An isolate of the diatom Staurosirella pinnata is a promising platform for drug discovery due to its ability to produce bioactive metabolites. As previously shown, S. pinnata extracts exhibit bioactivities, with hydrophilic fractions showing selective cytotoxicity against human melanoma cells and lipidic fractions promoting thermogenesis in murine white adipocytes. In this work, we focused on the interaction between S. pinnata metabolism and light irradiance exposure to evaluate bioactivity targeting medulloblastoma cells. Cultures under standard, control, irradiance (80 µmol photons m−2 s−1) were exposed in the stationary phase to increased light intensities (200 and 600 µmol photons m−2 s−1) for 126 h. Growth, photosynthetic performance and metabolic profile were monitored, while the bioactivity of small-molecule fractions was assessed at the end. Exposure to 200 µmol photons m−2 s−1 significantly enhanced growth (92.6% increase in absorbances compared to the control), whereas 600 µmol photons m−2 s−1 induced growth inhibition (41.3% decrease in absorbances with respect to the control culture) and impaired photosynthesis. Metabolomic analysis revealed a shift from carbohydrate to lipid metabolism. Bioactivity assays showed that extracts from the highest irradiance exhibited cytotoxic effects on medulloblastoma cells, similar to the 80 µmol photons m−2 s−1 cultures on DAOY (68% vs. 82% of cell death induction levels, respectively), while intermediate irradiance did not show a significant effect in any of the tested cell lines. The results showed that different light intensities impact S. pinnata metabolism, demonstrating effects exploitable for drug discovery and the importance of investigating the impact of cultivation parameters in modulating S. pinnata bioactivity potential.

Chronic obstructive pulmonary disease (COPD) is a complex, progressive inflammatory disorder characterized by airflow limitation and respiratory symptoms. Its heterogeneity is manifested at etiological, pathological and clinical levels, and leads to different phenotypes: chronic bronchitis, emphysema, asthma-COPD overlap, frequent exacerbator and eosinophilic phenotypes. COPD is also associated with systemic manifestations including cardiovascular diseases, muscle dysfunction, osteoporosis and mental-health issues, which require a comprehensive management approach. Key risk factors are tobacco smoke and air pollution, both of which induce oxidative stress and airway remodeling. Although there is still no definitive cure for COPD, an early diagnosis and a multidisciplinary treatment are essential to prevent or slow the disease progression and reduce the mortality rate. Molecular biomarkers, particularly those identified through metabolomics, show promise for early detection, phenotyping and precision therapies. Challenges in biomarker discovery include specimen variability and stability. Overall, metabolomics provides valuable insights into COPD's molecular pathways, supporting improved diagnosis, prognosis and tailored treatments. In this tutorial, we will explore metabolomics findings from different COPD matrices and their clinical implications for diagnosis, treatment and prognosis.

Odontella aurita is one of the few microalgal species and the only diatom currently approved as a food supplement in the European Union. This status underscores its relevance as a target for biotechnological innovation and positions it as an emerging model for biological research and metabolic studies. O. aurita is a chain-forming species (cell size approximately 60 μm) rich in carotenoids, lipids, and carbohydrates. To maximize microalgal growth and production and enhancing the synthesis of bioactive compounds, the optimization of large-scale industrial setup is essential. To address this need, the present study investigates the impact of physical disturbance on the growth performance of the O. aurita resource. Non-axenic O. aurita cultures were grown in agitation-based or agitation free cultivation in 6-L tanks under a 12 h : 12 h light : dark photoperiod with a sinusoidal light distribution peaking at 100 μmol m-2 s-1. Bacterial community composition, growth performance, photosynthetic efficiency, and biomass composition were analyzed together with a broad array of metabolites involved in key biochemical pathways, including carotenoids, vitamins, auxin, amino acids, and other polar compounds identified by NMR spectroscopy.Our findings show that agitation-based cultivation profoundly modifies the biological system at multiple levels. Resuspension of O. aurita cells caused by physical disturbance promoted a marked shift in the associated bacterial populations, potentially altering microalga–bacteria interactions, and coinciding with suppressed cell division. Cells that did not undergo division increased in size and exhibited distinct metabolic signatures, particularly in pathways related to sugars, amino acids, and vitamins.

The light environment is a key factor regulating the growth and biomass production of microalgae. Photon flux density and spectral composition i.e., the relative contribution of different wavelengths, are among the most important light parameters influencing microalgal efficiency. The red, green and blue bands are used by microalgae as both energy source for photosynthesis and as external cue that triggers biological signaling and physiological adjustments. This study mechanistically explores the effects of light modulation on key metabolites in the emerging model Odontella aurita, the only diatom species currently approved as a food supplement in the EU. Four spectral compositions with red (590–656 nm) ranging from 0% to 60% and blue (422–496 nm) from 60% to 20% were set up under two light conditions: limiting and saturating intensities. Growth and photosynthetic performances were assessed, together with a wide set of metabolites involved in various biochemical pathways including vitamins (A, B1, B2, B6, B8, B9, B12, K1, D2, D3, C and E), auxin, amino acids and other compounds identified by NMR. In addition, the biomass was characterized for its macromolecular composition, carotenoids, phytosterols, total flavonoid and total phenolic content, iron and zinc content, and total antioxidant capacity of the biomass using different assays were evaluated. Results revealed the complementary roles of blue and red lights: blue light enhanced growth and photosynthesis, as well as the use or regulation of photoenergy, whereas red light promoted the regulation of key metabolites e.g., B vitamins or auxin, involved in the modulation of metabolic pathways. These findings provide insight for optimizing diatom cultivation under controlled light environments e.g., with the aim to boost growth and metabolism.

Melanin, a pigment synthesized by melanocytes, serves as the primary defense against UV-induced skin damage due to its potent antioxidant properties. There is increasing interest in natural substances capable of modulating the melanogenic pathway, particularly in hypopigmentation disorders. This study investigated the effect of methanolic extracts from the diatom Odontella aurita-authorized as a food supplement in the EU-on melanogenesis in the B16-F0 murine melanoma cell line. The research evaluated melanin content, tyrosinase activity, and the expression of melanogenesis-related genes and proteins at defined time points. Metabolomic and biochemical analyses were performed to characterize the extract's composition. Treatment with O. aurita extract significantly increased melanin content in B16-F0 cells by 45% (p < 0.01) compared to control. Tyrosinase activity was elevated by 38% after 24 h (p < 0.01), with gene and protein expression analyses confirming upregulation of Tyrosinase (TYR) after 0.5 h, Tyrosinase Related Protein-1 (TRP1) after 1 h, and Tyrosinase Related Protein-2 (TRP2) after 8 h. The extract also enhanced the cellular antioxidant environment, as evidenced by increased levels of metabolic cofactors and pigment-precursor amino acids. O. aurita methanolic extract accelerates and sustains melanin synthesis and tyrosinase activity, distinguishing its effect from single-compound inducers. These findings support the therapeutic potential of O. aurita for pigmentary disorders and skin health. Further studies should investigate its efficacy and safety in vivo and explore its application in cosmeceutical and nutraceutical formulations.

The metabolite Glucose-1,6-bisphosphate (Glc-1,6-P2) plays a vital role in human metabolism, and is a crucial activator and stabilizer for phosphomannomutase-2 (PMM2) - mutations within this protein propagate the most common congenital disorder of glycosylation (PMM2-CDG). In vivo, Glc-1,6-P2 is hydrolysed by phosphomannomutase-1 (PMM1), predominantly in the brain, under the influence of inosine monophosphate (IMP). In the present study, we employed knock-out PMM1 in Arg141His/Phe119LeuPMM2 patient-derived fibroblasts and investigated the phenotypic improvement. Increased Glc-1,6-P2 was associated with glycosylation enhancement, confirmed by glycan profiling. Previously identified PMM2-CDG biomarkers, such as LAMP1, PTX3 and lysosomal enzymes showed empirical imrovement- these findings were corroborated by metabolomic and proteomic analysis. Moreover, our results support the potential of Glc-1,6-P2 modulation for PMM2-CDG, potentiating novel perspectives in drug discovery.

Familial Hypercholesterolemia (FH) is a common genetic disorder characterized by elevated LDL-cholesterol levels and an increased risk of premature cardiovascular disease. While pathogenic variants in LDLR, APOB, and PCSK9 are well-established causes, a substantial proportion of clinically suspected FH cases do not carry either pathogenic variants or rare variants of uncertain significance in these genes (FH/V-/USV-). This study aimed to characterize the metabolome/lipidome of genetically confirmed heterozygous FH (HeFH) patients compared to FH/V-/USV-, seeking to identify specific alterations associated with genetic status and phenotypic variability. Untargeted high-resolution mass spectrometry (UHPLC-Q-Exactive-MS)-based lipidomics and nuclear magnetic resonance-based metabolomics were performed on plasma samples of FH patients (n = 20 HeFH and n = 19 FH/V-/USV-) towards healthy controls (n = 22). PLS-DA analysis revealed group-level separation, suggesting differences in the circulating metabolome/lipidome. As expected, most of identified lipid classes were higher in both FH groups compared to normolipidemic controls. Notably, significant lipids (VIP > 1, p < 0.05) showed potential in distinguishing HeFH and FH/V-/USV- patients, particularly sphingomyelins. These data were confirmed by multivariable regression analysis controlling for age, sex, and lipid-lowering therapy as well as by ROC analysis. The evidence of a distinct lipidome signature in the HeFH subgroup may relate to the increased cardiovascular risk of HeFH patients compared to patients without pathogenic variants.

Quorum sensing (QS) is a cell-to-cell signaling system that takes place at a key concentration (quorum) of signal molecules and via a peculiar signaling pathway. Both bacteria and yeasts possess QS mechanisms, mediated by specific molecules (farnesol, tyrosol, 2-phenylethanol, tryptophol) in yeasts, and N-acylhomoserine lactones (AHLs) and modified oligopeptides in bacteria. Here, we report the first chemical evidence of bacterial QS activity in yeast Saccharomyces cerevisiae (OS3 and V5 strains) by UPLC-MS/MS identification of N-octanoyl- and N-decanoyl-L-homoserine lactones in cell-free culture media extracts. The AHLs' presence was unexpected, as they are produced exclusively by bacteria. Tyrosol, a yeast signal molecule, was identified and quantified by NMR analysis. Metataxonomic analysis suggested the existence inside S. cerevisiae cells of bacteria, including Firmicutes, Bacteroidota, and Proteobacteria. Our study paves the way for investigations into bacterial detection within S. cerevisiae cells and their role in biotechnological performance in the food fermentation fields.

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown. This study shows for the first time that Tbx1 haploinsufficiency causes brain metabolic imbalance. We studied two mouse models of 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, and transcriptomics. We found that Tbx1 +/- mice and Df1/+ mice, with a multigenic deletion that includes Tbx1, have elevated brain methylmalonic acid, which is highly brain-toxic. Focusing on Tbx1 mutants, we found that they also have a more general brain metabolomic imbalance that affects key metabolic pathways, such as glutamine-glutamate and fatty acid metabolism. We provide transcriptomic evidence of a genotype-vitamin B12 treatment interaction. In addition, vitamin B12 treatment rescued a behavioural anomaly in Tbx1 +/- mice. Further studies will be required to establish whether the specific metabolites affected by Tbx1 haploinsufficiency are potential biomarkers of brain disease status in 22q11.2DS patients.

Exhaled breath condensate (EBC) is used as a promising noninvasive diagnostic tool in the field of respiratory medicine. EBC is achieved by cooling exhaled air, which contains aerosolized particles and volatile compounds present in the breath. This method provides useful information on the biochemical and inflammatory state of the airways. In respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, EBC analysis can reveal elevated levels of biomarkers such as hydrogen peroxide, nitric oxide and various cytokines, which correlate with oxidative stress and inflammation. Furthermore, the presence of certain volatile organic compounds in EBC has been linked to specific respiratory conditions, potentially serving as disease-specific fingerprints. The noninvasive nature of EBC sampling makes it particularly useful for repeated measures and for use in vulnerable populations, including children and the elderly. Despite its potential, the standardization of collection methods, analytical techniques and interpretation of results currently limits its use in clinical practice. Nonetheless, EBC holds significant promise for improving the diagnosis, monitoring and therapy of respiratory diseases. In this tutorial we will present the latest advances in EBC research in airway diseases and future prospects for clinical applications of EBC analysis, including the application of the Omic sciences for its analysis.

Tattoos have been a ubiquitous phenomenon throughout history. Now, the demand for tattoo removal for aesthetic or practical reasons is growing rapidly. This study outlines the results of field investigations into the chemical and biological removal of tattoo inks (Hexadecachlorinate copper phthalocyanine—C32Cl16CuN8—CAS no° 1328-53-6). FTIR, Py-GC/MS, and NMR analyses yielded intriguing profiles pertaining to the primary chemical constituents, along with others of an ambiguous nature. A bioremoval protocol was developed on a pork rind surface to simulate human tattooing. Two previously studied microbial strains were included in this analysis: (i) a bacterial culture of Pseudomonas stutzeri 5190 DSMZ viable cells and (ii) a fungal culture of Alternaria infectoria strain NIS4, the latter already isolated and identified. A combination of physical, chemical, and microbiological analyses, along with microscopic observations, was conducted. In our experimental conditions, inocula from environmental samples (soil and compost) were capable of inducing changes in even trace organic matter (glycerin and additives in pigments) used as a binder in emulsifiers in tattoo inks. Furthermore, the two microbial strains demonstrated promising potential for removing green tattoo ink. Finally, wastewater effluents containing green ink were recovered via electrochemical treatment, and the environmental impact in terms of the CO2 equivalent of our experiments was assessed. The results are promising and warrant further investigation into the innovative biological and chemical removal of tattoo inks from human skin and wastewater, respectively.

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The short-chain fatty acids (SCFAs) acetate, propionate and butyrate, the major products of intestinal microbial fermentation of dietary fibres, are involved in fine-tuning brain functions via the gut-brain axis. However, the effects of SCFAs in the hypothalamic neuronal network regulating several autonomic-brain functions are still unknown. Using NMR spectroscopy, we detected a reduction in brain acetate concentrations in the hypothalamus of obese leptin knockout ob/ob mice compared to lean wild-type littermates. Therefore, we investigated the effect of acetate on orexin/hypocretin neurons (hereafter referred as OX or OX-A neurons), a subset of hypothalamic neurons regulating energy homeostasis, which we have characterized in previous studies to be over-activated by the lack of leptin and enhancement of endocannabinoid tone in the hypothalamus of ob/ob mice. We found that acetate reduces food-intake in concomitance with a reduction of orexin neuronal activity in ob/ob mice. This was demonstrated by evaluating food-intake behaviour and orexin-A/c-FOS immunoreactivity coupled with patch-clamp recordings in Hcrt-eGFP neurons, quantification of prepro-orexin mRNA, and immunolabeling of GPR-43, the main acetate receptor. Our data provide new insights into the mechanisms of the effects of chronic dietary supplementation with acetate, or complex carbohydrates, on energy intake and body weight, which may be partly mediated by inhibition of orexinergic neuron activity.

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown. This study shows for the first time thatTbx1haploinsufficiency causes brain metabolic imbalance. We studied two mouse models of 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, and transcriptomics. We found thatTbx1+/−mice andDf1/+mice, with a multigenic deletion that includesTbx1, have elevated brain methylmalonic acid, which is highly brain-toxic. Focusing onTbx1mutants, we found that they also have a more general brain metabolomic imbalance that affects key metabolic pathways, such as glutamine–glutamate and fatty acid metabolism. We provide transcriptomic evidence of a genotype–vitamin B12 treatment interaction. In addition, vitamin B12 treatment rescued a behavioural anomaly inTbx1+/−mice. Further studies will be required to establish whether the specific metabolites affected byTbx1haploinsufficiency are potential biomarkers of brain disease status in 22q11.2DS patients.

The brain-related phenotypes observed in 22q11.2 deletion syndrome (DS) patients are highly variable, and their origin is poorly understood. Changes in brain metabolism might contribute to these phenotypes, as many of the deleted genes are involved in metabolic processes, but this is unknown. This study shows for the first time that Tbx1 haploinsufficiency causes brain metabolic imbalance. We studied two mouse models of 22q11.2DS using mass spectrometry, nuclear magnetic resonance spectroscopy, and transcriptomics. We found that Tbx1(+/-) mice and Df1/(+) mice, with a multigenic deletion that includes Tbx1, have elevated brain methylmalonic acid, which is highly brain-toxic. Focusing on Tbx1 mutants, we found that they also have a more general brain metabolomic imbalance that affects key metabolic pathways, such as glutamine-glutamate and fatty acid metabolism. We provide transcriptomic evidence of a genotype-vitamin B12 treatment interaction. In addition, vitamin B12 treatment rescued a behavioural anomaly in Tbx1(+/-) mice. Further studies will be required to establish whether the specific metabolites affected by Tbx1 haploinsufficiency are potential biomarkers of brain disease status in 22q11.2DS patients.

Supplementary Figure S3. O2PLS regression coefficients representing correlation between polar (A-G) and lipophilic metabolites (H-I) with transcripts.