Gut microbiome and anti-viral immunity in COVID-19.

SARS-CoV-2 mainly affects the respiratory system, but the gastrointestinal tract is also a target. Prolonged gut disorders, in COVID-19 patients, were correlated with decreased richness and diversity of the gut microbiota, immune deregulation and delayed viral clearance. Although there are no definitive conclusions, ample evidence would suggest that the gut microbiome composition and function play a role in COVID-19 progression. Microbiome modulation strategies for population stratification and management of COVID-19 infection are under investigation, representing an area of interest in the ongoing pandemic. In this review, we present the existing data related to the interaction between gut microbes and the host's immune response to SARS-CoV-2 and discuss the implications for current disease management and readiness to face future pandemics.

Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters were analyzed including corticosterone, cytokine/chemokine concentrations and neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects of the excessive MS-induced stress response of the hypothalamic-pituitary-adrenal (HPA) axis, particularly corticosterone production at baseline and in response to subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down-regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN-γ]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA] and adrenaline [A] concentrations) at P21. These effects have a long-term impact on the central nervous system (CNS) of adult mice since MS mice fed B. pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice, as well as normal neurotransmitter levels in the hypothalamus. The anti-inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an improvement in glucocorticoid sensitivity in mesenteric lymph node immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT 7765 to MS animals also reversed intestinal dysbiosis affecting the proportions of ten Operational Taxonomic Units (OTUs) at P21, which could partly explain the restoration of immune, neuroendocrine and behavioral alterations caused by stress in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765 is able to beneficially modulate the consequences of chronic stress on the HPA response produced by MS during infancy with long-lasting effects in adulthood, via modulation of the intestinal neurotransmitter and cytokine network with short and long-term consequences in brain biochemistry and behavior.

The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing coeliac disease.

OBJECTIVE: Intestinal dysbiosis has been associated with coeliac disease (CD), but whether the alterations are cause or consequence of the disease is unknown. This study investigated whether the human leukocyte antigen (HLA)-DQ2 genotype is an independent factor influencing the early gut microbiota composition of healthy infants at family risk of CD. DESIGN: As part of a larger prospective study, a subset (n=22) of exclusively breastfed and vaginally delivered infants with either high genetic risk (HLA-DQ2 carriers) or low genetic risk (non-HLA-DQ2/8 carriers) of developing CD were selected from a cohort of healthy infants with at least one first-degree relative with CD. Infant faecal microbiota was analysed by 16S rRNA gene pyrosequencing and real time quantitative PCR. RESULTS: Infants with a high genetic risk had significantly higher proportions of Firmicutes and Proteobacteria and lower proportions of Actinobacteria compared with low-risk infants. At genus level, high-risk infants had significantly less Bifidobacterium and unclassified Bifidobacteriaceae proportions and more Corynebacterium, Gemella, Clostridium sensu stricto, unclassified Clostridiaceae, unclassified Enterobacteriaceae and Raoultella proportions. Quantitative real time PCR also revealed lower numbers of Bifidobacterium species in infants with high genetic risk than in those with low genetic risk. In high-risk infants negative correlations were identified between Bifidobacterium species and several genera of Proteobacteria (Escherichia/Shigella) and Firmicutes (Clostridium). CONCLUSIONS: The genotype of infants at family risk of developing CD, carrying the HLA-DQ2 haplotypes, influences the early gut microbiota composition. This finding suggests that a specific disease-biased host genotype may also select for the first gut colonisers and could contribute to determining disease risk.

Hepatic molecular responses to Bifidobacterium pseudocatenulatum CECT 7765 in a mouse model of diet-induced obesity.

BACKGROUND AND AIMS: Bifidobacterium pseudocatenulatum CECT 7765 moderates body weight gain and metabolic parameters in high-fat diet-(HFD)-fed mice but, the mechanisms of action are not yet understood. To further understand the effects of this bacterial strain, we have investigated the molecular changes in the liver of mice fed a HFD and supplemented with the bacteria. METHODS AND RESULTS: Gene expression and protein levels were measured in the liver of C57BL/6 male mice following sub-chronic consumption of a HFD and B. pseudocatenulatum CECT 7765. Our results show that the consumption of this bacterial strain modulated the expression of key genes involved in the regulation of energy metabolism and transport of lipids that were affected by the HFD.B. pseudocatenulatum CECT 7765 significantly counteracted the effects caused by the HFD on the fatty acid transporter CD36, the transcription regulator of lipid biosynthesis EGR1 and the regulators of glucose metabolism, IGFBP2 and PPP1R3B, both at the mRNA and protein levels. The bacterial strain slightly induced the transcript levels of PNPLA2, a lipase that hydrolyses triglycerides in lipid droplets. In the standard diet (SD)-fed mice, the administration of B. pseudocatenulatum CECT 7765 donwregulated the expression of INSIG1 and HMGCR critically involved in the regulation of cholesterol levels. CONCLUSION: B. pseudocatenulatum CECT 7765 modified the expression of key regulators of fatty acid and cholesterol metabolism and transport, lipid levels and glucose levels in the liver which supports the beneficial metabolic effects of this bacterial strain.

How Diet and Lifestyle Can Fine-Tune Gut Microbiomes for Healthy Aging.

Many physical, social, and psychological changes occur during aging that raise the risk of developing chronic diseases, frailty, and dependency. These changes adversely affect the gut microbiota, a phenomenon known as microbe-aging. Those microbiota alterations are, in turn, associated with the development of age-related diseases. The gut microbiota is highly responsive to lifestyle and dietary changes, displaying a flexibility that also provides anactionable tool by which healthy aging can be promoted. This review covers, firstly, the main lifestyle and socioeconomic factors that modify the gut microbiota composition and function during healthy or unhealthy aging and, secondly, the advances being made in defining and promoting healthy aging, including microbiome-informed artificial intelligence tools, personalized dietary patterns, and food probiotic systems.

Discerning the role of Bacteroides fragilis in celiac disease pathogenesis.

Celiac disease (CD) is associated with intestinal dysbiosis, which can theoretically lead to dysfunctions in host-microbe interactions and contribute to the disease. In the present study, possible differences in Bacteroides spp. and their pathogenic features between CD patients and controls were investigated. Bacteroides clones (n = 274) were isolated, identified, and screened for the presence of the virulence genes (bft and mpII) coding for metalloproteases. The proteolytic activity of selected Bacteroides fragilis strains was evaluated by zymography and, after gastrointestinal digestion of gliadin, by high-pressure liquid chromatography/electrospray ionization/tandem mass spectrometry. The effects of B. fragilis strains on Caco-2 cell culture permeability and inflammatory response to digested gliadin were determined. B. fragilis was more frequently identified in CD patients than in healthy controls, in contrast to Bacteroides ovatus. B. fragilis clones carrying virulence genes coding for metalloproteases were more abundant in CD patients than in controls. B. fragilis strains, representing the isolated clones and carrying metalloprotease genes, showed gelatinase activity and exerted the strongest adverse effects on the integrity of the Caco-2 cell monolayer. All B. fragilis strains also showed gliadin-hydrolyzing activity, and some of them generated immunogenic peptides that preserved or increased inflammatory cytokine production (tumor necrosis factor alpha) and showed increased ability to permeate through Caco-2 cell cultures. These findings suggest that increased abundance of B. fragilis strains with metalloprotease activities could play a role in CD pathogenesis, although further in vivo studies are required to support this hypothesis.

Immunostimulatory effect of faecal Bifidobacterium species of breast-fed and formula-fed infants in a peripheral blood mononuclear cell/Caco-2 co-culture system.

Bifidobacterium spp. typical of the human intestinal microbiota are believed to influence the balance of immune responses in the intestinal mucosa. The aim of the present study was to investigate the effect of different bifidobacterial species and their mixtures in in vitro experiments with peripheral blood mononuclear cells (PBMC) and Caco-2 cells. Bifidobacterium adolescentis, B. angulatum, B. breve, B. catenulatum, B. infantis, B. longum and two combinations of these bifidobacteria simulating the species composition found in faecal samples from breast-fed (BF) and formula-fed (FF) infants were used. The levels of several cytokines were measured by direct stimulation of PBMC and by stimulation of a Caco-2/PBMC co-culture with bifidobacteria. B. catenulatum and B. breve were the strongest enhancers of interferon-γ (IFN-γ) production by direct stimulation of PBMC. B. longum was the highest inducer of IL-10 and the lowest TNF-α stimulus. In the Caco-2/PBMC system, B. breve was the highest inducer of IL-8 production by Caco-2 cells, significantly different from B. infantis, B. adolescentis and the FF mixture (P < 0·05). IFN-γ produced by PBMC stimulated with the BF mixture (containing 22 % B. breve, compared with 7 % in the FF mixture) was significantly higher compared with B. adolescentis, B. infantis and B. longum. B. adolescentis also inhibited IFN-γ production compared with the FF mixture and B. longum. The proportion of different Bifidobacterium strains seems to be an important determinant of the cytokine balance in the simulated intestinal environment studied. B. breve and the combination of the Bifidobacterium species typically found in the microbiota of BF infants have shown the most significant effects.

Bifidobacteria inhibit the inflammatory response induced by gliadins in intestinal epithelial cells via modifications of toxic peptide generation during digestion.

Celiac disease (CD) is a chronic enteropathy triggered by intake of gliadin, the toxic component of gluten. This study aims at evaluating the capacity of different Bifidobacterium strains to counteract the inflammatory effects of gliadin-derived peptides in intestinal epithelial (Caco-2) cells. A commercial extract of several gliadin (Gld) types (alpha, beta, gamma, [symbol: see text] ) was subjected to in vitro gastrointestinal digestion (pepsin at pH 3, pancreatin-bile at pH 6), inoculated or not with cell suspensions (10(8) colony forming units/ml) of either B. animalis IATA-A2, B. longum IATA-ES1, or B. bifidum IATA-ES2, in a bicameral system. The generated gliadin-derived peptides were identified by reverse phase-HPLC-ESI-MS/MS. Caco-2 cell cultures were exposed to the different gliadin peptide digestions (0.25 mg protein/ml), and the mRNA expression of nuclear factor kappa-B (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), and chemokine CXCR3 receptor were analyzed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in stimulated cells. The production of the pro-inflammatory markers NF-kappaB p50, TNF-alpha, and IL-1beta (interleukine 1beta) by Caco-2 cells was also determined by ELISA. The peptides from gliadin digestions inoculated with bifidobacteria did not exhibit the toxic amino acid sequences identified in those noninoculated (alpha/beta-Gld [158-164] and alpha/beta-Gld [122-141]). The RT-PCR analysis evidenced a down-regulation in mRNA expression of pro-inflammatory biomarkers. Consistent with these results the production of NF-kappaB, TNF-alpha, and IL-1beta was reduced (18.2-22.4%, 28.0-64.8%, and abolished, respectively) in cell cultures exposed to gliadin digestions inoculated with bifidobacteria. Therefore, bifidobacteria change the gliadin-derived peptide pattern and, thereby, attenuate their pro-inflammatory effects on Caco-2 cells.

Interplay between human leukocyte antigen genes and the microbial colonization process of the newborn intestine.

Coeliac disease (CD) development involves genetic (HLA-DQ2/DQ8) and environmental factors. Herein, the influence of the HLA-DQ genotype on the gut colonization process of breast-fed children was determined. A cohort of 20 newborns, with at least one first-degree relative with CD, were classified according to their HLA-DQ genotype into high, intermediate and low genetic risk groups, showing 24-28%, 7-8% and less than 1% probability to develop CD, respectively. Faecal microbiota was analysed at 7 days, 1 and 4 months of children's age by fluorescence in situ hybridization. When considering all data, Gram-negative bacteria and Bacteroides-Prevotella group proportions were higher (P<0.05) in the high than in the intermediate and low genetic risk groups. E. coli, Streptococcus-Lactococcus, E. rectale-C. coccoides, sulphate-reducing bacteria, C. lituseburense and C. histolyticum group proportions were also significantly higher (P<0.05) in the high than in the low genetic risk group. Correlations between these bacterial groups and the genetic risk were also detected (P<0.05). In addition, the number and type of CD relative seemed to influence (P<0.050) these bacterial proportions in children at CD risk. At 4 months of age, similar relationships were established between the high genetic risk to develop CD and the proportions of Streptococcus-Lactococcus (P<0.05), E. rectale-C. coccoides (P<0.05), C. lituseburense (P<0.05), C. histolyticum (P<0.05), Bacteroides-Prevotella (P<0.10) groups and total Gram-negative bacteria (P<0.05). The results suggest a relationship between HLA-DQ genes and the gut microbial colonization process that could lead to a change in the way this disorder is investigated.

Interactions of gut microbiota with functional food components and nutraceuticals.

The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and nutraceuticals. Prebiotics, polyunsaturated fatty acids (PUFAs) and phytochemicals are the most well characterized dietary bioactive compounds. The beneficial effects of prebiotics mainly relay on their influence on the gut microbiota composition and their ability to generate fermentation products (short-chain fatty acids) with diverse biological roles. PUFAs include the omega-3 and omega-6 fatty acids, whose balance may influence diverse aspects of immunity and metabolism. Moreover, interactions between PUFAs and components of the gut microbiota may also influence their biological roles. Phytochemicals are bioactive non-nutrient plant compounds, which have raised interest because of their potential effects as antioxidants, antiestrogenics, anti-inflammatory, immunomodulatory, and anticarcinogenics. However, the bioavailability and effects of polyphenols greatly depend on their transformation by components of the gut microbiota. Phytochemicals and their metabolic products may also inhibit pathogenic bacteria while stimulate the growth of beneficial bacteria, exerting prebiotic-like effects. Therefore, the intestinal microbiota is both a target for nutritional intervention and a factor influencing the biological activity of other food compounds acquired orally. This review focuses on the reciprocal interactions between the gut microbiota and functional food components, and the consequences of these interactions on human health.

Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women.

Obesity is associated with complications during pregnancy and increased health risks in the newborn. The objective of the present study was to establish possible relationships between gut microbiota, body weight, weight gain and biochemical parameters in pregnant women. Fifty pregnant women were classified according to their BMI in normal-weight (n 34) and overweight (n 16) groups. Gut microbiota composition was analysed by quantitative real-time PCR in faeces and biochemical parameters in plasma at 24 weeks of pregnancy. Reduced numbers of Bifidobacterium and Bacteroides and increased numbers of Staphylococcus, Enterobacteriaceae and Escherichia coli were detected in overweight compared with normal-weight pregnant women. E. coli numbers were higher in women with excessive weight gain than in women with normal weight gain during pregnancy, while Bifidobacterium and Akkermansia muciniphila showed an opposite trend. In the whole population, increased total bacteria and Staphylococcus numbers were related to increased plasma cholesterol levels. Increased Bacteroides numbers were related to increased HDL-cholesterol and folic acid levels, and reduced TAG levels. Increased Bifidobacterium numbers were related to increased folic acid levels. Increased Enterobacteriaceae and E. coli numbers were related to increased ferritin and reduced transferrin, while Bifidobacterium levels showed the opposite trend. Therefore, gut microbiota composition is related to body weight, weight gain and metabolic biomarkers during pregnancy, which might be of relevance to the management of the health of women and infants.

Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents.

OBJECTIVE: To evaluate the effects of a multidisciplinary obesity treatment programme on fecal microbiota composition and immunoglobulin-coating bacteria in overweight and obese adolescents and their relationship to weight loss. DESIGN: Longitudinal intervention study based on both a calorie-restricted diet (calorie reduction=10-40%) and increased physical activity (calorie expenditure=15-23 kcal/kg body weight per week) for 10 weeks. PARTICIPANTS: Thirty-nine overweight and obese adolescents (BMI mean 33.1 range 23.7-50.4; age mean 14.8 range, 13.0-16.0). MEASUREMENTS: BMI, BMI z-scores and plasma biochemical parameters were measured before and after the intervention. Fecal microbiota was analyzed by fluorescent in situ hybridization. Immunoglobulin-coating bacteria were detected using fluorescent-labelled F(ab')2 antihuman IgA, IgG and IgM. RESULTS: Reductions in Clostridium histolyticum and E. rectale-C. coccoides proportions significantly correlated with weight and BMI z-score reductions in the whole adolescent population. Proportions of C. histolyticum, C. lituseburense and E. rectale-C. coccoides dropped significantly whereas those of the Bacteroides-Prevotella group increased after the intervention in those adolescents who lost more than 4 kg. Total fecal energy was almost significantly reduced in the same group of adolescents but not in the group that lost less than 2.5 kg. IgA-coating bacterial proportions also decreased significantly in participants who lost more than 6 kg after the intervention, paralleled to reductions in C. histolyticum and E. rectale-C. coccoides populations. E. rectale-C. coccoides proportions also correlated with weight loss and BMI z-score reduction in participants whose weight loss exceeded 4 kg. CONCLUSIONS: Specific gut bacteria and an associated IgA response were related to body weight changes in adolescents under lifestyle intervention. These results suggest interactions between diet, gut microbiota and host metabolism and immunity in obesity.

Comparison of in vitro models to study bacterial adhesion to the intestinal epithelium.

AIMS: To evaluate the adhesion ability of intestinal bacteria to different in vitro models of intestinal epithelia, and to estimate the suitability of these models and the type of interactions involved. METHODS AND RESULTS: The adhesion of probiotic (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12), commensal (B. animalis IATA-A2 and B. bifidum IATA-ES2) and potentially pathogenic bacteria (E. coli and L. monocytogenes) was determined. The adhesion models used were polycarbonate-well plates, with or without mucin, and different configurations of Caco-2 and/or HT29-MTX cell cultures. All bacteria adhered to wells without mucin (2.6-27.3%), the values being highly variable depending on the bacterial strain. Adhesion percentages of potentially probiotic bacteria to Caco-2 cultures were remarkably lower (P < 0.05) than those to mucin, and more similar to those of pathogenic strains. The lowest adhesion of different bacterial strains was detected on HT29-MTX (0.5-2.3%) cultures and Caco-2/HT29-MTX (0.6-3.2%) cocultures, while these values were increased in Caco-2 cultures plus mucin. CONCLUSIONS: The results suggested that bacterial strains exhibit different capacities to adhere to cellular components and several types of mucin present in different models, showing preferences for intestinal MUC2. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of Caco-2 cells monolayer plus mucin (type II) better approaches the physiological characteristics of in vivo situation, providing a reliable and suitable in vitro model to evaluate bacterial adhesion.

[Study of maternal nutrition and genetic on the foetal adiposity programming (The PREOBE study)]. / Estudio de la influencia de la nutrición y genética maternas sobre la programación del desarrollo del tejido adiposo fetal (Estudio PREOBE).

BACKGROUND: Maternal genetics and feeding before and during pregnancy, different maternal metabolic pathologies, as well as nutrient intakes of newborns in their first months of life may be involved in the obesity aetiology and its long-term consequences. The possible role of these and others factors, the mechanisms and the effects on the metabolism, and the development of this disease need further research. OBJECTIVE: To acquire more knowledge about foetal adipose tissue development and the influence of genetic, dietetic and environmental factors on the risk to suffer from obesity. METHODOLOGY: Four study groups have been established with 30 pregnant women in each one: 1) control group; 2) mothers with glucose intolerance/gestational diabetes; 3) women with low weight gain during pregnancy, and 4) women with overweight/obesity at the beginning of the pregnancy. The magnitudes to be studied are: 1) dietary intake; 2) life-style habits; 3) physical activity; 4) anthropometry and body composition; 5) haematological study; 6) biochemical study (lipid and metabolic biomarkers); 7) immune function profile related to nutritional status; 8) psychological profile; 9) genetic biomarkers, and 10) microbiological markers; all of them in relation to the development of the foetal adipose tissue in the first stages of life and the risk of suffering from obesity in the future. CONCLUSION: This project, coordinated by the Department of Paediatrics of the School of Medicine in the University of Granada, and with the collaboration of well-known and expert research groups, tries to contribute to the knowledge about the obesity aetiology in infancy and its subsequent development in later periods of life.

Microbiota in obesity: interactions with enteroendocrine, immune and central nervous systems.

Western diets, with high consumption of simple sugars and saturated fats, contribute to the rise in the prevalence of obesity. It now seems clear that high-fat diets cause obesity, at least in part, by modifying the composition and function of the microorganisms that colonize in the gastrointestinal tract, the microbiota. The exact pathways by which intestinal microbiota contribute to obesity remain largely unknown. High-fat diet-induced alterations in intestinal microbiota have been suggested to increase energy extraction, intestinal permeability and systemic inflammation while decreasing the capability to generate obesity-suppressing short-chain fatty acids. Moreover, by increasing systemic inflammation, microglial activation and affecting vagal nerve activity, 'obese microbiota' indirectly influence hypothalamic gene expression and promote overeating. Because the potential of intestinal microbiota to induce obesity has been recognized, multiple ways to modify its composition and function are being investigated to provide novel preventive and therapeutic strategies against diet-induced obesity.

Factors affecting the incidence of contrast-induced nephropathy in patients undergoing computed tomography. / Incidencia de nefropatía por contraste en pacientes sometidos a tomografía computarizada: ¿qué factores la condicionan?

OBJECTIVE: To analyze the incidence of contrast-induced nephropathy in a cohort of patients undergoing computed tomography (CT) with intravenous iodinated contrast material. To evaluate the efficacy of N-acetylcysteine in preventing contrast-induced nephropathy. PATIENTS AND METHODS: This prospective observational study was carried out in the months comprising March 2016 through July 2016. We selected the first five patients scheduled to undergo CT examination each day who agreed to participate and signed the informed consent form. We recorded patients' cardiovascular histories, chronic treatments, and indications for the CT examination. We measured blood levels of creatinine and urea before and after the CT examination. We used the Modification of Diet in Renal Disease (MDRD-4) equation to estimate the glomerular filtration rate. We analyzed the type and dose of contrast material. We recorded whether N-acetylcysteine was administered before the CT examination. We used SPSS 15.0® to compare means and proportions. Statistical significance was set at p < 0.05. RESULTS: No incidents of contrast-induced nephropathy were detected in any of the 202 patients included [mean age, 63.92 ± 12 years (range 22-87); 57.4% male; 21.8% diabetic; 39.6% hypertensive; 87.1% had MDRD4 ≥ 60 ml/min/1.73 m2 (89.45 ± 14, range 62.36-134.14) and 12.9% had MDRD4 < 60 ml/min/1.73 m2 (45.38 ± 11, range 9.16-58.90)]. The most common indication for CT examinations was oncologic (81.2%). The only contrast agent administered was iopamidol; the mean dose was 107.83 ± 11 ml (range 70-140). The mean interval between pre-CT and post-CT laboratory tests was 4.06 ± 1 days. Only 13 patients received N-acetylcysteine; 9 of these had MDRD < 60 ml/min/1.73 m2 and 4 had MDRD4 ≥ 60 ml/min/1.73 m2 (p = 0.000). CONCLUSIONS: The incidence of contrast-induced nephropathy was not significant in patients with glomerular filtration rates greater than 30 ml/min/1.73 m2: these favorable results might be due to analyzing only scheduled examinations and to using relatively low doses of a "nonionic" iodinated contrast agent.

Differential immunomodulatory properties of Bifidobacterium logum strains: relevance to probiotic selection and clinical applications.

Modulation of host immunity is one of the proposed benefits of the consumption of probiotics. Nonetheless, comparative studies on the immunological properties that support the selection of strains of the same species for specific health benefits are limited. In this study, the ability of different strains of Bifidobacterium longum to induce cytokine production by peripheral blood mononuclear cells (PBMCs) has been evaluated. Live cells of all B. longum strains greatly stimulated regulatory cytokine interleukin (IL)-10 and proinflammatory cytokine tumour necrosis factor (TNF)-alpha production. Strains of the same species also induced specific cytokine patterns, suggesting that they could drive immune responses in different directions. The probiotic strain B. longum W11 stimulated strongly the production of T helper 1 (Th1) cytokines while B. longum NCIMB 8809 and BIF53 induced low levels of Th1 cytokines and high levels of IL-10. The effects of cell-surface components obtained by sonication of B. longum strains overall confirm the effects detected by stimulation of PBMCs with live cells, indicating that these components are important determinants of the immunomodulatory activity of B. longum. Genomic DNA of some strains stimulated the production of the Th1 and pro-inflammatory cytokines, interferon (IFN)-gamma and TNF-alpha, but not that of IL-10. None of the cell-free culture supernatants of the studied strains was able to induce TNF-alpha production, suggesting that the proinflammatory component of these strains is associated mainly with structural cell molecules. The results suggest that despite sharing certain features, some strains can perform a better functional role than others and their careful selection for therapeutic use is desirable.

Sensory improvement of dry-fermented sausages by the addition of cell-free extracts from Debaryomyces hansenii and Lactobacillus sakei.

The effects of the addition of a combined cell-free extract from Lactobacillus sakei and Debaryomyces hansenii (D+L) or just a D. hansenii cell-free extract (D) to the initial formulation of a dry-fermented sausage were evaluated. The differences found among batches in the main microbial populations, pH, moisture content and global proteolytic and lipolytic indexes (total free amino acids, non protein nitrogen, acidity and tiobarbituric acid index) were not significant. Only, the acidity value of batch D was significantly higher (p<0.05) than that of batch D+L. Thus, cell-free extract from D. hansenii accelerated the lipolysis. Moreover, there were some significant differences (p<0.05) in the amino acid profile and, especially, in the aroma profile. The combination D+L and D promoted the generation of volatile compounds derived from lipid oxidation and carbohydrate fermentation. In batch D, the production of volatile compounds derived from amino acid catabolism and microbial fermentation was also enhanced. The overall quality was improved by both treatments (D+L, D) and also the aroma by addition of the combination of extracts (D+L). It is concluded that the addition of cell-free extracts from D. hansenii and, particularly, D. hansenii plus L. sakei could be useful to improve the final quality of fermented sausages.

Antimicrobial peptides are among the antagonistic metabolites produced by Bifidobacterium against Helicobacter pylori.

Sixty acid-resistant Bifidobacterium isolates were recovered from human faeces and identified by genus-specific PCR and RAPD-PCR. Helicobacter pylori strains were isolated from gastric biopsies and identified by species-specific PCR. Twenty-four of the 60 Bifidobacterium isolates were considered to be different strains by RAPD-PCR. Six of the twenty-four different strains were shown to inhibit H. pylori. These antagonistic effects were related to heat-stable proteinaceous compounds, resistant to heating at 100 degrees C for 10 min, but sensitive to proteases. H. pylori stains showed variable resistance to therapeutic antibiotics (metronidazole and clarithromycin), while all the selected bifidobacteria showed intrinsic resistance to metronidazole. These potentially probiotic bifidobacteria were able to inhibit the growth of both antibiotic sensitive and resistant H. pylori strains. Thus, the synthesis of antimicrobial peptides could be one of the mechanisms of bifidobacteria to combat H. pylori infections.