PubMed

Food Res Int. 2024 Aug;190:114601. doi: 10.1016/j.foodres.2024.114601. Epub 2024 Jun 4.ABSTRACTLipids from cow milk fat globule membranes (MFGMs) and extracellular vesicles (EVs) are considered beneficial for neurodevelopment, cognitive maintenance and human health in general. Nevertheless, it is largely unknown whether intake of infant formulas and medical nutrition products rich in these particles promote accretion of specific lipids and whether this affects metabolic homeostasis. To address this, we carried out a 16-week dietary intervention study where mice were supplemented with a MFGM/EV-rich concentrate, a control diet supplemented with a whey protein concentrate and devoid of milk lipids, or regular chow. Assessment of commonly used markers of metabolic health, including body weight, glucose intolerance and liver microanatomy, demonstrated no differences across the dietary regimes. In contrast, in-depth lipidomic analysis revealed accretion of milk-derived very long odd-chain sphingomyelins and ceramides in blood plasma and multiple tissues of mice fed the MFGM/EV diet. Furthermore, lipidomic flux analysis uncovered that mice fed the MFGM/EV diet have increased lipid metabolic turnover at the whole-body level. These findings help fill a long-lasting knowledge gap between the intake of MFGM/EV-containing foods and the health-promoting effects of their lipid constituents. In addition, the findings suggest that dietary sphingomyelins or ceramide-breakdown products with very long-chains can be used as structural components of cellular membranes, lipoprotein particles and signaling molecules that modulate metabolic homeostasis and health.PMID:38945615 | DOI:10.1016/j.foodres.2024.114601

Food Res Int. 2024 Aug;190:114592. doi: 10.1016/j.foodres.2024.114592. Epub 2024 Jun 2.ABSTRACTRadio frequency (RF) heating has been proved an alternative roasting method for peanuts, which could effectively degrade aflatoxins and possesses the advantages of greater heating efficiency and penetration depth. This study aimed to investigate the influences of RF roasting on the lipid profile of peanut oil under 150 °C target temperature with varied peanut moisture contents (8.29 % and 20 %) and holding times (0, 7.5, and 15 min), using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based lipidomics. In total, 2587 lipid species from 35 subclasses were identified. After roasting, the contents of sterol lipid (ST) and subclasses of glycerophospholipids (GPs) and glycoglycerolipids increased significantly, while fatty acid (FA), Oxidized (Ox-) FA, cholesterol (CE), and all subclasses of glycerolipids (GLs) decreased, and 1084 differential lipids were screened. The highest ST and lowest CE contents in peanut oil were achieved by medium roasting (7.5 min). The raise in moisture content of peanut simply affected a few GPs subclasses adversely. Compared with hot air (HA) roasting, RF decelerated lipid oxidation, showing higher levels of diacylglycerol, triacylglycerol and FA, with no additional negative impact and only 69 exclusive differential lipids. During RF roasting, hydrolysis and oxidation of fatty acyl chains into secondary oxides were the central behaviors of lipids transformation. This study could provide insights into the lipid changes and transformation mechanism of peanut oil by RF roasting processing.PMID:38945611 | DOI:10.1016/j.foodres.2024.114592

Food Res Int. 2024 Aug;190:114581. doi: 10.1016/j.foodres.2024.114581. Epub 2024 Jun 1.ABSTRACTMicroplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs have not been fully determined. To investigate the effect of PS-MPs on skeletal muscle, piglets were given diets supplementation with 0 mg/kg (CON group), 75 mg/kg (75 mg/kg PS-MPs group), and 150 mg/kg PS-MPs (150 mg/kg PS-MPs group), respectively. The results indicated that the average daily gain (ADG) of piglets in the 150 mg/kg PS-MPs group was significantly lower than that in the CON group. No significant differences were observed in the final body weight and ADG between the CON group and the 75 mg/kg PS-MPs group. Piglets in the 150 mg/kg PS-MPs group exhibited decreased meat redness index and type I muscle fiber density. Metabolomic analysis revealed that the contents of meat flavor compounds carnosine, beta-alanine, palmitic acid, and niacinamide in muscle were lower in the 150 mg/kg PS-MPs group than in the CON group. Additionally, piglets subjected to 150 mg/kg PS-MPs exhibited impaired muscle angiogenesis. Further analysis indicated that PS-MPs exposure up-regulated thrombospondin 1 (THBS1) expression by inhibiting THBS1 mRNA and protein degradation, thereby disrupting skeletal muscle angiogenesis. These findings indicate that PS-MPs exposure adversely affects meat quality and hinders skeletal muscle angiogenesis in pigs, providing deeper insights into the detrimental effects of PS-MPs on meat quality and skeletal muscle development.PMID:38945601 | DOI:10.1016/j.foodres.2024.114581

Food Res Int. 2024 Aug;190:114628. doi: 10.1016/j.foodres.2024.114628. Epub 2024 Jun 13.ABSTRACTAromatic compounds serve as the primary source of floral and fruity aromas in sauce-flavor (Maotai flavor) baijiu, constituting the skeleton components of its flavor profile. Nevertheless, the formation mechanism of these compounds and key aroma-producing enzymes in sauce-flavor Daqu (fermentation agent, SFD) remain elusive. Here, we combined metagenomics, metaproteomics, metabolomics, and key enzyme activity to verify the biosynthesis pathway of aromatic compounds and to identify key enzymes, genes, and characteristic microorganisms in SFD. The results showed that the later period of fermentation was critical for the generation of aromatic compounds in SFD. In-situ verification was conducted on the potential key enzymes and profiles in various metabolites, providing comprehensive evidence for the main synthetic pathways of aromatic compounds in SFD. Notably, our results showed that primary amine oxidase (PrAO) and aldehyde dehydrogenase (ALDH) emerged as two key enzymes promoting aromatic compound synthesis. Additionally, two potential key functional genes regulating aromatics generation were identified during SFD fermentation through correlation analysis between proteins and relevant metabolites, coupled with in vitro amplification test. Furthermore, original functional strains (Aspergillus flavus-C10 and Aspergillus niger-IN2) exhibiting high PrAO and ALDH production were successfully isolated from SFD, thus validating the results of metagenomics and metaproteomics analyses. This study comprehensively elucidates the pathway of aromatic compound formation in SFD at the genetic, proteomic, enzymatic, and metabolomic levels, providing new ideas for the investigation of key flavor substances in baijiu. Additionally, these findings offer valuable insights into the regulatory mechanisms of aromatic compounds generation.PMID:38945581 | DOI:10.1016/j.foodres.2024.114628

Food Res Int. 2024 Aug;190:114600. doi: 10.1016/j.foodres.2024.114600. Epub 2024 Jun 6.ABSTRACTBrowning commonly appeared in apple processing, which varied in different apple varieties. Present work investigated the metabolomics of four varieties apple of Yataka, Gala, Sansa, and Fuji, which possessed different browning characteristics and related enzymes. Sansa as browning insensitive apple variety, exhibited the least chroma change with the lowest PPO activity and the highest SOD activity among the four apple varieties. Browning inhibition pretreatment increased the activity of SOD and PAL and decreased PPO and POD activity. In addition, metabolomic variances among the four apple varieties (FC), their browning pulp (BR) and browning inhibition pulp (CM) were compared. And the key metabolites were in-depth analyzed to match the relevant KEGG pathways and speculated metabolic networks. There were 487, 644, and 494 significant differential metabolites detected in FC, BR and CM, which were consisted of lipids, benzenoids, phenylpropanoids, organheterocyclic compounds, organic acids, nucleosides, accounting for 23 %, 11 %, 15 %, 16 %, 11 % of the total metabolites. The differential metabolites were matched with 39, 49, and 36 KEGG pathways in FC, BR, and CM, respectively, in which other secondary metabolites biosynthesis metabolism was the most significant in FC, lipid metabolism was the most significant in BR and CM, and energy metabolism was markedly annotated in CM. Notably, Sansa displayed the highest number of differential metabolites in both its BR (484) and CM (342). The BR of Sansa was characterized by flavonoid biosynthesis, while the other three apple varieties were associated with α-linolenic acid metabolism. Furthermore, in browning sensitive apple varieties, the flavonoid and phenylpropanoid biosynthesis pathway was significantly activated by browning inhibition pretreatment. Phenolic compounds, lipids, sugars, organic acids, nucleotides, and adenosine were regulated differently in the four apple varieties, potentially serving as key regulatory sites. Overall, this work provides novel insight for browning prevention in different apple varieties.PMID:38945570 | DOI:10.1016/j.foodres.2024.114600

Food Res Int. 2024 Aug;190:114594. doi: 10.1016/j.foodres.2024.114594. Epub 2024 Jun 5.ABSTRACTPassion fruits are highly perishable during postharvest storage and transportation, prompting the exploration of natural preservatives. This study investigates the synergistic effects of Aloe vera (ALV) and tea polyphenols (TP) coatings on quality retention, ripening modulation, and associated regulatory mechanisms in stored "golden" passion fruit (Passiflora spp.) at 10 °C. The application of a composite coating comprising 40 % ALV and 0.1 g/L TP led to notable improvements in fruit preservation over a 28-day storage period. At the day of 28, quantitatively, the ALV + TP treatment reduced weight loss by 41.60 %, shrinkage index by 28.13 %, and decay index by 50 %, significantly outperforming the control and individual treatments; the treated fruits exhibited enhanced firmness, reduced ethylene production, and the respiration peak was delayed about 6 days. Metabolomic analysis revealed pronounced alterations in key metabolic pathways, notably phenylpropanoid and flavonoid biosynthesis. Specifically, significant increases in metabolites such as phenolic acids (Feruloylmalic acid and Acropyrone) and flavonoids (Okanin-4'-O-glucoside, Apigenin-8-C-Arabinoside, Quercetin-3-O- (2'-O-galloyl) galactoside, and Catechin callate) were observed. Concurrently, transcript levels of key biosynthetic genes including cinnamate 4-hydroxylase (PeC4H), 4-coumarate-coenzyme a ligase (PeC4L), hydroxycinnamoyl transferase (PeHCT) and flavonol synthase (PeFLS) were significantly up-regulated by ALV + TP coating, indicating a robust activation of these pathways. The findings underscore the effectiveness of the ALV + TP composite coating as an environmentally friendly strategy for enhancing postharvest quality by promoting the accumulation of beneficial phenolic acids and flavonoids in passion fruits.PMID:38945568 | DOI:10.1016/j.foodres.2024.114594

Food Res Int. 2024 Aug;190:113905. doi: 10.1016/j.foodres.2023.113905. Epub 2023 Dec 27.ABSTRACTBee bread is a product of honeybees, which collect and ferment pollen, that contains highly nutritious and easily digestible active substances. However, its nutritional composition varies significantly with fermentation strains and seasonal changes. To unveil the patterns of microbial community and nutritional component changes in bee bread across seasons, we employed high-throughput techniques to assess the diversity of bacteria and fungi in bee bread. The results indicated that the compositions of bacteria and fungi in bee bread undergo significant seasonal variation, with noticeable changes in the microbial diversity of bee bread from different bee species. Subsequently, metabolomic analysis revealed high activity of glycerophospholipid metabolism in bee bread. Furthermore, our analysis identifaied noteworthy differences in nutritional components, including pH values, sugar content, and free amino acid levels, in bee bread across different seasons.PMID:38945555 | DOI:10.1016/j.foodres.2023.113905

J Pediatr. 2024 Jun 28:114175. doi: 10.1016/j.jpeds.2024.114175. Online ahead of print.ABSTRACTOBJECTIVE: To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB).STUDY DESIGN: From a cohort of prospectively enrolled infants born preterm (N=92), plasma samples of very preterm (VPT; GA, 28+0 to 31+6 weeks, N =27) and moderate/late preterm (M/LPT; GA, 32+0 to 35+6 weeks, N =33) infants requiring phototherapy for NHB were collected prior to the initiation of phototherapy and 24 hours after starting phototherapy. An additional sample was collected 48 hours after starting phototherapy in a randomly selected subset (N=30; VPT N=15; M/LPT N=15). Metabolite profiles were determined using ultraperformance liquid chromatography tandem mass spectroscopy. Two-way ANCOVA was used to identify metabolites that differed between GA groups and timepoints after adjusting for total serum bilirubin (TSB) levels (FDR q-value<0.05). Top impacted pathways were identified using pathway over-representation analysis.RESULTS: Phototherapy was initiated at lower TSB (mean ± SD mg/dL) levels in VPT compared with M/LPT infants (7.3 ± 1.4 vs. 9.9 ± 1.9, p<0.01). We identified 664 metabolites that were significant for a phototherapy effect, 191 metabolites significant for GA, and 46 metabolites significant for GA x phototherapy interaction (FDR q-value<0.05). Longer duration phototherapy had a larger mean effect size (24 hours post-phototherapy: d=0.36; 48 hours post-phototherapy: d=0.43). Top pathways affected by phototherapy included membrane lipid metabolism, one-carbon metabolism, creatine biosynthesis, and oligodendrocyte differentiation.CONCLUSION: Phototherapy alters the plasma metabolite profile more than GA in preterm infants with NHB, affecting pathways related to lipid and one-carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation.PMID:38945444 | DOI:10.1016/j.jpeds.2024.114175

J Adv Res. 2024 Jun 28:S2090-1232(24)00263-7. doi: 10.1016/j.jare.2024.06.026. Online ahead of print.ABSTRACTINTRODUCTION: The postharvest physiological disorder known as 'black spot' in radish roots (Raphanus sativus) poses a significant challenge to quality maintenance during storage, particularly under summer conditions. The cause of this disorder, however, is poorly understood.OBJECTIVES: Characterize the underlying causes of 'black spot' disorder in radish roots and identify strategies to delay its onset.METHODS: Radish roots were placed in either polyvinyl chloride (PVC) or oriented polypropylene (OPP) packaging and stored for 4 days at 30 ℃. Appearance and physiological parameters were assessed and transcriptomic and metabolomic analyses were conducted to identify the key molecular and biochemical factors contributing to the disorder and strategies for delaying its onset and development.RESULTS: OPP packaging effectively delayed the onset of 'black spot' in radishes, potentially due to changes in phenolic and lipid metabolism. Regarding phenolic metabolism, POD and PPO activity decreased, RsCCR and RsPOD expression was downregulated, genes involved in phenols and flavonoids synthesis were upregulated and their content increased, preventing the oxidative browning of phenols and generally enhancing stress tolerance. Regarding lipid metabolism, the level of alpha-linolenic acid increased, and genes regulating cutin and wax synthesis were upregulated. Notably, high flavonoid and low ROS levels collectively inhibited RsPLA2G expression, which reduced the production of arachidonic acid, pro-inflammatory compounds (LTA4 and PGG2), and ROS, alleviating the inflammatory response and oxidative stress in radish epidermal tissues.CONCLUSION: PVC packaging enhanced the postharvest onset of 'black spot' in radishes, while OPP packaging delayed both its onset and development. Our study provides insights into the response of radishes to different packaging materials during storage, and the causes and host responses that either enhance or delay 'black spot' disorder onset. Further studies will be conducted to confirm the molecular and biochemical processes responsible for the onset and development of 'black spot' in radishes.PMID:38945295 | DOI:10.1016/j.jare.2024.06.026

Sci Total Environ. 2024 Jun 28:174333. doi: 10.1016/j.scitotenv.2024.174333. Online ahead of print.ABSTRACTThe rhizosphere microorganisms of blueberry plants have long coexisted with their hosts under distinctively acidic soil conditions, exerting a profound influence on host performance through mutualistic symbiotic interactions. Meanwhile, plants can regulate rhizosphere microorganisms by exerting host effects to meet the functional requirements of plant growth and development. However, it remains unknown how the developmental stages of blueberry plants affect the structure, function, and interactions of the rhizosphere microbial communities. Here, we examined bacterial communities and root metabolites at three developmental stages (flower and leaf bud development stage, fruit growth and development stage, and fruit maturation stage) of blueberry plants. The results revealed that the Shannon and Chao 1 indices as well as community composition varied significantly across all three developmental stages. The relative abundance of Actinobacteria significantly increased by 10 % (p < 0.05) from stage 1 to stage 2, whereas that of Proteobacteria decreased significantly. The co-occurrence network analysis revealed a relatively complex network with 1179 edges and 365 nodes in the stage 2. Niche breadth was highest at stage 2, while niche overlap tended to increase as the plant developed. Furthermore, the untargeted metabolome analysis revealed that the number of differential metabolites of vitamins, nucleic acids, steroids, and lipids increased between stage 1 to stage2 and stage 2 to stage 3, while those for differential metabolites of carbohydrates and peptides decreased. Significant changes in expression levels of levan, L-glutamic acid, indoleacrylic acid, oleoside 11-methyl ester, threo-syringoylglycerol, gingerglycolipid B, and bovinic acid were highly correlated with the bacterial community structure. Collectively, our study reveals that significant alterations in dominant bacterial taxa are strongly correlated with the dynamics of root metabolites. These findings lay the groundwork for developing prebiotic products to enhance the beneficial effects of root microorganisms and boosting blueberry productivity via a sustainable approach.PMID:38945231 | DOI:10.1016/j.scitotenv.2024.174333

Environ Pollut. 2024 Jun 28:124460. doi: 10.1016/j.envpol.2024.124460. Online ahead of print.ABSTRACTIt has been well-investigating that individual phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affect public health. However, there is still a gap that the mixture of PAEs and PAHs impacts birth outcomes. Through innovative methods for mixtures in epidemiology, we used a metabolome Exposome-Wide Association Study (mExWAS) to evaluate and explain the association between exposure to PAEs and PAHs mixtures and birth outcomes. Exposure to a higher level of PAEs and PAHs mixture was associated with lower birth weight (maximum cumulative effect: -143.5 g) rather than gestational age. Mono(2-ethlyhexyl) phthalate (MEHP) (posterior inclusion probability, PIP =0.51), 9-hydroxyphenanthrene (9-OHPHE) (PIP =0.53), and 1-hydroxypyrene (1-OHPYR) (PIP =0.28) were identified as the most important compounds in the mixture. In mExWAS, we successfully annotated four overlapping metabolites associated with both MEHP/9-OHPHE/1-OHPYR and birth weight, including arginine, stearamide, Arg-Gln, and valine. Moreover, several lipid-related metabolism pathways, including fatty acid biosynthesis and degradation, alpha-linolenic acid, and linoleic acid metabolism, were disturbed. In summary, these findings may provide new insights into the underlying mechanisms by which PAE and PAHs affect fetal growth.PMID:38945193 | DOI:10.1016/j.envpol.2024.124460

Poult Sci. 2024 Jun 13;103(9):103975. doi: 10.1016/j.psj.2024.103975. Online ahead of print.ABSTRACTSubmerged cultivation using low-value agro-industrial side streams allows large-scale and efficient production of fungal mycelia, which has a high nutritional value. As the dietary properties of fungal mycelia in poultry are largely unknown, the present study aimed to investigate the effect of feeding a Pleurotus sapidus (PSA) mycelium as a feed supplement on growth performance, composition of the cecal microbiota and several physiological traits including gut integrity, nutrient digestibility, liver lipids, liver transcriptome and plasma metabolome in broilers. 72 males, 1-day-old Cobb 500 broilers were randomly assigned to 3 different groups and fed 3 different adequate diets containing either 0% (PSA-0), 2.5% (PSA-2.5) and 5% (PSA-5.0) P. sapidus mycelium in a 3-phase feeding system for 35 d. Each group consisted of 6 cages (replicates) with 4 broilers/cage. Body weight gain, feed intake and feed:gain ratio and apparent ileal digestibility of crude protein, ether extract and amino acids were not different between groups. Metagenomic analysis of the cecal microbiota revealed no differences between groups, except that one α-diversity metric (Shannon index) and the abundance of 2 low-abundance bacterial taxa (Clostridia UCG 014, Eubacteriales) differed between groups (P < 0.05). Concentrations of total and individual short-chain fatty acids in the cecal digesta and concentrations of plasma lipopolysaccharide and mRNA levels of proinflammatory genes, tight-junction proteins, and mucins in the cecum mucosa did not differ between groups. None of the plasma metabolites analyzed using targeted-metabolomics differed across the groups. Hepatic transcript profiling revealed a total of 144 transcripts to be differentially expressed between group PSA-5.0 and group PSA-0 but none of these genes was regulated greater 2-fold. Considering either the lack of effects or the very weak effects of feeding the P. sapidus mycelium in the broilers it can be concluded that inclusion of a sustainably produced fungal mycelium in broiler diets at the expense of other feed components has no negative consequences on broilers´ performance and metabolism.PMID:38945001 | DOI:10.1016/j.psj.2024.103975

Poult Sci. 2024 Jun 6;103(9):103953. doi: 10.1016/j.psj.2024.103953. Online ahead of print.ABSTRACTIncreased consumption of folic acid is prevalent due to its beneficial effects, but growing evidence emphasizes the side effects pointing to excessive dietary folate intake. The effects of excessive paternal folic acid consumption on offspring and its transgenerational inheritance mechanism have not been elucidated. We hypothesize that excessive folic acid consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation and heritably influence offspring metabolic homeostasis. Here, we fed roosters either folic acid-control or folic acid-excess diet throughout life. Paternal chronic folic acid excessive supplementation increased hepatic lipogenesis and lipid accumulation but reduced lipolysis both in the roosters and their offspring, which was further confirmed to be induced by one-carbon metabolism inhibition and gene expression alteration associated with the Peroxisome proliferator-activated receptor pathway. Based on the spermatozoal genome-wide DNA methylome identified by Nanopore sequencing, multi-omics association analysis of spermatozoal and hepatic DNA methylome, transcriptome, and metabolome suggested that differential spermatozoal DNA 6mA and 5mC methylation could be involved in regulating lipid metabolism-related gene expression in offspring chickens. This model suggests that sperm DNA N6-methyladenine and 5-methylcytosine methylation were involved in epigenetic transmission and that paternal dietary excess folic acid leads to hepatic lipid accumulation in offspring.PMID:38945000 | DOI:10.1016/j.psj.2024.103953

Clin Investig Arterioscler. 2024 Jun 29:S0214-9168(24)00041-X. doi: 10.1016/j.arteri.2024.04.004. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Comprehensive assessment of pharmacotherapy effects on atherogenic parameters (AP) that influence the risk of cardiovascular disease (CVD) is challenging due to interactions among a large number of parameters that modulate CVD risk.METHODS: We developed an illustrative tool, athero-contour (AC), which incorporates weighted key lipid, lipo- and glycoprotein parameters, to readily illustrate their overall changes following pharmacotherapy. We demonstrate the applicability of AC to assess changes in AP in response to saroglitazar treatment in patients with metabolic associated fatty liver disease (MAFLD) in the EVIDENCES IV study.RESULTS: The baseline AC of saroglitazar and placebo groups was worse than the mean of the general population. After 16-week treatment, AC improved significantly in the saroglitazar group due to alterations in very low-density lipoprotein, triglyceride, and glycoproteins.CONCLUSION: Using AC, we could readily and globally evaluate and visualize changes in AP. AC improved in patients with MAFLD following saroglitazar therapy.PMID:38945785 | DOI:10.1016/j.arteri.2024.04.004

Inflamm Bowel Dis. 2024 Jun 29:izae143. doi: 10.1093/ibd/izae143. Online ahead of print.ABSTRACTBACKGROUND: It is crucial to pinpoint the metabolites that cause Crohn's disease (CD) and ulcerative colitis (UC) to comprehend their pathogenesis and identify possible targets for therapy. To achieve this goal, we performed the first metabolome-wide Mendelian randomization (MR) study of Japanese patients with CD and UC.METHODS: As exposure datasets, genetic instruments with blood-circulating metabolites were obtained from the Tohoku Medical Megabank Organization, which includes 204 metabolites from the genome-wide association study data of 7843 Japanese individuals. As outcome datasets, we enrolled Japanese patients with CD (n = 1803), Japanese patients with UC (n = 1992), and healthy controls (n = 2022). The main analysis utilized the inverse variance-weighted method, while stability of the findings was evaluated through sensitivity analyses.RESULTS: After single nucleotide polymorphism (SNP) filtering, 169 SNPs for 45 metabolites were available for MR. Genetically predicted elevated circulating trans-glutaconic acid and tryptophan were associated with a lower CD risk (odds ratio [OR], 0.68; P = 5.95 × 10-3; and OR, 0.64; P = 1.90 × 10-2, respectively). Genetically predicted elevated caffeic acid was associated with a lower UC risk (OR, 0.67; P = 4.2 × 10-4), which remained significant after multiple testing correction. We identified a causal link between UC and 3-hydroxybutyrate (OR, 2.21; P = 1.41 × 10-2), trans-glutaconic acid (OR, 0.72; P = 1.77 × 10-2), and 2-hydroxyvaleric acid (OR, 1.31; P = 4.23 × 10-2). There was no evidence of pleiotropy or reverse causal effects for these candidate metabolites.CONCLUSIONS: In our metabolome-wide MR study, we discovered a notable protective effect of caffeic acid against UC.PMID:38944808 | DOI:10.1093/ibd/izae143

Adv Gerontol. 2024;37(1-2):21-25.ABSTRACTMulti-omics methods for analysing postgenomic data have become firmly established in the tools of molecular gerontology only in recent years, since previously there were no comprehensive integrative approaches adequate to the task of calculating biological age. This paper provides an overview of existing papers on multi-omics integrative approaches in calculating the biological age of a human. An analysis of the most common options for integrating methylomic, transcriptomic, proteomic, microbiomic and metabolomic datasets was carried out. We defined (1) concatenation (machine learning), in which models are developed using a concatenated data matrix, formed by combining multiple omics data sets; (2) fusion model approaches that create multiple intermediate submodels for different omics data to then build a final integrated model from the various intermediate submodels; and (3) transformation methods (via artificial intelligence) that first transform each of the single omics data sets into core plots or matrices, and then combine them all into one graph before building an integral complex model. It is unlikely that multi-omics approaches will find application in anti-aging personalized medicine, but they will undoubtedly deepen and expand the understanding of the fundamental processes standing behind the phenomenon of the biological aging clocks.PMID:38944768

Am J Epidemiol. 2024 Jun 29:kwae167. doi: 10.1093/aje/kwae167. Online ahead of print.ABSTRACTWe aimed at examining the shared and unique associations of metabolites with multiple cardiometabolic diseases (CMD), i.e. type 2 diabetes (T2D), coronary heart disease (CHD) and stroke. In this study, a total of 168 plasma metabolites were measured by targeted high-throughput nuclear magnetic resonance spectroscopy among 98,162 participants free of T2D, CHD, and stroke at baseline. Cox proportional hazard models estimated hazard ratios for one SD increase in metabolite concentration levels, and false discovery rate (at 10%) was used to correct for multiple comparisons. Over 12.1 years of follow-up on average, 3,463 T2D, 6,186 CHD, and 1,892 stroke events were recorded. Most lipoprotein metabolites were associated with risks of T2D and CHD but not with the risk of stroke, with stronger associations for T2D than for CHD. Phospholipids within intermediate-density lipoprotein or large low-density lipoprotein particles showed positive associations with CHD and inverse associations with T2D. Metabolites indicating very small very low-density lipoprotein, histidine, creatinine, albumin, and glycoprotein acetyls were associated with risks of all three conditions. This large-scale metabolomics study revealed common and distinct metabolic biomarkers for T2D, CHD and stroke, providing instrumental information to possibly implement precision medicine for preventing and treating these conditions.PMID:38944759 | DOI:10.1093/aje/kwae167

NPJ Sci Food. 2024 Jun 28;8(1):42. doi: 10.1038/s41538-024-00285-8.ABSTRACTInflammation acts as a dual role in disease initiation and progression, while Cannabis sativa L. (hemp) seeds, known for their abundance of anti-inflammatory phytochemicals, present a promising food source. Additionally, fermentation may optimize the food matrix, thereby augmenting its developmental prospects. This study explores the anti-inflammatory potential of hemp seeds fermented with 10 different probiotic strains. Among these, Lactiplantibacillus plantarum fermented hemp seeds (FHS) demonstrated a significant anti-inflammatory ability, accompanied by a reduction in the expression of critical inflammatory markers such as TLR4, NF-κBp65, and iNOS. Moreover, there is a noteworthy dose-dependent inhibition of inflammatory cytokines TNF-α, IL-6, IL-1β, and NO within a concentration range of 50 to 500 µg/mL. Subsequently, metabolomics analysis using UHPLC-QTOF-MS highlighted significant metabolic alterations in FHS compared to raw hemp seeds (RHS). Through multivariate, univariate, and correlation analyses, indolelactic acid (IA) and homovanillic acid (HVA) emerged as the main anti-inflammatory metabolites in FHS. Validation via HPLC confirmed the concentration of IA and HVA in RHS and FHS and both organic acids demonstrated lower IC50 values for TNF-α, IL-1β, IL-6, IL-18, and NO inhibition, showcasing their potent anti-inflammatory abilities. Furthermore, in vitro gastro-intestinal digestion coupled with the Caco-2 cell monolayer model validates the uptake and bioaccessibility of FHS, further affirming IA and HVA as major anti-inflammatory compounds. Overall, this research sets the stage for the development of novel hemp seed-based products targeting inflammation-associated disorders.PMID:38944646 | DOI:10.1038/s41538-024-00285-8

Clin Chim Acta. 2024 Jun 27:119834. doi: 10.1016/j.cca.2024.119834. Online ahead of print.ABSTRACTBACKGROUND: This study aims to identify metabolomic signatures in uterine fluid of women with idiopathic recurrent spontaneous miscarriage (IRSM) during window of implantation (WOI). Also, glucose transporters GLUT3 and GLUT4 and proteins of PI3K-Akt signaling pathway in endometrial tissue are assessed.METHODS: Paired uterine fluid and endometrial biopsies were collected during WOI from women with IRSM (n = 24) and healthy women with azoospermic male partners as controls (n = 15). NMR metabolomics was used to identify the dysregulated metabolites in uterine fluid of IRSM women. Additionally, the proteins and glucose transporters were investigated in the endometrial tissue using immunohistochemistry (IHC) and western blotting.RESULTS: Uterine fluid metabolomics indicated eleven metabolites to be significantly downregulated in IRSM. While expression levels of PI3K (p85), PI3K (p110), p-Akt (Thr308), p-Akt (Ser473), GLUT3 and GLUT4 were significantly downregulated in endometrial tissue of these women, p-IKK α/β (Ser176/180) and p-NFkBp65 (Ser536) were significantly increased.CONCLUSION: Our findings suggest that dysregulation of PI3K/Akt pathway in the uterine microenvironment could be a likely cause of endometrial dysfunction, thereby affecting implantation. Further studies on the downstream effects of the Akt signaling pathway in-vitro for improved understanding of the Akt-mediated cellular responses in IRSM is, therefore, warranted.PMID:38944409 | DOI:10.1016/j.cca.2024.119834

Clin Chim Acta. 2024 Jun 27:119836. doi: 10.1016/j.cca.2024.119836. Online ahead of print.ABSTRACTBreast cancer (BC) remains the most prevalent cancer among women worldwide, despite significant advancements in its prevention and treatment. The escalating incidence of BC globally necessitates continued research into novel diagnostic and therapeutic strategies. Metabolomics, a burgeoning field, offers a comprehensive analysis of all metabolites within a cell, tissue, system, or organism, providing crucial insights into the dynamic changes occurring during cancer development and progression. This review focuses on the metabolic alterations associated with BC, highlighting the potential of metabolomics in identifying biomarkers for early detection, diagnosis, treatment and prognosis. Metabolomics studies have revealed distinct metabolic signatures in BC, including alterations in lipid metabolism, amino acid metabolism, and energy metabolism. These metabolic changes not only support the rapid proliferation of cancer cells but also influence the tumour microenvironment and therapeutic response. Furthermore, metabolomics holds great promise in personalized medicine, facilitating the development of tailored treatment strategies based on an individual's metabolic profile. By providing a holistic view of the metabolic changes in BC, metabolomics has the potential to revolutionize our understanding of the disease and improve patient outcomes.PMID:38944408 | DOI:10.1016/j.cca.2024.119836