PubMed

Anal Chem. 2024 Oct 31. doi: 10.1021/acs.analchem.4c01778. Online ahead of print.ABSTRACTBees produce honey through the collection and transformation of nectar, whose botanical origin impacts the taste, nutritional value, and, therefore, the market price of the resulting honey. This phenomenon has led some to mislabel their honey so that it can be sold at a higher price. Metabolomics has been gaining popularity in food authentication, but rapid data mining algorithms are needed to facilitate the discovery of new authenticity markers. A nontargeted high-resolution liquid chromatography-mass spectrometry (HR/LC-MS) analysis of 262 monofloral honey samples, of which 50 were blueberry honey, was performed. Data mining methods were demonstrated for the discovery of binary single-markers (compound was only detected in blueberry honey), threshold single-markers (compound had the highest concentration in blueberry honey), and interval ratio-markers (the ratio of two compounds was within a unique interval in blueberry honey). A novel convolutional algorithm was developed for the discovery of interval ratio-markers, which trained 14× faster and achieved a 0.2 Matthews correlation coefficient (MCC) units higher classification score than existing open-source implementations. The convolutional algorithm also had classification performance similar to that of a brute-force search but trained 1521× faster. A pipeline for shortlisting candidate authenticity markers from the LC-MS spectra that may be suitable for chemical structure identification was also demonstrated and led to the identification of niacin as a blueberry honey threshold single-marker. This work demonstrates an end-to-end approach to mine the honey metabolome for novel authenticity markers and can readily be applied to other types of food and analytical chemistry instruments.PMID:39479961 | DOI:10.1021/acs.analchem.4c01778

Cancer Sci. 2024 Oct 31. doi: 10.1111/cas.16347. Online ahead of print.ABSTRACTCancer cells rely on mitochondrial oxidative phosphorylation (OXPHOS) and the noncanonical tricarboxylic acid (TCA) cycle. In this paper, we shed light on the vital role played by the noncanonical TCA cycle in a host-side concession to mitochondria, especially in highly energy-demanding malignant tumor cells. Inhibition of ATP-citrate lyase (ACLY), a key enzyme in the noncanonical TCA cycle, induced apoptosis by increasing reactive oxygen species levels and DNA damage while reducing mitochondrial membrane potential. The mitochondrial membrane citrate transporter inhibitor, CTPI2, synergistically enhanced these effects. ACLY inhibition reduced cytosolic citrate levels and CTPI2 lowered ACLY activity, suggesting that the noncanonical TCA cycle is sustained by a positive feedback mechanism. These inhibitions impaired ATP production, particularly through OXPHOS. Metabolomic analysis of mitochondrial and cytosolic fractions revealed reduced levels of glutathione pathway-related and TCA cycle-related metabolite, except fumarate, in mitochondria following noncanonical TCA cycle inhibition. Despite the efficient energy supply to the cell by mitochondria, this symbiosis poses challenges related to reactive oxygen species and mitochondrial maintenance. In conclusion, the noncanonical TCA cycle is indispensable for the canonical TCA cycle and mitochondrial integrity, contributing to mitochondrial domestication.PMID:39479926 | DOI:10.1111/cas.16347

Food Sci Nutr. 2024 Aug 7;12(10):7719-7736. doi: 10.1002/fsn3.4397. eCollection 2024 Oct.ABSTRACTAs a plant classified under the "medicine food homology" concept, garlic offers various health benefits and comes in many different varieties. In this study, the metabolite composition of different garlic varieties were analyzed using LC-MS/MS quadrupole-Orbitrap mass spectrometry and ICP-MS. A total of 30 chemical elements and 1256 metabolites were identified. Significant differences in chemical elements and metabolomics profiles were observed among the five garlic groups (VIP > 1.5). Compared to WG, PG contained 5 unique compounds, HG had 15 unique compounds, SCG had 18 unique compounds, and SBG had 26 unique compounds. Furthermore, the results showed that WG had smaller differences with PG and HG, but significant differences with SBG and SCG. KEGG analysis revealed metabolic pathways associated with the formation of differential metabolites. These findings uncover the differences and mechanisms in the composition of various garlic varieties, providing a theoretical foundation for distinguishing the nutritional components of different garlic types.PMID:39479693 | PMC:PMC11521672 | DOI:10.1002/fsn3.4397

Food Sci Nutr. 2024 Jul 16;12(10):7186-7201. doi: 10.1002/fsn3.4307. eCollection 2024 Oct.ABSTRACTThe determination of optimal levels of green tea amount and brewing time would have a crucial role in the accumulation of desired aromatic volatile compounds to meet worldwide market demand. Aroma is the most important factor influencing tea consumers' choices along with taste, price, and brand. This study aims to determine how the brewing time and amount of green tea affect the aroma profile of green tea infusion. The effect of the amount of Turkish green tea (5-10 g) and brewing time (5-60 min) on aromatic volatile compounds was evaluated using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) technique. The SPME/GC-MS analysis identified 57 components in the aroma profile of green tea infusions including 13 esters, 12 alkanes, 7 unknowns, 6 ketones, 3 alcohols, 2 terpenes, 2 terpenoids, 1 alkaloid, 1 phenolic compound, 1 lactone, 1 pyrazine, and 1 norisoprenoid. The green tea amount and brewing time had significant effects on the number of chemical compounds. A total of 42, 47, and 36 aromatic volatile compounds were determined by brewing 5, 7.5, and 10 g of green tea. The most abundant constituents in green tea infusions were phytone, 2-decenal, lauric acid, unknown 1, methoxy-1-methylethyl pyrazine, α-ionone, β-ionone, and diethyl phthalate (DEP). With this study, the aroma structures of green tea infusion have been revealed for the first time depending on the brewing time and quantity.PMID:39479672 | PMC:PMC11521698 | DOI:10.1002/fsn3.4307

Front Plant Sci. 2024 Oct 16;15:1408141. doi: 10.3389/fpls.2024.1408141. eCollection 2024.ABSTRACTINTRODUCTION: Nitrogen (N) and iron (Fe) are involved in several biochemical processes in living organisms, and their limited bioavailability is a strong constraint for plant growth and yield. This work investigated the interplay between Fe and N nutritional pathways in tomato plants kept under N and Fe deficiency and then resupplied with Fe and N (as nitrate, ammonium, or urea) through a physiological, metabolomics and gene expression study.RESULTS: After 24 hours of Fe resupply, the Fe concentration in Fe-deficient roots was dependent on the applied N form (following the pattern: nitrate > urea > ammonium > Fe-deficient control), and whereas in leaves of urea treated plants the Fe concentration was lower in comparison to the other N forms. Untargeted metabolomics pointed out distinctive modulations of plant metabolism in a treatment-dependent manner. Overall, N-containing metabolites were affected by the treatments in both leaves and roots, while N form significantly shaped the phytohormone profile. Moreover, the simultaneous application of Fe with N to Fe-deficient plants elicited secondary metabolites' accumulation, such as phenylpropanoids, depending on the applied N form (mainly by urea, followed by nitrate and ammonium). After 4 hours of treatment, ammonium- and urea-treated roots showed a reduction of enzymatic activity of Fe(III)-chelate reductase (FCR), compared to nitrate or N-depleted plants (maintained in Fe deficiency, where FCR was maintained at high levels). The response of nitrate-treated plants leads to the improvement of Fe concentration in tomato roots and the increase of Fe(II) transporter (IRT1) gene expression in tomato roots.CONCLUSIONS: Our results strengthen and improve the understanding about the interaction between N and Fe nutritional pathways, thinning the current knowledge gap.PMID:39479546 | PMC:PMC11521840 | DOI:10.3389/fpls.2024.1408141

R Soc Open Sci. 2024 Oct 30;11(10):240930. doi: 10.1098/rsos.240930. eCollection 2024 Oct.ABSTRACTLack of maternal milk commonly leads to Asian elephant calves' death in captivity. Currently, available supplements seem inefficient. Hence, we aimed at characterizing the composition of Asian elephant milk to provide information on calves' nutritional needs. Seventy milk samples from 22 Asian elephants living in semi-captivity in their natural environment in Myanmar were collected. Samples were analysed through various techniques including liquid chromatography tandem mass spectrometry, gas chromatography-flame ionization detector, and bicinchoninic acid assay to determine total protein content and various metabolites. Associations with lactation stage (months postpartum) were investigated through repeated measure mixed models. We identified 160 compounds: 22 amino acids, 12 organic acids of the tricarboxylic acid cycle, 27 fatty acids, 15 acyl-carnitines and 84 phospholipids. The milk contained substantial amounts of free glutamate (median: 1727.9, interquartile range (IQR): 1278.4 µmol l-1) and free glycine (2541.7, IQR: 1704.1 µmol l-1). The fatty acid profile was mostly constituted by saturated fatty acids, particularly capric acid (40.1, IQR: 67.3 g l-1). Milk samples also contained high amounts of carnitines, phospholipids and organic acids. The wide array of metabolites identified and quantified, some of which present high concentrations in the milk from this species as opposed to other species, suggests underpinning physiological functions that might be crucial for the survival of Asian elephant calves.PMID:39479244 | PMC:PMC11522882 | DOI:10.1098/rsos.240930

Front Chem. 2024 Oct 16;12:1504501. doi: 10.3389/fchem.2024.1504501. eCollection 2024.NO ABSTRACTPMID:39478992 | PMC:PMC11521952 | DOI:10.3389/fchem.2024.1504501

Gut Pathog. 2024 Oct 30;16(1):64. doi: 10.1186/s13099-024-00652-6.ABSTRACTSpecific intestinal metabolites are closely associated with the classification, severity, and necrosis of acute pancreatitis (AP) and provide novel insights for in-depth clinical investigations. In this study, the gut microbiota and metabolites of 49 AP patients at different treatment stages and severities were analysed via 16S rDNA sequencing and untargeted metabolomics to investigate the trends in gut microbiota composition and metabolome profiles observed in patients with severe AP. These findings revealed an imbalance in intestinal flora homeostasis among AP patients characterized by a decrease in probiotics and an increase in opportunistic pathogens, which leads to damage to the intestinal mucosal barrier through reduced short-chain fatty acid (SCFA) secretion and disruption of the intestinal epithelium. This dysbiosis influences energy metabolism, anti-inflammatory responses, and immune regulation, and these results highlight significant differences in energy metabolism pathways. These findings suggest that the differential composition of intestinal flora, along with alterations in intestinal metabolites and metabolic pathways, contribute to the compromised integrity of the intestinal mucosal barrier and disturbances in energy metabolism in patients with severe AP.PMID:39478598 | DOI:10.1186/s13099-024-00652-6

Microbiome. 2024 Oct 30;12(1):223. doi: 10.1186/s40168-024-01944-4.ABSTRACTBACKGROUND: Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs' fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism?RESULTS: In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine.CONCLUSIONS: We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract.PMID:39478562 | DOI:10.1186/s40168-024-01944-4

BMC Neurol. 2024 Oct 31;24(1):423. doi: 10.1186/s12883-024-03926-3.ABSTRACTMultiple sclerosis (MS) is an autoimmune disorder caused by chronic inflammatory reactions in the central nervous system. Currently, little is known about the changes of plasma proteomic profiles in Chinese patients with MS (CpwMS) and its relationship with the altered profiles of multi-omics such as metabolomics and gut microbiome, as well as potential molecular networks that underlie the etiology of MS. To uncover the characteristics of proteomics landscape and potential multi-omics interaction networks in CpwMS, Plasma samples were collected from 22 CpwMS and 22 healthy controls (HCs) and analyzed using a Tandem Mass Tag (TMT)-based quantitative proteomics approach. Our results showed that the plasma proteomics pattern was significantly different in CpwMS compared to HCs. A total of 90 differentially expressed proteins (DEPs), such as LAMP1 and FCG2A, were identified in CpwMS plasma comparing to HCs. Furthermore, we also observed extensive and significant correlations between the altered proteomic profiles and the changes of metabolome, gut microbiome, as well as altered immunoinflammatory responses in MS-affected patients. For instance, the level of LAMP1 and ERN1 were significantly and positively correlated with the concentrations of metabolite L-glutamic acid and pro-inflammatory factor IL-17 (Padj < 0.05). However, they were negatively correlated with the amounts of other metabolites such as L-tyrosine and sphingosine 1-phosphate, as well as the concentrations of IL-8 and MIP-1α. This study outlined the underlying multi-omics integrated mechanisms that might regulate peripheral immunoinflammatory responses and MS progression. These findings are potentially helpful for developing new assisting diagnostic biomarker and therapeutic strategies for MS.PMID:39478468 | DOI:10.1186/s12883-024-03926-3

J Exp Bot. 2024 Oct 30:erae443. doi: 10.1093/jxb/erae443. Online ahead of print.ABSTRACTLeaves evolve shape diversity ranging from simple leaves with smooth margin to complicated shape with toothed/serrated, lobed and dissected leaves with leaflets. In the model plant Arabidopsis thaliana with simple leaves producing serrated margin, boundary regulatory factors CUP SHAPED COTYLEDON 2 (CUC2) and CUC3 play important roles in promoting leaf serration initiation and maintenance. Stem cell related WUSCHEL-RELATED HOMEOBOX1 (WOX1) and PRESSED FLOWER/WOX3 are also essential for leaf margin morphogenesis, but the role of WOX1 and PRS as well as the relationships between CUCs and WOXs on tooth development was unclear. In this study, we found that WOX1, but not PRS, prevents overproduction of tooth number and excessive tooth size by limiting CUC3 expression to a moderate level in a temporally regulated manner. We also revealed that BRASSINAZOLE RESISTANT 1 (BZR1), a known regulator for plant development including boundary regions, is involved in WOX1 negative regulation of tooth development by repressing CUC3 expression during the initiation/early stage of tooth development. WOX1 parallelly limits BZR1 and CUC3 expression from the late stage of the first 2 teeth, while restricts CUC3 activity in a BZR1 dependent manner from the initiation/early stage of subsequently developed teeth. This study uncovers a new mechanism for WOX1 in fine-tuning the leaf margin geometry.PMID:39478336 | DOI:10.1093/jxb/erae443

Sci Rep. 2024 Oct 30;14(1):26078. doi: 10.1038/s41598-024-77921-6.ABSTRACTAlzheimer's disease (AD) is a metabolic disorder. Discovering the metabolic products involved in the development of AD may help not only in the early detection and prevention of AD but also in understanding its pathogenesis and treatment. This study investigated the causal association between the latest large-scale plasma metabolites (1091 metabolites and 309 metabolite ratios) and AD. Through the application of Mendelian randomization analysis methods such as inverse-variance weighted (IVW), MR-Egger, and weighted median models, 66 metabolites and metabolite ratios were identified as potentially having a causal association with AD, with 13 showing significant causal associations. During the replication validation phase, six metabolites and metabolite ratios were confirmed for their roles in AD: N-lactoyl tyrosine, argininate, and the adenosine 5'-monophosphate to flavin adenine dinucleotide ratio were found to exhibit protective effects against AD. In contrast, ergothioneine, piperine, and 1,7-dimethyluric acid were identified as contributing to an increased risk of AD. Among them, argininate showed a significant effect against AD. Replication and sensitivity analyses confirmed the robustness of these findings. Metabolic pathway analysis linked "Vitamin B6 metabolism" to AD risk. No genetic correlations were found, but colocalization analysis indicated potential AD risk elevation through top SNPs in APOE and PSEN2 genes. This provides novel insights into AD's etiology from a metabolomic viewpoint, suggesting both protective and risk metabolites.PMID:39478193 | DOI:10.1038/s41598-024-77921-6

Acta Pharmacol Sin. 2024 Oct 30. doi: 10.1038/s41401-024-01405-6. Online ahead of print.ABSTRACTAstrocyte-derived IL-3 activates the corresponding receptor IL-3Rα in microglia. This cross-talk between astrocytes and microglia ameliorates the pathology of Alzheimer's disease in mice. In this study we investigated the role of IL-3/IL-3Rα cross-talk and its regulatory mechanisms in ischemic stroke. Ischemic stroke was induced in mice by intraluminal occlusion of the right middle cerebral artery (MCA) for 60 min followed by reperfusion (I/R). Human astrocytes or microglia subjected to oxygen-glucose deprivation and reoxygenation (OGD/Re) were used as in vitro models of brain ischemia. We showed that both I/R and OGD/Re significantly induced decreases in astrocytic IL-3 and microglial IL-3Rα protein levels, accompanied by pro-inflammatory activation of A1-type astrocytes and M1-type microglia. Importantly, astrocyte-derived VEGFD acting on VEGFR3 of astrocytes and microglia contributed to the cross-talk dysfunction and pro-inflammatory activation of the two glial cells, thereby mediating neuronal cell damage. By using metabolomics and multiple biochemical approaches, we demonstrated that IL-3 supplementation to microglia reversed OGD/Re-induced lipid metabolic reprogramming evidenced by upregulated expression of CPT1A, a rate-limiting enzyme for the mitochondrial β-oxidation, and increased levels of glycerophospholipids, the major components of cellular membranes, causing reduced accumulation of lipid droplets, thus reduced pro-inflammatory activation and necrosis, as well as increased phagocytosis of microglia. Notably, exogenous IL-3 and the VEGFR antagonist axitinib reestablished the cross-talk of IL-3/IL-3Rα, improving microglial lipid metabolic levels via upregulation of CPT1A, restoring microglial phagocytotic function and attenuating microglial pro-inflammatory activation, ultimately contributing to brain recovery from I/R insult. Our results demonstrate that VEGFD/VEGFR3 signaling contributes to the dysfunction of the astrocyte IL-3/microglia IL-3Rα cross-talk and drives pro-inflammatory activation, causing lipid metabolic reprogramming of microglia. These insights suggest VEGFR3 antagonism or restoring IL-3 levels as a potential therapeutic strategy for ischemic stroke.PMID:39478160 | DOI:10.1038/s41401-024-01405-6

Nat Cancer. 2024 Oct 30. doi: 10.1038/s43018-024-00831-z. Online ahead of print.ABSTRACTFamilial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation. These involve processes such as cell proliferation, immune response, metabolic alterations (including amino acids and lipids), hormones and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin and other nonsteroidal anti-inflammatory drugs, a preventative treatment under investigation in persons with FAP. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis.PMID:39478120 | DOI:10.1038/s43018-024-00831-z

Sci Rep. 2024 Oct 30;14(1):26122. doi: 10.1038/s41598-024-77746-3.ABSTRACTThis research aimed to analyze the volatile compounds emitted during the proliferation of Klebsiella pneumoniae (K. pneumoniae) in the laboratory setting using gas chromatography-ion mobility spectrometry (GC-IMS) and to investigate the potential of volatile metabolomics for detecting carbapenemase-producing strains of K. pneumoniae. The volatile metabolomics of K. pneumoniae were comprehensively analyzed using GC-IMS in tryptic soy broth (TSB) as the culture medium. Afterward, the growth stabilization period (T2) served as the primary time point for analysis, with the introduction of imipenem and carbapenemase inhibitors (avibactam sodium or EDTA) during the exponential growth phase (T0) to further investigate alterations in volatile molecules associated with K. pneumoniae. Standard strains were utilized as references, while clinical strains were employed for validation purposes. At T2, a total of 22 volatile organic compounds (VOCs) associated with K. pneumoniae were identified (3 VOCs found in both monomer and dimer forms). Significant differences in VOCs were observed between carbapenemase-negative and carbapenemase-positive strains, both standard and clinical, following the introduction of imipenem. Furthermore, the addition of avibactam sodium led to distinct changes in the VOC content of strains producing class A carbapenemase, while the addition of EDTA resulted in specific alterations in the volatile metabolic profiles of strains producing class B carbapenemase. GC-IMS demonstrated significant promise for analyzing bacterial volatile metabolomics, and its application in evaluating the volatolomics of K. pneumoniae may facilitate the timely detection of carbapenemase-producing strains.PMID:39478041 | DOI:10.1038/s41598-024-77746-3

NPJ Parkinsons Dis. 2024 Oct 30;10(1):208. doi: 10.1038/s41531-024-00816-w.ABSTRACTPathological forms of α-synuclein contribute to synucleinopathies, including Parkinson's disease (PD). Most cases of PD arise from gene-environment interactions. Microbiome composition is altered in PD, and gut bacteria are causal to symptoms in animal models. We quantitatively profiled nearly 630 metabolites in the gut, plasma, and brain of α-synuclein-overexpressing (ASO) mice, compared to wild-type (WT) animals, and comparing germ-free (GF) to specific pathogen-free (SPF) animals (n = 5 WT-SPF; n = 6 ASO-SPF; n = 6 WT-GF; n = 6 ASO-GF). Many differentially expressed metabolites in ASO mice are also dysregulated in human PD patients, including amine oxides, bile acids and indoles. The microbial metabolite trimethylamine N-oxide (TMAO) strongly correlates from the gut to the plasma to the brain in mice, notable since TMAO is elevated in the blood and cerebrospinal fluid of PD patients. These findings uncover broad metabolomic changes that are influenced by the intersection of host genetics and microbiome in a mouse model of PD.PMID:39477976 | DOI:10.1038/s41531-024-00816-w

Sci Rep. 2024 Oct 30;14(1):26135. doi: 10.1038/s41598-024-75941-w.ABSTRACTThe global aging population has led to a rise in age-related health issues, such as malnutrition, metabolic disorders, and even immune decline. Among these concerns, periodontitis holds particular significance for the well-being of the elderly. This study aimed to investigate the impact of aging on inflammatory resorption of alveolar bone in mice with periodontitis, with a specific focus on alterations in the intestinal microenvironment. To achieve this, we established a D-galactose (D-gal)-induced aging mouse model with periodontitis and employed histopathological staining, oxidative stress, and inflammatory factors analyses to assess the severity of periodontitis and the health status. Additionally, the 16S rRNA sequencing and untargeted metabolomics analysis were employed to investigate alterations in the intestinal microbiota and metabolites. Our results showed that D-gal-induced aging mice with periodontitis experienced more pronounced alveolar bone inflammatory resorption and disruptions in the gut barrier, accompanied by an overall decline in physical condition. The microbial composition and structure of aged mice also underwent significant modifications, with a decreased Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, metabolomics analysis demonstrated that D-gal-induced aging primarily influenced lipids and lipid-like molecules metabolism, and enrichment observed in the rheumatoid arthritis and histidine metabolism pathways. These findings provide further evidence that the aging process exacerbates age-related alveolar bone loss (ABL) through disturbances in intestinal homeostasis.PMID:39477973 | DOI:10.1038/s41598-024-75941-w

Nat Commun. 2024 Oct 30;15(1):9371. doi: 10.1038/s41467-024-53670-y.ABSTRACTThe trillions of microorganisms inhabiting the human gut are intricately linked to human health. While specific microbes have been associated with diseases, microbial abundance alone cannot reveal the molecular mechanisms involved. One such important mechanism is the biosynthesis of functional metabolites. Here, we develop a biosynthetic enzyme-guided disease correlation approach to uncover microbial functional metabolites linked to disease. Applying this approach, we negatively correlate the expression of gut microbial sulfonolipid (SoL) biosynthetic enzymes to inflammatory bowel disease (IBD). Targeted chemoinformatics and metabolomics then confirm that SoL abundance is significantly decreased in IBD patient data and samples. In a mouse model of IBD, we further validate that SoL abundance is decreased while inflammation is increased in diseased mice. We show that SoLs consistently contribute to the immunoregulatory activity of different SoL-producing human microbes. We further reveal that sulfobacins A and B, representative SoLs, act on Toll-like receptor 4 (TLR4) and block lipopolysaccharide (LPS) binding, suppressing both LPS-induced inflammation and macrophage M1 polarization. Together, these results suggest that SoLs mediate a protective effect against IBD through TLR4 signaling and showcase a widely applicable biosynthetic enzyme-guided disease correlation approach to directly link the biosynthesis of gut microbial functional metabolites to human health.PMID:39477928 | DOI:10.1038/s41467-024-53670-y

Ren Fail. 2024 Dec;46(2):2420830. doi: 10.1080/0886022X.2024.2420830. Epub 2024 Oct 30.ABSTRACTAIMS: Diabetic kidney disease (DKD) develops in approximately 40% of patients with type 2 diabetes mellitus (T2DM). The role of folate metabolites in the progression from T2DM to DKD has not been clearly articulated. Our aim was to assess the association of folate metabolites with DKD.METHODS: We conducted a cross-sectional study sourced from the U.S. National Health and Nutrition Examination Survey from 2011 to 2020. Several forms of folate were measured. DKD was defined as diabetes with albuminuria or impaired glomerular filtration rate. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.RESULTS: Of the 3,461 diabetes patients, 1,349 (38.98%) were diagnosed with DKD. Serum total folate and 5-Methyl-THF were negatively associated with DKD, the OR for comparing extreme quintile were both 0.73 (0.57-0.94). However, a positive association of RBC folate, UMFA, Non-5-Methyl-THF, and MeFox with DKD was observed with extreme quintile OR of 1.41 (1.10-1.82), 1.60 (1.24-2.07), 1.53 (1.20-1.96), and 3.45 (2.65-4.50). Furthermore, the ratio of UMFA to 5-Methyl-THF exhibited a positive association with DKD, with extreme quintile OR of 1.94 (1.50-2.50).CONCLUSIONS: Our findings suggested that guidelines and interventions highlighting the importance of promoting 5-Methyl-THF and reducing UMFA might have significant benefit for the management of patients with diabetes.PMID:39477815 | DOI:10.1080/0886022X.2024.2420830

Pestic Biochem Physiol. 2024 Nov;205:106146. doi: 10.1016/j.pestbp.2024.106146. Epub 2024 Sep 24.ABSTRACTFlupyrimin (FLP) is a novel class of insecticide acting on insect nicotinic acetylcholine receptor (nAChR) and shows robust insecticidal activity. However, the toxicological effects of FLP on Spodoptera litura have not been revealed. In this study, the results showed that the larval survival rate decreased significantly with increasing concentration of FLP. The hematoxylin-eosin (HE) staining showed that FLP exposure damages the structure of the larval midgut. Additionally, FLP treatments significantly increased the activities of detoxification (GST and CarE) and digestive (α-Amylase and Trypsin) enzymes and reduced lipase activity. Transcriptome sequencing identified 855, 1493 and 735 differentially expressed genes (DEGs) at 12 h, 24 h and 48 h after exposure to 3 mM FLP, respectively. Gene function enrichment analysis revealed that DEGs were mainly related to fatty acid metabolic, protein processing in the endoplasmic reticulum and drug metabolism-cytochrome P450. The DEGs associated with food digestion and detoxification was validated by reverse-transcription quantitative PCR (RT-qPCR). Furthermore, a total of fifteen energy-related metabolites were identified, among which thirteen metabolisms were significantly influenced after FLP treatment based on 1H NMR-based metabolome analysis, including tyrosine, glucose, trehalose, malate, threonine, proline, glycine, lysine, citrate, alanine, lactate, valine, and leucine. Taken together, these results provide useful information for revealing the toxicological effect of FLP against S. litura.PMID:39477599 | DOI:10.1016/j.pestbp.2024.106146