY DESIGN AND METHODS: A cluster randomized multi-centre study, which will allow the comparison of a group benefiting from the intervention with a control group after a year of monitoring. Patients were recruited from 11 hospitals in the ambulatory diagnostic units and day care centres. The baseline interview include: sociodemographic and socioeconomic variables (age, gender, educational level, marital status); diagnostic, treatments, MMS, a list of comorbid conditions; activities of daily living (ADL, IADL), Zarit Scale, brief-NPI, Cornell scale and nutritional status as measured by the Mini Nutritional Assessment. All participants or their family signed the inform consent form. BASELINE CHARACTERISTICS: Total of 946 patients were included, with a mean (+/- SD) of 79 +/- 7.3 year of age; 68,1 % were women; 44,9% lives with their partner, only 3% lives alone; 79.8% had Alzheimer's dementia, 5.25 +/- 3.0 years since symptoms of dementia and 2.8 +/- 2.11 years since diagnosis. Mean MMSE score was 15.4 +/- 6.2; mean weight was 64.4 +/- 12.5 kg; mean BMI was 27.0 +/- 4.5 (with 3% below 19, 5% between 19-21, 10% between 21-23, and 82% above 23). Mean ADL without difficulties was 3.2 +/- 2.1; mean IADL without difficulties was 0.7 +/- 1.6; mean number of symptoms in the NPI was 4.4 +/- 2.59, with severity score of 7.9 +/- 5.9 and distress score of 11.3 +/- 9.0; mean Zarit scale was 27.4 +/- 15.5; mean MNA was 23.2 +/- 3.5 with 5 % as malnourished, 32 % at risk of malnutrition, and 63 % with adequate nutritional status.

Systemic inflammatory markers in older persons: the effect of oral nutritional supplementation with prebiotics.

OBJECTIVE: To evaluate the effect of oral nutritional supplementation with and without oligosaccharides on gut bacteriology, in particular the bifidogenic flora, and on immunology and inflammatory parameters in older persons at risk of malnutrition. DESIGN: Prospective, randomized, double-blind, controlled study. SETTING: Division of Geriatric Medicine, St. Louis University, Missouri, United States. PARTICIPANTS: Seventy-four community dwelling elderly and/or nursing home subjects (age superior 70 y; 84 +/- 7 years) either undernourished or at risk of undernutrition. INTERVENTION: Daily liquid supplements, with (1.3 g/250 ml) and without oligosaccharides (OS) for 12 weeks. MEASUREMENTS: Nutritional evaluation, serum immunoglobulins, lymphocyte subsets, various cytokines and the endotoxin soluble receptor CD14 (sCD14) in serum, and cytokines specific mRNA in peripheral blood mononuclear cells at baseline and 12 weeks, and fecal bacteriologicy. RESULTS: Specific mRNA extracted from blood leucocytes showed a different level of pro-inflammatory gene activation: TNF-alpha mRNA and IL-6 mRNA diminished in the OS group after 12 weeks, while no changes were detected in the control group (P=0.05 and P=0.04 respectively). Serum levels of sCD14, a product shed by activated macrophages, decreased only in the OS group without reaching statistical significance (P=0.08). No significant differences were detected in the fecal gut flora or in the nutritional parameters. CONCLUSIONS: This study shows that the administration of supplements in older persons at risk of malnutrition may benefit from the addition of prebiotics that can improve the low noise inflammatory process frequently observed in this population.

Ontogeny of intestinal epithelium immune functions: developmental and environmental regulation.

Intestinal mucosa integrates primary digestive functions with immune functions such as pathogen surveillance, antigen transport and induction of mucosal immunity and tolerance. Intestinal adaptive immunity is elicited in organized mucosa-associated lymphoid tissue (O-MALT) that is composed of antigen-presenting cells and lymphocytes and achieved by effector cells widely distributed in mucosa (diffuse MALT or D-MALT). Interaction between the intestinal epithelium, the O-MALT and the diffuse MALT plays a critical role in establishing an adequate immune response. In regions associated to O-MALT, lympho-epithelial cross-talks lead to acquisition of a specific epithelial phenotype that contributes to O-MALT organization and functionality. Beyond the expression of several innate immune functions, the intestinal epithelium may directly take up and present antigens due to the expression of major histocompatibility complex (MHC) and MHC-related molecules. A complex genetic program that will be outlined in the present review controls the development of immune functions of the intestinal epithelium. The effect of environmental signals on the modulation of this ontogenetic program during development and neonatal life, from bioactive components of amniotic fluid to lactation and bacterial colonization, will be discussed.

Enterococcus faecium SF68 enhances the immune response to Giardia intestinalis in mice.

We studied the ability of the probiotic organism Enterococcus faecium SF68 to antagonize Giardia intestinalis infection in mice. Oral feeding of E. faecium strain SF68 starting 7 d before inoculation with Giardia trophozoites significantly increased the production of specific anti-Giardia intestinal IgA and blood IgG. This humoral response was mirrored at the cellular level by an increased percentage of CD4(+) T cells in the Peyer's patches and in the spleens of SF68-fed mice. The improvement of specific immune responses in probiotic-fed mice was associated with a diminution in the number of active trophozoites in the small intestine as well as decreased shedding of fecal Giardia antigens (GSA65 protein). The ability of SF68 to stimulate the immune system at both mucosal and systemic levels highlights mechanisms by which this probiotic might antagonize pathogens in vivo. Taken together, the data demonstrate the strong potential of strain SF68 to prevent protozoa from causing intestinal infections.

The chronic colitis developed by HLA-B27 transgenic rats is associated with altered in vivo mucin synthesis.

HLA-B27 transgenic rats spontaneously developing a chronic inflammation mainly involving the colon are recognized as a powerful animal model for IBD. We investigated the mucin production in 6-month-old HLA-B27 rats by measuring in vivo fractional synthesis rate (FSR) and expression of mucins. In the inflamed colon of HLA-B27 rats, the mucin FSR was stimulated by 75% compared to F-344 controls, while MUC2,3 mRNA expression was unchanged. A local depletion in mucus-containing goblet cells was observed, suggesting a rapid mucin production/release and/or a real global decrease in goblet cell number. In the noninflamed jejunum of HLA-B27 rats, the mucin FSR was reduced by 35% compared to controls, while MUC2,3 mRNA expression was unchanged. Different alterations in mucin metabolism and expression are observed between HLA-B27 rats and a model of chemically induced chronic colitis (DSS-treated rats), suggesting that mucin alterations may be dependent on the animal model and colitis underlying mechanism.

Oligofructose does not affect the development of type 1 diabetes mellitus induced by dietary proteins in the diabetes-prone BB rat model.

BACKGROUND: Prevention of Type 1 diabetes mellitus (T1DM), a major childhood chronic disease with rapidly increasing incidence, is an urgent topic of research. We investigated whether 5% oligofructose (OF) as compared to 5% cellulose had a protective effect against diet-induced T1DM in the diabetes-prone BioBreeding (BB) rat model. METHODS: Groups of BB rats were fed the experimental diets from weaning. The diets were a cereal-based rodent diet (diabetogenic, positive control) and semi-synthetic rodent diets containing hydrolysed casein (non-diabetogenic, negative control), soy or whey as the sole protein source and 5% cellulose as fibre source. In additional groups fed soy and whey protein, the fibre source was 5% OF. T1DM incidence up to the age of 160 days was recorded applying biochemical and morphological criteria. Physiological effects of fibre were assessed through the analysis of biochemical parameters in plasma and of the protein/DNA ratio in intestinal mucosa. RESULTS: T1DM incidence was diet-dependent. Cereal-, soy- and whey-based diets were significantly more diabetogenic than the hydrolysed casein-based diet. Five per cent OF did not affect the incidence of T1DM induced by either soy or whey proteins as compared to cellulose, nor induce any of the biological effects attributed to a fermentable fibre. CONCLUSIONS: In the BB rat model, 5% OF in the diet did not have any protective effects against diet-induced T1DM. The present data do not suggest dietary OF as a promising approach for the dietary prevention of T1DM.

Mucin production and composition is altered in dextran sulfate sodium-induced colitis in rats.

We evaluated the small and large intestinal mucin production in a rat model of human ulcerative colitis by measuring the in vivo fractional synthesis rate (FSR) and the expression of mucins. A chronic colitis was induced by oral administration of 5% dextran sulfate sodium (DSS) for 9 days followed by 2% DSS for 18 days. DSS-treated rats showed increased colonic MUC2,3 mRNA levels compared pair-fed controls. The mucin FSR was unaffected while mucin-containing goblet cells were depleted in the vicinity of lesions. In the small intestine, no inflammatory lesions were observed but ileal MUC2 mRNA levels and mucin FSR were decreased by 46% and 21%, respectively. Finally, DSS-treated rats showed a marked decrease in mucin's threonine + serine content all along the gut, which may lead to a reduction of potential O-glycosylation sites. Our data indicate that the chronic colitis may impair the mucus layer protective function all along the gut.

Interactions between the microbiota and the intestinal mucosa.

The intestinal microflora can be considered as a postnatally aquired organ composed of a large diversity of bacterial cells that can perform different functions for the host. This organ is highly exposed to environmental influences and thus modulated in its composition and functions by external factors, such as nutrition. Specific components of the intestinal microflora, including lactobacilli and bifidobacteria, have been associated with beneficial effects on the host, such as promotion of gut maturation and integrity, antagonisms against pathogens and immune modulation. In addition, the microflora seem to play a significant role in the maintenance of intestinal immune homeostasis and prevention of inflammation. At the present time, the contribution of intestinal epithlial cell in the first line of defence against pathogenic bacteria and microbial antigens has been recognized, in contrast, the interactions of intestinal epithelial cells with commensal bacteria are less understood. The present work summarizes the increasing scientific attention for mechanisms of the innate immune response of the host to different components of the autochthonous microflora and suggests a potential role for selected probiotic bacteria in the regulation of intestinal inflammation.

Activation of human NK cells by staphylococci and lactobacilli requires cell contact-dependent costimulation by autologous monocytes.

NK cells are instrumental in innate immune responses, in particular for the early production of gamma interferon (IFN-gamma) and other cytokines necessary to control certain bacterial, parasitic, and viral infections. NK cell-mediated effector functions are controlled by a fine balance between distinct receptors mediating activating and inhibitory signals; however, little is known about activating receptors on NK cells and their corresponding ligands. Several studies have shown that commensal lactobacilli isolated from the human gastrointestinal tract activate human mononuclear cells and are potent inducers of IFN-gamma and monocyte-derived interleukin 12 (IL-12). NK cell activation was shown for Lactobacillus johnsonii La1. In this study the cellular mechanisms of in vitro NK cell activation by gram-positive bacteria were analyzed. Staphylococcus aureus- and L. johnsonii La1-mediated activation of CD3(-) CD16(+) CD56(+) human peripheral blood NK cells, including expression of the activation antigen CD69 and secretion of IFN-gamma, required cell contact-dependent costimulation by autologous monocytes. S. aureus- and L. johnsonii-preactivated monocytes retained their capacity to induce NK cell activation. In contrast, cytokine-primed monocytes completely failed to induce NK cell activation unless bacteria were present. This suggests that phagocytosis of bacteria provided additional coactivation signals on accessory cells that may differ from those induced by tumor necrosis factor and IFN-gamma. Blocking of costimulatory molecules by B7.1, B7.2, and IL-12 but not CD14 monoclonal antibodies inhibited S. aureus- and L. johnsonii-induced effector function of NK cells. Our data suggest an important role for accessory cell-derived signals in the process of NK cell activation by gram-positive bacteria.

The intestinal mucosa as a target for dietary polyunsaturated fatty acids.

Several studies have reported beneficial effects of dietary polyunsaturated fatty acids (PUFA) on various aspects of both human and animal health, and particular reference has been made to their effects on systemic immune responses. Both immune stimulation and immune suppression have been reported, with the outcome dependent on the type of PUFA, the target cell, as well as the immune competence of the cells before exposure. The systemic and the mucosal immune systems are discrete entities, which have evolved specific approaches in the defense of the host. The latter comprises several interconnected tissues, which communicate with one another through the action of soluble mediators and the trafficking of cellular components. After the oral mucosa, the intestinal epithelium and its associated gut-associated lymphoid tissue are the primary targets of dietary components. Absorption of dietary PUFA and its incorporation into intestinal tissues has been well studied, but the consequences of these events in relation to local immune responses have received little attention. This article describes some of the immune mechanisms operating at this barrier and, where possible, pinpoints areas for which a modulatory role for PUFA has already been demonstrated. Although not an exhaustive treatise of the subject, it is hoped that this review will foster research into the specific interaction between dietary PUFA and cell populations comprising the intestinal barrier.

Food processing: probiotic microorganisms for beneficial foods.

Human studies have demonstrated that selected probiotic strains can influence the composition of the intestinal microflora and modulate the host immune system. Considerable promise was also demonstrated for the application of probiotics in human disease. However, the extension of probiotic applications demands increasing scientific attention to their functionality and the identification of molecular structures.

Soluble CD14 in human breast milk and its role in innate immune responses.

Immune factors secreted in milk are important for health in the neonatal gut. We have detected the bacterial pattern recognition receptor, soluble CD14 (sCD14) in human breast milk at different times during lactation. The molecule occurs in a single form in milk, in contrast to human serum, in which there are two isoforms. Produced by mammary epithelial cells, milk sCD14 mediates secretion of innate immune response molecules such as interleukin-8, tumor necrosis factor-alpha, and epithelial neutrophil activator-78 by CD14-negative intestinal epithelial cells exposed to lipopolysaccharide (LPS) or bacteria. Although present at low concentrations in milk, LPS-binding protein may be implicated in the biological effects observed. Our findings support the premise that milk sCD14 acts as a 'sentinel' molecule and immune modulator in homeostasis and in the defense of the neonatal intestine. In so doing, it may prevent the immune and inflammatory conditions of the gut to which non-breastfed infants are predisposed.

Inhibition of Giardia intestinalis by extracellular factors from Lactobacilli: an in vitro study.

The aim of the present work was to evaluate the effect of spent culture supernatants of different strains of lactobacilli on giardia trophozoites. The growth of Giardia intestinalis strain WB, as well as the attachment to the human intestinal epithelial cell line Caco-2, was evaluated by using proliferation and adhesion assays with radiolabeled parasites. In addition, scanning electron microscopy and flow cytometric analysis were performed. The effect of spent culture supernatants from lactobacilli was strain dependent. Lactobacillus johnsonii La1 significantly inhibited the proliferation of G. intestinalis trophozoites. Although the effect was strongly pH dependent, it was not simply due to lactic acid. According to flow cytometric analysis, trophozoites were arrested in G(1) phase but neither significant necrosis nor apoptosis could be detected. Bacterial cells or their spent culture supernatants were unable to modify trophozoite attachment to Caco-2 cells. However, trophozoites treated with spent culture supernatants had little, if any, proliferative capacity. These results suggest that La1 produces some substance(s) able to inhibit proliferation of Giardia trophozoites. Partial characterization of the factors involved in the antigiardiasic action showed that they have a low molecular mass and are inactivated by heating. On this basis, it seems worthwhile to explore how colonization of the proximal small bowel with these lactic acid bacteria could interfere with giardiasis in vivo.

Induction by a lactic acid bacterium of a population of CD4(+) T cells with low proliferative capacity that produce transforming growth factor beta and interleukin-10.

We investigated whether certain strains of lactic acid bacteria (LAB) could antagonize specific T-helper functions in vitro and thus have the potential to prevent inflammatory intestinal immunopathologies. All strains tested induced various levels of both interleukin-12 (IL-12) and IL-10 in murine splenocytes. In particular, Lactobacillus paracasei (strain NCC2461) induced the highest levels of these cytokines. Since IL-12 and IL-10 have the potential to induce and suppress Th1 functions, respectively, we addressed the impact of this bacterium on the outcome of CD4(+) T-cell differentiation. For this purpose, bacteria were added to mixed lymphocyte cultures where CD4(+) T-cells from naive BALB/c mice were stimulated weekly in the presence of irradiated allogeneic splenocytes. In these cultures, L. paracasei NCC2461 strongly inhibited the proliferative activity of CD4(+) T cells in a dose-dependent fashion. This was accompanied by a marked decrease of both Th1 and Th2 effector cytokines, including gamma interferon, IL-4, and IL-5. In contrast, IL-10 was maintained and transforming growth factor beta (TGF-beta) was markedly induced in a dose-dependent manner. The bacteria were not cytotoxic, because cell viability was not affected after two rounds of stimulation. Thus, unidentified bacterial components from L. paracasei NCC2461 induced the development of a population of CD4(+) T cells with low proliferative capacity that produced TGF-beta and IL-10, reminiscent of previously described subsets of regulatory cells implicated in oral tolerance and gut homeostasis.

Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures.

BACKGROUND AND AIM: Intestinal epithelial cells (IEC) are thought to participate in the mucosal defence against bacteria and in the regulation of mucosal tissue homeostasis. Reactivity of IEC to bacterial signals may depend on interactions with immunocompetent cells. To address the question of whether non-pathogenic bacteria modify the immune response of the intestinal epithelium, we co-cultivated enterocyte-like CaCO-2 cells with human blood leucocytes in separate compartments of transwell cultures. METHODS: CaCO-2/PBMC co-cultures were stimulated with non-pathogenic bacteria and enteropathogenic Escherichia coli. Expression of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-8, monocyte chemoattracting protein 1 (MCP-1), and IL-10 was studied by enzyme linked immunosorbent assays (cytokine secretion) and by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: Challenge of CaCO-2 cells with non-pathogenic E coli and Lactobacillus sakei induced expression of IL-8, MCP-1, IL-1beta, and TNF-alpha mRNA in the presence of underlying leucocytes. Leucocyte sensitised CaCO-2 cells produced TNF-alpha and IL-1beta whereas IL-10 was exclusively secreted by human peripheral blood mononuclear cells. CaCO-2 cells alone remained hyporesponsive to the bacterial challenge. Lactobacillus johnsonii, an intestinal isolate, showed reduced potential to induce proinflammatory cytokines but increased transforming growth factor beta mRNA in leucocyte sensitised CaCO-2 cells. TNF-alpha was identified as one of the early mediators involved in cellular cross talk. In the presence of leucocytes, discriminative activation of CaCO-2 cells was observed between enteropathogenic E coli and non-pathogenic bacteria. CONCLUSION: The differential recognition of non-pathogenic bacteria by CaCO-2 cells required the presence of underlying leucocytes. These results strengthen the hypothesis that bacterial signalling at the mucosal surface is dependent on a network of cellular interactions.