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Abstract Stuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation.

Endometriosis is a common gynecological disease that affects approximately 10–15% of reproductive-aged women worldwide. This debilitating disease has a negative impact on the quality of life of those affected. Despite this condition being very common, the pathogenesis is not well understood. Metabolomics is the study of the array of low-weight metabolites in a given sample. This emerging field of omics-based science has proved to be effective at furthering the understanding of endometriosis. In this systematic review, we seek to provide an overview of the application of metabolomics in endometriosis. We highlight the use of metabolomics in locating biomarkers for identification, understanding treatment mechanisms and symptoms, and relating external factors to endometriosis. The literature search took place in the Web of Science, Pubmed, and Google Scholar based on the keywords “metabolomics” AND “endometriosis” or “metabolome” AND “endometriosis”. We found 58 articles from 2012 to 2024 that met our search criteria. Significant alterations of lipids, amino acids, as well as other compounds were present in human and animal models. Discrepancies among studies of significantly altered metabolites make it difficult to make general conclusions on the metabolic signature of endometriosis. However, several individual metabolites were elevated in multiple studies of women with endometriosis; these include 3-hydroxybutyrate, lactate, phosphatidic acids, succinate, pyruvate, tetradecenoylcarnitine, hypoxanthine, and xanthine. Accordingly, L-isoleucine and citrate were reduced in multiple studies of women with endometriosis. Including larger cohorts, standardizing testing methods, and studying the individual phenotypes of endometriosis may lead to more separable results.

Sorghum is a self-pollinating species belonging to the Poaceae family characterized by a resistance to drought higher than that of corn. Sorghum (Sorghum bicolor L. Moench) has been grown for centuries as a food crop in tropical areas where it has an increasing importance, particularly as a cereal option for people with celiac disease. Over the past fifty years, food-grade varieties and hybrid seeds with white pericarp have been developed, particularly in the United States, to maximize sorghum food quality. Nutrient composition, including moisture, protein, carbohydrates, dietary fiber, fat content, fatty acid composition, and mineral content, was determined for nine inbred varieties with a stabilized food-grade sorghum genotype selected in the USA and grown under typical Mediterranean conditions. Differences in these nutritional components were observed among the varieties considered. Notable differences were found for monounsaturated and polyunsaturated fats, while saturated fatty acids were similar in all varieties. Oleic, linoleic, and palmitic acids were the most abundant fatty acids in all nine lines. Differences were also noted in mineral content, particularly for K, Mg, Al, Mn, Fe, Cu, Zn, and Ba. Enzyme-linked immunosorbent assays (ELISAs) demonstrated the absence of gliadin-like peptides in all the sorghum varieties analyzed, confirming, thus, that these analyzed varieties are safe for consumption by celiac patients. Knowledge of the nutritional values of sorghum lines is relevant for breeding programs devoted to sorghum nutritional content and for beneficial properties to human health.

Abstract Duchenne muscular dystrophy (DMD) is a progressive severe muscle‐wasting disease caused by mutations in DMD, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria support the muscle immune response in mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. Furthermore, the absence of gut microbes through the generation of mdx germ‐free animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD.

In recent years, metabolomics has become a valuable new resource in environmental monitoring programs based on the use of bio-indicators such as Mytilus galloprovincialis. The reproductive system is extremely susceptible to the effects of environmental pollutants, and in a previous paper, we showed metabolomic alterations in mussel spermatozoa exposed to metal chlorides of copper, nickel, and cadmium, and the mixture with these metals. In order to obtain a better overview, in the present work, we evaluated the metabolic changes in the male gonad under the same experimental conditions used in the previous work, using a metabolomic approach based on GC-MS analysis. A total of 248 endogenous metabolites were identified in the male gonads of mussels. Statistical analyses of the data, including partial least squares discriminant analysis, enabled the identification of key metabolites through the use of variable importance in projection scores. Furthermore, a metabolite enrichment analysis revealed complex and significant interactions within different metabolic pathways and between different metabolites. Particularly significant were the results on pyruvate metabolism, glycolysis, and gluconeogenesis, and glyoxylate and dicarboxylate metabolism, which highlighted the complex and interconnected nature of these biochemical processes in mussel gonads. Overall, these results add new information to the understanding of how certain pollutants may affect specific physiological functions of mussel gonads.

Metabolomics is a method that provides an overview of the physiological and cellular state of a specific organism or tissue. This method is particularly useful for studying the influence the environment can have on organisms, especially those used as bio-indicators, e.g., Mytilus galloprovincialis. Nevertheless, a scarcity of data on the complete metabolic baseline of mussel tissues still exists, but more importantly, the effect of mussel exposure to certain heavy metals on spermatozoa is unknown, also considering that, in recent years, the reproductive system has proved to be very sensitive to the effects of environmental pollutants. In order to fill this knowledge gap, the similarities and differences in the metabolic profile of spermatozoa of mussels exposed to metallic chlorides of copper, nickel, and cadmium, and to the mixture to these metals, were studied using a metabolomics approach based on GC–MS analysis, and their physiological role was discussed. A total of 237 endogenous metabolites were identified in the spermatozoa of these mussel. The data underwent preprocessing steps and were analyzed using statistical methods such as PLS-DA. The results showed effective class separation and identified key metabolites through the VIP scores. Heatmaps and cluster analysis further evaluated the metabolites. The metabolite-set enrichment analysis revealed complex interactions within metabolic pathways and metabolites, especially involving glucose and central carbon metabolism and oxidative stress metabolism. Overall, the results of this study are useful to better understand how some pollutants can affect the specific physiological functions of the spermatozoa of this mussel, as well as for further GC–MS-based metabolomic health and safety studies of marine bivalves.

Abstract Background The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. Results Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. Conclusions Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract

Abstract Background Celiac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD. Results Toward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3 months and 6 months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects. Conclusions Overall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects. Video Abstract

Milk breastfeeding and prebiotic-supplemented formulas have varying effects on the infant gut microbiome. Here, in a randomized controlled clinical trial, the authors investigate the effects of a Lactobacillus paracasei-fermented formula on the immune defense mechanisms, microbiota and its metabolome in full term infants.

Fetal growth restriction is an obstetrical pathological condition that causes high neonatal mortality and morbidity. The mechanisms of its onset are not completely understood. Metabolites were extracted from 493 placentas from non-complicated pregnancies in Hamilton Country, TN (USA), and analyzed by gas chromatography–mass spectrometry (GC–MS). Newborns were classified according to raw fetal weight (low birth weight (LBW; 2500 g)), and according to the calculated birth weight centile as it relates to gestational age (small for gestational age (SGA), large for gestational age (LGA), and adequate for gestational age (AGA)). Mothers of LBW infants had a lower pre-pregnancy weight (66.2 ± 17.9 kg vs. 73.4 ± 21.3 kg, p < 0.0001), a lower body mass index (BMI) (25.27 ± 6.58 vs. 27.73 ± 7.83, p < 0.001), and a shorter gestation age (246.4 ± 24.0 days vs. 267.2 ± 19.4 days p < 0.001) compared with non-LBW. Marital status, tobacco use, and fetus sex affected birth weight centile classification according to gestational age. Multivariate statistical comparisons of the extracted metabolomes revealed that asparagine, aspartic acid, deoxyribose, erythritol, glycerophosphocholine, tyrosine, isoleucine, serine, and lactic acid were higher in both SGA and LBW placentas, while taurine, ethanolamine, β-hydroxybutyrate, and glycine were lower in both SGA and LBW. Several metabolic pathways are implicated in fetal growth restriction, including those related to the hypoxia response and amino-acid uptake and metabolism. Inflammatory pathways are also involved, suggesting that fetal growth restriction might share some mechanisms with preeclampsia.

COVID-19 is characterized by the immune system’s overreaction resulting in a ‘cytokine storm’, consisting in a massive release of cytokine into the bloodstream, leading to local and systemic inflammatory response. This clinical picture is further complicated in case of infection of patients with a peculiar immunological status, such as pregnancy. In this paper, we focused on Interferon-γ, which plays a pivotal immunomodulatory role in normal pregnancy and fetal development, as well as in defense against pathogens. In this study, we compared the levels of Interferon-γ and the Interferon autoantibodies of the peripheral and cord blood of pregnant women with confirmed mild COVID-19 and healthy pregnant women. The Interferon-γ was significantly lower both in the peripheral and cord blood of SARS-CoV-2-positive mothers, suggesting that infection can affect the fetal microenvironment even without severe maternal symptoms. In conclusion, further studies are needed to clarify whether lower levels of Interferon-γ due to SARS-CoV-2 infection affect the development or infection susceptibility of infants born to SARS-CoV-2-infected mothers.

Abstract Background Congenital malformations of the central nervous system (CNS) consist of a wide range of birth defects of multifactorial origin. Methods Concentrations of 44 metals were determined by Inductively Coupled Plasma Mass Spectrometry in serum of 111 mothers in the second trimester of pregnancy who carried a malformed fetus and compared them with serum concentrations of the same metals in 90 mothers with a normally developed fetus at the same week of pregnancy. Data are reported as means ± standard deviations. Results We found a direct relationship between congenital defects of the CNS and maternal serum concentration of aluminum: it was statistically higher in women carrying a fetus with this class of malformation, compared both to mothers carrying a fetus with another class of malformation (6.45 ± 15.15 μg/L Vs 1.44 ± 4.21 μg/L, p

Abstract Background Polycystic ovarian syndrome (PCOS) is a highly variable syndrome and one of the most common female endocrine disorders. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet. Results Fifteen PCOS-patients and 15 controls were enrolled. Patients were treated with myo-inositol (1.75 g/day), D-chiro-inositol (0.25 g/day) and glucomannan (4 g/day) for 3 months. Blood concentrations of glucose, insulin, triglycerides and cholesterol, and ovary volumes and antral follicles count, as well as metabolomic profiles, were evaluated for control subjects and for cases before and after treatment. PCOS-patients had higher BMI compared with Controls, BMI decreased significantly after 3 months of treatment although it remained significantly higher compared to controls. 3-methyl-1-hydroxybutyl-thiamine-diphosphate, valine, phenylalanine, ketoisocapric, linoleic, lactic, glyceric, citric and palmitic acid, glucose, glutamine, creatinine, arginine, choline and tocopherol emerged as the most relevant metabolites for distinguishing cases from controls. Conclusion Our pilot study has identified a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan. Trial registration ClinicalTial.gov, NCT03608813. Registered 1st August 2018 - Retrospectively registered, .

Endometrial cancer (EC) is the most common gynecological neoplasm in high-income countries. Five-year survival rates are related to stage at diagnosis, but currently, no validated screening tests are available in clinical practice. The metabolome offers an unprecedented overview of the molecules underlying EC. In this study, we aimed to validate a metabolomics signature as a screening test for EC on a large study population of symptomatic women. Serum samples collected from women scheduled for gynecological surgery (n = 691) were separated into training (n = 90), test (n = 38), and validation (n = 563) sets. The training set was used to train seven classification models. The best classification performance during the training phase was the PLS-DA model (96% accuracy). The subsequent screening test was based on an ensemble machine learning algorithm that summed all the voting results of the seven classification models, statistically weighted by each models’ classification accuracy and confidence. The efficiency and accuracy of these models were evaluated using serum samples taken from 871 women who underwent endometrial biopsies. The EC serum metabolomes were characterized by lower levels of serine, glutamic acid, phenylalanine, and glyceraldehyde 3-phosphate. Our results illustrate that the serum metabolome can be an inexpensive, non-invasive, and accurate EC screening test.

Grain sorghum (Sorghum bicolor) is a gluten-free cereal grown around the world and is a food staple in semi-arid and subtropical regions. Sorghum is a diverse crop with a range of pericarp colour including white, various shades of red, and black, all of which show health-promoting properties as they are rich sources of antioxidants such as polyphenols, carotenoids, as well as micro- and macro-nutrients. This work examined the grain composition of three sorghum varieties possessing a range of pericarp colours (white, red, and black) grown in the Mediterranean region. To determine the nutritional quality independent of the contributions of phenolics, mineral and fatty acid content and composition were measured. Minor differences in both protein and carbohydrate were observed among varieties, and a higher fibre content was found in both the red and black varieties. A higher amount of total saturated fats was found in the white variety, while the black variety had a lower amount of total unsaturated and polyunsaturated fats than either the white or red varieties. Oleic, linoleic, and palmitic were the primary fatty acids in all three analysed sorghum varieties. Significant differences in mineral content were found among the samples with a greater amount of Mg, K, Al, Mn, Fe, Ni, Zn, Pb and U in both red and black than the white sorghum variety. The results show that sorghum whole grain flour made from grain with varying pericarp colours contains unique nutritional properties.

Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

The aim of the study is to verify the feasibility of a radiomics based approach for the detection of LV remodeling in patients with arterial hypertension. Cardiac Computed Tomography (CCT) and clinical data of patients with and without history of arterial hypertension were collected. In one image per patient, on a 4-chamber view, left ventricle (LV) was segmented using a polygonal region of interest by two radiologists in consensus. A total of 377 radiomics features per region of interest were extracted. After dataset splitting (70:30 ratio), eleven classification models were tested for the discrimination of patients with and without arterial hypertension based on radiomics data. An Ensemble Machine Learning (EML) score was calculated from models with an accuracy >60%. Boruta algorithm was used to extract radiomic features discriminating between patients with and without history of hypertension. Pearson correlation coefficient was used to assess correlation between EML score and septum width in patients included in the test set. EML showed an accuracy, sensitivity and specificity of 0.7. Correlation between EML score and LV septum width was 0.53 (p-value < 0.0001). We considered LV septum width as a surrogate of myocardial remodeling in our population, and this is the reason why we can consider the EML score as a possible tool to evaluate myocardial remodeling. A CCT-based radiomic approach for the identification of LV remodeling is possible in patients with past medical history of arterial hypertension.

Colorectal cancer (CRC) is a high incidence disease, characterized by high morbidity and mortality rates. Early diagnosis remains challenging because fecal occult blood screening tests have performed sub-optimally, especially due to hemorrhoidal, inflammatory, and vascular diseases, while colonoscopy is invasive and requires a medical setting to be performed. The objective of the present study was to determine if serum metabolomic profiles could be used to develop a novel screening approach for colorectal cancer. Furthermore, the study evaluated the metabolic alterations associated with the disease. Untargeted serum metabolomic profiles were collected from 100 CRC subjects, 50 healthy controls, and 50 individuals with benign colorectal disease. Different machine learning models, as well as an ensemble model based on a voting scheme, were built to discern CRC patients from CTRLs. The ensemble model correctly classified all CRC and CTRL subjects (accuracy = 100%) using a random subset of the cohort as a test set. Relevant metabolites were examined in a metabolite-set enrichment analysis, revealing differences in patients and controls primarily associated with cell glucose metabolism. These results support a potential use of the metabolomic signature as a non-invasive screening tool for CRC. Moreover, metabolic pathway analysis can provide valuable information to enhance understanding of the pathophysiological mechanisms underlying cancer. Further studies with larger cohorts, including blind trials, could potentially validate the reported results.

Abstract Background Drinking tea constitutes a tradition which is deeply rooted in the culture of several countries. Moreover, in recent years, tea consumption is growing all over the world. Improper herbal tea storage (long periods, humid environments) represents a relevant health hazard for consumers because of the growth of bacteria and molds. Results This study analyzed 32 samples of commercially available black and green teas – purchased from southern Italy markets and online-shops – and the monitoring of microbiological quality of the tea bag content was performed. Evaluations were conducted with the aim of characterizing pathogens indicated by the European and American guidelines (total bacterial count, fungi and Escherichia coli) and on the research of Pseudomonas spp. and Clostridium perfringens. The presence of ochratoxin A in tea matrix-leaves and infusions was further assessed, using a validated and accredited HPLC-FLD method. Microbial loads, for over 80% samples, ranged from 1.0 × 102 to 2.8 × 105 CFU/g tea: most of identified microorganisms were classified as Bacillaceae. The utilization of rapid detection and identification methods (PCR and sequencing), allowed the characterization of strains of Pseudomonas psychrotolerans, Staphylococcus warneri, Pantoea gaviniae and the isolation of one strain of Clostridium perfringens, whose ability to produce toxins can result in harmful outcomes for consumers. Fungi were isolated from 70% samples: the most prevalent molds were Aspergillus niger strains, followed by Aspergillus tubingensis. Ochratoxin A was detected in 22 of 32 tea solid samples investigated: concentrations resulted over the indicated limits for food products for 50% samples. Conclusions Results obtained demonstrated the need to develop targeted regulations for the safety of herbal teas.

Bladder cancer has a high incidence and is marked by high morbidity and mortality. Early diagnosis is still challenging. The objective of this study was to create a metabolomics-based profile of bladder cancer in order to provide a novel approach for disease screening and stratification. Moreover, the study characterized the metabolic changes associated with the disease. Serum metabolomic profiles were obtained from 149 bladder cancer patients and 81 healthy controls. Different ensemble machine learning models were built in order to: (1) differentiate cancer patients from controls; (2) stratify cancer patients according to grading; (3) stratify patients according to cancer muscle invasiveness. Ensemble machine learning models were able to discriminate well between cancer patients and controls, between high grade (G3) and low grade (G1-2) cancers and between different degrees of muscle invasivity; ensemble model accuracies were ≥80%. Relevant metabolites, selected using the partial least square discriminant analysis (PLS-DA) algorithm, were included in a metabolite-set enrichment analysis, showing perturbations primarily associated with cell glucose metabolism. The metabolomic approach may be useful as a non-invasive screening tool for bladder cancer. Furthermore, metabolic pathway analysis can increase understanding of cancer pathophysiology. Studies conducted on larger cohorts, and including blind trials, are needed to validate results.

Plants emit volatile organic compounds (VOCs) that induce metabolomic, transcriptomic, and behavioral reactions in receiver organisms, including insect pollinators and herbivores. VOCs’ composition and concentration may influence plant-insect or plant-plant interactions and affect soil microbes that may interfere in plant-plant communication. Many Trichoderma fungi act as biocontrol agents of phytopathogens and plant growth promoters. Moreover, they can stimulate plant defense mechanisms against insect pests. This study evaluated VOCs’ emission by olive trees (Olea europaea L.) when selected Trichoderma fungi or metabolites were used as soil treatments. Trichoderma harzianum strains M10, T22, and TH1, T. asperellum strain KV906, T. virens strain GV41, and their secondary metabolites harzianic acid (HA), and 6-pentyl-α-pyrone (6PP) were applied to olive trees. Charcoal cartridges were employed to adsorb olive VOCs, and gas chromatography mass spectrometry (GC-MS) analysis allowed their identification and quantification. A total of 45 volatile compounds were detected, and among these, twenty-five represented environmental pollutants and nineteen compounds were related to olive plant emission. Trichoderma strains and metabolites differentially enhanced VOCs production, affecting three biosynthetic pathways: methylerythritol 1-phosphate (MEP), lipid-signaling, and shikimate pathways. Multivariate analysis models showed a characteristic fingerprint of each plant-fungus/metabolite relationship, reflecting a different emission of VOCs by the treated plants. Specifically, strain M10 and the metabolites 6PP and HA enhanced the monoterpene syntheses by controlling the MEP pathway. Strains GV41, KV906, and the metabolite HA stimulated the hydrocarbon aldehyde formation (nonanal) by regulating the lipid-signaling pathway. Finally, Trichoderma strains GV41, M10, T22, TH1, and the metabolites HA and 6PP improve aromatic syntheses at different steps of the shikimate pathway.

Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response.

Dendritic cells (DCs) are the most potent antigen-presenting cells able to trigger the adaptive immune response to specific antigens. When non-self-antigens are captured, DCs switch from an “immature” to a “mature” state to fulfill their function. Among the several surface proteins involved in DCs maturation, the role of aquaporins (AQPs) is still poorly understood. Here we investigated the expression profile of Aqps in murine bone marrow derived dendritic cells (BMDCs). Among the Aqps analyzed, Aqp9 was the most expressed by DCs. Its expression level was significantly upregulated 6 h following LPS exposure. Chemical inhibition of Aqp9 led to a decreased inflammatory cytokines secretion. BMDCs from AQP9-KO mice release lower amount of inflammatory cytokines and chemokines and increased release of IL-10. Despite the reduced release of inflammatory cytokines, Aqp9-KO mice were not protected from DSS induced colitis. All together, our data indicate that AQP9 blockade can be an efficient strategy to reduce DCs inflammatory response but it is not sufficient to protect from acute inflammatory insults such as DSS induced colitis.

[This corrects the article DOI: 10.1371/journal.pone.0178262.].

In this study, we used several molecular techniques to develop a fast and reliable protocol (DNA Verity Test, DVT) for the characterization and confirmation of the species or taxa present in herbal infusions. As a model plant for this protocol, Camellia sinensis, a traditional tea plant, was selected due to the following reasons: its historical popularity as a (healthy) beverage, its high selling value, the importation of barely recognizable raw product (i.e., crushed), and the scarcity of studies concerning adulterants or contamination. The DNA Verity Test includes both the sequencing of DNA barcoding markers and genotyping of labeled-PCR DNA barcoding fragments for each sample analyzed. This protocol (DVT) was successively applied to verify the authenticity of 32 commercial teas (simple or admixture), and the main results can be summarized as follows: (1) the DVT protocol is suitable to detect adulteration in tea matrices (contaminations or absence of certified ingredients), and the method can be exported for the study of other similar systems; (2) based on the BLAST analysis of the sequences of rbcL+matK±rps7-trnV(GAC) chloroplast markers, C. sinensis can be taxonomically characterized; (3) rps7-trnV(GAC) can be employed to discriminate C. sinensis from C. pubicosta; (4) ITS2 is not an ideal DNA barcode for tea samples, reflecting potential incomplete lineage sorting and hybridization/introgression phenomena in C. sinensis taxa; (5) the genotyping approach is an easy, inexpensive and rapid pre-screening method to detect anomalies in the tea templates using the trnH(GUG)-psbA barcoding marker; (6) two herbal companies provided no authentic products with a contaminant or without some of the listed ingredients; and (7) the leaf matrices present in some teabags could be constituted using an admixture of different C. sinensis haplotypes and/or allied species (C. pubicosta).

Seeds of the Andean seed crop quinoa (Chenopodium quinoa Willd.) usually contain saponins in the seed coat. Saponins give a bitter taste sensation and are a serious antinutritional factor, therefore selection of sweet genotypes with a very low saponin content in the seeds is a main breeding goal. The objective of this work was to identify, within germplasm lines of quinoa, previously selected for production and quality traits, superior genotypes low in saponins. For this purpose the total saponin content was determined in seeds of eight lines of quinoa and one variety (cv. Regalona Baer) as a control, previously evaluated over a 2-year period in a Southern Italy environment. Significant variation for the saponin content was observed among the evaluated genotypes. The total saponin content ranged from 0.10 to 1.80%, with the Q12 genotype showing the lowest value, suggesting the possibility of selecting genotypes sweet to be used in subsequent genetic improvement programs. Based on these results, in fact, it was possible to identify, among the accessions previously selected, particularly suitable for growing in Mediterranean area, some genotypes with high yields of seed (2.5 tha–1, on average), high protein (17%, on average) and fibres (13%, on average) and low content in saponins (0.57%, on average).