PubMed

Appl Microbiol Biotechnol. 2023 Jun 5. doi: 10.1007/s00253-023-12600-6. Online ahead of print.ABSTRACTFormate is a promising energy carrier that could be used to transport renewable electricity. Some acetogenic bacteria, such as Eubacterium limosum, have the native ability to utilise formate as a sole substrate for growth, which has sparked interest in the biotechnology industry. However, formatotrophic metabolism in E. limosum is poorly understood, and a system-level characterisation in continuous cultures is yet to be reported. Here, we present the first steady-state dataset for E. limosum formatotrophic growth. At a defined dilution rate of 0.4 d-1, there was a high specific uptake rate of formate (280 ± 56 mmol/gDCW/d; gDCW = gramme dry cell weight); however, most carbon went to CO2 (150 ± 11 mmol/gDCW/d). Compared to methylotrophic growth, protein differential expression data and intracellular metabolomics revealed several key features of formate metabolism. Upregulation of phosphotransacetylase (Pta) appears to be a futile attempt of cells to produce acetate as the major product. Instead, a cellular energy limitation resulted in the accumulation of intracellular pyruvate and upregulation of pyruvate formate ligase (Pfl) to convert formate to pyruvate. Therefore, metabolism is controlled, at least partially, at the protein expression level, an unusual feature for an acetogen. We anticipate that formate could be an important one-carbon substrate for acetogens to produce chemicals rich in pyruvate, a metabolite generally in low abundance during syngas growth. KEY POINTS: First Eubacterium limosum steady-state formatotrophic growth omics dataset High formate specific uptake rate, however carbon dioxide was the major product Formate may be the cause of intracellular stress and biofilm formation.PMID:37272938 | DOI:10.1007/s00253-023-12600-6

Microb Genom. 2023 Jun;9(6). doi: 10.1099/mgen.0.001029.ABSTRACTKazachstania aerobia and Kazachstania servazzii can affect wine aroma by increasing acetate ester concentrations, most remarkably phenylethyl acetate and isoamyl acetate. The genetic basis of this is unknown, there being little to no sequence data available on the genome architecture. We report for the first time the near-complete genome sequence of the two species using long-read (PacBio) sequencing (K. aerobia 20 contigs, one scaffold; and K. servazzii 22 contigs, one scaffold). The annotated genomes of K. aerobia (12.5 Mb) and K. servazzii (12.3 Mb) were compared to Saccharomyces cerevisiae genomes (laboratory strain S288C and wine strain EC1118). Whilst a comparison of the two Kazachstania spp. genomes revealed few differences between them, divergence was evident in relation to the genes involved in ester biosynthesis, for which gene duplications or absences were apparent. The annotations of these genomes are valuable resources for future research into the evolutionary biology of Kazachstania and other yeast species (comparative genomics) as well as understanding the metabolic processes associated with alcoholic fermentation and the production of secondary 'aromatic' metabolites (transcriptomics, proteomics and metabolomics).PMID:37272916 | DOI:10.1099/mgen.0.001029

J Cell Sci. 2023 Jun 5:jcs.260717. doi: 10.1242/jcs.260717. Online ahead of print.ABSTRACTMyofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibrils. Muscle contraction is achieved by the simultaneous shortening of sarcomeres, which requires all sarcomeres to be the same size. Muscles have a variety of ways to ensure sarcomere homogeneity. We previously showed that the controlled oligomerization of Zasp proteins sets the diameter of the myofibril. Here we looked for Zasp-binding proteins at the Z-disc to identify additional proteins coordinating myofibril growth and assembly. We found that the E1 subunit of the oxoglutarate dehydrogenase complex localizes to both the Z-disc and the mitochondria, and is recruited to the Z-disc by Zasp52. The three subunits of the oxoglutarate dehydrogenase complex are required for myofibril formation. Using super-resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Metabolomics identified an amino acid imbalance affecting protein synthesis as a possible cause of myofibril defects, which is supported by OGDH-dependent localization of ribosomes at the Z-disc.PMID:37272588 | DOI:10.1242/jcs.260717

Plant Signal Behav. 2023 Dec 31;18(1):2215618. doi: 10.1080/15592324.2023.2215618.ABSTRACTArabidopsis NADK2 (NAD kinase 2) is a chloroplast-localized enzyme involved in NADP+ synthesis, which acts as the final electron acceptor in the photosynthetic electron transfer chain. The NADK2-deficient mutant (nadk2) was used to analyze the effect of NAD(P)(H) unbalance in the dark-induced leaf senescence. During senescence, WT plants and nadk2 mutants showed a similar reduction in chlorophyll content. NAD(P)(H) quantification showed that the amount of total NAD(P)(H) decreased on the day 7 in WT but on the day 3 in nadk2. The phosphorylation ratio (i.e. NADP(H)/NAD(H)) decreased on day 1 in WT. In contrast, the nadk2 showed lower phosphorylation ratio at 0 day and no change throughout the aging process. Metabolome analysis showed that the metabolic profiles of both WT plants and nadk2 mutants subjected to dark-induced senescence adopted similar patterns as the senescence progressed. However, the changes in individual metabolites in the nadk2 mutants were different from those of the WT during dark-induced senescence.PMID:37272565 | DOI:10.1080/15592324.2023.2215618

Plant J. 2023 Jun 5. doi: 10.1111/tpj.16277. Online ahead of print.ABSTRACTThe process of crop domestication leads to a dramatic reduction in the gene expression associated with metabolic diversity. Genes involved in specialized metabolism appear to be particularly affected. Although there is ample evidence of these effects at the genetic level, a reduction in diversity at the metabolite level has been taken for granted despite having never been adequately accessed and quantified. Here we leveraged the high coverage of ultra high performance liquid chromatography-high-resolution mass spectrometry based metabolomics to investigate the metabolic diversity in the common bean (Phaseolus vulgaris). Information theory highlights a shift towards lower metabolic diversity and specialization when comparing wild and domesticated bean accessions. Moreover, molecular networking approaches facilitated a broader metabolite annotation than achieved to date, and its integration with gene expression data uncovers a metabolic shift from specialized metabolism towards central metabolism upon domestication of this crop.PMID:37272491 | DOI:10.1111/tpj.16277

Biotechnol Bioeng. 2023 Jun 5. doi: 10.1002/bit.28450. Online ahead of print.ABSTRACTOptimization and monitoring of bioprocesses requires the measurement of several process parameters and quality attributes. Mass spectrometry (MS)-based techniques such as those coupled to gas chromatography (GCMS) and liquid Chromatography (LCMS) enable the simultaneous measurement of hundreds of metabolites with high sensitivity. When applied to spent media, such metabolome analysis can help determine the sequence of substrate uptake and metabolite secretion, consequently facilitating better design of initial media and feeding strategy. Furthermore, the analysis of metabolite diversity and abundance from spent media will aid the determination of metabolic phases of the culture and the identification of metabolites as surrogate markers for product titer and quality. This review covers the recent advances in metabolomics analysis applied to the development and monitoring of bioprocesses. In this regard, we recommend a stepwise workflow and guidelines that a bioprocesses engineer can adopt to develop and optimize a fermentation process using spent media analysis. Finally, we show examples of how the use of MS can revolutionize the design and monitoring of bioprocesses.PMID:37272489 | DOI:10.1002/bit.28450

Environ Microbiol. 2023 Jun 5. doi: 10.1111/1462-2920.16433. Online ahead of print.NO ABSTRACTPMID:37272427 | DOI:10.1111/1462-2920.16433

Basic Clin Pharmacol Toxicol. 2023 Jun 5. doi: 10.1111/bcpt.13909. Online ahead of print.ABSTRACTIn this study, we aimed to determine whether asiatic acid (AA) exerts any therapeutic effects on rifampicin (RFP)-and isoniazid (INH)-induced liver injury and elucidate the underlying mechanisms. Briefly, liver injury in mice was induced via RFP and INH administration. We investigated the effects and potential action mechanisms of AA on liver injury using transcriptomics, metabolomics, and various examinations. We found that AA significantly ameliorated the pathological changes in liver tissues and decreased the transaminase activity, inflammation, and oxidative stress damage. Transcriptomics revealed 147 differentially expressed genes (DEGs) between the AA and model groups that were enriched in metabolic and mitogen-activated protein kinase (MAPK) signaling pathways. Metabolomics revealed 778 differentially expressed metabolites between the AA and model groups. Furthermore, integrated transcriptomics and metabolomics analyses revealed strong correlations between DEGs and differentially expressed metabolites and indicated that AA regulates the sphingolipid metabolism by inhibiting the expression of delta 4-desaturase, sphingolipid 1. Experimental results confirmed that AA inhibited the MAPK signaling pathway. In summary, AA inhibits inflammation and oxidative stress damage by regulating sphingolipid metabolism pathway and blocking the MAPK signaling pathway, thereby relieving the RFP/INH-induced liver injury.PMID:37272388 | DOI:10.1111/bcpt.13909

Mol Omics. 2023 Jun 5. doi: 10.1039/d3mo00040k. Online ahead of print.ABSTRACTThe interactive network of hosts with pathogenic microbes is still questionable. It has been hypothesized and reported that the host shows altered regulatory mechanisms for different pathogens. Several studies using transcriptomics and proteomics revealed the altered pathways and sequential regulations displayed by the host during bacterial interactions. Still, there is a gap in understanding the triggering molecule at transcriptomic and proteomic levels due to the lack of the knowledge of the interactive metabolites produced during their interactions. In this study, the global metabolomic approach was performed in the nematode model organism Caenorhabditis elegans upon exposure to a Gram-negative bacteria, Salmonella enterica Serovar Typhi, and a Gram-positive bacteria, Staphylococcus aureus, and the whole metabolome was categorized as endo-metabolome (internally produced) and exo-metabolome (externally releasing). The extracted metabolites were subjected to liquid chromatography mass spectrometry (ESI-LC/qToF-MS/MS). In total 5578, 4554 and 4046 endo-metabolites and 4451, 3625 and 1281 exo-metabolites were identified in C. elegans when exposed to E. coli OP50, S. Typhi and S. aureus, respectively. Both the multivariate and univariate analyses were performed. The variation in endo- and exo-metabolome during candidate bacterial interactions was observed. The results indicated that, during S. aureus interaction, the exclusively enriched metabolites were significantly involved in alpha-linoleic acid metabolism. Similarly, the exclusively enriched metabolites during the interaction of S. Typhi were significantly involved in the phosphatidylinositol signalling system. The whole metabolomic profile presented here will build the scope to understand the role of metabolites and the respective pathways in host response during the early period of bacterial infections.PMID:37272185 | DOI:10.1039/d3mo00040k

Animal Model Exp Med. 2023 Jun 4. doi: 10.1002/ame2.12328. Online ahead of print.ABSTRACTBACKGROUND: The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development.METHODS: Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways.RESULTS: In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma-glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid-like molecules. The most obvious age-related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway.CONCLUSION: This study revealed many age-related metabolite alterations in the feline plasma. These age-varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.PMID:37271879 | DOI:10.1002/ame2.12328

J Nutr. 2023 Jun 2:S0022-3166(23)72201-3. doi: 10.1016/j.tjnut.2023.05.030. Online ahead of print.ABSTRACTINTRODUCTION: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version; DGA-15) are limited. The goal was to determine a pattern of metabolites associated with the Healthy Eating Index-2015 (HEI-2015), which measures adherence to the DGA.METHODS: The analysis examined 3557 adult men and women from the longitudinal cohort Multi-Ethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens, diet and demographic questionnaires were assessed at baseline. Untargeted 1H NMR 1DNMR spectroscopy (600 MHz) was used to generate metabolomics and lipidomics. A metabolome-wide association study (MWAS) specified each spectral feature as outcomes, HEI-2015 score as predictor, adjusting for age, gender, race, and study site in linear regression analyses. Subsequently, hierarchical clustering defined discrete groups of correlated NMR features associated with named metabolites and linear regression analysis assessed for associations with HEI-2015 total and component scores.RESULTS: The sample included 50% women with average age of 63 years, with 40% identifying as White, 23% Black, 24% Hispanic and 13% Chinese American. The average HEI-2015 score was 66. MWAS identified 179 spectral features significantly associated with HEI-2015 score. Cluster analysis identified seven clusters representing 4 metabolites; HEI-2015 score was significantly associated with all. HEI-2015 score was associated with proline betaine (ß 0.12 [0.02]; p=4.70 E-13) and was inversely related to proline (ß -0.13 [0.02]; p=4.45 E-14), 1,5 anhydrosorbitol (ß -0.08 [0.02]; p=4.37 E-07) and unsaturated fatty acyl chains (ß 0.08 [0.02]; p=8.98 E-07). Intake of total fruit, whole grains and seafood and plant proteins was associated with proline betaine.CONCLUSIONS: Diet quality was significantly associated with unsaturated fatty acyl chains, proline betaine, proline. Further analysis may clarify the link between diet quality, metabolites, and pathogenesis of cardiometabolic disease.PMID:37271414 | DOI:10.1016/j.tjnut.2023.05.030

Fish Shellfish Immunol. 2023 Jun 2:108876. doi: 10.1016/j.fsi.2023.108876. Online ahead of print.ABSTRACTAeromonas hydrophila frequently has harmful effects on aquatic organisms. The intestine is an important defense against stress. In this study, we investigated the intestinal microbiota and transcriptomic and metabolomic responses of Cyprinus carpio subjected to A. hydrophila infection. The results showed that obvious variation in the intestinal microbiota was observed after infection, with increased levels of Firmicutes and Bacteroidetes and decreased levels of Proteobacteria. Several genera of putatively beneficial microbiota (Cetobacterium, Bacteroides, and Lactobacillus) were abundant, while Demequina, Roseomonas, Rhodobacter, Pseudoxanthomonas, and Cellvibrio were decreased; pathogenic bacteria of the genus Vibrio were increased after microbiota infection. The intestinal transcriptome revealed several immune-related differentially expressed genes associated with the cytokines and oxidative stress. The metabolomic analysis showed that microbiota infection disturbed the metabolic processes of the carp, particularly amino acid metabolism. This study provides insight into the underlying mechanisms associated with the intestinal microbiota, immunity, and metabolism of carp response to A. hydrophila infection; eleven stress-related metabolite markers were identified, including N-acetylglutamic acid, capsidiol, sedoheptulose 7-phosphate, prostaglandin B1, 8,9-DiHETrE, 12,13-DHOME, ADP, cellobiose, 1H-Indole-3-carboxaldehyde, sinapic acid and 5,7-dihydroxyflavone.PMID:37271325 | DOI:10.1016/j.fsi.2023.108876

J Allergy Clin Immunol. 2023 Jun 2:S0091-6749(23)00706-6. doi: 10.1016/j.jaci.2023.05.013. Online ahead of print.ABSTRACTBACKGROUND: Growing up on traditional European, and U.S. Amish, dairy farms, in close contact with cows and hay, protects children against asthma, and airway administration of extracts from dust collected from cowsheds of those farms prevents allergic asthma in mice.OBJECTIVES: This study sought to begin identifying farm-derived asthma-protective agents.METHODS: Our work unfolded along two unbiased, independent but complementary discovery paths. Dust extracts from protective and non-protective farms (European and Amish cowsheds vs. European sheep sheds) were analyzed by comparative nuclear magnetic resonance fingerprinting and differential proteomics. Bioactivity-guided size fractionation focused on protective Amish cowshed dust extracts. Multiple in vitro and in vivo functional assays were used in both paths. Some of the proteins thus identified were characterized by in-solution and in-gel SDS-PAGE enzymatic digestion/peptide mapping followed by liquid chromatography/mass spectrometry. The cargo carried by these proteins was analyzed by untargeted liquid chromatography-high resolution mass spectrometry.RESULTS: Twelve carrier proteins of animal and plant origin, including the bovine lipocalins Bos d2 and odorant binding protein, were enriched in dust extracts from protective European cowsheds. A potent asthma-protective fraction of Amish cowshed dust extracts (≈0.5% of the total carbon content of unfractionated extracts) contained seven animal and plant proteins, including Bos d2 and odorant binding protein loaded with fatty acid metabolites from plants, bacteria and fungi.CONCLUSIONS: Animals and plants from traditional farms produce proteins that transport hydrophobic microbial and plant metabolites. When delivered to mucosal surfaces, these agents might regulate airway responses.PMID:37271318 | DOI:10.1016/j.jaci.2023.05.013

Free Radic Biol Med. 2023 Jun 2:S0891-5849(23)00473-2. doi: 10.1016/j.freeradbiomed.2023.05.032. Online ahead of print.ABSTRACTNAD+ and glutathione precursors are currently used as metabolic modulators for improving the metabolic conditions associated with various human diseases, including non-alcoholic fatty liver disease, neurodegenerative diseases, mitochondrial myopathy, and age-induced diabetes. Here, we performed a one-day double blinded, placebo-controlled human clinical study to assess the safety and acute effects of six different Combined Metabolic Activators (CMAs) with 1 g of different NAD+ precursors based on global metabolomics analysis. Our integrative analysis showed that the NAD+ salvage pathway is the main source for boosting the NAD+ levels with the administration of CMAs without NAD+ precursors. We observed that incorporation of nicotinamide (Nam) in the CMAs can boost the NAD+ products, followed by niacin (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), but not flush free niacin (FFN). In addition, the NA administration led to a flushing reaction, accompanied by decreased phospholipids and increased bilirubin and bilirubin derivatives, which could be potentially risky. In conclusion, this study provided a plasma metabolomic landscape of different CMA formulations, and proposed that CMAs with Nam, NMN as well as NR can be administered for boosting NAD+ levels to improve altered metabolic conditions.PMID:37271226 | DOI:10.1016/j.freeradbiomed.2023.05.032

Metabolomics. 2023 Jun 5;19(6):53. doi: 10.1007/s11306-023-02020-y.ABSTRACTINTRODUCTION: A decrease in sperm cell count has been observed along the last several decades, especially in the most developed regions of the world. The use of metabolomics to study the composition of the seminal fluid is a promising approach to gain access to the molecular mechanisms underlying this fact.OBJECTIVES: In the present work, we aimed at relating metabolomic profiles of young healthy men to their semen quality parameters obtained from conventional microscopic analysis.METHODS: An untargeted metabolomics approach focusing on low- to mid-polarity compounds was used to analyze a subset of seminal fluid samples from a cohort of over 2700 young healthy men.RESULTS: Our results show that a broad metabolic profiling comprising several families of compounds (including acyl-carnitines, steroids, and other lipids) can contribute to effectively distinguish samples provided by individuals exhibiting low or high absolute sperm counts.CONCLUSION: A number of metabolites involved in sexual development and function, signaling, and energy metabolism were highlighted as being distinctive of samples coming from either group, proving untargeted metabolomics as a promising tool to better understand the pathophysiological processes responsible for male fertility impairment.PMID:37271779 | DOI:10.1007/s11306-023-02020-y

NPJ Parkinsons Dis. 2023 Jun 3;9(1):84. doi: 10.1038/s41531-023-00531-y.ABSTRACTWe performed liquid chromatography tandem mass spectrometry analysis with the targeted metabolomic kit Biocrates MxP Quant 500, in human brain cortex (Brodmann area 9) and putamen, to reveal metabolic changes characteristic of Parkinson's disease (PD) and PD-related cognitive decline. This case-control study involved 101 subjects (33 PD without dementia, 32 PD with dementia (cortex only), 36 controls). We found changes associated with PD, cognitive status, levodopa levels, and disease progression. The affected pathways include neurotransmitters, bile acids, homocysteine metabolism, amino acids, TCA cycle, polyamines, β-alanine metabolism, fatty acids, acylcarnitines, ceramides, phosphatidylcholines, and several microbiome-derived metabolites. Previously reported levodopa-related homocysteine accumulation in cortex still best explains the dementia status in PD, which can be modified by dietary supplementation. Further investigation is needed to reveal the exact mechanisms behind this pathological change.PMID:37270646 | DOI:10.1038/s41531-023-00531-y

Nat Commun. 2023 Jun 3;14(1):3215. doi: 10.1038/s41467-023-39028-w.ABSTRACTOur previous studies have shown that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). Considering antimicrobial resistance of K. pneumoniae and dysbacteriosis caused by antibiotics, phage therapy might have potential in treatment of HiAlc Kpn-induced NAFLD, because of the specificity targeting the bacteria. Here, we clarified the effectiveness of phage therapy in male mice with HiAlc Kpn-induced steatohepatitis. Comprehensive investigations including transcriptomes and metabolomes revealed that treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. In contrast, such treatment did not cause significantly pathological changes, either in functions of liver and kidney, or in components of gut microbiota. In addition to reducing alcohol attack, phage therapy also regulated inflammation, and lipid and carbohydrate metabolism. Our data suggest that phage therapy targeting gut microbiota is an alternative to antibiotics, with potential efficacy and safety, at least in HiAlc Kpn-caused NAFLD.PMID:37270557 | DOI:10.1038/s41467-023-39028-w

Clin Nutr. 2023 May 4:S0261-5614(23)00141-3. doi: 10.1016/j.clnu.2023.04.027. Online ahead of print.ABSTRACTBACKGROUND: Western dietary habits (WD) have been shown to promote chronic inflammation, which favors the development of many of today's non-communicable diseases. Recently, ketogenic diets (KD) have emerged as an immune-regulating countermeasure for WD-induced metaflammation. To date, beneficial effects of KD have been solely attributed to the production and metabolism of ketone bodies. Given the drastic change in nutrient composition during KD, it is reasonable to assume that there are widespread changes in the human metabolome also contributing to the impact of KD on human immunity. The current study was conducted to gain insight into the changes of the human metabolic fingerprint associated with KD. This could allow to identify metabolites that may contribute to the overall positive effects on human immunity, but also help to recognize potential health risks of KD.METHODS: We conducted a prospective nutritional intervention study enrolling 40 healthy volunteers to perform a three-week ad-libitum KD. Prior to the start and at the end of the nutritional intervention serum metabolites were quantified, untargeted mass spectrometric metabolome analyses and urine analyses of the tryptophan pathway were performed.RESULTS: KD led to a marked reduction of insulin (-21.45% ± 6.44%, p = 0.0038) and c-peptide levels (-19.29% ± 5.45%, p = 0.0002) without compromising fasting blood glucose. Serum triglyceride concentration decreased accordingly (-13.67% ± 5.77%, p = 0.0247), whereas cholesterol parameters remained unchanged. LC-MS/MS-based untargeted metabolomic analyses revealed a profound shift of the human metabolism towards mitochondrial fatty acid oxidation, comprising highly elevated levels of free fatty acids and acylcarnitines. The serum amino acid (AA) composition was rearranged with lower abundance of glucogenic AA and an increase of BCAA. Furthermore, an increase of anti-inflammatory fatty acids eicosatetraenoic acid (p < 0.0001) and docosahexaenoic acid (p = 0.0002) was detected. Urine analyses confirmed higher utilization of carnitines, indicated by lower carnitine excretion (-62.61% ± 18.11%, p = 0.0047) and revealed changes to the tryptophan pathway depicting reduced quinolinic acid (-13.46% ± 6.12%, p = 0.0478) and elevated kynurenic acid concentrations (+10.70% ± 4.25%, p = 0.0269).CONCLUSIONS: A KD fundamentally changes the human metabolome even after a short period of only three weeks. Besides a rapid metabolic switch to ketone body production and utilization, improved insulin and triglyceride levels and an increase in metabolites that mediate anti-inflammation and mitochondrial protection occurred. Importantly, no metabolic risk factors were identified. Thus, a ketogenic diet could be considered as a safe preventive and therapeutic immunometabolic tool in modern medicine.TRIAL REGISTRATION: German Clinical Trials Register; DRKS-ID: DRKS00027992 (www.drks.de).PMID:37270344 | DOI:10.1016/j.clnu.2023.04.027

BMJ Open Respir Res. 2023 Jun;10(1):e001683. doi: 10.1136/bmjresp-2023-001683.ABSTRACTBACKGROUND: The L-arginine metabolome is dysregulated in asthma, though it is not understood how longitudinal changes in L-arginine metabolism differ among asthma phenotypes and relate to disease outcomes.OBJECTIVES: To determine the longitudinal associations between phenotypic characteristics with L-arginine metabolites and their relationships with asthma morbidity.METHODS: This is a prospective cohort study of 321 patients with asthma followed semiannually for over 18 months with assessments of plasma L-arginine metabolites, asthma control, spirometry, quality of life and exacerbations. Metabolite concentrations and ratios were transformed using the natural logarithm.RESULTS: There were many differences in L-arginine metabolism among asthma phenotypes in the adjusted models. Increasing body mass index was associated with increased asymmetric dimethylarginine (ADMA) and depleted L-citrulline. Latinx was associated with increased metabolism via arginase, with higher L-ornithine, proline and L-ornithine/L-citrulline levels, and was found to have higher L-arginine availability compared with white race. With respect to asthma outcomes, increasing L-citrulline was associated with improved asthma control and increasing L-arginine and L-arginine/ADMA were associated with improved quality of life. Increased variability in L-arginine, L-arginine/ADMA, L-arginine/L-ornithine and L-arginine availability index over 12 months were associated with increased exacerbations, OR 4.70 (95% CI 1.35 to 16.37), OR 8.69 (95% CI 1.98 to 38.08), OR 4.17 (95% CI 1.40 to 12.41) and OR 4.95 (95% CI 1.42 to 17.16), respectively.CONCLUSIONS: Our findings suggest that L-arginine metabolism is associated with multiple measures of asthma control and may explain, in part, the relationship between age, race/ethnicity and obesity with asthma outcomes.PMID:37270184 | DOI:10.1136/bmjresp-2023-001683

Sci Total Environ. 2023 Jun 1:164619. doi: 10.1016/j.scitotenv.2023.164619. Online ahead of print.ABSTRACTPolystyrene microplastics (PS-MPs) have emerged as a concerning pollutant in modern society due to their widespread production and usage. Despite ongoing research efforts, the impact of PS-MPs on mammalian behavior and the mechanisms driving these effects remain incompletely elucidated. Consequently, effective strategies for prevention have yet to be developed. To fill these gaps, C57BL/6 mice were orally administered with 5 μm PS-MPs for 28 consecutive days in this study. The open-field test and the elevated plus-maze test were performed to evaluate the anxiety-like behavior, 16S rRNA sequencing and untargeted metabolomics analysis were used to detect the changes of gut microbiota and serum metabolites. Our results indicated that PS-MPs exposure activated hippocampal inflammation and induced anxiety-like behavior in mice. Meanwhile, PS-MPs disturbed the gut microbiota, impaired the intestinal barrier, and aroused peripheral inflammation. Specifically, PS-MPs increased the abundance of pathogenic microbiota Tuzzerella, while lowered the abundance of probiotics Faecalibaculum and Akkermansia. Interestingly, eliminating the gut microbiota protected against the deleterious effects of PS-MPs on intestinal barrier integrity, reduced the levels of peripheral inflammatory cytokines, and ameliorated anxiety-like behavior. Additionally, green tea's primary bioactive constituent, epigallocatechin-3-gallate (EGCG), optimized gut microbial composition, improved intestinal barrier function, reduced peripheral inflammation, and exerted anti-anxiety effects by inhibiting the hippocampal TLR4/MyD88/NF-κB signaling cascade. EGCG also remodeled serum metabolism, especially modulated purine metabolism. These findings suggested that gut microbiota participates in PS-MPs-induced anxiety-like behavior by modulating the gut-brain axis, and that EGCG could serve as a potential preventive strategy.PMID:37269995 | DOI:10.1016/j.scitotenv.2023.164619