Toxic iron species in lower-risk myelodysplastic syndrome patients : course of disease and effects on outcome

Item does not contain fulltex

Towards the Human Colorectal Cancer Microbiome

Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions

Differentiating iron-loading anemias using a newly developed and analytically validated ELISA for human serum erythroferrone

International audienceErythroferrone (ERFE), the erythroid regulator of iron metabolism, inhibits hepcidin to increase iron availability for erythropoiesis. ERFE plays a pathological role during ineffective erythropoiesis as occurs in X-linked sideroblastic anemia (XLSA) and β-thalassemia. Its measurement might serve as an indicator of severity for these diseases. However, for reliable quantification of ERFE analytical characterization is indispensable to determine the assay’s limitations and define proper methodology. We developed a sandwich ELISA for human serum ERFE using polyclonal antibodies and report its extensive analytical validation. This new assay showed, for the first time, the differentiation of XLSA and β-thalassemia major patients from healthy controls (p = 0.03) and from each other (p<0.01), showing the assay provides biological plausible results. Despite poor dilution linearity, parallelism and recovery in patient serum matrix, which indicated presence of a matrix effect and/or different immunoreactivity of the antibodies to the recombinant standard and the endogenous analyte, our assay correlated well with two other existing ERFE ELISAs (both R 2 = 0.83). Nevertheless, employment of one optimal dilution of all serum samples is warranted to obtain reliable results. When adequately performed, the assay can be used to further unravel the human erythropoiesis-hepcidin-iron axis in various disorders and assess the added diagnostic value of ERFE

Selective antibody response to Streptococcus gallolyticus pilus proteins in colorectal cancer patients

Item does not contain fulltextStreptococcus gallolyticus subsp. gallolyticus (previously called Streptococcus bovis biotype I) infections have long been associated with colorectal cancer (CRC). This work aimed to investigate the CRC-associated humoral immune response to four pilus proteins of this bacterium by newly developed ELISAs. Pilus proteins are interesting diagnostic targets as they are the building blocks of pilin-like structures that mediate bacterial virulence and are readily exposed to the host immune system upon infection. The presence of serum antibodies against these pilus proteins was evaluated in Dutch and American populations. These analyses showed that an immune response to these antigens was specific for clinical S. gallolyticus subsp. gallolyticus infections, but that increased serum antibody titers to multiple pilus proteins in single individuals were rarely observed. However, a multiplex approach based on antibody titers against any of these four antigens resulted in assay sensitivities between 16% and 43% for the detection of early-stage CRC. Together these findings underscore the potential of a multi-antigen approach to complement diagnosis of S. gallolyticus subsp. gallolyticus-associated CRC

Partial associations of dietary iron, smoking and intestinal bacteria with colorectal cancer risk

Item does not contain fulltextSmoking and high red meat intake have been associated with colorectal cancer (CRC) risk. Increased iron exposure may be a common factor, favoring the colonization of certain bacterial pathogens that preferentially grow in an iron-rich luminal environment. We analyzed the data from a population-based case-control study of CRC and measured antibody levels against flagelin of Salmonella (FliC), one of the irontrophic bacteria, in 2 independent blood collections. The risk of CRC synergistically increased by combined exposures to heme iron intake and pack-yr (PY) of cigarette smoking (P value for the interaction = 0.039 on the continuous scale). There was a marginally significant interaction between heme iron intake and PY in increasing FliC antibody in the U.S. control subjects (P = 0.055), although no iron or smoking data were available for Dutch samples. Furthermore, FliC antibody levels were significantly higher in patients with colorectal polyps and cancer than in controls in both Dutch (3.93 vs. 2.23) (P = 0.014) and U.S. samples (6.65 vs. 4.37) (P < 0.001). Potential roles of iron from cigarette smoking and dietary heme in CRC through altering irontrophic luminal bacterial population may warrant further investigation