In this issue of report a study which used

In this issue of , report a study which used the publicly available data from the American Gut Project including questionnaires and fecal 16S rRNA sequence data. The report focuses on associations between self-reported allergies and the adult fecal microbiota composition. Self-reported allergy prevalence among the 1879 subjects was more that 80% which is likely to have overestimated the problem. Subjects with self-reported allergies had significantly less diverse microbiota with differences also in specific components of the microbiota as compared to individuals with no reported allergies.
Introduction The Philadelphia chromosome-negative (Ph−) MPNs include clonal disorders of myeloid progenitor cells, such as polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). The latter can be sub-categorized as either primary (PMF) or as transformed from PV or ET (post-PV/ET MF) (Tefferi et al., 2009a). The incidence of classic Ph− MPNs in Europe is 1.8 cases per 100,000person-years (Visser et al., 2012). In the US, between 2008 and 2010 (as assessed by a review of two large health plans), the prevalences of PV, ET, and MF were 44–57, 38–57, and 4–6 per 100,000, respectively (Mehta et al., 2012). In general, the MPNs may be associated with an increased risk of morbidity and mortality and may lead to a significant decrement in quality of life (QOL). Generally, MF differs from PV and ET in that it typically carries a worse prognosis and high symptom burden related to elevated cytokine levels, cytopenias, splenomegaly, and extramedullary hematopoiesis, all of which can result in fatigue, early satiety, abdominal discomfort, inactivity, night sweats, pruritus, bone pain and weight loss (Emanuel et al., 2012). Transformation to acute myelogenous leukemia (AML) has been the most feared complication of MPNs, particularly of MF. Prognosis of MPNs varies greatly based on subtype. ET is associated with a 10-year and 15-year survival of 89 and 80%, leukemic transformation rate of 0.7% and 2.1%, and rate of progression to MF of 0.8% and 9.3%, respectively (Barbui et al., 2011). Among patients with PV, median survival has been shown to be 14.1years, which is worse than that of the age- and sex-matched control neurokinin receptor antagonist of the US (Tefferi et al., 2013). Evolution to MDS and leukemia was the main cause of death in a phase 3 study comparing the use of hydroxyurea (HU) to pibobroman among treatment-naïve PV patients under the age of 65years (Kiladjian et al., 2011) In a large European epidemiological study of PV, 41% of deaths (1.5 deaths per 100 persons per year) were attributable to cardiovascular events (Marchioli et al., 2005). The median survival for patients with MF was shown to be 6.5years, between years 1996 and 2007, in a European population (Cervantes et al., 2012). A better understanding of the molecular pathogenesis of Ph− MPNs has been greatly facilitated by the 2005 discovery of the point mutation JAK2 V617F, which is present in almost 95% of PV cases and 50–60% of ET and PMF cases (Kralovics et al., 2005; Rampal and Levine, 2014). The mutation leads to constitutive activation of Janus kinase 2 (JAK2), a member of the Janus family of kinases, normally phosphorylated/activated by various cytokine receptors to drive signal transducer and activator of transcription (STAT) pathways in hematopoiesis (Fig. 1). The thrombopoietin receptor mutation MPL W515L, identified shortly after the discovery of JAK2 V617F, is another driver mutation that leads to activation of the JAK–STAT pathway and is present in a minority JAK2 V617F-negative cases of MF and ET (Pikman et al., 2006). In 2013, mutations of CALR, the gene that encodes the endoplasmic reticulum chaperone calreticulin, were identified among 67–88% of patients with JAK2/MPL negative ET and MF (Klampfl et al., 2013; Nangalia et al., 2013). The presence of these mutations may have prognostic implications for patients. For example, MF patients with CALR mutations have an improved overall survival as compared to patients with JAK2 mutations (Klampfl et al., 2013; Nangalia et al., 2013), and ET patients with CALR mutations have a decreased incidence of thrombosis (Rumi et al., 2014a). The absence of mutations of JAK2, CALR, and MPL (“triple negative” PMF) appears to ultimately promote leukemic transformation, as compared with CALR-mutated or JAK2-mutated patients (Rumi et al., 2014b). These findings suggest that mutational status may be able to serve as a prognosticator independently from established prognostic models that are based on clinical features. Since the discovery of JAK2 V617F, there has been the identification of numerous other somatic mutations in MPNs (e.g., JAK2 exon 12, IKZF1, DNMT3A, TP53, TET2, SRSF2, SF3B1, ASXL1, IDH1/2, and EZH2). Many of these genes play roles in epigenetic processes, leading to activation or suppression of gene expression, suggesting a rationale for epigenetic therapies. Among MF patients, mutations in ASXL1, SRSF2, IDH, or EZH2 have been associated with a poor survival or an increased risk for leukemic transformation (Vannucchi et al., 2013). Many of the other mutations seen in MPNs involve mRNA splicing and genes controlling cellular metabolism, and some may facilitate clonal selection and promote dominance of JAK2 V617F subclones (Nangalia and Green, 2014; Vainchenker et al., 2011). The role of systematic mutational profiling to predict for benefit to therapy is the subject of current investigations, which will likely be challenging endeavors given the clonal complexity of MPNs (Lundberg et al., 2014).