No abstract

Nutritional iron deficiency (ID) causes not only anemia but also malfunction of the entire human organism. Recently, a role of the gut microbiota has been hypothesized, but limited data are available especially in infants. Here, we performed a pilot study to explore the gut microbiota in 10 patients with iron deficiency anemia (IDA) and 10 healthy controls aged 6-34 months. Fresh stool samples were collected from diapers, and the fecal microbiota was profiled by next-generation sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. Except for diet diversity, the breastfeeding status at the enrollment, the exclusive breastfeeding duration, and the introduction of complementary foods did not differ between groups. Distinct microbial signatures were found in IDA patients, with increased relative abundance of Enterobacteriaceae (mean relative abundance, patients vs. controls, 4.4% vs. 3.0%) and Veillonellaceae (13.7% vs. 3.6%), and reduced abundance of Coriobacteriaceae (3.5% vs. 8.8%) compared to healthy controls. A decreased Bifidobacteriaceae/ Enterobacteriaceae ratio was observed in IDA patients. Notwithstanding the low sample size, our data highlight microbiota dysbalance in IDA worth for further investigations, aimed at unraveling the ID impact on the microbiome trajectory in early life, and the possible long-term consequences.

Background: Variants in recombination-activating genes (RAG) are common genetic causes of autosomal recessive forms of combined immunodeficiencies (CID) ranging from severe combined immunodeficiency (SCID), Omenn syndrome (OS), leaky SCID, and CID with granulomas and/or autoimmunity (CID-G/AI), and even milder presentation with antibody deficiency.Objective: We aim to estimate the incidence, clinical presentation, genetic variability, and treatment outcome with geographic distribution of patients with the RAG defects in populations inhabiting South, West, and East Slavic countries.Methods: Demographic, clinical, and laboratory data were collected from RAG-deficient patients of Slavic origin via chart review, retrospectively. Recombinase activity was determined in vitro by flow cytometry-based assay.Results: Based on the clinical and immunologic phenotype, our cohort of 82 patients from 68 families represented a wide spectrum of RAG deficiencies, including SCID (n = 20), OS (n = 37), and LS/CID (n = 25) phenotypes. Sixty-seven (81.7%) patients carried RAG1 and 15 patients (18.3%) carried RAG2 biallelic variants. We estimate that the minimal annual incidence of RAG deficiency in Slavic countries varies between 1 in 180,000 and 1 in 300,000 live births, and it may vary secondary to health care disparities in these regions. In our cohort, 70% (n = 47) of patients with RAG1 variants carried p.K86Vfs * 33 (c.256_257delAA) allele, either in homozygous (n = 18, 27%) or in compound heterozygous (n = 29, 43%) form. The majority (77%) of patients with homozygous RAG1 p.K86Vfs * 33 variant originated from Vistula watershed area in Central and Eastern Poland, and compound heterozygote cases were distributed among all Slavic countries except Bulgaria. Clinical and immunological presentation of homozygous RAG1 p.K86Vfs * 33 cases was highly diverse (SCID, OS, and AS/CID) suggestive of strong influence of additional genetic and/or epigenetic factors in shaping the final phenotype. Conclusion:We propose that RAG1 p.K86Vfs * 33 is a founder variant originating from the Vistula watershed region in Poland, which may explain a high proportion of homozygous cases from Central and Eastern Poland and the presence of the variant in all Slavs. Our studies in this cohort of RAG1 founder variants confirm that clinical and immunological phenotypes only partially depend on the underlying genetic defect. As access to HSCT is improving among RAG-deficient patients in Eastern Europe, we anticipate improvements in survival.

Background: Parenteral nutrition is commonly used to ensure nutrition support and prevent the harmful effects of malnutrition, which frequently occurs after allogeneic hematopoietic stem cell transplantation (aHSCT). Nevertheless, enteral nutrition supports the restoration of the gut barrier and microbiome as well as protects against infectious complications and acute graft-vs-host disease. Percutaneous endoscopic gastrostomy (PEG) may also be beneficial for gastric decompression and drug administration. Methods: We performed a retrospective cohort study to evaluate the impact of PEG on treatment outcomes in 75 children who underwent aHSCT with (n = 34) or without (n = 41) PEG from 2005 to 2016.Results: In 34 patients, PEG was used to ensure enteral nutrition support (n = 30), oral drug intake (n = 28), and abdominal decompression (n = 2). During the study period, we observed a beneficial association between PEG placement and transplant-related mortality as well as 5-year overall survival compared with the non-PEG group (12.9% vs 59.0%, P = 0.000; 85.3% vs 35.1%, P = 0.000, respectively). The beneficial impact of PEG was most prominent on 5-year overall survival in older children (12-17 years) with grafts from matched unrelated donors.Conclusions: PEG placement had a positive association with transplant outcomes in pediatric patients undergoing aHSCT. To confirm these results, larger prospective studies are needed.