Altered Amino Acid Metabolism Research Articles

Aminogram in Egyptian Patients Experiencing Myocardial Infarction

Background: Myocardial infarction is one of the leading causes of death worldwide. Altered amino acids metabolism is linked to cardiovascular disorders. A cross-sectional case control study was set to profile amino acids explore their potential as diagnostic and prognostic tool.
 Methods: Total of 60 subjects was recruited, comprising 40 myocardial infarction patients and 20 controls. High pressure liquid chromatography was applied to quantify the plasma amino acids.
 Results: Fourteen amino acids exhibited discriminative values between cases and controls. Leucine, isoleucine, methionine, glycine, threonine, serine, ornithine, arginine, histidine, and tyrosine exhibited low levels compared to healthy controls (p ≤0.001). Meanwhile, cases displayed higher abundance of cysteine, taurine (p ≤ 0.05), total aromatic amino acids (p ≤ 0.01), and asparagine (p ≤ 0.001). Only leucine, isoleucine, and asparagine were correlated to GRACE risk score. Methionine and glycine scored highly (AUC > 0.95), sensitivity (>97%), and specificity (>95%) followed by histidine (AUC > 0.92), sensitivity (>82%), and specificity (>85%).
 Conclusion: Our study designated a panel of 14 plasma circulating amino acids. Methionine, glycine and histidine were found to be potential markers to differentiate cases from healthy Individuals. Plasma amino acids profiling could help in the diagnosis but is less powerful as a prognostic tool of Myocardial infarction.

Effects of early sub-therapeutic antibiotic administration on body tissue deposition, gut microbiota and metabolite profiles of weaned piglets.

This study aimed to evaluate the effects of sub-therapeutic antibiotic (STA) administration and its subsequent withdrawal on the body tissue deposition, gut microbiota, and metabolite profiles of piglets. The piglets in the experimental group were fed with STA (30 mg kg-1 bacitracin methylene disalicylate, 75 mg kg-1 chlortetracycline, 300 mg kg-1 calcium oxytetracycline) for 14 days and the target bodyweight of the withdrawal period was 25 kg. The experiment was divided into two periods: the administration period and the withdrawal period. The results showed that STA did not improve piglets' growth performance during the two periods. Piglets treated with STA had lower body water deposition during the withdrawal period and tended to increase body lipid deposition during the withdrawal period and the whole period in comparison with the piglets in the control group. It was found that STA markedly altered the colonic microbiota and their metabolites in the piglets. Sub-therapeutic antibiotics were initially effective in decreasing the abundance of pathogenic bacteria during the administration period; however, STA could not continue the effect during the withdrawal period, leading to a rebound of pathogenic bacteria such as Alloprevotella and the increased abundance of other pathogenic bacteria like Oscillibacter. Remarkably, STA treatment decreased Blautia abundance. This bacterium plays a potential protective role against obesity. Metabolomic analysis indicated that STA mainly altered amino acid metabolism, lipid metabolism, and carbohydrate metabolism during the two periods. Spearman's correlation analysis showed that the gut microbiota was highly correlated with microbial metabolite changes. These results suggest that early STA administration may alter body tissue deposition later in life by reshaping the gut microbiota and their metabolite profiles. © 2022 Society of Chemical Industry.

Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism

Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor.

Migraine signaling pathways: amino acid metabolites that regulate migraine and predispose migraineurs to headache

Migraine is a common, debilitating disorder for which attacks typically result in a throbbing, pulsating headache. Although much is known about migraine, its complexity renders understanding the complete etiology currently out of reach. However, two important facts are clear, the brain and the metabolism of the migraineur differ from that of the non-migraineur. This review centers on the altered amino acid metabolism in migraineurs and how it helps define the pathology of migraine.

Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool

The mechanisms by which exercise benefits patients with non-alcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, remain poorly understood. A non-targeted liquid chromatography-mass spectrometry (LC–MS)-based metabolomics analysis was used to identify metabolic changes associated with NAFLD in humans upon exercise intervention (without diet change) across four different sample types—adipose tissue (AT), plasma, urine, and stool. Altogether, 46 subjects with NAFLD participated in this randomized controlled intervention study. The intervention group (n = 21) performed high-intensity interval training (HIIT) for 12 weeks while the control group (n = 25) kept their sedentary lifestyle. The participants' clinical parameters and metabolic profiles were compared between baseline and endpoint. HIIT significantly decreased fasting plasma glucose concentration (p = 0.027) and waist circumference (p = 0.028); and increased maximum oxygen consumption rate and maximum achieved workload (p < 0.001). HIIT resulted in sample-type-specific metabolite changes, including accumulation of amino acids and their derivatives in AT and plasma, while decreasing in urine and stool. Moreover, many of the metabolite level changes especially in the AT were correlated with the clinical parameters monitored during the intervention. In addition, certain lipids increased in plasma and decreased in the stool. Glyco-conjugated bile acids decreased in AT and urine. The 12-week HIIT exercise intervention has beneficial ameliorating effects in NAFLD subjects on a whole-body level, even without dietary changes and weight loss. The metabolomics analysis applied to the four different sample matrices provided an overall view on several metabolic pathways that had tissue-type specific changes after HIIT intervention in subjects with NAFLD. The results highlight especially the role of AT in responding to the HIIT challenge, and suggest that altered amino acid metabolism in AT might play a critical role in e.g. improving fasting plasma glucose concentration.Trial registration ClinicalTrials.gov (NCT03995056).

Targeted Metabolomic Analysis in Alzheimer's Disease Plasma and Brain Tissue in Non-Hispanic Whites.

Background:Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer’s disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis.Objective:In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers.Methods:This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer’s Research and Care Consortium – TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP® Quant 500).Results:We discovered disturbances (FDR≤0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC = 82% (CI95 = 75–88%); for females specifically, AUC = 88% (CI95 = 80–95%). A reduced model using 20 features achieves AUC = 79% (CI95 = 71–85%); for females AUC = 84% (CI95 = 74–92%).Conclusion:Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.

The C-22 sterol desaturase Erg5 is responsible for ergosterol biosynthesis and conidiation in Aspergillus fumigatus

Aspergillus fumigatus is the most prevalent saprophytic fungi and can cause severe invasive aspergillosis in immunocompromised individuals. For infection of A. fumigatus, the small hydrophobic conidia have been shown to play a dominant role. In this study, we found that deletion of erg5, a C-22 sterol desaturase gene which function in the last two steps of ergosterol biosynthesis, was sufficient to block ergosterol biosynthesis and conidiation. The deletion phenotype was further verified by a conditional expression strain of erg5 using the inducible tet-on system. Strikingly, erg5 mutant displays increased susceptibility to antifungal azoles itraconazole. RNA sequencing analysis showed that erg5 deficiency resulted in changes in transcription mainly related to lipid, carbohydrate, and amino acid metabolism. Genes encoding ergosterol biosynthesis-related enzymes were found to be up-regulated in erg5 null mutants. However, genes involved in asexual development, including upstream regulators, melanin biosynthesis enzymes, heterotrimeric G proteins, and MAPK signaling, were down-regulated to various degrees. Furthermore, metabolomic study revealed that erg5 deficiency also resulted in altered lipid and amino acid metabolism, which was consistent with our transcriptomics analysis. Collectively, our study established a link between ergosterol biosynthesis and asexual development at the transcriptomics and metabolomics level in A. fumigatus.

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation.

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum-fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H2S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo-irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H2S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo-irradiated BM and BM HSPCs. The exogenous addition of H2S inhibited Ten eleven translocation 2 (TET2) activity in vitro, thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H2S generation, with translational implications for radiation treatment and aging.

Distinct Roles of Honeybee Gut Bacteria on Host Metabolism and Neurological Processes.

ABSTRACTThe honeybee possesses a limited number of bacterial phylotypes that play essential roles in host metabolism, hormonal signaling, and feeding behavior. However, the contribution of individual gut members in shaping honeybee brain profiles remains unclear. By generating gnotobiotic bees which were mono-colonized by a single gut bacterium, we revealed that different species regulated specific modules of metabolites in the hemolymph. Circulating metabolites involved in carbohydrate and glycerophospholipid metabolism pathways were mostly regulated by Gilliamella, while Lactobacillus Firm4 and Firm5 mainly altered amino acid metabolism pathways. We then analyzed the brain transcriptomes of bees mono-colonized with these three bacteria. These showed distinctive gene expression profiles, and genes related to olfactory functions and labor division were upregulated by Lactobacillus. Interestingly, differentially spliced genes in the brains of gnotobiotic bees largely overlapped with those of bees unresponsive to social stimuli. The differentially spliced genes were enriched in pathways involved in neural development and synaptic transmission. We showed that gut bacteria altered neurotransmitter levels in the brain. In particular, dopamine and serotonin, which show inhibitory effects on the sensory sensitivity of bees, were downregulated in bacteria-colonized bees. The proboscis extension response showed that a normal gut microbiota is essential for the taste-related behavior of honeybees, suggesting the contribution of potential interactions among different gut species to the host’s physiology. Our findings provide fundamental insights into the diverse functions of gut bacteria which likely contribute to honeybee neurological processes.IMPORTANCE The honeybee possesses a simple and host-restricted gut community that contributes to the metabolic health of its host, while the effects of bacterial symbionts on host neural functions remain elusive. We found that the colonization of specific bee gut bacteria regulates distinct circulating metabolites enriched in carbohydrate, amino acid, and glycerophospholipid metabolic pathways. The brains of bees colonized with different gut members display distinct transcriptomic profiles of genes crucial for bee behaviors and division of labor. Alternative splicing of genes related to disordered bee behaviors is also mediated. The presence of gut bacteria promotes sucrose sensitivity with major neurotransmitters being regulated in the brain. Our findings demonstrate how individual bee gut species affect host behaviors, highlighting the gut-brain connections important for honeybee neurobiological and physiological states.

Multi-omics data integration reveals metabolome as the top predictor of the cervicovaginal microenvironment.

Emerging evidence suggests that host-microbe interaction in the cervicovaginal microenvironment contributes to cervical carcinogenesis, yet dissecting these complex interactions is challenging. Herein, we performed an integrated analysis of multiple “omics” datasets to develop predictive models of the cervicovaginal microenvironment and identify characteristic features of vaginal microbiome, genital inflammation and disease status. Microbiomes, vaginal pH, immunoproteomes and metabolomes were measured in cervicovaginal specimens collected from a cohort (n = 72) of Arizonan women with or without cervical neoplasm. Multi-omics integration methods, including neural networks (mmvec) and Random Forest supervised learning, were utilized to explore potential interactions and develop predictive models. Our integrated analyses revealed that immune and cancer biomarker concentrations were reliably predicted by Random Forest regressors trained on microbial and metabolic features, suggesting close correspondence between the vaginal microbiome, metabolome, and genital inflammation involved in cervical carcinogenesis. Furthermore, we show that features of the microbiome and host microenvironment, including metabolites, microbial taxa, and immune biomarkers are predictive of genital inflammation status, but only weakly to moderately predictive of cervical neoplastic disease status. Different feature classes were important for prediction of different phenotypes. Lipids (e.g. sphingolipids and long-chain unsaturated fatty acids) were strong predictors of genital inflammation, whereas predictions of vaginal microbiota and vaginal pH relied mostly on alterations in amino acid metabolism. Finally, we identified key immune biomarkers associated with the vaginal microbiota composition and vaginal pH (MIF), as well as genital inflammation (IL-6, IL-10, MIP-1α).

The KRAS-G12D mutation induces metabolic vulnerability in B-cell acute lymphoblastic leukemia

SummaryMutations in RAS pathway genes are highly prevalent in acute lymphoblastic leukemia (ALL). However, the effects of RAS mutations on ALL cell growth have not been experimentally characterized, and effective RAS-targeting therapies are being sought after. Here, we found that Reh ALL cells bearing the KRAS-G12D mutation showed increased proliferation rates in vitro but displayed severely compromised growth in mice. Exploring this divergence, proliferation assays with multiple ALL cell lines revealed that the KRAS-G12D rewired methionine and arginine metabolism. Isotope tracing results showed that KRAS-G12D promotes catabolism of methionine and arginine to support anabolism of polyamines and proline, respectively. Chemical inhibition of polyamine biosynthesis selectively killed KRAS-G12D B-ALL cells. Finally, chemically inhibiting AKT/mTOR signaling abrogated the altered amino acid metabolism and strongly promoted the in vivo growth of KRAS-G12D cells in B-ALL xenograft. Our study thus illustrates how hyperactivated AKT/mTOR signaling exerts distinct impacts on hematological malignancies vs. solid tumors.

Impact of reduced uterine perfusion pressure model of preeclampsia on metabolism of placenta, maternal and fetal hearts

Preeclampsia is a cardiovascular pregnancy complication characterised by new onset hypertension and organ damage or intrauterine growth restriction. It is one of the leading causes of maternal and fetal mortality in pregnancy globally. Short of pre-term delivery of the fetus and placenta, treatment options are limited. Consequently, preeclampsia leads to increased cardiovascular disease risk in both mothers and offspring later in life. Here we aim to examine the impact of the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia on the maternal cardiovascular system, placental and fetal heart metabolism. The surgical RUPP model was induced in pregnant rats by applying silver clips around the aorta and uterine arteries on gestational day 14, resulting in ~ 40% uterine blood flow reduction. The experiment was terminated on gestational day 19 and metabolomic profile of placentae, maternal and fetal hearts analysed using high-resolution 1H NMR spectroscopy. Impairment of uterine perfusion in RUPP rats caused placental and cardiac hypoxia and a series of metabolic adaptations: altered energetics, carbohydrate, lipid and amino acid metabolism of placentae and maternal hearts. Comparatively, the fetal metabolic phenotype was mildly affected. Nevertheless, long-term effects of these changes in both mothers and the offspring should be investigated further in the future.

Arginine Increases Tolerance to Nitrogen Deficiency in Malus hupehensis via Alterations in Photosynthetic Capacity and Amino Acids Metabolism.

Arginine plays an important role in the nitrogen (N) cycle because it has the highest ratio of N to carbon among amino acids. In recent years, there has been increased research interest in improving the N use of plants, reducing the use of N fertilizer, and enhancing the tolerance of plants to N deficiency. Here, the function of arginine in the growth of apple (Malus hupehensis) under N deficiency was explored. The application of 100 μmol L–1 arginine was effective for alleviating N-deficiency stress. Exogenous arginine promoted the absorption and use of N, phosphorus (P), and potassium (K) under low N stress. The net photosynthetic rate, maximal photochemical efficiency of photosystem II, and chlorophyll content were higher in treated plants than in control plants. Exogenous arginine affected the content of many metabolites, and the content of many amino acids with important functions was significantly increased, such as glutamate and ornithine, which play an important role in the urea cycle. Half of the metabolites were annotated to specialized metabolic pathways, including the synthesis of phenolic substances, flavonoids, and other substances with antioxidant activity. Our results indicate that arginine promotes the plant photosynthetic capacity and alters amino acid metabolism and some antioxidants including phenolic substances and flavonoids to improve the tolerance of apple to N deficiency, possibly through the improvement of arginine content, and the absorption of mineral.

Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection

Despite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5 years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon, and India, respectively, to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.

Metabolomic analysis of amino acids and organic acids in aging mouse eyes using gas chromatography-tandem mass spectrometry.

This is a metabolomics study for monitoring altered amino acid (AA) and organic acid (OA) metabolism of in eyes from aging an mouse model at 8 and 18 weeks and 18 months. Simultaneous metabolic profiling analysis of OAs and AAs was performed as ethoxycarbonyl/methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-tandem mass spectrometry. A total of 42 metabolites-24 AAs and 18 OAs-were determined and their composition values were normalized to the corresponding mean values of 8-week-old mice as the control group. Then their normalized values were plotted as star graphs, which were distorted and readily distinguishable for each age-related group. Among the 42 metabolites, 18 AAs and 11 OAs were age dependent and significantly different (p < 0.05). Principal component analysis and partial least squares discriminant analysis showed unclear separation between 8- and 18-week-old mice but clear separation between these and 18-month-old mice. In particular, the variable importance in projection scores of 4-hydroxyproline, cis-aconitic acid, glycine, isocitric acid, leucine, pipecolic acid and lysine from partial least-squares-discriminant analysis were higher than 1.3. A heatmap for the classification and visualization of 42 metabolites showed differences in metabolite changes with aging. Altered AA and OA profiles were monitored, which may explain the metabolic disturbance of AA and OA. These findings are related to mitochondrial dysfunctions related to energy metabolism and the impaired antioxidant system in the aging eye. Therefore, the present metabolomics results of the association between physiological states and altered metabolism of AA and OA will be useful for understanding the aging eye and related diseases.

Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell Line SH-SY5Y Differentiated with Retinoic Acid.

Manganese (Mn) is an important element; yet acute and/or chronic exposure to this metal has been linked to neurotoxicity and neurodegenerative illnesses such as Parkinson’s disease and others via an unknown mechanism. To better understand it, we exposed a human neuroblastoma cell model (SH-SY5Y) to two Mn chemical species, MnCl2 and Citrate of Mn(II) (0–2000 µM), followed by a cell viability assay, transcriptomics, and bioinformatics. Even though these cells have been chemically and genetically modified, which may limit the significance of our findings, we discovered that by using RA-differentiated cells instead of undifferentiated SH-SY5Y cell line, both chemical species induce a similar toxicity, potentially governed by disruption of protein metabolism, with some differences. The MnCl2 altered amino acid metabolism, which affects RNA metabolism and protein synthesis. Citrate of Mn(II), however, inhibited the E3 ubiquitin ligases–target protein degradation pathway, which can lead to the buildup of damaged/unfolded proteins, consistent with histone modification. Finally, we discovered that Mn(II)-induced cytotoxicity in RA-SH-SY5Y cells shared 84 percent of the pathways involved in neurodegenerative diseases.

Differential and Synergistic Effects of Low Birth Weight and Western Diet on Skeletal Muscle Vasculature, Mitochondrial Lipid Metabolism and Insulin Signaling in Male Guinea Pigs.

Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male “lean” offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload.

Alterations of amino acid metabolism and intestinal microbiota in Chinese mitten crab (Eriocheir sinensis) fed on formulated diet and iced trash fish

Formulated diet (FD) and iced trash fish (ITF) are common diets during E. sinensis farming. However, whether FD can completely replace ITF during long-term E. sinensis farming is still unclear. Thus this study was conducted to compare the differences in amino acid metabolism and intestinal microbiota of the E. sinensis fed on different diets. The crabs were randomly divided into three groups fed on FD, ITF and mixed diet (MD, FD: ITF = 1:1), respectively. The results showed that there were no significant differences in amino acid composition among FD, MD and ITF groups. The activities of AST and ALT, and the mRNA levels of amino acid metabolism-related genes were significantly up-regulated in FD or/and MD groups compared with ITF group. The diversity of intestinal bacterial community was similar between the FD and ITF groups, but the relative abundance of dominant taxa showed marked differences between the two groups. At the phylum level, the relative abundance of Firmicutes was significantly higher, but the relative abundance of Proteobacteria was significantly lower in the FD group than that in ITF group. Meanwhile, at genus level, the relative abundance of Candidatus_Hepatoplasma in FD was higher than that in ITF group. Data related to functional prediction demonstrated that the significantly differenced pathways between the two groups were observed in metabolism (Pyrimidine metabolism, Glycolysis/Gluconeogenesis and Citrate cycle) and environmental information processing (transporters). The overall results indicated that replacement of ITF by FD did not affect amino acid composition, but altered amino acid metabolism and the relative abundance of intestinal microbiota. Our data provided a valuable reference for FD application replacing ITF during long-term E. sinensis farming.

Immunomodulatory Effects of Tryptophan Metabolism in the Glioma Tumor Microenvironment.

Gliomas are the most common primary malignant tumor in adults’ central nervous system. While current research on glioma treatment is advancing rapidly, there is still no breakthrough in long-term treatment. Abnormalities in the immune regulatory mechanism in the tumor microenvironment are essential to tumor cell survival. The alteration of amino acid metabolism is considered a sign of tumor cells, significantly impacting tumor cells and immune regulation mechanisms in the tumor microenvironment. Despite the fact that the metabolism of tryptophan in tumors is currently discussed in the literature, we herein focused on reviewing the immune regulation of tryptophan metabolism in the tumor microenvironment of gliomas and analyzed possible immune targets. The objective is to identify potential targets for the treatment of glioma and improve the efficiency of immunotherapy.

Untargeted analysis of the serum metabolome in cats with exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI) causes chronic digestive dysfunction in cats, but its pathogenesis and pathophysiology are poorly understood. Untargeted metabolomics is a promising analytic methodology that can reveal novel metabolic features and biomarkers of clinical disease syndromes. The purpose of this preliminary study was to use untargeted analysis of the serum metabolome to discover novel aspects of the pathobiology of EPI in cats. Serum samples were collected from 5 cats with EPI and 8 healthy controls. The diagnosis of EPI was confirmed by measurement of subnormal serum feline trypsin-like immunoreactivity (fTLI). Untargeted quantification of serum metabolite utilized ultra-high-performance liquid chromatography-tandem mass spectroscopy. Cats with EPI had significantly increased serum quantities of long-chain fatty acids, polyunsaturated fatty acids, mevalonate pathway intermediates, and endocannabinoids compared with healthy controls. Diacylglycerols, phosphatidylethanolamines, amino acid derivatives, and microbial metabolites were significantly decreased in cats with EPI compared to healthy controls. Diacyclglycerols and amino acid metabolites were positively correlated, and sphingolipids and long-chain fatty acids were negatively correlated with serum fTLI, respectively. These results suggest that EPI in cats is associated with increased lipolysis of peripheral adipose stores, dysfunction of the mevalonate pathway, and altered amino acid metabolism. Differences in microbial metabolites indicate that feline EPI is also associated with enteric microbial dysbiosis. Targeted studies of the metabolome of cats with EPI are warranted to further elucidate the mechanisms of these metabolic derangements and their influence on the pathogenesis and pathophysiology of EPI in cats.