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Background: Lactiplantibacillus plantarum can inhibit the growth of multidrug-resistant organisms (MDROs) and modulate the gut microbiome. However, data on hematopoietic stem cell transplantation (HSCT) are scarce. Aim: In an observational study, we assessed the impact of L. plantarum on the modulation of the gut microbiome in HSCT patients colonized by MDROs. Methods: Participants were allocated to an intervention group (IG = 22) who received capsules of L. plantarum (5 × 109 CFU) twice per day until the onset of neutropenia or a control group (CG = 20). The V4 region of the 16S bacterial rRNA gene was sequenced in 87 stool samples from a subset of 33 patients (IG = 20 and CG = 13). The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) program was used to predict metagenome functions. Results: L. plantarum demonstrated an average 86% (±11%) drug-target engagement at 43 (±29) days of consumption and was deemed safe, well-tolerated, and associated with an increase in the abundance of the Lactobacillales (p < 0.05). A significant increase in Lactococcus and a reduction in Turicibacter (p < 0.05) were identified on the second week of L. plantarum use. Although Enterococcus abundance had a greater rise in the CG (p = 0.07), there were no significant differences concerning the Gram-negative MDROs. No serious adverse effects were reported in the IG. We observed a greater, non-significant pyruvate fermentation to propanoate I (p = 0.193) relative abundance in the IG compared with the CG. L. plantarum use was safe and tolerable by HSCT patients. Conclusions: While L. plantarum is safe and may impact Enterococcus and Turicibacter abundance, it showed no impact on Gram-negative MDRO abundance in HSCT patients. [ABSTRACT FROM AUTHOR]

Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 × 10−8). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment. [ABSTRACT FROM AUTHOR]

Background: Obesity is one of the main health problems in the world today, and dysbiosis seems to be one of the factors involved. The aim of this study was to examine the impact of synbiotic supplementation on obesity and the microbiota in ob/ob mice. Twenty animals were divided into four groups: obese treated (OT), obese control (OC), lean treated (LT) and lean control (LC). All animals received a standard diet for 8 weeks. The treated groups received a synbiotic (Simbioflora-Invictus Farmanutrição Ltd., Sao Paulo, Brazil) in water, while the nontreated groups received only water. After 8 weeks, all animals were sacrificed, and gut tissue and stool samples were collected for mRNA isolation and microbiota analysis, respectively. β-Catenin, occludin, cadherin and zonulin in the gut tissue were analyzed via RT-qPCR. Microbiome DNA was extracted from stool samples and sequenced using an Ion PGM Torrent platform., Results: Synbiotic supplementation reduced body weight gain in the OT group compared with the OC group ( p = 0.0398) and was associated with an increase in Enterobacteriaceae ( p = 0.005) and a decrease in Cyanobacteria ( p = 0.047), Clostridiaceae ( p = 0.026), Turicibacterales ( p = 0.005) and Coprococcus ( p = 0.047). On the other hand, a significant reduction in Sutterella ( p = 0.009) and Turicibacter ( p = 0.005) bacteria was observed in the LT group compared to the LC group. Alpha and beta diversities were different among all treated groups. β-Catenin gene expression was significantly decreased in the gut tissue of the OT group ( p ≤ 0.0001) compared to the other groups. No changes were observed in occludin, cadherin or zonulin gene expression in the gut tissue., Conclusions: Synbiotic supplementation prevents excessive weight gain, modulates the gut microbiota, and reduces β-catenin expression in ob/ob mice.