Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome.

Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.

Serum IL-9 levels depend on allergen exposure: preliminary study.

BACKGROUND: Th9 is a new T cell subset characterized by interleukin 9 (IL-9) production. Serum IL-9 levels are related to symptom severity in patients with allergic rhinitis (AR). This study aimed at investigating whether IL-9 may depend on allergen exposure. METHODS: 35 AR patients (16 males, mean age 33.2 years) with monosensitization to Parietaria were studied when symptomatic; 38 AR patients (22 males, mean age 30.9 years) with monosensitization to birch were recruited at the same time, but were symptom free. Serum IL-9 was assayed in all patients. RESULTS: Patients with Parietaria allergy and exposed to allergen had higher serum IL-9 levels than patients with birch allergy and not exposed to allergen (p<0.05). CONCLUSIONS: This preliminary study shows that serum IL-9 levels may depend on allergen exposure: symptomatic patients with pollen-induced AR, evaluated during the pollen season, have higher values than patients studied outside the pollen season and without symptoms.

Probiotics and health: an evidence-based review.

The intestinal microbiota is an ecosystem formed by a variety of ecological niches, made of several bacterial species and a very large amount of strains. The microbiota is in close contact with the intestinal mucosa or epithelial interface which is, after the respiratory area, the largest surface of the body, occupying approximately 250-400 m(2). The physiological activities of the microbiota are manifold and are just being unraveled. Based on the observations of the multiple roles played by the microbiota in health and disease, the notion of modifying it with appropriate formulations, i.e. probiotics, is being tested in several settings. This review summarizes the current knowledge on probiotics and discusses both limitations and acquired evidence to support their use in preventive and therapeutic medicine.

Serum eosinophilic cationic protein: is there a role in respiratory disorders?

BACKGROUND: Eosinophilic cationic protein (ECP) has been widely investigated in the clinical practice as a potential biomarker for asthma. However, there are conflicting data concerning its validity in other respiratory disorders. METHODS: Serum ECP levels were retrospectively analyzed in 441 patients (227 males and 214 females) suffering from respiratory disease and visited for the first time, and in 33 healthy subjects (17 males and 16 females). RESULTS: The mean of ECP was significantly higher (p = .0001) in patients compared with healthy volunteers. No correlation was found between serum ECP value and peripheral eosinophil absolute number (p = .881; r = .007). The predictive model was significant only for asthma, with a sensitivity of 70% and a specificity of 74% (efficiency 73%). CONCLUSIONS: This study demonstrates that serum ECP may be considered a marker for identifying only asthmatic patients with an efficiency of 73% and is not useful for the differentiation of other respiratory disorders.

Clinical assessment of nasal decongestion test by VAS in adolescents.

Nasal airflow, as measured by rhinomanometry, is frequently impaired in allergic rhinitis (AR). The decongestion test evaluates whether the application of an intranasal vasoconstrictor drug increases nasal airflow. The aim of this study was to verify the suitability of the use of the visual analogue scales (VAS) as a surrogate for rhinomanometry in the decongestion test assessment in adolescents with atopic rhinitis. Forty adolescents [16 males and 24 females, mean age 15 (s.d. 2) yr] with AR were studied. Nasal symptoms, VAS, rhinomanometry, and nasal decongestion test were assessed in all patients. A significant association was observed between VAS and nasal airflow after performing the decongestion test (Spearman's r is -51.7%, p < 0.001). The associated sensitivity and specificity were 84.8 (95% confidence interval, CI 68.1-94.8) and 85.7 (95% CI 42.2-97.6), respectively. The corresponding area under the receiver operating characteristic (ROC) curve of 0.83 (95% CI 0.67-0.93) indicated a good discriminating ability for the decongestion measured on the VAS scale. In conclusion, the use of VAS appears as clinically relevant, in that it allows, with a fair reliability, to perform the decongestion test in the absence of rhinomanometry.

Role of adenoids and adenoiditis in children with allergy and otitis media.

Adenoids and/or tonsil inflammation with concomitant obstructive hypertrophy is one of the oldest and most common pediatric problems. Adenoids are a component of Waldeyer's ring and because of their anatomic position can be relevant in the pathogenesis of otitis media when they are inflamed and/or enlarged. Adenoid pads can create mechanical eustachian tube obstruction. Therefore, in some cases, adenoidectomy may have a role in the clinical management of otitis media with effusion. However, eustachian tube dysfunction related to the adenoids may also have an allergy-related functional component. Allergic inflammation has been described for middle ear effusion, and some studies have reported that mast cells increase and allergic mediators release in adenoids as well. Nasal endoscopy has a key role in confirming a diagnosis of adenoid hypertrophy and/or adenoiditis and in detecting an association between adenoid inflammation/infection and otitis media with effusion, especially during infancy and early childhood.

Lutein concentration in human milk during early lactation and its relationship with dietary lutein intake.

OBJECTIVE: The present study aimed to estimate the lutein concentration in human milk during early lactation and its relationship with dietary lutein intake measured through the administration of a short FFQ. DESIGN: A cross-sectional study in which an FFQ was administered twice: on day 3 (T0) and day 30 (T1) postpartum; meanwhile two breast milk samples were collected. Maternal plasma samples were obtained at T0. The comparison of dietary lutein intakes and likewise lutein concentrations in breast milk at T0 and T1 were analysed with Student's t test. Pearson's correlation coefficient was used to determine the association between dietary lutein intake and lutein concentration in milk and plasma, respectively, as well as the correlation between breast milk and plasma lutein concentrations at T0. SETTING: Pavia, northern Italy. SUBJECTS: Twenty-one pregnant women, age range 24-42 years, were recruited during their last trimester on a voluntary basis. RESULTS: Both breast milk and plasma lutein concentrations were significantly correlated with dietary lutein intake (r = 0.86, P = 0.0001 and r = 0.94, P = 0.0001, respectively). There was a clear significant correlation between milk and plasma lutein concentrations (r = 0.87, P = 0.0001). Mature milk lutein concentration, although significantly reduced at T1 (P < 0.01), maintained a fairly high correlation with dietary lutein intake (r = 0.82, P = 0.0001). CONCLUSIONS: Even though milk lutein concentration decreased during early lactation, it remained significantly correlated with daily lutein intake. Therefore, while awaiting further research, dietary recommendations advising intake of fresh fruit and vegetables rich in lutein, throughout the whole duration of pregnancy and lactation, are extremely useful.

Children with recurrent otitis show defective IFN gamma-producing cells in adenoids.

Infectious diseases are frequently observed in children and their recurrence represents a demanding challenge for the paediatrician. It has been hypothesized that a defective immune response may occur in these patients. The aim of the present study was to evaluate whether children presenting with recurrent otitis have a defective interferon (IFN)gamma production by the lymphocytes of peripheral blood and of adenoid tissue, in comparison with children without recurrent otitis. Our study group was represented by 58 children undergoing adenoidectomy for adenoidal hypertrophy. They were subdivided into two groups according to the recurrence of otitis (>or=3 per year) or not (<3 per year). Intracellular cytokine profile of lymphocyte subsets in adenoids and peripheral blood was evaluated by flow cytometry analysis. Children with recurrent otitis showed a significantly lower percentage of CD8+-producing IFN gamma cells in adenoids than children with <3 otitis per year (p = 0.003). The reduced capability of the adenoid cells to produce INF-gamma may induce a high susceptibility to the recurrence of otitis in children.

Increased risk of otitis media with effusion in allergic children presenting with adenoiditis.

OBJECTIVE: Otitis media with effusion (OME) is a common disorder in childhood. The aim of the study was to assess the association of atopy and endoscopic features with the presence of OME. SUBJECTS AND METHODS: This cross-sectional study evaluated 287 children presenting with acute upper-airway infections persistent for at least ten days and tested through nasal endoscopy and skin-prick test. RESULTS: Fifty-three patients had a diagnosis of OME; out of them, 23 showed acute rhinosinusitis, ten adenoiditis, and 20 both features. OME was diagnosed in 26 atopic children and in 27 nonatopic ones. On a multivariable analysis, allergic rhinitis, endoscopic pattern of adenoiditis, and younger age were all shown to be independently associated with a diagnosis of OME. CONCLUSIONS: This study suggests that allergic rhinitis and adenoiditis are significant risk factors to OME development and that the risk becomes higher when these two conditions are concomitantly present.

Effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial.

BACKGROUND: Evidence suggests a role of intestinal microbiota-host interactions in the pathophysiology and symptoms of irritable bowel syndrome (IBS). OBJECTIVE: The objective of this article is to assess the effects of Lactobacillus paracasei CNCM I-1572 on clinical and gut microbiota-related factors in IBS. METHODS: We conducted a multicenter, randomized, double-blind, cross-over, 18-week, placebo-controlled, pilot trial assessing the effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota composition, fecal short chain fatty acid (SCFA), immunoglobulin A, and cytokines in IBS. The intestinal microbial ecosystem was characterized by 16S rRNA gene profiling. RESULTS: Forty IBS patients were enrolled from five Italian centers. Lactobacillus paracasei CNCM I-1572 did not significantly improve IBS symptoms, including primary efficacy variables worst abdominal pain/discomfort and IBS degree of relief. Interestingly, Lactobacillus paracasei CNCM I-1572 induced a significant reduction in genus Ruminococcus, dominated by taxa related to Ruminococcus bromii and Ruminococcus callidus, a significant increase in the SCFAs acetate and butyrate, and a significant reduction in the pro-inflammatory cytokine interleukin-15. CONCLUSIONS: This pilot study shows that Lactobacillus paracasei CNCM I-1572 is able to modulate gut microbiota structure/function and reduce immune activation in IBS. As no statistically significant effect on IBS-symptoms was found, further studies are necessary to determine the role of this probiotic in IBS. The study was registered at ClinicalTrials.gov registry under identifier NCT02371499.

Nasal decongestion test in allergic rhinitis: definition of responder.

BACKGROUND: Nasal airflow, as measured by rhinomanometry, is frequently impaired in allergic rhinitis (AR). The decongestion test evaluates whether the application of an intranasal vasoconstrictor drug increases nasal airflow. OBJECTIVE: The aim of this study was to define the characteristics of decongestion test responders. METHODS: 123 subjects (112 males and 11 females, mean age 22.9+/-5.7 years) with AR were studied. Nasal eosinophils, rhinomanometry, and decongestion test were assessed in all subjects. RESULTS: The optimal cut-off for % variation of nasal airflow and nasal eosinophils >5 was = 34.4, with sensibility = 82.7% (95%CI 73.7-89.6) and specificity = 80% (95%CI 59.3-93.1). CONCLUSIONS: The clinical relevance of this study is that non-responders may have a likely moderate-severe allergic inflammation that should be adequately evaluated and treated.

Using probiotics in clinical practice: Where are we now? A review of existing meta-analyses.

The scientific literature has demonstrated that probiotics have a broad spectrum of activity, although often the results are contradictory. This study provides a critical overview of the current meta-analyses that have evaluated the efficacy of probiotics in physiologic and pathological conditions, such as metabolic disease, antibiotic-associated and Clostridium difficile-associated diarrhea, IBS, constipation, IBD, chemotherapy-associated diarrhea, respiratory tract infection, ventilator-associated pneumonia, NAFLD, liver encephalopathy, periodontitis, depression, vaginosis, urinary tract infections, pancreatitis, incidence of ventilator-associated pneumonia, hospital infection and stay in ICU, mortality of post-trauma patients, necrotising enterocolitis in premature infants. Only for antibiotic- and Clostridium difficile-associated diarrhea, and respiratory tract infections the effects of probiotics are considered "evidence-based." Concerning other fields, meta-analyses lacks to define type and biologic effect of probiotic strains, as well as the outcome in a disease state. Therefore, the results presented should be a stimulus for further studies which will provide clinical recommendations.

Review on microbiota and effectiveness of probiotics use in older.

The aim of the present systematic review is to summarize the existing knowledge about the human microbiota in the elderly and the effects of probiotics in elderly population. The elderly subjects, compared to adult population, show a reduction in the diversity of the microbiota, characterized by a large interindividual variability, with lower numbers of Firmicutes, Bifidobacteria, Clostridium cluster XIV, Faecalibacterium Prausnitzii, Blautia coccoides-Eubacterium rectal and higher presence of Enterobacteriaceae and Bacteroidetes. These differences of the intestinal microbiota of the elderly may not necessarily be caused by aging, but they could be associated with the decline of the general state of health with malnutrition and with increased need for medication, such as antibiotics and nonsteroidal anti-inflammatory drugs, situations that occur frequently in the elderly. Differences have been demonstrated in the composition of the microbiota between healthy elderly subjects and hospitalized or institutionalized elderly subjects. These findings which further indicates that the living conditions, health status, nutrition and drugs have a significant effect on the composition of the microbiota. According to the available knowledge, the use of probiotics is safe and could represent an useful intervention to prevent or treat antibiotic-associated diarrhea, in addition to reducing the severity of symptoms, other than to help the management of constipation.

Impact of passive smoke and/or atopy on adenoid immunoglobulin production in children.

The adenoids are exposed to a wide number and variety of microbes, environmental pollutants, and food antigens. Atopy and passive smoke may significantly affect immune responses, mainly in children. The aim of the present study was to investigate whether passive exposure to tobacco smoke and/or atopy could affect immunoglobulin production by adenoidal lymphocytes in a cohort of children presenting with adenoid hypertrophy. A total of 277 children (151 males and 126 females; median age 5.5 years), with adenoidal hypertrophy requiring adenoidectomy and or adeno-tonsillectomy, were consecutively enrolled in the study. Adenoid mononuclear cells were in vitro stimulated with LPS or CpG. When considering both the presence of smoke exposure and atopy, we observed that the CpG-induced decrease in IgA and IgM production was significantly associated with this combination of risk factors. In the T-independent immunoglobulin production assay we found a positive association between the two risk factors and IgA and IgM production. In particular, the presence of both risk factors, showed a significant increase in IgA and IgM production after stimulation. In conclusion, this is the first study that investigated the in vitro adenoidal B cell response after different stimuli in children, also evaluating possible exposure to passive smoke and/or an atopic condition.

Probiotics and food allergy.

The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the "hygiene hypothesis" low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions.Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells.Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.

Early-life gut microbiota under physiological and pathological conditions: the central role of combined meta-omics-based approaches.

The establishment of gut microbiota immediately after birth is modulated by different mechanisms that can be considered specific determinants of temporal and spatial variability. Over the last few years, molecular methods have been offering a complementary support to the classical microbiology, often underpowered by its inability to provide unbiased representation of gut microbiota. The advent of high-throughput-omics-based methods has opened new avenues in the knowledge of the gut ecosystem by shedding light on its shape and modulation. Such methods may unveil taxa distribution, role and density of microbial habitants, hence highlighting individual phenotyping (physiological traits) and their relationship with gut dysbiosis, inflammation processes, metabolic disorders (pathological conditions). Synergic meta-omics or "systems biology"-based approaches may concur in providing advanced information on microbiota establishment and pathogen control. During early-life stages this massive amount of data may provide gut microbiota descriptive and functional charts which can be exploited to perform a good practice in childcare and pediatrics, thus providing nutraceutical benefits and endorsing healthy development and aging. This article is part of a Special Issue entitled: Translational Proteomics.

Acute isolated sphenoid sinusitis in children.

BACKGROUND: Isolated pediatric sphenoidal sinusitis is an uncommon disorder with sphenoiditis more commonly found as part of pansinusitis. Recognizing the condition on history and examination alone is difficult and delayed diagnosis many occur in many cases. Nasal endoscopy, computed tomography (CT), and magnetic resonance imaging (MRI) are essential adjuncts to confirm diagnosis. This study was designed to confirm the clinical features and diagnostic difficulties associated with isolated sphenoidal sinusitis in children. METHODS: A 16-year review was performed of cases diagnosed and treated in a tertiary teaching hospital. RESULTS: Two different groups of patients were identified. One group presented with fever and headache, frequently associated with neurological complications. Swimming and/or diving could be identified as possible causative agents. The second group presented with headache alone and a less severe clinical presentation. CONCLUSION: Isolated pediatric sphenoidal sinusitis may be more prevalent than was previously thought with CT/MRI helping establish the diagnosis in many cases. Pediatricians should be aware of this unusual but still potentially devastating condition. A nasal endoscopy is a useful diagnostic tool in this patient group, being noninvasive and well tolerated in children and adolescents.

Passive exposure to smoke results in defective interferon-gamma production by adenoids in children with recurrent respiratory infections.

There is evidence that exposure to passive smoke is associated with an increased susceptibility to respiratory infections. Indeed, cigarette smoke extracts may interfere with the immune system, even though the precise mechanism has not been fully understood yet. Recurrent respiratory infections may be sustained by a defective immune response. The aim of the present study was to evaluate whether, in a cohort of children presenting both with recurrent respiratory infections and with a history of exposure to tobacco smoke, these factors were related to a lower local production of interferon-gamma (IFN-gamma) when compared to a similar non-exposed population. The study group included 128 children undergoing adenoidectomy, presenting with more than three respiratory infections per year, independently of exposure to passive smoke at home. The intracellular cytokine profile of lymphocyte subsets in adenoids was evaluated by flow cytometry analysis. Children exposed to tobacco smoke suffered from a significantly greater number of respiratory infections and had a lower percentage of IFN-gamma-producing CD8+ cells in adenoids than non-exposed children, while other T-cell subsets were not affected. The effect of smoke exposure seems to be specific to the IFN-gamma-producing CD8+ cells in adenoids and may contribute to the increased susceptibility to the recurrence of respiratory infections.

Efficacy of Bacillus clausii spores in the prevention of recurrent respiratory infections in children: a pilot study.

Probiotic milk has been previously demonstrated to reduce the number of respiratory infections (RI) among children attending day care centres. Thus, this pilot study was aimed to assess the efficacy and the safety of 3 month treatment with Bacillus clausii in the prevention of recurrent respiratory infections (RRI) in children. Eighty children with RRI were studied: 40 of them were randomly treated with B. clausii for 3 months, and followed up for further 3 months; 40 were included in the control group during the same period. Children treated with B. clausii had shorter duration of RI in comparison with the control group both during the treatment phase (mean 11.7 days vs 14.37; p=0.037) and the follow-up period (mean 6.6 days vs 10.92; p=0.049). This effect was evident also in allergic children during the follow-up. In conclusion, this pilot study provides the first preliminary evidence that B. clausii may exert a significant and persistent impact on RI in children and is safe and well tolerated.

Age-related changes in intracellular TH1/TH2 cytokine production, immunoproliferative T lymphocyte response and natural killer cell activity in newborns, children and adults.

To evaluate the development of the neonatal immune system, we measured T lymphocyte response to Con A, intracellular IL-2, IL-4, IFN-gamma and IL-10 production, and natural killer cell (NKC) activity in 12 very preterm, 12 preterm and 20 term neonates, 10 children and 10 adults. Immunoproliferation to Con A was significantly lower in cord blood than in children or adults. The percentage of CD4+ lymphocytes was significantly higher in newborns while CD8+ cells were higher at older ages, with a resulting gradual decline of the CD4+/CD8+ ratio. The percentage of IL-2-producing CD4+ and CD8+ cells was higher in all newborn groups than in children and adults, while the percentage of IL-4-producing cells was higher for CD8+ and lower for CD4+ cells in cord blood than in children and adults. Neonates had substantially lower percentages of CD4+ and CD8+ IFN-gamma-producing cells. A significant negative correlation was observed between gestational age and IFN-gamma-CD4+-, IL-2-CD8+-, and IL-10- CD4+-producing cells. In addition, a positive correlation was found between gestational age and IL-10-CD8+-producing cells. Percentages of CD4+/CD45RA+ cells were higher and CD4+/CD45RO+ percentages were lower in newborns than in children and adults. NKC activity in infants was significantly correlated with gestational age and significantly impaired compared to children and adults. On the whole, these results suggest a gradual development of immunity during gestation and show significant immaturity of cellular immune response at birth. The reduction of NKC activity, the lower proliferative response of T cells, the reduced cytotoxic response and a dysregulated cytokine production may contribute to the neonatal increased risk of infection and to the low incidence of graft-versus-host disease after cord blood transplantation.