The Origin of Plasma-Derived Bacterial Extracellular Vesicles in Healthy Individuals and Patients with Inflammatory Bowel Disease: A Pilot Study.

The gastrointestinal tract harbors the gut microbiota, structural alterations of which (dysbiosis) are linked with an increase in gut permeability ("leaky gut"), enabling luminal antigens and bacterial products such as nanosized bacterial extracellular vesicles (BEVs) to access the circulatory system. Blood-derived BEVs contain various cargoes and may be useful biomarkers for diagnosis and monitoring of disease status and relapse in conditions such as inflammatory bowel disease (IBD). To progress this concept, we developed a rapid, cost-effective protocol to isolate BEV-associated DNA and used 16S rRNA gene sequencing to identify bacterial origins of the blood microbiome of healthy individuals and patients with Crohn's disease and ulcerative colitis. The 16S rRNA gene sequencing successfully identified the origin of plasma-derived BEV DNA. The analysis showed that the blood microbiota richness, diversity, or composition in IBD, healthy control, and protocol control groups were not significantly distinct, highlighting the issue of 'kit-ome' contamination in low-biomass studies. Our pilot study provides the basis for undertaking larger studies to determine the potential use of blood microbiota profiling as a diagnostic aid in IBD.

Effects of probiotics on body adiposity and cardiovascular risk markers in individuals with overweight and obesity: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Evidence suggests that gut microbiota is a potential factor in the pathophysiology of both obesity and related metabolic disorders. While individual randomized controlled trials (RCTs) have evaluated the effects of probiotics on adiposity and cardiovascular disease (CVD) risk factors in subjects with overweight and obesity, the results are inconsistent. Thus, this systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation on body weight, body adiposity and CVD risk markers in overweight and obese subjects. METHODS: A systematic search for RCTs published up to December 2020 was conducted in MEDLINE (via PubMed), EMBASE, Scopus and LILACS. Meta-analysis using a random-effects model was chosen to analyze the impact of combined trials. RESULTS: Twenty-six RCTs (n = 1720) were included. Data pooling showed a significant effect of probiotics in reducing body weight (MD:-0.70 kg; 95%CI:-1.04,-0.35 kg; P < 0.0001), body mass index (BMI) (MD:-0.24 kg/m2; 95%CI:-0.35,-0.12 kg/m2; P = 0.0001), waist circumference (WC) (MD:-1.13 cm; 95%CI:-1.54,-0.73 cm; P < 0.0001), fat mass (MD:-0.71 kg; 95%CI:-1.10,-0.32 kg; P = 0.0004), tumor necrosis factor-α (MD:-0.16 pg/ml; 95%CI:-0.24,-0.08 pg/ml; P = 0.0001), insulin (MD:-0.85mcU/ml; 95%CI:-1.50,-0.21mcU/ml; P = 0.010), total cholesterol (MD:-0.16 mmol/l; 95%CI:-0.26,-0.05 mmol/l; P = 0.003) and LDL (MD:-0.09 mmol/l; 95%CI:-0.16,-0.03 mmol/l; P = 0.006) compared with control groups. There was a significant decrease in body weight, BMI and WC in studies using both single and multi-bacterial species. Decreases in body adiposity parameters were only observed in studies using a probiotic dose of ≥ 1010 CFU and for ≥8 weeks duration. CONCLUSIONS: The present meta-analysis suggests that probiotics consumption may be helpful for improving body weight, body adiposity and some CVD risk markers in individuals with overweight and obesity. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42020183136.

The Impact of Bacterial Biofilms on End-Organ Disease and Mortality in Patients with Hematologic Malignancies Developing a Bloodstream Infection.

Bacterial bloodstream infection (BSI) represents a significant complication in hematologic patients. However, factors leading to BSI and progression to end-organ disease and death are understood only partially. The study analyzes host and microbial risk factors and assesses their impact on BSI development and mortality. A total of 96 patients with hematological malignancies and BSI were included in the study. Host-associated risk factors and all causes of mortality were analyzed by multivariable logistic regression at 30 days after BSI onset of the first neutropenic episode. The multidrug-resistant profile and biofilm production of bacterial isolates from primary BSI were included in the analysis. Median age was 60 years. The underlying diagnoses were acute leukemia (55%), lymphoma (31%), and myeloma (14%). A total of 96 bacterial isolates were isolated from BSIs. Escherichia coli was the most common isolate (29.2%). Multidrug-resistant bacteria caused 10.4% of bacteremia episodes. Weak biofilm producers (WBPs) were significantly (P < 0.0001) more abundant (72.2%) than strong biofilm producers (SBPs) (27.8%). Specifically, SBPs were 7.1% for E. coli, 93.7% for P. aeruginosa, 50% for K. pneumoniae, and 3.8% for coagulase-negative staphylococci. Mortality at day 30 was 8.3%, and all deaths were attributable to Gram-negative bacteria. About 22% of all BSIs were catheter-related BSIs (CRBSIs) and mostly caused by Gram-positive bacteria (79.0%). However, CRBSIs were not correlated with biofilm production levels (P = 0.75) and did not significantly impact the mortality rate (P = 0.62). Conversely, SBP bacteria were an independent risk factor (P = 0.018) for developing an end-organ disease. In addition, multivariate analysis indicated that SBPs (P = 0.013) and multidrug-resistant bacteria (P = 0.006) were independent risk factors associated with 30-day mortality. SBP and multidrug-resistant (MDR) bacteria caused a limited fraction of BSI in these patients. However, when present, SBPs raise the risk of end-organ disease and, together with an MDR phenotype, can independently and significantly concur at increasing the risk of death. IMPORTANCE Bacterial bloodstream infection (BSI) is a significant complication in hematologic patients and is associated with high mortality rates. Despite improvements in BSI management, factors leading to sepsis are understood only partially. This study analyzes the contribution of bacterial biofilm on BSI development and mortality in patients with hematological malignancies (HMs). In this work, weak biofilm producers (WBPs) were significantly more abundant than strong biofilm producers (SBPs). However, when present, SBP bacteria raised the risk of end-organ disease in HM patients developing a BSI. Besides, SBPs, together with a multidrug-resistant (MDR) phenotype, independently and significantly concur at increasing the risk of death in HM patients. The characterization of microbial biofilms may provide key information for the diagnosis and therapeutic management of BSI and may help develop novel strategies to either eradicate or control harmful microbial biofilms.