Fecal Microbiota and Diet of Children with Chronic Constipation.

Many factors explain dysbiosis in chronic constipation (CC), such as a low-fiber diet. The objective of this study was to compare the fecal microbiota of constipated and nonconstipated children and their intake frequencies of food. Methods. This observational study included 79 children (M/F 43/36) aged six to 36 months divided into two groups: cases (39 constipated children) and controls (40 nonconstipated children). We used a structured form to collect demographic variables, conducted anthropometric assessment, and collected food intake frequency data. The fecal microbiota of the stool samples was analyzed by real-time polymerase chain reaction (PCR) using the fluorophore SYBR® Green. Results. Constipated children had a smaller concentration of Lactobacillus per milligram of stool (p = 0.015) than nonconstipated children, but the concentration of Bifidobacterium per milligram of stool (p = 0.323) and the intake of fruits, vegetables (p = 0.563), and junk food (p = 0.093) of the two groups did not differ. Constipated children consumed more dairy products (0.45 ± 0.8; p > 0.001), were more frequently delivered via caesarean section (69.2%), were weaned earlier (median: 120; 60Q1-240Q3), and had a family history of constipation (71.8%). Conclusions. Children with CC have a smaller concentration of Lactobacillus in their stools and consume more dairy products.

IL-23 activates innate lymphoid cells to promote neonatal intestinal pathology.

Interleukin-23 (IL-23) responsive group 3 innate lymphoid cells (ILC3s) have been implicated in immune homeostasis and pathogenesis in the adult, but little is known about their roles in the newborn. Here we show that IL-23 promotes conversion of embryonic intestinal Lin(-)IL-23R(+)Thy1(+) cells into IL-22-producing Thy1(+)Sca-1(hi) ILC3s in vitro. Gut-specific expression of IL-23 also activated and expanded Thy1(+)Sca-1(hi) ILC3s, which produced IL-22, IL-17, interferon gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) and were distinct from canonical CD4(+) lymphoid tissue inducer (LTi) cells. These ILC3s accumulated under the epithelium in intercellular adhesion molecule (ICAM)-1-positive cell aggregates together with neutrophils that disrupted the epithelium, leading to the formation of discrete intestinal erosions, bleeding, and neonatal death. Genetic and antibody depletion of ILC3s rescued the mice from neonatal death. Antibiotic treatment of pregnant mothers and offspring prolonged survival of IL-23 transgenic mice, suggesting a role for the commensal flora on ILC3-induced pathogenesis. Our results reveal a novel role for the IL-23-ILC3s axis in the pathogenesis of neonatal intestinal inflammation.

Site of infections associated with human papillomavirus.

INTRODUCTION: Human papillomavirus (HPV) is the most clinically common sexually transmitted infection due to its carcinogenic power and the high number of lesions that it causes at different sites of the human body. MATERIAL AND METHODS: Genital tract organs are the most common sites where the virus can be found, but by increasing the sensitivity of diagnostic technique, it is possible to identify viral presence in different regions of the body such as the stomach, the lung, and the urinary tract. These findings break with the traditional HPV skin/genital tropic profile and demonstrate that the virus is capable of infecting a wide variety of cells, tissues, and organs or can, at least, survive in these areas. The widespread presence of the HPV in the human body, often in latent form, led us to consider the hypothesis that HPV latency may be associated with no disease. CONCLUSION: This observation raises further questions about the possibility of the virus not causing disease in specific sites of the human body, but rather, behaving like a commensal/opportunistic microorganism.

BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups.

Langerhans cell histiocytosis (LCH) is a clonal disorder with elusive etiology, characterized by the accumulation of CD207(+) dendritic cells (DCs) in inflammatory lesions. Recurrent BRAF-V600E mutations have been reported in LCH. In this study, lesions from 100 patients were genotyped, and 64% carried the BRAF-V600E mutation within infiltrating CD207(+) DCs. BRAF-V600E expression in tissue DCs did not define specific clinical risk groups but was associated with increased risk of recurrence. Strikingly, we found that patients with active, high-risk LCH also carried BRAF-V600E in circulating CD11c(+) and CD14(+) fractions and in bone marrow (BM) CD34(+) hematopoietic cell progenitors, whereas the mutation was restricted to lesional CD207(+) DC in low-risk LCH patients. Importantly, BRAF-V600E expression in DCs was sufficient to drive LCH-like disease in mice. Consistent with our findings in humans, expression of BRAF-V600E in BM DC progenitors recapitulated many features of the human high-risk LCH, whereas BRAF-V600E expression in differentiated DCs more closely resembled low-risk LCH. We therefore propose classification of LCH as a myeloid neoplasia and hypothesize that high-risk LCH arises from somatic mutation of a hematopoietic progenitor, whereas low-risk disease arises from somatic mutation of tissue-restricted precursor DCs.