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Context Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO). Objective This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs). Methods Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components. Results At recruitment, when patients were hyperthyroid and TRAb positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HCs. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HCs. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and free thyroxine, respectively, and was also significantly associated with smoking in GO; smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAb more than 200 days after commencing antithyroid drug treatment. Conclusion The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAb is predictive of relapse; identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales.

The human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases., This work was supported by the European Research Council (ERC-STG project MetaPG-716575 and ERC-CoG microTOUCH-101045015) to N.S. and by EMBO ALTF 593–2020 to M.V.-C. The work was also partially supported by MIUR ‘Futuro in Ricerca’ (grant no. RBFR13EWWI_001) to N.S., by the European H2020 programme (ONCOBIOME-825410 project, MASTER-818368 project, and IHMCSA-964590) to N.S., by the National Cancer Institute of the National Institutes of Health (1U01CA230551) to N.S., by the Premio Internazionale Lombardia e Ricerca 2019 to N.S., by the Simons Foundation (award ID 648614) to E.D. and N.S., and by the European Research Council (ERC-STG project Mami-639226) to M.C.C

Psoriasis is a systemic immune-mediated disease primarily manifesting as skin redness and inflammation that affects 2–3% of the world population. No cure is currently available for this condition, and patients are offered pharmacological and non-pharmacological options to alleviate the discomfort and symptoms. Among non-pharmacological treatments for psoriasis, balneotherapy proved to be successful in reducing the skin areas affected by the disease. However, the specific mechanisms underlying the effect of thermal treatment on psoriatic skin have not been elucidated yet, and this effect could be in part mediated by the microbial population colonizing the skin, i.e. the skin microbiome. To gain some insights into this hypothesis, in this study we enrolled psoriasis patients and monitored changes in their skin and gut microbiome after a 12-bath balneotherapy course. The amplicon sequencing analysis of the skin microbiome showed that after thermal treatment the microbiome complexity and composition of skin areas affected by psoriasis improve to approach those typical of unaffected skin. We moreover identify some bacterial biomarkers indicative of disease status and treatment efficacy, and we show via metagenomic sequencing that thermal treatments and thermal water drinking affect the fecal microbiome composition to host more bacterial species associated with favorable metabolic health. Taken together, these findings highlight the relevance of studying the microbiome in balneotherapy-based treatments and call for more in-depth investigations of the effects of thermal treatments not only on the skin manifestations of psoriasis but also on its systemic complications.

Context: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves’ disease (GD; hyperthyroidism caused by autoantibodies, TRAB, to the thyrotropin receptor, TSHR) and its progression to Graves’ orbitopathy (GO). Objective: To compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HC). Design, Setting and Patients: Patients were recruited from four European countries (105 GD, 41 HC) for an observational study with cross-sectional and longitudinal components. Results: At recruitment, when patients were hyperthyroid and TRAB positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HC. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HC. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and FT4 respectively and was also significantly associated with smoking in GO, where smoking is a risk factor, but not in GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAB 200+ days after commencing anti-thyroid drug treatment. Conclusions: The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAB is predictive of relapse, identification of these patients at diagnosis, via their microbiome, would improve management with potential to eradicate Clostridiales.

This 9-month randomised, parallel, double-blind, single-centre, placebo-controlled study (PROBE, ISRCTN18030882) assessed the impact of probiotic supplementation on bodyweight. Seventy overweight Bulgarian participants aged 45–65 years with BMI 25–29.9 kg/m2 received a daily dose of the Lab4P probiotic comprising lactobacilli and bifidobacteria (50 billion cfu/day). Participants maintained their normal diet and lifestyle over the duration of the study. The primary outcome was change from baseline in body weight and secondary outcomes included changes in waist circumference, hip circumference and blood pressure. A significant between group decrease in body weight (3.16 kg, 95% CI 3.94, 2.38, p p p

The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies in silico, in vitro, and in vivo suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol via the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.

A large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut microbiome can influence the antitumor activity of neo-epitope-based cancer vaccines in a BALB/c-CT26 cancer mouse model. Similarly to that observed in the C57BL/6-B16 model, Bifidobacterium administration per se has a beneficial effect on CT26 tumor inhibition. Furthermore, the combination of Bifidobacterium administration and vaccination resulted in a protection which was superior to vaccination alone and to Bifidobacterium administration alone, and correlated with an increase in the frequency of vaccine-specific T cells. The gut microbiome analysis by 16S rRNA gene sequencing and shotgun metagenomics showed that tumor challenge rapidly altered the microbiome population, with Muribaculaceae being enriched and Lachnospiraceae being reduced. Over time, the population of Muribaculaceae progressively reduced while the Lachnospiraceae population increased—a trend that appeared to be retarded by the oral administration of Bifidobacterium. Interestingly, in some Bacteroidales, Prevotella and Muribaculacee species we identified sequences highly homologous to immunogenic neo-epitopes of CT26 cells, supporting the possible role of “molecular mimicry” in anticancer immunity. Our data strengthen the importance of the microbiome in cancer immunity and suggests a microbiome-based strategy to potentiate neo-epitope-based cancer vaccines.

In this study, we present the draft genome sequences of the Lab4 probiotic consortium using whole genome sequencing. Draft genome sequences were retrieved and deposited for each of the organisms; PRJNA559984 for B. bifidum CUL20, PRJNA482335 for Lactobacillus acidophilus CUL60, PRJNA482434 for Lactobacillus acid. Probiogenomic in silico analyses confirmed existing taxonomies and identified the presence putative gene sequences that were functionally related to the performance of each organism during in vitro assessments of bile and acid tolerability, adherence to enterocytes and susceptibility to antibiotics. Predictions of genomic stability identified no significant risk of horizontal gene transfer in any of the Lab4 strains and the absence of both antibiotic resistance and virulence genes. These observations were supported by the outcomes of acute phase and repeat dose tolerability studies in Wistar rats where challenge with high doses of Lab4 did not result in any mortalities, clinical/histopathological abnormalities nor indications of systemic toxicity. Detection of increased numbers of lactobacilli and bifidobacteria in the faeces of supplemented rats implied an ability to survive transit through the gastrointestinal tract and/or impact upon the intestinal microbiota composition. In summary, this study provides in silico, in vitro and in vivo support for probiotic functionality and the safety of the Lab4 consortium.

Gut microbiome manipulation to alter the gut-lung axis may potentially protect humans against respiratory infections, and clinical trials of probiotics show promise in this regard in healthy adults and children. However, comparable studies are lacking in overweight/obese people, who have increased risks in particular of viral upper respiratory tract infections (URTI). This Addendum further analyses our recent placebo-controlled trial of probiotics in overweight/obese people (focused initially on weight loss) to investigate the impact of probiotics upon the occurrence of URTI symptoms. As well as undergoing loss of weight and improvement in certain metabolic parameters, study participants taking probiotics experienced a 27% reduction in URTI symptoms versus control, with those ≥45 years or BMI ≥30 kg/m2 experiencing greater reductions. This symptom reduction is apparent within 2 weeks of probiotic use. Gut microbiome diversity remained stable throughout the study in probiotic-treated participants. Our data provide support for further trials to assess the potential role of probiotics in preventing viral URTI (and possibly also COVID-19), particularly in overweight/obese people.

Background: Studies from animal models of autoimmunity have highlighted the potential importance of microorganisms and their metabolic products in shaping the immune system. Summary: This review provides an introduction to the current state-of-the-art in microbiome research both from the perspective of “what is known” and of methodologies for its investigation. It then summarises the evidence for a role for the microbiome in the pathogenesis of Graves’ disease and Graves’ orbitopathy with reference to animal models and studies in human cohorts, from both published and ongoing sources. Key Message: Microbiome research is in its infancy but has already provided novel insights into disease pathogenesis across the spectrum from cancer to mental health and autoimmunity.

Background: The present study aimed to evaluate the effects of a new food-grade bioavailable delivery system of bergamot on human gut microbiota, in order to demonstrate the potential correlation of microbiota modulation in cardiovascular health.The identification of human gut microbiota modification was performed after ex-vivo incubation with bergamot phytosome (Vazguard™) of individual faecal slurries from healthy women (45–53 years) as follows: after incubation at 37°C in anaerobic condition, DNA was extracted and a 16S Metagenomic Sequencing Analysis performed. Results: Twenty-five different phyla were identified, among which 4 were modulated: Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria. The decreased Firmicutes/Bacteroidetes ratio and the increase of Proteobacteria were observed indicating a positive modulation of microbiota possibly linked to cardiovascular health. 418 different genera were also identified, among which several of them were mildly modulated.Conclusions: For the first time, a gut microbiome modulation was associated to the new delivery system of bergamot phytosome, supporting its clinical efficacy for cardiovascular health. New potential applications in weight control and gastrointestinal benefits were suggested.

We read with interest Rodriguez and colleagues’ study, using microbiota transfer from obese stool donors into inulin-treated hum-ob mice, to define a gut microbiome signature predicting response to prebiotic.1 However, the impact of other microbiome-based interventions (and particularly probiotics) on weight loss in humans is highly-variable between individuals.2 We were interested as to whether baseline gut microbiota, or aspects of host physiology, may predict weight loss during probiotic studies. In our recent double-blind study (ISRCTN12562026), overweight/obese adults were randomised to either 6 months of Lab4P probiotic (containing lactobacilli and bifidobacteria) or placebo.3 A higher proportion of participants receiving probiotic lost weight compared with those receiving placebo, and the extent of weight loss in the probiotic arm was greater than the placebo group.3 We subsequently performed metataxonome and metabonome analysis on stool samples from study participants (using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry bile acid profiling, respectively, applying established protocols4 5). We observed no difference in stool microbiota alpha-diversity at baseline between participants losing weight during the study versus those who did not (figure 1A); furthermore, no differences were observed in microbiota composition between groups at any taxonomic level. Conversely, on stool bile acid profiling, …

In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25–34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p 2, p p p p p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (−2.5%, p p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p

The &ldquo, vaccine hesitancy&rdquo, and the consequent lowering of vaccination coverage have, on one hand, pushed the Italian government to reintroduce some new compulsory vaccinations for access to schools and, on the other, have imposed a greater effort on health operators to understand the causes and, consequently, to intervene with tools for promotion and health education. In Ferrara, we administered 201 non-self-filling questionnaires to 201 pregnant women within a cross-sectional multicenter study, consisting of 63 items divided into 7 sections. In particular, we wanted to investigate the correlation between the socio-demographic characteristics of the interviewees and the sources used to obtain information and, on the other side, the intention to vaccinate in relation to the perception of the diffusion and of the risk of vaccine-preventable diseases. The institutional information sources are less used by foreigners, primiparous, and women with a low education level. The perception of the severity of vaccine-preventable diseases was greater in those inquiring from institutional sources. In a public health perspective, knowing the profile of future mothers in terms of socio-demographic characteristics and of the quality of the used information channels may help to guide the choices of communication in the vaccination field.

Herpes zoster (HZ) is an acute vesicular dermatitis with a typical dermatomal distribution, caused by the varicella zoster virus (VZV), often preceded and accompanied by prodromal pain or pruritus. HZ may be related to several complications such as postherpetic neuralgia (PHN). The incidence and severity of the disease increase with aging, due to immunosenescence and in particular to the decline of the specific cell-mediated immunity (CMI). The impact of HZ in terms of morbidity and short- and long-term complications, the availability of suboptimal treatment options to date, and the high costs for the diagnostic and clinical-therapeutic management of patients have motivated the search for a new preventive approach through the development of a vaccine. The vaccine currently in use with live-attenuated virus (ZVL) has been shown to be effective in reducing the incidence of HZ, its impact, and the onset of PHN, although the efficacy is lower in older subjects and tends to decrease some years after immunization. A new adjuvanted recombinant subunit vaccine (HZ/su), containing the VZV glycoprotein E (gE) and the AS01B adjuvant system, is now a very promising alternative to ZVL; in several clinical studies, it showed a good safety profile and was able to elicit high immune humoral and cell-mediated responses, both maintained up to 9 years. Furthermore, HZ/su vaccine was effective both in preventing HZ and in reducing the onset of PHN and other complications. HZ/su has been recommended and preferred over ZVL by the Advisory Committee on Immunization Practices (ACIP) for the prevention of HZ and its complications in immunocompetent adults aged ≥50 years, even if already vaccinated with ZVL, through a two-dose schedule. HZ/su has been approved in Canada, USA, Europe, and Japan and is currently being approved in Australia. The aim of this review was to describe the epidemiological data, HZ and PHN risks and their impact on the social life and common life of infected people, and ZVL and HZ/su vaccine development including various clinical trials and efficacy, safety, and tolerability profiles.

Experimental models of hyperthyroid Graves’ disease (GD) and Graves’ orbitopathy (GO) are efficiently developed by genetic immunisation by electroporation with human thyrotropin hormone receptor (hTSHR) A-subunit plasmid in female BALB/c (H-2d) mice. We investigated susceptibility in C57BL/6 J (H-2b) animals to allow studies on disease mechanisms in transgenic and immune response gene knock-out mice. Higher numbers of female C57BL/6 J were positive for pathogenic thyroid stimulating antibodies, but induced hyperthyroidism remained at a low frequency compared to BALB/c animals. Assessment of hTSHR specific T cells showed reduced proliferation in C57BL/6 J animals accompanied with anti-inflammatory IL-10, with less pro-inflammatory IFN-γ compared to BALB/c. Whilst the orbital tissue from immune BALB/c mice showed inflammation and adipogenesis, in contrast C57BL/6 J animals showed normal pathology. We characterised the gut microbiota using 16 S ribosomal RNA gene sequencing to explore its possible pathogenic role in the model. Despite being housed under identical conditions, we observed significantly different organisation of the microbiota (beta-diversity) in the two strains. Taxonomic differences were also noted, with C57BL/6 J showing an enrichment of Operational Taxonomic Units (OTUs) belonging to the Paludibacter and Allobaculum, followed by Limibacter, Anaerophaga and Ureaplasma genera. A higher number of genera significantly correlating with clinical features was observed in C57BL/6 J compared to BALB/c; for example, Limibacter OTUs correlated negatively with thyroid-stimulating antibodies in C57BL/6 J mice. Thus, our data suggest gut microbiota may play a pivotal immunomodulatory role that differentiates the thyroid function and orbital pathology outcome in these two inbred strains undergoing experimental GO.

Population aging is a worldwide phenomenon with significant and manifold impacts on society. Advanced age correlates with the onset of frailty. In this vulnerable state, the immune response is weakened and a higher susceptibility to infectious diseases is observed. The present narrative review aims to cover the topic of herpes zoster (HZ) and its complications in frail populations. The lifetime risk of developing HZ is estimated at about 20-30%, and the risk increases with age. In older people, HZ can lead to the inability to recover the lifestyle, the interests, and the level of activity that existed before its development. Severity of the disease at presentation and depression are the major correlates of pain burden in patients with acute HZ and postherpetic neuralgia (PHN). The frail elderly need careful assessment prior to treatment initiation and could be affected to a greater extent by treatment-related adverse events. In light of the significant burden caused by HZ and its complications in the frail elderly, the adoption of a preventive strategy appears to be promising, particularly using vaccination in appropriate age- and risk-groups. Although very few vaccine studies consider explicitly the frail elderly as their study population, there is evidence that the live, attenuated vaccine induces significant immunological responses. An adjuvanted recombinant subunit vaccine has recently been approved in Canada, in the United States, in the European Union, and in Japan, and will likely provide additional opportunities for prevention.

Background Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves’ disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves’ orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. Results We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice. Conclusions The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease. Electronic supplementary material The online version of this article (10.1186/s40168-018-0478-4) contains supplementary material, which is available to authorized users.

As known, an imbalance of the gut microbiota is associated with a higher risk for autoimmune diseases. Moreover the increased rates of autoimmunity reported in urban residential areas worldwide suggest a possible influence of diet. We report on the antibody response to food antigens in GD patients. Since 10% of celiac patients develop an autoimmune thyreopathy we focused on gliadin (DGP), transglutaminases (tTG) and 40 other food antigens (FA). Commercially available ELISA assays were performed according to the manufacturer’s instructions. 105 and 108 sera from 5 European endocrine centres have been tested for IgG and IgA to tTG and DGP. Results have been compared to epidemiological data. 71 sera have also been tested for IgG to FA and compared to 25 healthy controls. 6 out of 105 sera (5.7%) showed positive tTG; 16 and 7 out of 108 (15 and 6.5%) positive DGP-IgA and IgG, respectively; a higher prevalence compared to the worldwide prevalence of celiac disease (1%) (chi-squared test; p-value < 0.001).\ud Prevalence of smokers and ocular involvement was not higher in patients with positive sera compared to negative. 23 out of 71 (32.3%) GD sera showed sensitivity against a food antigens, compared to 25% (6 out of 24) positive results among healthy controls (chi-squared test; P-value=0.4). Interestingly, some antigens (cow’s milk, egg white, wheat, yeast) are more frequently positive than others. The distribution of antibodies against TSH receptor (TRAb) values was not different in positive or negative sera. In conclusion, the prevalence of positive tTG antibodies is higher in GD patients than worldwide. Even though autoantibodies to DGP and tTG were equally distributed between all 5 centres we observed the highest percentage of positive responses to other food antigens in Cardiff, suggesting that diet may contribute to the increased sensitivity. More studies are needed to confirm these data.

Motivations. Cell line misidentification is a critical issue in molecular experiments that use normal and/or tumor cell lines as tools for disease characterization and pharmaceutical treatments. Thus, confirmation of cell line genetic identities is crucial to validate the obtained results. DNA fingerprinting of Short Tandem Repeats (STR) has become a standard technique used to identify the unique genetic profile of a cell line, based on the comparison of its microsatellite loci pattern with a known profile. The efficiency of this approach depends on the number of loci analysed, as well as on the existence of a large reference dataset. We applied a large scale STR characterization of 16 loci to a panel of about 300 commercially available tumor cell lines, generating an unprecedented dataset with uniform characterization. In order to maximize its exploitation by the scientific community, we developed an interactive software tool which allows to easily perform the automated comparison of the STR profile obtained for a cell line of interest against Nerviano Medical Sciences cell line database, facilitating the identification of the cell line and the potential discovery of unreported similarities. Methods. We designed and developed an easy-to-use software tool which allows to quickly retrieve STR profiles based on the degree of similarity to the input profile of the cell line of interest. The tool is built on a dataset which includes about 300 commercially available human tumor cell lines, profiled in house. The panel is representative of diverse tumor tissue types. Users can insert data relative to a cell line of interest specifying either the cell line name or its STR profile. Then a query is run against the dataset in order to compute a similarity score versus each cell line and to generate the final summary table. The similarity is computed using a score that we implemented in order to account for multiallelic values at individual loci, which may be easily found in aberrant tumor cell line genomes. The similarity threshold by which two cell lines are considered identical is set at 80%. This cut-off value has been defined through a sensitivity analysis of available profiles. The tool has been developed using the Java programming language, which makes it easily portable on different platforms. The Graphical User Interface is composed of four main sections: i) the "Cell line" identification section by which the user may enter a specific identifier name or choose a cell line from the underlying dataset; ii) the "Loci" input pane, where the user can enter allelic values for each locus, or automatically retrieve loci values for an available cell line; iii) the "Command" pane containing the search task launcher button; iv) the "Result table" section, which reports all cell line matches found with a similarity score of at least 80%. Results. The tool has been implemented and used to perform a complete characterization of the STR profiles of a 300 tumor cell line panel. Query automation allowed to calibrate optimal settings for the parameters involved in cell identification. In particular, the optimal threshold cut-off value has been identified through a sensitivity analysis using the available profiles. Moreover, the similarity value that we computed overcomes critical aspects of other adopted scores, which usually either do not take into account or provide inconsistent values for multiallelic loci. The availability of a portable tool will allow bench scientists to have an immediate authentication of the cell line of interest, which is nowadays a mandatory requirement for paper submission to most scientific journals.

The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host–Prevotella symbiotic relationship in the context of maintaining human health. Prevotella is a genus of bacteria that commonly associate with humans, in various body sites. In this Review, Segata, Ercolini and colleagues discuss Prevotella diversity and the evidence for the involvement of these bacteria in human health and disease.