RESUMO
BACKGROUND: Wnt/ß-catenin signalling impairment accounts for 85% of colorectal cancers (CRCs), including sporadic and familial adenomatous polyposis (FAP) settings. An altered PI3K/mTOR pathway and gut microbiota also contribute to CRC carcinogenesis. We studied the interplay between the two pathways and the microbiota composition within each step of CRC carcinogenesis. METHODS: Proteins and target genes of both pathways were analysed by RT-qPCR and IHC in tissues from healthy faecal immunochemical test positive (FIT+, n = 17), FAP (n = 17) and CRC (n = 15) subjects. CRC-related mutations were analysed through NGS and Sanger. Oral, faecal and mucosal microbiota was profiled by 16 S rRNA-sequencing. RESULTS: We found simultaneous hyperactivation of Wnt/ß-catenin and PI3K/mTOR pathways in FAP-lesions compared to CRCs. Wnt/ß-catenin molecular markers positively correlated with Clostridium_sensu_stricto_1 and negatively with Bacteroides in FAP faecal microbiota. Alistipes, Lachnospiraceae, and Ruminococcaceae were enriched in FAP stools and adenomas, the latter also showing an overabundance of Lachnoclostridium, which positively correlated with cMYC. In impaired-mTOR-mutated CRC tissues, p-S6R correlated with Fusobacterium and Dialister, the latter also confirmed in the faecal-ecosystem. CONCLUSIONS: Our study reveals an interplay between Wnt/ß-catenin and PI3K/mTOR, whose derangement correlates with specific microbiota signatures in FAP and CRC patients, and identifies new potential biomarkers and targets to improve CRC prevention, early adenoma detection and treatment.
Assuntos
Carcinogênese , Neoplasias Colorretais , Fosfatidilinositol 3-Quinases , Serina-Treonina Quinases TOR , Via de Sinalização Wnt , Humanos , Neoplasias Colorretais/microbiologia , Serina-Treonina Quinases TOR/metabolismo , Projetos Piloto , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Feminino , Polipose Adenomatosa do Colo/microbiologia , Polipose Adenomatosa do Colo/genética , Pessoa de Meia-Idade , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Fezes/microbiologia , Microbioma Gastrointestinal , Idoso , Adulto , Mutação/genética , MicrobiotaRESUMO
BACKGROUND: Fever is one of the most frequent symptoms highlighted during medical assistance. Due to this great impact, our study has the purpose of analyzing the demographic and laboratory characteristics of patients hospitalized in our center and identifying predictive markers to make the differential diagnosis between infectious and non-infectious fever. METHODS: Our population included 220 children, collected from January 2017 to August 2022, hospitalized for continuous fever (4 days or more in duration with at least one temperature peak ≥37.5 °C) and excluded cases of discharge against medical advice and/or transfer to other operating units. Demographic (mean age at the time of admission, frequency of hospitalization, and mean days of hospitalization), laboratory, and instrumental variables were analyzed in order to find correlation with fever etiology. RESULTS: Older age at the time of hospitalization, family history of periodic fever, fever lasting more than 8 days, and longer hospitalization are strongly associated with non-infectious fever, together with anemia, high platelet count, high CRP and ferritin, and hyponatremia at the time of admission. Paracetamol is the preferred antipyretic treatment. Echocardiogram has shown anomalies in patients with infectious fever, while ECG anomalies were detected in non-infectious fever. CONCLUSIONS: Our data underline the importance of predictive markers, such as clinical and laboratory parameters, to differentiate infectious from non-infectious fevers, but further studies are necessary.
RESUMO
OBJECTIVE: Fecal microbiota was investigated in adult patients with chronic intestinal failure (CIF) due to short bowel syndrome (SBS) with jejunocolonic anastomosis (SBS-2). Few or no data are available on SBS with jejunostomy (SBS-1) and CIF due to intestinal dysmotility (DYS) or mucosal disease (MD). We profiled the fecal microbiota of various pathophysiological mechanisms of CIF. METHODS: Cross-sectional study on 61 adults with CIF (SBS-1 30, SBS-2 17, DYS 8, MD 6). Fecal samples were collected and profiled by 16S rRNA amplicon sequencing. Healthy controls (HC) were selected from pre-existing cohorts, matched with patients by sex and age. RESULTS: Compared to HC, SBS-1, SBS-2 and MD patients showed lower alpha diversity; no difference was found for DYS. In beta diversity analysis, SBS-1, SBS-2 and DYS groups segregated from HC and from each other. Taxonomically, the CIF groups differed from HC even at the phylum level. In particular, CIF patients' microbiota was dominated by Lactobacillaceae and Enterobacteriaceae, while depleted in typical health-associated taxa belonging to Lachnospiraceae and Ruminococcaceae. Notably, compositional peculiarities of the CIF groups emerged. Furthermore, in the SBS groups, the microbiota profile differed according to the amount of parenteral nutrition required and the duration of CIF. CONCLUSIONS: CIF patients showed marked intestinal dysbiosis with microbial signatures specific to the pathophysiological mechanism of CIF as well as to the severity and duration of SBS.
Assuntos
Fezes , Microbioma Gastrointestinal , Síndrome do Intestino Curto , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Fezes/microbiologia , Adulto , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/fisiopatologia , Doença Crônica , Idoso , Insuficiência Intestinal/microbiologia , RNA Ribossômico 16S/genéticaRESUMO
Background & Aims: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT). Methods: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG). Results: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients. Conclusions: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis. Impact and implications: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.
RESUMO
Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific receptors. Initial studies on NTs have identified them only as functional molecules of the nervous system. However, recent research have shown that some tissues and organs (such as the lungs, skin, and skeletal and smooth muscle) as well as some structural cells can secrete and respond to NTs. In addition, NTs perform several roles in normal and pathological conditions at different anatomical sites, in both fetal and postnatal life. During pregnancy, NTs are produced by the mother, placenta, and fetus. They play a pivotal role in the pre-implantation process and in placental and embryonic development; they are also involved in the development of the brain and respiratory system. In the postnatal period, it appears that NTs are associated with some diseases, such as sudden infant death syndrome (SIDS), asthma, congenital central hypoventilation syndrome (CCHS), and bronchopulmonary dysplasia (BPD).
RESUMO
The human gut microbiome is losing biodiversity, due to the "microbiome modernization process" that occurs with urbanization. To keep track of it, here we applied shotgun metagenomics to the gut microbiome of the Baka, a group of forager-horticulturalists from Cameroon, who combine hunting and gathering with growing a few crops and working for neighboring Bantu-speaking farmers. We analyzed the gut microbiome of individuals with different access to and use of wild plant and processed foods, to explore the variation of their gut microbiome along the cline from hunter-gatherer to agricultural subsistence patterns. We found that 26 species-level genome bins from our cohort were pivotal for the degradation of the wild plant food substrates. These microbes include Old Friend species and are encoded for genes that are no longer present in industrialized gut microbiome. Our results highlight the potential relevance of these genes to human biology and health, in relation to lifestyle.
RESUMO
OBJECTIVES: Aim of this study was to identify risk factors for a progression to cystic fibrosis (CF) in individuals detected as CF Screening Positive, Inconclusive Diagnosis (CFSPID). METHODS: This is a systematic review through literature databases (2015-2023). Blood immunoreactive trypsinogen (b-IRT) values, CFTR genotype, sweat chloride (SC) values, isolation of Pseudomonas aeruginosa (Pa) from respiratory samples, Lung Clearance Index (LCI) values in CFSPIDs who converted to CF (CFSPID > CF) and age at CF transition were assessed. RESULTS: Percentage of CFSPID > CF varies from 5.3 % to 44 %. Presence of one CF-causing CFTR variant in trans with a variant with variable clinical consequences (VVCC), an initial SC ≥ 40 mmol/L, an increase of SC > 2.5 mmol/L/year and recurrent isolation of pseudomonas aeruginosa (Pa) from airway samples could allow identification of subjects at risk of progression to CF. CONCLUSIONS: CFSPIDs with CF causing variant/VVCC genotype and first SC in the higher borderline range may require more frequent and prolonged clinical follow-up.
RESUMO
To investigate the possibility of phosphorus (P) recovery from marine sediment and explore the role of the carbon: nitrogen ratio in affecting the internal P release under anaerobic conditions, we experimented with the external addition of carbon (acetic acid and glucose) and ammonia nitrogen (NH4-N) to expose P release mechanisms. The 24-day anaerobic incubations were conducted with four different carbon: nitrogen dosing groups including no NH4-N addition and COD/N ratios of 100, 50, and 10. The P release showed that extra NH4-N loading significantly suppressed the decomposition of P (p < 0.05) from the marine sediment, the maximum P release was 4.07 mg/L and 7.14 mg/L in acetic acid- and glucose-fed systems, respectively, without extra NH4-N addition. Additionally, the results exhibited that the imbalance of carbon: nitrogen not only failed to induce the production of organic P mineralization enzyme (alkaline phosphatase) in the sediment but also suppressed its activity under anaerobic conditions. The highest enzyme activity was observed in the group without additional NH4-N dosage, with rates of 1046.4 mg/(kgâh) in the acetic acid- and 967.8 mg/(kgâh) in the glucose-fed system, respectively. Microbial data analysis indicated that a decrease in the abundance of P release-regulating bacteria, including polyphosphate-accumulating organisms (Rhodobacteraceae) and sulfate-reducing bacteria (Desulfosarcinaceae), was observed in the high NH4-N addition groups. The observed reduction in enzyme activity and suppression of microbial activity mentioned above could potentially account for the inhibited P decomposition in the presence of high NH4-N addition under anaerobic conditions. The produced P-enriched solution from the bioreactors may offer a promising source for future recovery endeavors.
Assuntos
Carbono , Nitrogênio , Anaerobiose , Fósforo , Reatores Biológicos , Sedimentos Geológicos , Acetatos , GlucoseRESUMO
Poultry farms are hotspots for the development and spread of antibiotic resistance genes (ARGs), due to high stocking densities and extensive use of antibiotics, posing a threat of spread and contagion to workers and the external environment. Here, we applied shotgun metagenome sequencing to characterize the gut microbiome and resistome of poultry, workers and their households - also including microbiomes from the internal and external farm environment - in three different farms in Italy during a complete rearing cycle. Our results highlighted a relevant overlap among the microbiomes of poultry, workers, and their families (gut and skin), with clinically relevant ARGs and associated mobile elements shared in both poultry and human samples. On a finer scale, the reconstruction of species-level genome bins (SGBs) allowed us to delineate the dynamics of microorganism and ARGs dispersion from farm systems. We found the associations with worker microbiomes representing the main route of ARGs dispersion from poultry to human populations. Collectively, our findings clearly demonstrate the urgent need to implement more effective procedures to counteract ARGs dispersion from poultry food systems and the relevance of metagenomics-based metacommunity approaches to monitor the ARGs dispersion process for the safety of the working environment on farms.
Assuntos
Microbiota , Aves Domésticas , Animais , Humanos , Fazendas , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos/genética , Genes BacterianosRESUMO
Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a "healthy" gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients' health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.
RESUMO
The gut microbiome has received a crescendo of attention in recent years due to myriad influences on human pathophysiology, including cancer. Anticancer therapy research is constantly looking for new hints to improve response to therapy while reducing the risk of relapse. In this scenario, Bifidobacterium, which inhabits the gut microbial ecosystem (especially that of children) and is considered a health-associated microbe, has emerged as a key target to assist anticancer treatments for a better prognosis. However, some researchers have recently hypothesized an unfavorable role of Bifidobacterium spp. in anticancer immunochemotherapy, leading to some confusion in the field. This narrative review summarizes the current knowledge on the role of Bifidobacterium spp. in relation to anticancer treatments, discussing the pros and cons of its presence in the gut microbiome of cancer patients. The current intervention strategies based on the administration of probiotic strains of Bifidobacterium are then discussed. Finally, the need to conduct further studies, especially functional ones, is underlined to provide robust experimental evidence, especially on the underlying molecular mechanisms, and thus resolve the controversies on this microbe for the long-term success of immunochemotherapy.
RESUMO
PURPOSE: Juvenile Idiopathic Arthritis (JIA) is a chronic inflammatory disease characterized by chronic synovitis, sometimes associated with fever, rash, pericarditis and uveitis. Limited data are available concerning autoimmune diseases associated with JIA in childhood. THE AIMS OF OUR STUDY WERE: (a) evaluating the thyroid function in a group of Italian children affected by JIA; (b) identifying which Autoimmune Thyroid Diseases (ATDs) are related to JIA in this population. METHODS: A population of 51 patients with JIA was investigated. Each patient enrolled was evaluated clinically (family history for Autoimmune Diseases (ADs), personal history and physical examination). In the sample were evaluated thyroid function, inflammation's index and anti-thyroid antibodies. RESULTS: The 68.6% (35) of our patients had the oligoarticular form, 27.5% (14) had the polyarticular one, 2% (1) had systemic onset and 2% (1) had undifferentiated arthritis. We focused our attention on the differences between the first two forms. We did not find any difference on the gender prevalence (p > 0.05). A higher presence of anti-TPO antibodies was found in the polyarticular form, with a significant difference with the oligoarticular one (p = 0.032). We researched the anti-hTG antibodies (p > 0.05) and ANA for each group (p > 0.05). We found a significant prevalence of family history for ADs in the polyarticular form (p < 0.05). CONCLUSION: Our findings show the necessity to focus on thyroid function in patients with JIA. Although the oligoarticular form is the most frequent, the polyarticular form shows a higher frequency of thyroid function's alteration. This suggests the need for specific attention in polyarticular form.
RESUMO
The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.
Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Homólogo , Doença Enxerto-Hospedeiro/microbiologia , ProbabilidadeRESUMO
Introduction: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospitalization in infants worldwide. The nasopharyngeal microbiota has been suggested to play a role in influencing the clinical course of RSV bronchiolitis, and some evidence has been provided regarding oral and gut microbiota. However, most studies have focused on a single timepoint, and none has investigated all three ecosystems at once. Methods: Here, we simultaneously reconstructed the gut, oral and nasopharyngeal microbiota dynamics of 19 infants with RSV bronchiolitis in relation to the duration of hospitalization (more or less than 5 days). Fecal samples, oral swabs, and nasopharyngeal aspirates were collected at three timepoints (emergency room admission, discharge and six-month follow-up) and profiled by 16S rRNA amplicon sequencing. Results: Interestingly, all ecosystems underwent rearrangements over time but with distinct configurations depending on the clinical course of bronchiolitis. In particular, infants hospitalized for longer showed early and persistent signatures of unhealthy microbiota in all ecosystems, i.e., an increased representation of pathobionts and a depletion of typical age-predicted commensals. Discussion: Monitoring infant microbiota during RSV bronchiolitis and promptly reversing any dysbiotic features could be important for prognosis and long-term health.
Assuntos
Microbiota , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Lactente , RNA Ribossômico 16S/genética , Vírus Sincicial Respiratório Humano/genética , Progressão da DoençaRESUMO
Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.
Assuntos
Microbioma Gastrointestinal , Melanoma , Neoplasias Cutâneas , Humanos , Microbioma Gastrointestinal/fisiologia , Melanoma/terapia , RNA Ribossômico 16S/genética , Neoplasias Cutâneas/terapia , Metaboloma , Fezes/microbiologia , Composição CorporalRESUMO
Background: Insufficient data are available on the long-term "real-life" safety profile of omalizumab in children. This study evaluated the long-term safety of omalizumab in a pediatric cohort with severe asthma or chronic spontaneous urticaria (CSU). Methods: A monocentric, prospective study evaluated the long-term safety of omalizumab in patients aged 6-18 years. Each patient completed the standardized MedDRA questionnaire to identify adverse events (AEs). Results: In total, 23 patients, median age 15 (14-18) years, affected by severe asthma (60.8%) or CSU (39.2%), treated with omalizumab for 2 (1-4) years were enrolled. The most common AEs belong to the system organ class (SOC) of general disorders and administration-site conditions (37.17%). Skin and subcutaneous tissue problems represent the second most frequently reported AEs (24.35%). Central nervous system and musculoskeletal disorders were quite frequent (15.38% and 8.97%, respectively). Other adverse events were tachycardia (5.12%), vertigo and abdominal pain (2.60% and 3.86%, respectively), and dry eye (1.3%). Only one patient reported herpes virus infection during treatment (1.3%). No cases of anaphylaxis, hemopathies, uronephropathies, respiratory, psychiatric, hepatobiliary, or oncological pathologies were reported. Conclusions: Long-term "real-life" treatment with omalizumab in children appears well tolerated. Its safety and efficacy profile makes omalizumab an excellent alternative in severe asthma and CSU in children.
RESUMO
PURPOSE OF REVIEW: The gut microbiota is involved in several aspects of host health and disease, but its role is far from fully understood. This review aims to unveil the role of our microbial community in relation to frailty and clinical outcomes. RECENT FINDINGS: Ageing, that is the continuous process of physiological changes that begin in early adulthood, is mainly driven by interactions between biotic and environmental factors, also involving the gut microbiota. Indeed, our gut microbial counterpart undergoes considerable compositional and functional changes across the lifespan, and ageing-related processes may be responsible for - and due to - its alterations during elderhood. In particular, a dysbiotic gut microbiota in the elderly population has been associated with the development and progression of several age-related disorders. SUMMARY: Here, we first provide an overview of the lifespan trajectory of the gut microbiota in both health and disease. Then, we specifically focus on the relationship between gut microbiota and frailty syndrome, that is one of the major age-related burdens. Finally, examples of microbiome-based precision interventions, mainly dietary, prebiotic and probiotic ones, are discussed as tools to ameliorate the symptoms of frailty and its overlapping conditions (e.g. sarcopenia), with the ultimate goal of actually contributing to healthy ageing and hopefully promoting longevity.
Assuntos
Fragilidade , Microbioma Gastrointestinal , Sarcopenia , Humanos , Idoso , Adulto , Microbioma Gastrointestinal/fisiologia , Idoso Fragilizado , Envelhecimento/fisiologiaRESUMO
The gut microbiome (GM) has shown to influence hematopoietic stem cell transplantation (HSCT) outcome. Evidence on levofloxacin (LVX) prophylaxis usefulness before HSCT in pediatric patients is controversial and its impact on GM is poorly characterized. Post-HSCT parenteral nutrition (PN) is oftentimes the first-line nutritional support in the neutropenic phase, despite the emerging benefits of enteral nutrition (EN). In this exploratory work, we used a global-to-local networking approach to obtain a high-resolution longitudinal characterization of the GM in 30 pediatric HSCT patients receiving PN combined with LVX prophylaxis or PN alone or EN alone. By evaluating the network topology, we found that PN, especially preceded by LVX prophylaxis, resulted in a detrimental effect over the GM, with low modularity, poor cohesion, a shift in keystone species and the emergence of modules comprising several pathobionts, such as Klebsiella spp., [Ruminococcus] gnavus, Flavonifractor plautii and Enterococcus faecium. Our pilot findings on LVX prophylaxis and PN-related disruption of GM networks should be considered in patient management, to possibly facilitate prompt recovery/maintenance of a healthy and well-wired GM. However, the impact of LVX prophylaxis and nutritional support on short- to long-term post-HSCT clinical outcomes has yet to be elucidated.
Assuntos
Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Levofloxacino/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Nutrição Parenteral/métodos , Nutrição Enteral/métodosRESUMO
Clostridioides difficile is an obligate anaerobic pathogen among the most common causes of healthcare-associated infections. It poses a global threat due to the clinical outcomes of infection and resistance to antibiotics recommended by international guidelines for its eradication. In particular, C. difficile infection can lead to fulminant colitis associated with shock, hypotension, megacolon, and, in severe cases, death. It is therefore of the utmost urgency to fully characterize this pathogen and better understand its spread, in order to reduce infection rates and improve therapy success. This review aims to provide a state-of-the-art overview of the genetic variation of C. difficile, with particular regard to pathogenic genes and the correlation with clinical issues of its infection. We also summarize the current typing techniques and, based on them, the global distribution of the most common ribotypes. Finally, we discuss genomic surveillance actions and new genetic engineering strategies as future perspectives to make it less difficile.
Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Clostridioides difficile/genética , Clostridioides/genética , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/genética , Evolução Molecular , RibotipagemRESUMO
BACKGROUND: Obesity and related co-morbidities represent a major health challenge nowadays, with a rapidly increasing incidence worldwide. The gut microbiome has recently emerged as a key modifier of human health that can affect the development and progression of obesity, largely due to its involvement in the regulation of food intake and metabolism. However, there are still few studies that have in-depth explored the functionality of the human gut microbiome in obesity and even fewer that have examined its relationship to eating behaviors. METHODS: In an attempt to advance our knowledge of the gut-microbiome-brain axis in the obese phenotype, we thoroughly characterized the gut microbiome signatures of obesity in a well-phenotyped Italian female cohort from the NeuroFAST and MyNewGut EU FP7 projects. Fecal samples were collected from 63 overweight/obese and 37 normal-weight women and analyzed via a multi-omics approach combining 16S rRNA amplicon sequencing, metagenomics, metatranscriptomics, and lipidomics. Associations with anthropometric, clinical, biochemical, and nutritional data were then sought, with particular attention to cognitive and behavioral domains of eating. RESULTS: We identified four compositional clusters of the gut microbiome in our cohort that, although not distinctly associated with weight status, correlated differently with eating habits and behaviors. These clusters also differed in functional features, i.e., transcriptional activity and fecal metabolites. In particular, obese women with uncontrolled eating behavior were mostly characterized by low-diversity microbial steady states, with few and poorly interconnected species (e.g., Ruminococcus torques and Bifidobacterium spp.), which exhibited low transcriptional activity, especially of genes involved in secondary bile acid biosynthesis and neuroendocrine signaling (i.e., production of neurotransmitters, indoles and ligands for cannabinoid receptors). Consistently, high amounts of primary bile acids as well as sterols were found in their feces. CONCLUSIONS: By finding peculiar gut microbiome profiles associated with eating patterns, we laid the foundation for elucidating gut-brain axis communication in the obese phenotype. Subject to confirmation of the hypotheses herein generated, our work could help guide the design of microbiome-based precision interventions, aimed at rewiring microbial networks to support a healthy diet-microbiome-gut-brain axis, thus counteracting obesity and related complications.