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Stress affects the immune system and intestinal microbiota composition and can lead to imbalance between pro- and anti-inflammatory cytokines or to uncontrolled production of cytokines. The effect of emotional stress on secretory IgA levels also indicates that stress decreases mucosal integrity. Our aim was to evaluate whether a probiotic product (Lactoflorene® Plus) can prevent alterations in the immune response associated with self-reported stress and microbiota composition. Healthy adult volunteers who self-reported psychological stress were enrolled and randomised into a placebo and a probiotic group. Salivary stress markers (α-amylase, cortisol, chromogranin A) and immunological parameters (sIgA, NK cell activity, IL-8, IL-10, TNF-α) in feces and the composition of intestinal microbiota were evaluated. Administration of the product did not exert a direct effect on the salivary stress markers or NK cell activity but did reduce abdominal pain and increase faecal IgA and IL-10 levels. The probiotic product induced a moderate increase in Bifidobacterium and Lactobacillus spp., as expected, and in Faecalibacterium spp., and decreased the size of the Dialister spp. and Escherichia and Shigella populations. Administration of the product helped protect the mucosal barrier by supporting the number of short-chain fatty acid producers and decreasing the load of potentially harmful bacteria, thus reducing intestinal inflammation and abdominal discomfort. CLINICALTRIALSGOV: NCT03234452.

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BACKGROUND & AIMS: Safety and growth adequacy of infant formulae enriched by functional ingredients need stringent evaluation by means of randomized controlled trials (RCTs), therefore we performed a double-blind RCT to evaluate an infant formula enriched with galacto-oligosaccharides, beta-palmitate, and acidified milk vs. a standard infant formula. METHODS: Weight, length, head circumference and fecal bacteria (Bifidobacteria, BIF/Clostridia, CLO) were measured in healthy full term infants, at baseline - as before 21 days of life - at 60 and 135 days thereafter. A group of 51 neonates received the enriched formula (ENR), 59 the standard one (ST). Parents were trained to daily register gastrointestinal diseases. RESULTS: All the infants grew homogeneously increasing the anthropometric parameters and complying with WHO and Italian standards: the mean (SD) difference in daily weight between ENR and ST groups was -0.74 (1.13) g/day, corresponding to a 90% CI of -2.62 to 1.13 g/day, well within the postulated interval of equivalence of -3.9 to +3.9 g/day. A statistical improvement in BIF concentration in the microbiota of infants fed by ENR was recorded. There was no between-group change in log10CLO, but log10BIF increase was higher at T2 vs. T0 in ENR (treatment × time interaction = 0.71, 95% CI 0.08-1.34, p = 0.028) than in ST neonates. This corresponds to estimated mean (95% CI) values of 8.37 (8.04-8.69) log10-units for ENR vs. 8.08 (7.77-8.39) log10-units for ST neonates. Gastrointestinal effects were mild and similar, with no statistical difference between two groups. CONCLUSION: Safety and growth ability of the enriched formula has been confirmed. A positive effect on neonatal gut microbiota, consisting of increased fecal BIF counts at T2 vs. baseline has been shown too. Nonetheless, larger RCTs are needed to estimate with greater precision the effective potential attributable to the enriched formula on neonatal microbiota, with particular reference to the mode of delivery.

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Intestinal microbiota is composed by symbiotic innocuous bacteria and potential pathogens also called pathobionts. The human gut normally hosts roughly 1014 bacterial organisms of up to 1000 different species. The genome size of this microbial organ, collectively named microbiome, exceeds the size of the human nuclear genome by 2 orders of magnitude.

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BACKGROUND: Functional gastrointestinal disorders (FGIDs) are chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. FGIDs are multifactorial conditions with different pathophysiologic mechanisms including altered motility, visceral hyperalgesia, brain-gut disturbance, genetic, environmental and psychological factors. Although in most cases gastrointestinal symptoms are transient and with spontaneous resolution in infancy multiple dietary changes and pharmacological therapy are often started despite a lack of evidence-based data. Our aim was to update and critically review the current literature to assess the effects and the clinical appropriateness of drug treatment in early (occurring in infants and toddlers) FGIDs. METHODS: We systematically searched the Medline and GIMBE (Italian Group on Medicine Based on Evidence) databases, according to the methodology of the Critically Appraised Topics (CATs). We included reviews, clinical studies, and evidence-based guidelines reporting on pharmacological treatments. Systematic reviews and randomized controlled trials (RCTs) concerning pharmacologic therapies in children with early FGIDs were included, and data were extracted on participants, interventions, and outcomes. RESULTS: We found no evidence-based guidelines or systematic reviews about the utility of pharmacological therapy in functional regurgitation, infant colic and functional diarrhea. In case of regurgitation associated with marked distress, some evidences support a short trial with alginate when other non pharmacological approach failed (stepped-care approach). In constipated infants younger than 6 months of age Lactulose is recommended, whilst in older ages Polyethylene glycol (PEG) represents the first-line therapy both for fecal disimpaction and maintenance therapy of constipation. Conversely, no evidence supports the use of laxatives for dyschezia. Furthermore, we found no RCTs regarding the pharmacological treatment of cyclic vomiting syndrome, but retrospective studies showed a high percentage of clinical response using cyproheptadine, propanolol and pizotifen. CONCLUSION: There is some evidence that a pharmacological intervention is necessary for rectal disimpaction in childhood constipation and that PEG is the first line therapy. In contrast, for the other early FGIDs there is a lack of well-designed high-quality RCTs and no evidence on the use of pharmacological therapy was found.

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Adenoids are strategically located for mediating local and regional immune functions as they are exposed to antigens from both the outside air and the alimentary tract. Recurrent or chronic respiratory infections can induce histomorphological and functional changes in the adenoidal immunological barrier, sometimes making surgical treatment necessary. Our aim in this review is to summarize the crucial points about not only the immunological histopathology of adenoidal tissue, especially in patients with adenoid hypertrophy, but also the most common and useful diagnostic techniques and surgical options.

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Obesity could be interpreted as a low grade inflammatory state. The role of cytokines for innate and acquired immune response and adipocytokines in pathogenesis of obesity is not completely understood. The aim of the study was to evaluate anthropometric parameters, adipocytokines and inflammatory cytokine levels as biomarkers of childhood obesity. This investigation was designed as a longitudinal observational study. Forty-seven obese children (19 males and 28 females) were enrolled by Pediatric Clinic of the Foundation IRCCS Policlinico San Matteo, Pavia, Italy. For each patients a blood sample, used for other biochemical evaluations, was collected. Cytokines and adipocytokines plasmatic levels were determined using an ELISA method. Plasma leptin levels are in correlation with age (r=0.5; P<0.001) and BMI-z score (r=0.36; P<0.001), particularly in girls; plasma resistin levels are in inverse correlation with age, particularly in boys (r=-0.67; P<0.001) and in correlation with BMI-z score (r=0.52; P=0.002). Plasma leptin and resistin levels show a good correlation with antrophometric parameters of child obesity (sex and BMI z score). This study suggests that leptin and resistin can be considered as biomarker of childhood obesity and its comorbility. We observed a statistically significant correlation between plasma leptin and resistin levels and antrophometric parameters of child obesity (sex and BMI z score). This study suggests that adipocytokines, such as leptin and resistin, can be considered as biomarkers of childhood obesity.

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PROBLEM: In order to investigate the role of amniotic fluid cells (AFC) in the establishment of feto-maternal immune relationship, we evaluated their phenotype and capacity to produce cytokines. METHODS OF STUDY: CK 7-8, human leukocyte antigen (HLA)-I, HLA-DR, HLA-G, CD1d, CD34, CD45, CD14 surface antigens expression and the intracellular production of IL-4, IL-6, IL-8, IL-10, IL-12, interferon-gamma and tumor necrosis factor-1 were studied in cultured AFC and in eight samples immediately after amniocentesis using flow cytometry. IL-6 and IL-8 were detected by ELISA in all amniotic fluids and in all culture supernatants. Moreover, IL-6 and IL-8 mRNA were tested in nine samples. RESULTS: Cultured AFC express HLA-I, HLA-G and CK 7-8 and are able to produce IL-6 and IL-8, confirmed by presence of their mRNA. We quantified IL-6 and IL-8 levels in all amniotic fluids and in all supernatants. CONCLUSION: Surface antigen expression of AFC are not specific of immune cells, but AFC are able to produce cytokines and we can postulate that they may participate in mechanisms involved in normal as well as pathological pregnancy.

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