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Food is a complex matter, literally. From production to functionalization, from nutritional quality engineering to predicting effects on health, the interest in finding an efficient physicochemical characterization of food has boomed in recent years. The sheer complexity of characterizing food and its interaction with the human organism has however made the use of data driven approaches in modeling a necessity. High-throughput techniques, such as nuclear magnetic resonance (NMR) spectroscopy, are well suited for omics data production and, coupled with machine learning, are paving a promising way of modeling food-human interaction. The foodomics approach sets the framework for omic data integration in food studies, in which NMR experiments play a key role. NMR data can be used to assess nutritional qualities of food, helping the design of functional and sustainable sources of nutrients; detect biomarkers of intake and study how they impact the metabolism of different individuals; study the kinetics of compounds in foods or their by-products to detect pathological conditions; and improve the efficiency of in silico models of the metabolic network.
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Alimentos , Imageamento por Ressonância Magnética , Biomarcadores , Humanos , Aprendizado de Máquina , Espectroscopia de Ressonância MagnéticaRESUMO
Curing salts composed of mixtures of nitrates and nitrites are preservatives widely used in processed meats. Despite many desirable technological effects, their use in meat products has been linked to methemoglobinemia and the formation of nitrosamines. Therefore, an increasing "anti-nitrite feeling" has grown among meat consumers, who search for clean label products. In this view, the use of natural compounds as alternatives represents a challenge for the meat industry. Processing (including formulation and fermentation) induces chemical or physical changes of food matrix that can modify the bioaccessibility of nutrients and the formation of peptides, impacting on the real nutritional value of food. In this study we investigated the effect of nitrate/nitrite replacement with a combination of polyphenols, ascorbate, and nitrate-reducing microbial starter cultures on the bioaccessibility of fatty acids, the hydrolysis of proteins and the release of bioactive peptides after in vitro digestion. Moreover, digested salami formulations were investigated for their impacts on cell proliferation and genotoxicity in the human intestinal cellular model (HT-29 cell line). The results indicated that a replacement of synthetic nitrates/nitrites with natural additives can represent a promising strategy to develop innovative "clean label" salamis without negatively affecting their nutritional value.
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Produtos da Carne , Nitrosaminas , Humanos , Nitratos/metabolismo , Sais , Nitritos/metabolismo , Carne/análise , Nutrientes , Ácidos GraxosRESUMO
Reducing the salt content in food is an important nutritional strategy for decreasing the risk of diet-related diseases. This strategy is particularly effective when applied to highly appreciated food having good nutritional characteristics, if it does not impact either upon sensory or nutritional properties of the final product. This work aimed at evaluating if the reduction of salt content by decreasing the brine soaking time modifies fatty acid and protein bioaccessibility and bioactive peptide formation in a 30-month-ripened Parmigiano Reggiano cheese (PRC). Hence, conventional and hyposodic PRC underwent in vitro static gastrointestinal digestion, and fatty acid and protein bioaccessibility were assessed. The release of peptide sequences during digestion was followed by LC-HRMS, and bioactive peptides were identified using a bioinformatic approach. At the end of digestion, fatty acid and protein bioaccessibility were similar in conventional and hyposodic PRC, but most of the bioactive peptides, mainly the ACE-inhibitors, were present in higher concentrations in the low-salt cheese. Considering that the sensory profiles were already evaluated as remarkably similar in conventional and hyposodic PRC, our results confirmed that shortening brine soaking time represents a promising strategy to reduce salt content in PRC.
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Queijo/análise , Manipulação de Alimentos/métodos , Nutrientes/análise , Biossíntese Peptídica , Sais/metabolismo , Água/química , Humanos , Cloreto de Sódio , SolubilidadeRESUMO
OBJECTIVE: The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study. DESIGN: Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi.Array, while the metabolome was assessed by 1H nuclear magnetic resonance. RESULTS: Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy. CONCLUSIONS: Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease.
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Diverticulose Cólica/metabolismo , Diverticulose Cólica/microbiologia , Microbioma Gastrointestinal , Metaboloma , Adulto , Idoso , Estudos de Casos e Controles , Contagem de Células , Colo/metabolismo , Estudos Transversais , Fezes/microbiologia , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Mastócitos/metabolismo , Pessoa de Meia-Idade , Projetos PilotoRESUMO
The measurement of food intake biomarkers (FIBs) in biofluids represents an objective tool for dietary assessment. FIBs of milk and cheese still need more investigation due to the absence of candidate markers. Thus, an acute intervention study has been performed to sensitively and specifically identify candidate FIBs. Eleven healthy male and female volunteers participated in the randomized, controlled crossover study that tested a single intake of milk and cheese as test products, and soy-based drink as a control. Urine samples were collected at baseline and up to 24 h at distinct time intervals (0-1, 1-2, 2-4, 4-6, 6-12, and 12-24 h) and were analyzed using an untargeted multiplatform approach (GC-MS and 1H NMR). Lactose, galactose, and galactonate were identified exclusively after milk intake while for other metabolites (allantoin, hippurate, galactitol, and galactono-1,5-lactone) a significant increase has been observed. Urinary 3-phenyllactic acid was the only compound specifically reflecting cheese intake although alanine, proline, and pyroglutamic acid were found at significantly higher levels after cheese consumption. In addition, several novel candidate markers for soy drink were identified, such as pinitol and trigonelline. Together, these candidate FIBs of dairy intake could serve as a basis for future validation studies under free-living conditions.
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Queijo/análise , Ingestão de Alimentos/fisiologia , Metaboloma , Leite/metabolismo , Leite de Soja/metabolismo , Adulto , Alcaloides/urina , Alantoína/urina , Animais , Biomarcadores/urina , Estudos Cross-Over , Feminino , Galactose/urina , Cromatografia Gasosa-Espectrometria de Massas , Voluntários Saudáveis , Hipuratos/urina , Humanos , Inositol/análogos & derivados , Inositol/urina , Lactatos/urina , Lactose/urina , Espectroscopia de Ressonância Magnética , Masculino , Leite/química , Leite de Soja/administração & dosagemRESUMO
Bacterial vaginosis (BV) is a common vaginal disorder characterized by the decrease of lactobacilli and overgrowth of Gardnerella vaginalis and resident anaerobic vaginal bacteria. In the present work, the effects of rifaximin vaginal tablets on vaginal microbiota and metabolome of women affected by BV were investigated by combining quantitative PCR and a metabolomic approach based on (1)H nuclear magnetic resonance. To highlight the general trends of the bacterial communities and metabolomic profiles in response to the antibiotic/placebo therapy, a multivariate statistical strategy was set up based on the trajectories traced by vaginal samples in a principal component analysis space. Our data demonstrated the efficacy of rifaximin in restoring a health-like condition in terms of both bacterial communities and metabolomic features. In particular, rifaximin treatment was significantly associated with an increase in the lactobacillus/BV-related bacteria ratio, as well as with an increase in lactic acid concentration and a decrease of a pool of metabolites typically produced by BV-related bacteria (acetic acid, succinate, short-chain fatty acids, and biogenic amines). Among the tested dosages of rifaximin (100 and 25 mg for 5 days and 100 mg for 2 days), 25 mg for 5 days was found to be the most effective.
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Antibacterianos/uso terapêutico , Gardnerella vaginalis/crescimento & desenvolvimento , Metaboloma , Microbiota , Rifamicinas/uso terapêutico , Vaginose Bacteriana/tratamento farmacológico , Ácido Acético , Adulto , Feminino , Humanos , Ácido Láctico , Lactobacillus/crescimento & desenvolvimento , Masculino , Pessoa de Meia-Idade , Rifaximina , Ácido Succínico , Vagina/microbiologia , Vaginose Bacteriana/microbiologiaRESUMO
The present work describes a foodomics protocol coupling an in vitro static simulation of digestion to a combination of omics techniques, to grant an overview of the protein digestibility of a meat-based food, namely Bresaola. The proteolytic activity mediated by the digestive enzymes is evaluated through Bradford and SDS-PAGE assays, combined to NMR relaxometry and spectroscopy, to obtain information ranging from the microscopic to the molecular level, respectively. The simple proteomics tool adopted here points out that a clear increase of bioaccessible proteins occurs in the gastric phase, rapidly disappearing during the following duodenal digestion. However, SDS-PAGE and the Bradford assay cannot follow the fate of the digested proteins when the products are sized <5 kDa. Conversely, NMR spectroscopy is able to capture the overall molecular profile of small fragments and peptides, which are mainly formed during the duodenal phase, thus giving the kinetics of the whole digestion process. Time domain NMR relaxometry, finally, detects the swelling phenomenon occurring during the gastric phase, when the digestion fluid enters the meat matrix.
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Carne , Proteínas/metabolismo , Proteólise , Proteômica/métodos , Animais , Duodeno/metabolismo , Eletroforese em Gel de Poliacrilamida/métodos , Análise de Alimentos/métodos , Mucosa Gástrica/metabolismo , Humanos , Carne/análise , Ressonância Magnética Nuclear Biomolecular/métodos , Proteínas/análiseRESUMO
The antimicrobial effects of high hydrostatic pressure (HHP) treatments on chill-stored seafood are well-documented, while their impact on the metabolic profile of seafood, especially the metabolome of fish flesh, and remains underexplored. Addressing this gap, this study investigates the effects of HHP on the metabolome of chill-stored rose shrimp by conducting multivariate data analysis based on untargeted proton nuclear magnetic resonance observations. Vacuum-packed rose shrimp samples were subjected to HHP at 0, 400, 500, and 600 MPa for 10 min and then stored at 2-4°C. The microorganism analysis and metabolic analysis were carried out on days 1 and 14. HHP treatment effectively deactivated Lactobacillus spp., Escherichia coli, Pseudomonas spp., total Coliforms, and sulfite-reducing anaerobic bacteria. Consequently, HHP treatment significantly reduced the formation rate of decay-related metabolites, such as hypoxanthine, trimethylamine, and biogenic amines, which exhibited significant accumulation in untreated samples. Multivariate unsupervised analyses provided insights into the overall changes in the metabolite profile induced by HHP. Metabolic pathway analysis revealed several pathways underlying spoilage, including pyruvate metabolism, valine, leucine, and isoleucine biosynthesis, purine metabolism, methane metabolism, glycine, serine, and threonine metabolism, citrate cycle (TCA cycle), glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism, sulfur metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and glyoxylate and dicarboxylate metabolism. Importantly, these pathways underwent alterations due to the application of HHP, particularly at high-pressure levels. In summary, the results unveil the potential mechanisms of HHP effects on chill-stored rose shrimps.
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Fish freshness and quality can be measured through several indices that can be both chemical and physical. The storage temperature and the time that elapses following the catching of the fish are fundamental parameters that define and influence both the degree of freshness and nutritional quality. Moreover, they particularly effect the kind of fish we considered. In this research, it was observed how different temperatures of storage and shelf-life (+4 °C and 0 °C) may affect the metabolic profile of red mullet (Mullus barbatus) and bogue (Boops boops) fish samples over time, specifically observing the alteration of freshness and quality. In particular, a High-Resolution Nuclear Magnetic Resonance (HR-NMR)-based metabolomics approach was applied to study the metabolic profile changes that occur in fish spoilage. The HR-NMR spectroscopy data were useful for calculating a kinetic model that was able to predict the evolution of different compounds related to fish freshness, such as trimethylamine (TMA-N) and adenosine-5'-triphosphate (ATP) catabolites for the K-index. Furthermore, NMR in combination with chemometrics allowed us to estimate a further kinetic model able to represent the spoilage evolution by considering the entire metabolome. In this way, it was also possible to detect further biomarkers characterizing the freshness and quality status of both red mullets and bogues.
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Buckwheat is a pseudo-cereal widely grown and consumed throughout the world. Buckwheat is recognized as a good source of nutrients and, in combination with other health-promoting components, is receiving increasing attention as a potential functional food. Despite the high nutritional value of buckwheat, a variety of anti-nutritional features makes it difficult to exploit its full potential. In this framework, sprouting (or germination) may represent a process capable of improving the macromolecular profile, including reducing anti-nutritional factors and/or synthesizing or releasing bioactives. This study addressed changes in the biomolecular profile and composition of buckwheat that was sprouted for 48 and 72 h. Sprouting increased the content of peptides and free-phenolic compounds and the antioxidant activity, caused a marked decline in the concentration of several anti-nutritional components, and affected the metabolomic profile with an overall improvement in the nutritional characteristics. These results further confirm sprouting as a process suitable for improving the compositional traits of cereals and pseudo-cereals, and are further steps towards the exploitation of sprouted buckwheat as a high-quality ingredient in innovative products of industrial interest.
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Background: The results of omic methodologies are often reported as separate datasets. In this study we applied for the first time multi-omic features clustering and pathway enrichment to clarify the biological impact of vitamin B2 supplementation on broiler caeca microbiome. Methods: The caeca contents of broilers fed +50 and +100 mg/kg vitamin B2 were analyzed by shotgun metagenomic and metabolomic. Latent variables extracted from NMR spectra, as well as taxonomic and functional features profiled from metagenomes, were integrated to characterize the effect of vitamin B2 in modulating caeca microbiome. A pathway-based network was obtained by mapping the observed input genes and compounds, highlighting connected strands of metabolic ways through pathway-enrichment analysis. Results: At day 14, the taxonomic, functional and metabolomic features in the caeca of tested broilers showed some degree of separation between control and treated groups, becoming fully clear at 28 days and persisting up to 42 days. In the caeca of birds belonging to the control group Alistipes spp. was the signature species, while the signature species in the caeca of broilers fed +50 and +100 mg/kg vitamin B2 were Bacteroides fragilis and Lactobacillus crispatus, Lactobacillus reuteri, Ruminococcus torques, Subdoligranum spp., respectively. The pathway enrichment analysis highlighted that the specific biochemical pathways enhanced by the supplementations of vitamin B2 were N-Formyl-L-aspartate amidohydrolase, producing Aspartate and Formate; L-Alanine:2-oxoglutarate amino transferase, supporting the conversion of L-Alanine and 2-Oxoglutarate in Pyruvate and L-Glutamate; 1D-myo-inositol 1/4 phosphate phosphohydrolase, converting Inositol 1/4-phosphate and water in myo-Inositol and Orthophosphate. The results of this study demonstrated that the caeca of birds fed +50 and + 100 mg/kg were those characterized by taxonomic groups more beneficial to the host and with a higher concentration of myo-inositol, formic acid, amino acids and pyruvate involved in glycolysis and amino acid biosynthesis. Conclusion: In this study we demonstrated how to perform multi-omic features integration to describe the biochemical mechanisms enhanced by the supplementation of different concentrations of vitamin B2 in the poultry diet. The relationship between vitamin B2 supplementation and myo-inositol production was highlighted in our study for the first time.
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Sour meat is a highly appreciated traditional fermented product, mainly from the Guizhou, Yunnan, and Hunan provinces. The flavor profiles of sour meat from goose and pork were evaluated using gas chromatography-ion mobility spectrometry (GC-IMS) combined with an electronic nose (E-nose) and tongue (E-tongue). A total of 94 volatile compounds were characterized in fermented sour meat from both pork and goose using GC-IMS. A data-mining protocol based on univariate and multivariate analyses revealed that the source of the raw meat plays a crucial role in the formation of flavor compounds during the fermentation process. In detail, sour meat from pork contained higher levels of hexyl acetate, sotolon, heptyl acetate, butyl propanoate, hexanal, and 2-acetylpyrrole than sour goose meat. In parallel, sour meat from goose showed higher levels of 4-methyl-3-penten-2-one, n-butyl lactate, 2-butanol, (E)-2-nonenal, and decalin than sour pork. In terms of the odor and taste response values obtained by the E-nose and E-tongue, a robust principal component model (RPCA) could effectively differentiate sour meat from the two sources. The present work could provide references to investigate the flavor profiles of traditional sour meat products fermented from different raw meats and offer opportunities for a rapid identification method based on flavor profiles.
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Fish is a fundamental component of the human diet, and in the near future the proportion of aquatic foods originating from aquaculture production is expected to increase to over 56%. The sustainable growth of the aquaculture sector involves the use of new sustainable raw materials as substitutes for traditional fishmeal and fish oil ingredients, but it is crucial that the substitution maintains the nutritional value of the fish meat. In addition, the preservation of the nutritional value should be a mandatory requirement of new technologies that extend the shelf life of fish. In this context, we evaluated the impact of a newly formulated feed and three preservation treatments (brine, pulsed electric field (PEF), and PEF plus brine) on the fatty acid composition and protein and lipid digestibility of sea bass fillets. In non-digested fillets, although slightly reduced by the newly formulated feed (standard = 2.49 ± 0.14; newly formulated = 2.03 ± 0.10) the n-3/n-6 PUFA ratio indicated good nutritional value. The preservation treatments did not modify the fatty acid content and profile of non-digested fillets. Conversely, protein and lipid digestibility were not affected by the different diets but were significantly reduced by brine, with or without PEF, while PEF alone had no effect. Overall, our results indicated that the newly formulated feed containing 50% less fishmeal is a good compromise between the sustainability and nutritional value of cultivated seabass, and PEF is a promising preservation technology deserving of further study.
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A variety of metabolites contribute to the freshness and taste characteristics of seafood. This study investigated the effects of high hydrostatic pressure (HHP; 400, 500, and 600 MPa) for 10 min) on the metabolome of striped prawn during chilled storage, in relation to microorganisms' development. All treated samples showed lower viable counts throughout storage compared to the untreated counterparts. The limit of acceptability from a microbiological point of view was extended from 9 to as many as 35 days by 600 MPa treatment. Metabolites were quantified by 1H-NMR through a targeted-untargeted metabolomic approach. Molecules linked to nucleotides' degradation and amines' anabolism suggested an overall freshness improvement granted by HHP. Notably, putrescine and cadaverine were detected only in untreated prawn samples, suggesting the inactivation of degradative enzymes by HHP. The concentration of molecules that influence umami perception was significantly elevated by HHP, while in untreated samples, the concentration of molecules contributing to a sour taste gradually increased during storage. As metabolomics was applied in its untargeted form, it allowed us to follow the overall set of metabolites related to HHP processing and storage, thus providing novel insights into the freshness and taste quality of striped prawn as affected by high hydrostatic pressure.
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Although epidemiological studies indicate a strong correlation between high sugar intake and metabolic diseases, the biological mechanisms underlying this link are still controversial. To further examine the modification and crosstalk occurring in enterocyte metabolism during sugar absorption, in this study we evaluate the diffusion and intestinal metabolism of glucose, fructose and sucrose, which were supplemented in equimolar concentration to Caco-2 cells grown on polyester membrane inserts. At different time points after supplementation, changes in metabolite concentration were evaluated in the apical and basolateral chambers by nuclear magnetic resonance (NMR) and gas-chromatography (GC). Sucrose was only minimally hydrolyzed by Caco-2 cells. Upon supplementation, we observed a faster uptake of fructose than glucose, the pentose sugar being also faster catabolized. Monosaccharide absorption was concomitant to the synthesis/transport of other metabolites, which occurred differently in glucose and fructose supplemented cells. Our results confirm the prominent role of intestinal cells in fructose metabolism and clearance after absorption, representing a further step forward in the understanding of the role of dietary sugars. Future research, including targeted analysis on specific transporters/enzymes and the use of labeled substrates, will be helpful to confirm the present results and their interpretation.
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Frutose , Glucose , Células CACO-2 , Enterócitos/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Humanos , Transportador 1 de Glucose-Sódio/metabolismoRESUMO
The availability of omics data providing information from different layers of complex biological processes that link nutrition to human health would benefit from the development of integrated approaches combining holistically individual omics data, including those associated with the microbiota that impacts the metabolisation and bioavailability of food components. Microbiota must be considered as a set of populations of interconnected consortia, with compensatory capacities to adapt to different nutritional intake. To study the consortium nature of the microbiome, we must rely on specially designed data analysis tools. The purpose of this work is to propose the construction of a general correlation network-based explorative tool, suitable for nutritional clinical trials, by integrating omics data from faecal microbial taxa, stool metabolome (1H NMR spectra) and GC-MS for stool volatilome. The presented approach exploits a descriptive paradigm necessary for a true multiomics integration of data, which is a powerful tool to investigate the complex physiological effects of nutritional interventions.
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The content of essential amino acids is an important aspect for determining the nutritional value of food proteins, but their digestibility is also a key property, deeply affected by food processing. The production of Parmigiano Reggiano cheese is closely related to the nutritional quality of the final product; in particular the high digestibility of its proteins is claimed to be proportional to cheese aging. Two different kinds of Parmigiano Reggiano, young (aged 15 months) and old (aged 30 months), were separately digested using an in vitro system that simulates digestive processes in the mouth, stomach and small intestine. Samples were collected at different stages of digestion and the process of protein hydrolysis was explored and compared by low-field (LF) and high-resolution (HR) NMR, together with other biochemical methods. HR-NMR allowed to simultaneously observe the quantity of free amino acids, peptides and proteins, also giving for these latter qualitative information about their dimension. LF-NMR, instead, gave the possibility to observe digestion with no treatments whatsoever, thus representing a technique suitable for on-line measurements. The results pointed out that cheeses with different aging times, although starting from distinct initial compositions, conclude digestion in a similar way, in terms of free amino acids and small organic compounds, but evolve with different kinetics of hydrolysis and peptide formation, discriminating the young from the old cheese.
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Queijo/análise , Queijo/classificação , Manipulação de Alimentos , Espectroscopia de Ressonância Magnética , Digestão , Eletroforese em Gel de Poliacrilamida , HumanosRESUMO
The balsamic vinegar of Modena (BVM), a food specialty under the European Protected Geographical Indication system, is made from grape must blended with wine vinegar exclusively in the Italian province of Modena or Reggio Emilia. Vinegar is associated to an improved digestive function and glycemic response to carbohydrate-rich meals, appetite stimulation, and reduction of hyperlipidemia and obesity. Although many of these effects are attributed to the high concentration of bioactive molecules, the modulation of digestive enzymes activity could have a role. The aim of this study was to investigate the effect of BVM on the digestibility and component release of three foods that are often seasoned with this dressing but have different composition: Parmigiano Reggiano cheese, Bresaola (cured meat), and boiled potatoes. BVM modulated the protein digestion of protein-rich foods (cheese and cured meat) in a matrix-dependent manner, and the BVM effect was mainly related to the inhibition of pepsin in the gastric phase. In the starch-rich food (boiled potatoes), the most impressive effect of BVM was the lower release of anomeric and total carbohydrates, which was consistent with the observed reduction of pancreatic amylase activity. The present investigation shed a new light on the impact of BVM on the digestion process.
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Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on their metabolic landscape and map connections between metabolic and genomic profiles. Combined serum and urine metabolomics improved AML characterization compared with individual biofluid analysis. At intracellular level, AML displayed dysregulated amino acid, nucleotide, lipid, and bioenergetic metabolism. The integration of intracellular and biofluid metabolomics provided a map of alterations in the metabolism of polyamine, purine, keton bodies and polyunsaturated fatty acids and tricarboxylic acid cycle. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis. Interestingly, integrated genomic-metabolic profiles defined two subgroups of NPM1-mut AML. One was enriched for mutations in cohesin/DNA damage-related genes (NPM1/cohesin-mut AML) and showed increased serum choline + trimethylamine-N-oxide and leucine, higher mutation load, transcriptomic signatures of reduced inflammatory status and better ex-vivo response to EGFR and MET inhibition. The transcriptional differences of enzyme-encoding genes between NPM1/cohesin-mut and NPM1-mut allowed in silico modeling of intracellular metabolic perturbations. This approach predicted alterations in NAD and purine metabolism in NPM1/cohesin-mut AML that suggest potential vulnerabilities, worthy of being therapeutically explored.
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Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Dano ao DNA/genética , Leucemia Mieloide Aguda/genética , Mutação/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatina/genética , Feminino , Genômica/métodos , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Adulto Jovem , CoesinasRESUMO
Nowadays, the strong demand for adequate nutrition is accompanied by concern about environmental pollution and there is a considerable emphasis on the recovery and recycling of food by-products and wastes. In this study, we focused on the exploitation of olive pomace as functional ingredient in biscuits and bread. Standard and enriched bakery products were made using different flours and fermentation protocols. After characterization, they were in vitro digested and used for supplementation of intestinal cells (Caco-2), which underwent exogenous inflammation. The enrichment caused a significant increase in the phenolic content in all products, particularly in the sourdough fermented ones. Sourdough fermentation also increased tocol concentration. The increased concentration of bioactive molecules did not reflect the anti-inflammatory effect, which was modulated by the baking procedure. Conventionally fermented bread enriched with 4% pomace and sourdough fermented, not-enriched bread had the greatest anti-inflammatory effect, significantly reducing IL-8 secretion in Caco-2 cells. The cell metabolome was modified only after supplementation with sourdough fermented bread enriched with 4% pomace, probably due to the high concentration of tocopherol that acted synergistically with polyphenols. Our data highlight that changes in chemical composition cannot predict changes in functionality. It is conceivable that matrices (including enrichment) and processing differently modulated bioactive bioaccessibility, and consequently functionality.