The Influence of the Gut Microbiome in Paediatric Cancer Origin and Treatment

Knowledge of the complexity of the gut microbiota is expanding, and its importance in physiological processes and disease development is widely studied. The aim of this review is to present the most relevant and recent research on the associations between gut microbiota and oncologic disease. Recently, a number of associations between the gut microbiome and neoplasms—regarding tumorigenesis, prognosis and therapeutic efficacy—have been reported. The effects of the gut microbiome on these processes are via the direct and indirect immunomodulating effects of bacteria. Studies have been done mainly in adult populations, where its effect on immunomodulating therapies was unambiguous. In paediatric populations, however, due to the low number of cases and the complex therapeutic approaches, there have been only a few studies. Among them, children with acute lymphoblastic leukaemia were mainly involved. Significant alterations in the abundance of certain bacteria were associated with altered therapeutic responses. Regarding solid tumours, studies with low case numbers have been reported; no significant discoveries have been described so far. In the future, studies with larger cohorts are needed in order to better understand the associations between bacteria and neoplasms and to improve prognosis in the paediatric oncologic population

Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels

Balance between the microbiome associated with bladder mucosa and human beta defensin (HBD) levels in urine is a dynamic, sensitive and host-specific relationship. HBD1—possessing both antitumor and antibacterial activity—is produced constitutively, while the inducible production of antibacterial HBD2 and HBD3 is affected by bacteria. Elevated levels of HBD2 were shown to cause treatment failure in anticancer immunotherapy. Our aim was to assess the relationship between microbiome composition characteristic of tumor tissue, defensin expression and HBD levels measured in urine. Tissue samples for analyses were removed during transurethral resection from 55 bladder carcinoma and 12 prostatic hyperplasia patients. Microbiome analyses were carried out with 16S rRNS sequencing. Levels of HBD mRNA expression were measured with qPCR from the same samples, and urinary amounts of HBD1, 2 and 3 were detected with ELISA in these patients, in addition to 34 healthy volunteers. Mann–Whitney U test, Wilcoxon rank sum test (alpha diversity) and PERMANOVA analysis (beta diversity) were performed. Defensin-levels expressed in the tumor did not clearly determine the amount of defensin measurable in the urine. The antibacterial and antitumor defensin (HBD1) showed decreased levels in cancer patients, while others (HBD2 and 3) were considerably increased. Abundance of Staphylococcus, Corynebacterium and Oxyphotobacteria genera was significantly higher, the abundance of Faecalibacterium and Bacteroides genera were significantly lower in tumor samples compared to non-tumor samples. Bacteroides, Parabacteroides and Faecalibacterium abundance gradually decreased with the combined increase in HBD2 and HBD3. Higher Corynebacterium and Staphylococcus abundances were measured together with higher HBD2 and HBD3 urinary levels. Among other factors, defensins and microorganisms also affect the development, progression and treatment options for bladder cancer. To enhance the success of immunotherapies and to develop adjuvant antitumor therapies, it is important to gain insight into the interactions between defensins and the tumor-associated microbiome

Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus

Abstract Human beta defensins (hBDs) may play an important role in the progression of lichen sclerosus (LS), due to their ability to induce excessive stimulation of extracellular matrix synthesis and fibroblast activation. The genetic ability of the individual to produce defensins, the presence of microbes influencing defensin production, and the sensitivity of microbes to defensins together regulate the formation of an ever-changing balance between defensin levels and microbiome composition. We investigated the potential differences in postmenopausal vaginal microbiome composition and vaginal hBD levels in LS patients compared to non-LS controls. LS patients exhibited significantly lower levels of hBD1 (p = 0.0003), and significantly higher levels of hBD2 (p = 0.0359) and hBD3 (p = 0.0002), compared to the control group. The microbiome of the LS patients was dominated by possibly harmful bacteria including Lactobacillus iners, Streptococcus anginosus or Gardnerella vaginalis known to initiate direct or indirect damage by increasing defensin level production. Our observations highlight that correcting the composition of the microbiome may be applicable in supplementary LS therapy by targeting the restoration of the beneficial flora that does not increase hBD2-3 production

Composition and changes of blood microbiota in adult patients with community-acquired sepsis: A pilot study from bench to bedside

BackgroundCharacteristics of the blood microbiota among adult patients with community-acquired sepsis are poorly understood. Our aim was to analyze the composition of blood microbiota in adult patients with community-acquired sepsis, and correlate changes with non-septic control patients.MethodsA prospective observational study was carried out by including adult patients hospitalized for community-acquired sepsis at our center between January and November 2019, by random selection from a pool of eligible patients. Study inclusion was done on the day of sepsis diagnosis. Community acquisition was ascertained by a priori exclusion criteria; sepsis was defined according to the SEPSIS-3 definitions. Each included patient was matched with non-septic control patients by age and gender in a 1:1 fashion enrolled from the general population. Conventional culturing with BacT/ALERT system and 16S rRNA microbiota analysis were performed from blood samples taken in a same time from a patient. Abundance data was analyzed by the CosmosID HUB Microbiome software.ResultsAltogether, 13 hospitalized patients were included, 6/13 (46.2%) with sepsis and 7/13 (53.8%) with septic shock at diagnosis. The most prevalent etiopathogen isolated from blood cultures was Escherichia coli, patients mostly had intraabdominal septic source. At day 28, all-cause mortality was 15.4% (2/13). Compared to non-septic control patients, a relative scarcity of Faecalibacterium, Blautia, Coprococcus and Roseburia genera, with an abundance of Enhydrobacter, Pseudomonas and Micrococcus genera was observed among septic patients. Relative differences between septic vs. non-septic patients were more obvious at the phylum level, mainly driven by Firmicutes (25.7% vs. 63.1%; p<0.01) and Proteobacteria (36.9% vs. 16.6%; p<0.01). The alpha diversity, quantified by the Chao1 index showed statistically significant difference between septic vs. non-septic patients (126 ± 51 vs. 66 ± 26; p<0.01). The Bray-Curtis beta diversity, reported by principal coordinate analysis of total hit frequencies, revealed 2 potentially separate clusters among septic vs. non-septic patients.ConclusionIn adult patients with community-acquired sepsis, specific changes in the composition and abundance of blood microbiota could be detected by 16S rRNA metagenome sequencing, compared to non-septic control patients. Traditional blood culture results only partially correlate with microbiota test results

Gut microbiome in patients with obstructive sleep apnoea

Background: Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular disease. Alterations in the gut microbiome have been implicated in the development of cardiovascular disease and may potentially link OSA to its cardiovascular consequences. However, only one study to date has investigated gut microbiomes in adult patients with OSA. Methods: 19 patients with OSA and 20 non-OSA controls participated in the study. Following a diagnostic sleep study, blood was collected for metabolic profiling, and the subjects provided a stool sample for microbiome analysis. The gut microbiome was investigated using the 16S ribosomal RNA method. Results: Patients with OSA had a higher relative abundance of the Proteobacteria phylum (p = 0.03), Gammaproteobacteria class (p = 0.01), Lactobacillae family (p = 0.02), Lactobacillus (p = 0.03), and Roseburia genus (p = 0.03), and a lower abundance of the Actinobacteria phylum (p = 0.03). The abundance of Proteobacteria, Gammaproteobacteria, Lactobacillae, and Lactobacillus were related to disease severity and dyslipidaemia (all p < 0.05), whilst the abundance of Proteobacteria and Gammaproteobacteria was also related to hypertension and cardiovascular disease (all p < 0.05). However, following adjustment for relevant confounders only the association between OSA and Actinobacteria remained significant (p = 0.04). Conclusions: Obstructive sleep apnoea is associated with only subtle changes in gut microbiome. Further studies should investigate gut dysbiosis in OSA

Colonization Dynamics of Multidrug-Resistant Klebsiella pneumoniae Are Dictated by Microbiota-Cluster Group Behavior over Individual Antibiotic Susceptibility: A Metataxonomic Analysis

Gastrointestinal carriage of multidrug-resistant (MDR) bacteria is one of the main risk factors for developing serious, difficult-to-treat infections. Given that there is currently no all-round solution to eliminate colonization with MDR bacteria, it is particularly important to understand the dynamic process of colonization to aid the development of novel decolonization strategies. The aim of our present study was to perform metataxonomic analyses of gut microbiota dynamics during colonization with an extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing Klebsiella pneumoniae (ECKP) strain in mice; additionally, to ascertain the effects of antibiotic administration (ampicillin, ceftazidime, and ciprofloxacin) on the establishment and elimination of ECKP intestinal colonization. We have found that the phyla Bacteroidetes and Firmicutes were most dominant in all of the treatment groups; however, Bacteroidetes was more common in the groups treated with antibiotics compared to the control group. Significant differences were observed among the different antibiotic-treated groups in beta but not alpha diversity, implying that the difference is the relative abundance of some bacterial community members. Bacteria from the Lachnospiraceae family (including Agathobacter, Anaerostipes, Lachnoclostridium 11308, Lachnospiraceae UCG-004, Lachnospiraceae NK3A20 group 11318, Lachnospiraceae NK4A136 group 11319, Roseburia, and Tyzzerella) showed an inverse relationship with the carriage rate of the ECKP strain, whereas members of Enterobacteriaceae and the ECKP strain have shown a correlational relationship. Our results suggest that the composition of the microbial community plays a primary role in the MDR-colonization rate, whereas the antibiotic susceptibility of individual MDR strains affects this process to a lesser extent. Distinct bacterial families have associated into microbial clusters, collecting taxonomically close species to produce survival benefits in the gut. These associations do not develop at random, as they may be attributed to the presence of specific metabolomic networks. A new concept should be introduced in designing future endeavors for MDR decolonization, supplemented by knowledge of the composition of the host bacterial community and the identification of bacterial clusters capable of suppressing or enhancing the invader species