Exploring the resident gut microbiota of stranded odontocetes: high similarities between two dolphin species Tursiops truncatus and Stenella coeruleoalba

AbstractThe evaluation of symbiotic microbial communities occurring in the intestinal tract of animals has received great interest in recent years. However, little is known about gut microbial communities in cetaceans, despite their relevance in the ecology of marine communities. Here, we report an investigation using 16S rRNA gene amplicon sequencing of the resident gut microbiota of the two cetacean species Stenella coeruleoalba and Tursiops truncatus by sampling intestinal mucosa from specimens retrieved stranded along the Tyrrhenian coast of Tuscany (Italy). We found an abundance of members from Clostridiaceae and Fusobacteriaceae, which in total accounted for more than 50% of reads, in agreement with gut microbiota composition of other carnivorous mammals. Probably due to the limited number of samples available, sex, preservation status and also species, did not correlate with overall differences in the microbiota. Indeed, a high similarity of the taxonomic (family-level) composition between the gut microbiota of the two species was found. However, Pedobacter spp. was found abundant in amplicon sequencing libraries from S. coeruleoalba, while clostridia were more abundant from T. truncatus samples. Our results shed some light on the gut microbiota composition of two dolphin (S. coeruleoalba and T. truncatus) species, with specimens collected in the wild. Studies with a larger number of individuals are now needed to confirm these first results and evaluate the interspecific differences in relation to sex and age

Composition of supralittoral sediments bacterial communities in a Mediterranean island

Marine coasts represent highly dynamic ecosystems, with sandy beaches being one of the most heterogeneous. Despite the key importance of sandy beaches as transition ecosystems between sea and land, very few studies on the microbiological composition of beach sediments have been performed. To provide a first description of microbial composition of supralittoral sediments, we investigated the composition of bacterial communities of three sandy beaches, at Favignana Island, Italy, using metagenetic approaches (Terminal-Restriction Fragment Length Polymorphism, sequencing of 16S rRNA genes by Illumina-Solexa technology, functional genes detection, and quantitative Real-Time PCR). Results showed that the investigated beaches are harboring a rich bacterial diversity, mainly composed by members of classes Alphaproteobacteria, Gammaproteobacteria, Flavobacteria and Actinobacteria. The metagenetic analysis showed profiles of decreasing beta diversity and increasing richness, as well as a differentiation of communities, along the sea-to-land axis. In particular, members of Firmicutes and Proteobacteria displayed contrasting profiles of relative abundance (to decrease and to increase, respectively) along the sea-to-land axis of the beach. Finally, a search for the presence of genes related to the nitrogen and carbon biogeochemical cycle (nifH, nosZ, pmoA/amoA) detected the presence of ammonia monoxygenase sequences (amoA) only, suggesting the presence of bacterial ammonia oxidation to some extent, probably due to members of Nitrospira, but with the lack of nitrogen fixation and denitrification

IgM-Rheumatoid factor confers primary resistance to anti-PD-1 immunotherapies in NSCLC patients by reducing CD137 + T-cells

Background: ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137+T-cells are largely known to be the anti-tumor activated effector cells, but they have never been associated with the response to immunotherapies. Methods: Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant'Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated. Findings: IgM-RF in NSCLC patient sera strongly predicted the development of early progression to ICIs. Also, a significant reduction of progression-free survival rate in anti-PD-1 treated patients could be identified when patients were stratified based on IgM-RF positivity and titers. IgM-RF bound preferentially circulating naïve and central memory T-cells and a significant reduction of CD137+ anti-tumor T effector cells was found in IgM-RF positive patients. In addition, a higher percentage of CD137+T-cells in peripheral blood of NSCLC patients at baseline resulted as a strong independent prognostic factor for a better outcome in terms of PFS and OS after the anti-PD-1 treatment. Furthermore, T-cells exposed to IgM-RF showed a robust defect in their migratory ability in response to CCL19 chemokine. Interpretation: In this study we showed that serum IgM-RF can be regarded as predictive factor for the development of early progression and prognostic factor of a reduced progression-free survival and overall-survival in anti-PD-1 treated NSCLC patients. The ability of IgM-RF to bind naïve and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137+ T-cells population that may cause a non-effectiveness of these T-cells targeting drugs

Soluble Immune checkpoints, gut metabolites and performance status as parameters of response to Nivolumab treatment in NSCLC patients

Patients with non-small cell lung cancer (NSCLC) have been shown to benefit from the introduction of anti-PD1 treatment. However, not all patients experience tumor regression and durable response. The identification of a string of markers that are direct or indirect indicators of the immune system fitness is needed to choose optimal therapeutic schedules in the management of NSCLC patients. We analyzed 34 immuno-related molecules (14 soluble immune checkpoints, 17 cytokines/chemokines, 3 adhesion molecules) released in the serum of 22 NSCLC patients under Nivolumab treatment and the gut metabolomic profile at baseline. These parameters were correlated with performance status (PS) and/or response to treatment. Nivolumab affected the release of soluble immune checkpoints (sICs). Patients with a better clinical outcome and with an optimal PS (PS = 0) showed a decreased level of PD1 and maintained low levels of several sICs at first clinical evaluation. Low levels of PDL1, PDL2, Tim3, CD137 and BTLA4 were also correlated with a long response to treatment. Moreover, responding patients showed a high proportion of eubiosis-associated gut metabolites. In this exploratory study, we propose a combination of immunological and clinical parameters (sICs, PS and gut metabolites) for the identification of patients more suitable for Nivolumab treatment. This string of parameters validated in a network analysis on a larger cohort of patients could help oncologists to improve their decision-making in an NSCLC setting

The R521K polymorphism of EGFR influences the risk of colorectal cancer

In colorectal cancer (CRC) epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and HER4) have been found frequently over-expressed. New therapies directed against EGFR have been developed in many human cancers. Unexpectedly, EGFR alterations could be good prognostic indicators, like in lung cancer, where an EGFR variant in non-smoker female patients is associated with higher survival after surgery and increases the efficiency of therapy based on EGFR inhibitors. The role of the genetic polymorphisms of the EGFR family members in colorectal cancer development has not been completely explored. In our preliminary study, three missense polymorphisms mapping in EGFR family members have been investigated in the peripheral blood of a small Italian sample size of 70 patients and 72 controls to verify if they could be considered CRC susceptibility factors. For the first time, the evidence of genotype association was found for the R521K EGFR polymorphism: the protective effect for this variant allele has been found to reduce the risk for colon cancer onset

Rapporto 2007 su consumo e dipendenze da sostanze in Emilia-Romagna.

Report on the state of legal and illegal substances use in the territory of Emilia-Romagna Region.Il report analizza il fenomeno delle dipendenze nel territorio della Regione Emilia-Romagna. La descrizione del fenomeno si sviluppa intorno all\u27analisi degli indicatori individuati dall\u27Osservatorio Europeo delle Dipendenze di Lisbona (OEDT): 1-uso di sostanze nella popolazione generale (questo indicatore va a rilevare i comportamenti nei confronti di alcol e sostanze psicoattive da parte della popolazione generale); 2-prevalenza d\u27uso problematico delle sostanze psicoattive; 3-domanda di trattamento degli utilizzatori di sostanze; 4-mortalit? degli utilizzatori di sostanze; 5-malattie infettive. Altri due importanti indicatori che si stanno sviluppando, e che vengono qui illustrati, sono l\u27analisi delle Schede di Dimissione Ospedaliera (SDO) e gli indicatori relativi alle conseguenza sociali dell\u27uso di droghe (criminalit? droga correlata). Inoltre sono state applicate diverse metodologie standard di stima sia per quantificare la quota parte sconosciuta di utilizzatori di sostanze che non afferiscono ai servizi, sia per identificarne alcune caratteristiche