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Background: Colorectal Cancer (CRC) is a prevalent digestive system tumour with significant mortality and recurrence rates. Serum metabolomics, with its high sensitivity and high throughput, has shown potential as a tool to discover biomarkers for clinical screening and monitoring of the CRC patients. Methods: Serum metabolites of 61 sex and age-matched healthy controls and 62 CRC patients (before and after surgical intervention) were analyzed using a ultraperformance liquid chromatography-high resolution mass spectrometer (UPLCMS). Statistical methods and pathway enrichment analysis were used to identify potential biomarkers and altered metabolic pathways. Results: Our analysis revealed a clear distinction in the serum metabolic profile between CRC patients and healthy controls (HCs). Pathway analysis indicated a significant association with arginine biosynthesis, pyrimidine metabolism, pantothenate, and CoA biosynthesis. Univariate and multivariate statistical analysis showed that 9 metabolites had significant diagnostic value for CRC, among them, Guanosine with Area Under the Curve (AUC) values of 0.951 for the training group and0.998 for the validation group. Furthermore, analysis of four specific metabolites (N-Phenylacetylasparticacid, Tyrosyl-Gamma-glutamate, Tyr-Ser and Sphingosine) in serum samples of CRC patients before and after surgery indicated a return to healthy levels after an intervention. Conclusion: Our results suggest that serum metabolomics may be a valuable tool for the screening and monitoring of CRC patients. [ABSTRACT FROM AUTHOR]

Introduction: Metabolomic signatures of type 2 diabetes mellitus (T2DM) in Tibetan Chinese population, a group with high diabetes burden, remain largely unclear. Identifying the serum metabolite profile of Tibetan T2DM (T-T2DM) individuals may provide novel insights into early T2DM diagnosis and intervention. Methods: Hence, we conducted untargeted metabolomics analysis of plasma samples from a retrospective cohort study with 100 healthy controls and 100 T-T2DM patients by using liquid chromatography–mass spectrometry. Results: The T-T2DM group had significant metabolic alterations that are distinct from known diabetes risk indicators, such as body mass index, fasting plasma glucose, and glycosylated hemoglobin levels. The optimal metabolite panels for predicting T-T2DM were selected using a tenfold cross-validation random forest classification model. Compared with the clinical features, the metabolite prediction model provided a better predictive value. We also analyzed the correlation of metabolites with clinical indices and found 10 metabolites that were independently predictive of T-T2DM. Conclusion: By using the metabolites identified in this study, we may provide stable and accurate biomarkers for early T-T2DM warning and diagnosis. Our study also provides a rich and open-access data resource for optimizing T-T2DM management. [ABSTRACT FROM AUTHOR]

The effects of vitamin E supplementation on cancer and other chronic diseases are not clear. We compared the serum metabolomic profile of differing vitamin E dosages in order to re-examine the previously observed changes in a novel C22 lactone sulfate compound, androgenic steroids, and other metabolites. A total of 3409 women and men previously selected for metabolomics studies in the PLCO Cancer Screening Trial were included in this investigation. Serum metabolites were profiled using ultrahigh-performance liquid and gas chromatography/tandem mass spectrometry. Seventy known metabolites including C22 lactone sulfate and androgens were significantly associated with vitamin E supplementation. In the sex-stratified analysis, 10 cofactors and vitamins (e.g., alpha-CEHC sulfate and alpha-CEHC glucuronide), two carbohydrates (glyceric and oxalic acids), and one lipid (glycocholenate sulfate) were significantly associated with vitamin E dose in both males and females (FDR-adjusted p-value < 0.01). However, the inverse association between C22 lactone sulfate and daily vitamin E supplementation was evident in females only, as were two androgenic steroids, 5-androstenediol and androsterone glucuronide. Our study provides evidence of distinct steroid hormone pathway responses based on vitamin E dosages. Further studies are needed to gain biological insights into vitamin E biochemical effects relevant to cancer and other chronic diseases. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is intricately linked to intestinal damage and barrier dysfunction. At present times, there is a growing interest in a metabolite-based therapy for multiple diseases. Methods: Serum samples from septic patients and healthy individuals were collected and their metabonomics profiling assessed using Ultra-Performance Liquid Chromatography-Time of Flight Mass Spectrometry (UPLC-TOFMS). The eXtreme Gradient Boosting algorithms (XGBOOST) method was used to screen essential metabolites associated with sepsis, and five machine learning models, including Logistic Regression, XGBoost, GaussianNB(GNB), upport vector machines(SVM) and RandomForest were constructed to distinguish sepsis including a training set (75%) and validation set(25%). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. Pearson analysis was used to analysis the relationship between the metabolites and the severity of sepsis. Both cellular and animal models were used to HYPERLINK "javascript:;" assess the function of the metabolites. Results: The occurrence of sepsis involve metabolite dysregulation. The metabolites mannose-6-phosphate and sphinganine as the optimal sepsis-related variables screened by XGBOOST algorithm. The XGBoost model (AUROC=0.956) has the most stable performance to establish diagnostic model among the five machine learning methods. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOSTmodel. Pearson analysis reinforced the expression of Sphinganine, Mannose 6-phosphate were positively associated with the APACHE-II, PCT, WBC, CRP, and IL-6. We also demonstrated that sphinganine strongly diminished the LDH content in LPS-treated Caco-2 cells. In addition, using both in vitro and in vivo examination, we revealed that sphinganine strongly protects against sepsis-induced intestinal barrier injury. Discussion: These findings highlighted the potential diagnostic value of the ML, and also provided new insight into enhanced therapy and/or preventative measures against sepsis. [ABSTRACT FROM AUTHOR]

Objective Based on the liquid chromatography-tandem mass spectormetry (LC-MS/MS), to study the effects of Pogostemon cablin on serum metabolism of Guizhou miniature pigs， and to explore its pharmacological mechanism. Methods Nine healthy Guizhou miniature pigs were divided into two groups, namely Pogostemon cablin drug group (n=5) and control group (n=4). The pigs in Pogostemon cablin drug group were orally fed with traditional Chinese medicine formula granules, each 0.5 g per day, for consecutive 8 days, while those in control group were given normal feeding without additional treatment. After the feeding experiment, serum samples were collected and analyzed using the LC-MS/MS technology. The metabolomics data was annotated and compared with KEGG, HMDB and Lipidmaps databases. Bioinformatics analysis methods including partial least squares discriminant analysis (PLS-DA), intergroup clustering, differential metabolite analysis and functional enrichment were used to screen differential metabolic biomarkers and their possible metabolic pathways. Results Forty-four differential metabolites (P<0.05) were screened out from the 443 metabolites, eight differential metabolites were significantly up-regulated (P<0.01), namely cinnamoylglycine, N-benzyl-N-isopropyl-N'-[4-(trifluoromethoxy) phenyl]urea, hypotaurine, D-glucose 6-phosphate, cis-2-decenoic acid, 11(Z), 14(Z) -eicosadienoic acid, prostaglandin A2 and 10-hydroxydecanoic acid, and three differential metabolites were significantly downregulated (P<0.01), namely lysophosphatidyl choline 22:5, lysophosphatidic acid 22:6 and lysophosphatidic acid 22:5. The differential metabolites were mainly enriched in the metabolic pathways of alanine, aspartate and glutamate metabolism (MapID: map00250) and taurine and hypotaurine metabolism (MapID: map00430). Conclusion Pogostemon cablin can significantly affect the metabolism of lysophosphatidic acids in porcine, and relieve the disorder of amino acids metabolism and regulate the occurrence of inflammation by affecting the metabolic pathways of alanine, aspartate and glutamate metabolism and taurine and hypotaurine metabolism. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. Methods: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). Results: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20–28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. Conclusions: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males. [ABSTRACT FROM AUTHOR]

Abstract Background Traditional Chinese Medicine (TCM) has been practiced and developed in China over thousands of years under the guidance of a series of complicated traditional theories. Herbs within TCM usually are classified according to their different properties ranging from cold, cool, warm to hot, which are simplified as Cold and Hot properties. TCM with either Cold or Hot properties are used in various formulae designed for the purpose of restoring the balance of patients. Emerging evidence has highlighted that an altered gut microbiota or host metabolism are critically involved in affecting the healing properties of TCM. However, at present the exact influences and crosstalk on the gut microbiota and host metabolism remain poorly understood. Methods In the present study, the divergent impacts of six TCMs with either Cold or Hot properties on gut microbiome and host metabolism during short- or long-term intervention in mice were investigated. Six typical TCMs with Hot or Cold properties including Cinnamomi Cortex (rougui, RG), Zingiberis Rhizoma (ganjiang, GJ), Aconiti Lateralis Radix Praeparata (fuzi, FZ), Rhei Radix et Rhizoma (dahuang, DH), Scutellariae Radix (huangqin, HQ), and Copitdis Rhizoma (huanglian, HL) were selected and orally administered to male C57BL/6J mice for a short- or a long-term (7 or 35 days). At the end of experiments, serum and cecal contents were collected for metabolomic and gut microbiome analyses using gas chromatography–tandem mass spectrometry (GC–MS) or 16S ribosomal deoxyribonucleic acid (16S rDNA) sequencing. Results The results revealed that the gut microbiome underwent divergent changes both in its composition and functions after short-term intervention with TCM possessing either Cold or Hot properties. Interestingly, the number of changed genus and bacteria pathways was reduced in Hot_LT, but was increased in Cold_LT, especially in the HL group. Increased α diversity and a reduced F/B ratio revealed the changes in Hot_ST, but a reduced Shannon index and increased altered bacteria function was evident in Cold_LT. The serum metabolic profile showed that the influence of TCM on host metabolism was gradually reduced over time. Glycolipid metabolism related pathways were specifically regulated by Hot_ST, but also surprisingly by Cold_LT. Reduced lactic acid in Cold_ST, increased tryptophan concentrations and decreased proline and threonine concentrations in Cold_LT perhaps highlighting the difference between the two natures influence on serum metabolism. These metabolites were closely correlated with altered gut microbiota shown by further correlation analyses. Conclusion The results indicated that TCM properties could be, at least partially characterized by an alteration in the gut microbiota and metabolic profile, implying that the divergent responses of gut microbiome and host metabolism are involved in different responses to TCM. Graphic Abstract

Stress is a common factor that reduces production performance. However, the physiology of stress is not fully understood. In this study, 40-day-old rabbits were injected 1.0 mg/kg BW Dexamethasone to induce stress. A metabolomic study on serum of stress-induced rabbits was performed to research the metabolism mechanism of stress by using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC–MS). Clear separations between stress rabbits and control rabbits were observed by principal component analysis (PCA) based on the data obtained using both analytical techniques and 90 significantly changed metabolites were identified as potential biomarkers of stress. Stress rabbits were characterised by altered levels of serum lysophosphatidylcholines, amino acids, phosphatidyl choline, and nucleosides, which were related to multiple perturbed metabolic pathways and contributed to the elucidation of the complex mechanism of stress. These were main linked to three different pathways: pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and biosynthesis of amino acid. In summary, we provided a comprehensive understanding of metabolic alterations in the main stress-targeted tissues, helping to understand the potential mechanisms underlying stress.HIGHLIGHTS Stress alters the metabolic composition of serum in rabbits. In rabbits, dexamethasone‐induced chronic stress alters 90 metabolites in serum.

Introduction Qishenbuqi capsule (QSBQC), a listed Chinese patent prescription, comprises of 4 herbs. Clinically, it has been shown to improve immune functions. Methods Subjects with Qi deficiency and non- Qi deficiency were recruited, who then took QSBQC for 4 weeks. Traditional Chinese medicine (TCM) syndrome scores and the levels of white blood cells, CD3+ T cells (CD3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), and CD4+/CD8+ were determined. Serum metabolomics was used to explore the metabolic mechanisms of QSBQC on improving immunity. Meanwhile, the potential active ingredients, targets, and pathways of QSBQC on enhancing immunity were screened by network pharmacology. Results QSBQC significantly improved TCM syndrome scores and increased the number of CD8+ T cells of both Qi deficiency and non- Qi deficiency subjects. Serum metabolomics revealed that QSBQC regulated 18 differential metabolites and 8 metabolic pathways of Qi deficiency, and 12 differential metabolites and 7 metabolic pathways of non- Qi deficiency subjects. The "herbs-compounds-pathways" diagram showed that PQ-2, cimifugin, and divaricatol were the main active components. Pathways in cancer and arginine and proline metabolism could be the most important pathways. Conclusion Our research revealed the immunoenhancing mechanisms of QSBQC and improved the combination of TCM theory and modern western medicine theory. [ABSTRACT FROM AUTHOR]

Polysaccharides are important biological macromolecules in all organisms, and have recently been studied as therapeutic agents for ulcerative colitis (UC). However, the effects of Pinus yunnanensis pollen polysaccharides on ulcerative colitis remains unknown. In this study, dextran sodium sulfate (DSS) was used to induce the UC model to investigate the effects of Pinus yunnanensis pollen polysaccharides (PPM60) and sulfated polysaccharides (SPPM60) on UC. We evaluated the improvement of polysaccharides on UC by analyzing the levels of intestinal cytokines, serum metabolites and metabolic pathways, intestinal flora species diversity, and beneficial and harmful bacteria. The results show that purified PPM60 and its sulfated form SPPM60 effectively alleviated the disease progression of weight loss, colon shortening and intestinal injury in UC mice. On the intestinal immunity level, PPM60 and SPPM60 increased the levels of anti-inflammatory cytokines (IL-2, IL-10, and IL-13) and decreased the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α). On the serum metabolism level, PPM60 and SPPM60 mainly regulated the abnormal serum metabolism of UC mice by regulating the energy-related and lipid-related metabolism pathways, respectively. On the intestinal flora level, PPM60 and SPPM60 reduced the abundance of harmful bacteria (such as Akkermansia and Aerococcus) and induced the abundance of beneficial bacteria (such as lactobacillus). In summary, this study is the first to evaluate the effects of PPM60 and SPPM60 on UC from the joint perspectives of intestinal immunity, serum metabolomics, and intestinal flora, which may provide an experimental basis for plant polysaccharides as an adjuvant clinical treatment of UC. [ABSTRACT FROM AUTHOR]

As an easy recurrent metabolic disease, hyperuricemia affected the life quality of patients seriously. Inonotus hispidus is a kind of edible and medicinal fungi with hypouricemic effect. However, the mechanism remains unclear. In this study, cell metabolomics integrated with serum metabolomics were carried out to explore the potential mechanism of Inonotus hispidus in the treatment of hyperuricemia. The results indicate that the potential regulatory mechanism was mainly related to amino acid metabolism and glycerophospholipid metabolism, involving the regulation of 27 metabolites, including 12 in HHL-5 human primary hepatocytes and 15 in mouse plasma. Inonotus hispidus may show efficacy by regulating the synthesis of uric acid, and the fungi can also regulate the lipid disturbances caused by hyperuricemia. This work elucidated potential biomarkers and mechanisms of action in the hypouricemic effect of Inonotus hispidus from the perspective of endogenous metabolites, which provides a scientific basis for its further development and application.

This study was conducted to explore the potential effect of Yucca schidigera extract (YSE) on the metabolism of beef cattle. Thirty Angus crossbreed steers were selected, with an initial mean body weight of 506.6 ± 33.3 kg, and assigned to two treatments: a diet with no additives (CON group) and a diet supplemented with 1.75 g/kg of YSE (YSE group) (on a dry matter basis). The experiment lasted for 104 days, with 14 days for adaptation. The results showed that adding YSE could significantly improve the average daily gain (ADG) from 1 to 59 d (15.38%) (p = 0.01) and 1 to 90 d (11.38%) (p < 0.01), as well as dry matter digestibility (DMD) (0.84%) (p < 0.05). The contents of alanine aminotransferase, aspartate aminotransferase, and bilirubin and the total antioxidant capacity were increased and blood urea was reduced in the YSE group, compared to the CON group (p < 0.05). Both the glycerophospholipids and bile acids, including phosphocholine, glycerophosphocholine, PC(15:0/18:2(9Z,12Z)), PE(18:0/20:3(5Z,8Z,11Z)), PE(18:3(6Z,9Z,12Z)/P-18:0), LysoPC(15:0), LysoPC(17:0), LysoPC(18:0), LysoPC(20:5(5Z,8Z,11Z,14Z,17Z)), deoxycholic acid, glycocholic acid, and cholic acid, were upregulated by the addition of YSE. In summary, YSE may improve the ADG by increasing the blood total antioxidant capacity and glycerophospholipid synthesis, maintaining steers under a healthy status that is beneficial for growth. Furthermore, YSE may also increase the expression of bile acid synthesis, thereby promoting DMD, which, in turn, offers more nutrients available for growth.

Abstract Background Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease. Deficiency pattern (DP) and excess pattern (EP), as crucial types of Chinese medicine pattern diagnoses published by International Classification of Diseases 11th Revision (ICD-11), could provide new strategies for RA diagnosis. However, the biological basis of DP and EP of RA is not explicit. Methods 19 female RA DP patients, 41 female RA EP patients and 30 female healthy participants were included in the study. The serums of participants were collected and analyzed by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to profile metabolic characteristics of RA DP and EP. Furthermore, bioinformatics analysis results were obtained by using Ingenuity Pathway Analysis (IPA) and statistical analysis was performed by SAS version 9.4 for further identification of potential biomarkers. Results Serum metabolic profiling revealed 25 and 24 differential metabolites in RA DP and EP respectively, and 19 metabolites were common to RA DP and EP. Compared with DP group, L-Homocysteic acid, LysoPE(P-16:0/0:0), N(omega)-Hydroxyarginine and LysoPC(16:0/0:0) decreased (P

Capsaicin, a natural bioactive component, has been reported to improve cognition and ameliorate the pathology of Alzheimer's disease (AD). Studies have linked AD to alterations in gut microbiota composition and serum metabolites. In the present study, we examined the alterations in serum metabolome and gut microbiome in APPswe/PS1dE9 (APP/PS1) mice treated with capsaicin. Capsaicin treatments resulted in a significant increase in the abundance of Akkermansia, Faecalibaculum, Unclassified_f_Atopobiaceae, and Gordonibacter and a significant decrease in the abundance of Adlercreutzia, Peptococcaceae, Alistipes, Oscillibacter and Erysipelatoclostridium. Furthermore, the species Akkermansia muciniphila (A. muciniphila) was significantly enriched in capsaicin-treated APP/PS1 mice (p = 0.0002). Serum metabolomic analysis showed that capsaicin-treated APP/PS1 mice had a significant higher level of tryptophan (Trp) metabolism and a significantly lower level of lipid metabolism compared with vehicle-treated mice. Capsaicin altered serum metabolites, including Kynurenine (Kyn), 5-Hydroxy-L-tryptophan (5-HIT), 5-Hydroxyindoleacetic acid (5-HIAA), indoxylsulfuric acid, lysophosphatidyl cholines (LysoPCs), and lysophosphatidyl ethanolamine (LysoPE). Significant correlations were observed between the gut bacteria and serum metabolite. With regard to the increased abundance of A. muciniphila and the ensuing rise in tryptophan metabolites, our data show that capsaicin alters both the gut microbiota and blood metabolites. By altering the gut microbiome and serum metabolome, a diet high in capsaicin may reduce the incidence and development of AD. [ABSTRACT FROM AUTHOR]

Background: Traditional Chinese Medicine (TCM) has been practiced and developed in China over thousands of years under the guidance of a series of complicated traditional theories. Herbs within TCM usually are classified according to their different properties ranging from cold, cool, warm to hot, which are simplified as Cold and Hot properties. TCM with either Cold or Hot properties are used in various formulae designed for the purpose of restoring the balance of patients. Emerging evidence has highlighted that an altered gut microbiota or host metabolism are critically involved in affecting the healing properties of TCM. However, at present the exact influences and crosstalk on the gut microbiota and host metabolism remain poorly understood. Methods: In the present study, the divergent impacts of six TCMs with either Cold or Hot properties on gut microbiome and host metabolism during short- or long-term intervention in mice were investigated. Six typical TCMs with Hot or Cold properties including Cinnamomi Cortex (rougui, RG), Zingiberis Rhizoma (ganjiang, GJ), Aconiti Lateralis Radix Praeparata (fuzi, FZ), Rhei Radix et Rhizoma (dahuang, DH), Scutellariae Radix (huangqin, HQ), and Copitdis Rhizoma (huanglian, HL) were selected and orally administered to male C57BL/6J mice for a short- or a long-term (7 or 35 days). At the end of experiments, serum and cecal contents were collected for metabolomic and gut microbiome analyses using gas chromatography–tandem mass spectrometry (GC–MS) or 16S ribosomal deoxyribonucleic acid (16S rDNA) sequencing. Results: The results revealed that the gut microbiome underwent divergent changes both in its composition and functions after short-term intervention with TCM possessing either Cold or Hot properties. Interestingly, the number of changed genus and bacteria pathways was reduced in Hot_LT, but was increased in Cold_LT, especially in the HL group. Increased α diversity and a reduced F/B ratio revealed the changes in Hot_ST, but a reduced Shannon index and increased altered bacteria function was evident in Cold_LT. The serum metabolic profile showed that the influence of TCM on host metabolism was gradually reduced over time. Glycolipid metabolism related pathways were specifically regulated by Hot_ST, but also surprisingly by Cold_LT. Reduced lactic acid in Cold_ST, increased tryptophan concentrations and decreased proline and threonine concentrations in Cold_LT perhaps highlighting the difference between the two natures influence on serum metabolism. These metabolites were closely correlated with altered gut microbiota shown by further correlation analyses. Conclusion: The results indicated that TCM properties could be, at least partially characterized by an alteration in the gut microbiota and metabolic profile, implying that the divergent responses of gut microbiome and host metabolism are involved in different responses to TCM. [ABSTRACT FROM AUTHOR]

Background: Renshen-Fuzi herb pair (RS-FZ) is often used in the clinical treatment of heart failure (HF) and has a remarkable therapeutic effect. However, the mechanism of RS-FZ for treating HF remains unclear. In our study, we explored the mechanism of RS-FZ for treating HF. Methods: Evaluation of RS-FZ efficacy by cardiovascular pharmacology. Moreover, Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. Multivariate statistics analyzed the specific serum metabolites and corresponding metabolic pathways. Combining serum metabolomics with network pharmacology, animal experiments screened and validated the critical targets of RS-FZ intervention in HF. Results: RS-FZ significantly ameliorated myocardial fibrosis, enhanced cardiac function, and reduced the serum HF marker (brain natriuretic peptide) level in rats with HF. Through topological analysis of the “Metabolite-TargetComponent” interaction network, we found that 79 compounds of RS-FZ directly regulated the downstream specific serum metabolites by acting on four critical target proteins (CYP2D6, EPHX2, MAOB, and ENPP2). The immunohistochemistry results showed that RS-FZ observably improved the expression of CYP2D6 and ENPP2 proteins while decreasing the expression of EPHX2 and MAOB proteins dramatically. Conclusion: The integrated cardiovascular pharmacological assessment with serum metabolomics revealed that RS-FZ plays a crucial role in the treatment of HF by intervening in CYP2D6, EPHX2, MAOB, and ENPP2 target proteins. It provides a theoretical basis for RS-FZ for treating HF. [ABSTRACT FROM AUTHOR]

Stress is a common factor that reduces production performance. However, the physiology of stress is not fully understood. In this study, 40-day-old rabbits were injected 1.0 mg/kg BW Dexamethasone to induce stress. A metabolomic study on serum of stress-induced rabbits was performed to research the metabolism mechanism of stress by using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC–MS). Clear separations between stress rabbits and control rabbits were observed by principal component analysis (PCA) based on the data obtained using both analytical techniques and 90 significantly changed metabolites were identified as potential biomarkers of stress. Stress rabbits were characterised by altered levels of serum lysophosphatidylcholines, amino acids, phosphatidyl choline, and nucleosides, which were related to multiple perturbed metabolic pathways and contributed to the elucidation of the complex mechanism of stress. These were main linked to three different pathways: pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and biosynthesis of amino acid. In summary, we provided a comprehensive understanding of metabolic alterations in the main stress-targeted tissues, helping to understand the potential mechanisms underlying stress. Stress alters the metabolic composition of serum in rabbits. In rabbits, dexamethasone‐induced chronic stress alters 90 metabolites in serum. [ABSTRACT FROM AUTHOR]

In recent years, the relationship between Lycium ruthenicum Murr. anthocyanins (LRA) and health has attracted increasing attention. The purpose of this study is to investigate the anti-aging effect and mechanism of LRA through a D-galactose (DG)-induced aging rat model. Our results showed that the long-term intake of LRA, for 8 weeks, improved motor function, reduced serum aging markers, promoted the endogenous antioxidant system, and suppressed the serum inflammatory cytokines in aging rats. Besides, the LRA treatment alleviated DG-induced liver injuries by relieving the inflammation and inhibiting Fas/FasL-mediated cell death. More importantly, the abnormal serum metabolome profiles of the aging rats were restored by the LRA, relating to 38 metabolites and 44 pathways. Specifically, the LRA significantly affected the amino acid and protein-related metabolic pathways by regulating the levels of L-threonine, L-aspartic acid, glycine, L-histidine, D-homocysteine, L-homocitrulline, L-homoserine, guanidineacetic acid, and kynurenine. These results have important implications for the development of LRA as an anti-aging and liver-protective ingredient. [ABSTRACT FROM AUTHOR]

Abstract Background The establishment of the piglet gut microbiome has a prolonged influence on host health, as it sets the stage for establishment of the adult swine microbiome. Substantial changes in host metabolism and immunity around the time of weaning may be accompanied by alterations in the gut microbiome. In this study, we systematically evaluated differences in the gut microbiome and host metabolites among three weaning periods using shotgun metagenomic sequencing and untargeted metabolomic profiling in piglets. Results We identified that P. copri was the most significantly different species among three weaning periods, and was the key bacterial species for mitigating piglet adaptation during the weaning transition, while Bacillus_phage_BCD7, the only differential bacteriophages, was significantly and positively correlated with P. copri enriched in day 28 group. Additionally, P. copri and Bacillus_phage_BCD7 was significantly correlated with the shifts of functional capacities of the gut microbiome and several CAZymes in day 28 group. Furthermore, the altered metabolites we observed were enriched in pathways matched to the functional capacity of the gut microbiome e.g., aminoacyl-tRNA biosynthesis. Conclusion The results from this study indicate that the bacteria-phage interactions and host-microbial interactions during the weaning transition impact host metabolism, leading to beneficial host changes among three weaning periods.

Angelica sinensis (Oliv.) Diels (AS) is a commonly used herbal medicine and culinary spice known for its gastrointestinal protective properties. Angelica sinensis oil (AO) is the main bioactive component of AS. However, the therapeutic effects and mechanisms of AO on the gastrointestinal tract remain unclear. In this study, we aim to investigated the potential of AO in restoring gut microbiota disorder and metabolic disruptions associated with ulcerative colitis (UC). A systematic chemical characterization of AO was conducted using GC×GC-Q TOF-MS. A UC mouse model was established by freely drinking DSS to assess the efficacy of AO. Utilizing 16 S rRNA sequencing in combination with untargeted metabolomics analysis of serum, we identified alterations in gut microbiota, differential metabolites, and pathways influenced by AO in UC treatment, thereby elucidating the therapeutic mechanism of AO in UC management. Pharmacodynamic results indicated that AO effectively inhibited the content of inflammation mediators, such as Interleukin-1β, Interleukin-6 and tumor necrosis factor-α, and proserved colon tissue integrity in UC mice. Furthermore, AO significantly downregulated the abundance of pathogenic bacteria (Bacteroidetes , Proteobacteria , and Desulfobacteriaceae) while increasing the abundance of beneficial bacteria (Firmicutes , Blautia , Akkermansia , and Lachnospiraceae). Metabolomics analysis highlighted significant disruptions in endogenous metabolism in UC mice, with a notable restoration of SphK1 and S1P levels following AO administration. Besides, we discovered that AO regulated the balance of sphingolipid metabolism and protected the intestinal barrier, potentially through the SphK1/MAPK signaling pathway. Overall, this study indicated that AO effectively ameliorates the clinical manifestations of UC by synergistically regulating gut microbe and metabolite homeostasis. AO emerges as a potential functional and therapeutic ingredient for UC treatment. [Display omitted] • AO effectively alleviated intestinal inflammation in experimental UC mice induced by DSS. • AO systematically regulated the structural disorder of gut microbiota in UC mice and restored the balance of gut microbiota. • AO effectively improved lipid metabolism disorder induced by DSS in mice with UC. • AO could balance dysmetabolism of sphingolipids and improve ulcerative colitis via SphK1/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

The number of gluten-restricted dieters is growing, yet its impact on healthy diets and serum profiles is unclear. This study investigated the effects of a 2-week low-gluten diet (LGD) on the dietary patterns, serum metabolic profiles, and health status of 61 young individuals from a university in southeastern China. Data on food intake, serum metabolomics, blood biochemistry, and fecal SCFA were collected. This population was divided into four dietary patterns by k-means method:1 Processed food group (PB, n = 17), 2 Rice group (RB, n = 10), 3 Fish/shrimp-based group (SB, n = 4), and 4 Vegetable group (VB, n = 30). Serum metabolites and fecal SCFA were measured using HPLC-MS and GC-MS, respectively. After 2-week of LGD, the SB group had the highest diet diversity. There were remarked differences in nutrient intake among the four dietary patterns, but no differences in health indices or fecal SCFA. WGCNA method revealed the differences in metabolite metabolite modules 4 and 5, and 3-hydroxybutyric acid, hydrolyzed fumonisin（HFB1）, and palmitoleic acid were the different metabolites among clusters. Following a 2-week LGD, different dietary patterns lead to different nutrient intakes and serum metabolite profiles. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC) therapy offers a promising cure for Crohn's disease (CD), however, its therapeutic effects vary significantly due to individual differences. Therefore, identifying easily detectable biomarkers is essential to assess the efficacy of MSC therapy. In this study, SAMP1/Yit mice were used as a model of CD, which develop spontaneous chronic ileitis, closely resembling the characteristics present in CD patients. Serum metabolic alterations during treatment were analyzed, through the application of differential 12C-/13C-dansylation labeling liquid chromatography-mass spectrometry. Based on the significant differences and time-varying trends of serum amine/phenol-containing metabolites abundance between the control group, the model group, and the treatment group, four serum biomarkers were ultimately screened for evaluating the efficacy of MSC treatment for CD, namely 4-hydroxyphenylpyruvate, 4-hydroxyphenylacetaldehyde, caffeate, and N-acetyltryptamine, whose abundances both increased in the serum of CD model mice and decreased after MSC treatment. These metabolic alterations were associated with tyrosine metabolism, which was validated by the dysregulation of related enzymes. The discovery of biomarkers may help to improve the targeting and effectiveness of treatment and provide innovative prospects for the clinical application of MSC for CD. [Display omitted] • Mesenchymal stem cell therapy for Crohn's disease efficacy based on metabonomics. • The therapy's effectiveness was associated with tyrosine metabolism. • Four serum biomarkers were screened to evaluate the treatment efficacy. [ABSTRACT FROM AUTHOR]

Qingwanzi Pills (QP) were first mentioned in the "Puji Fang" of the Ming Dynasty, with a history of approximately 600 years. The formula consisted of Gypsum Fibrosum and Indigo Naturalis. It is a famous classical formula with antipyretic effects frequently utilized in ancient China, although our knowledge about the overall antipyretic mechanism of QP remains limited. Therefore, we replicated the fever model in New Zealand rabbits induced by lipopolysaccharide, performed the pharmacodynamic evaluation of QP, identified the differential metabolites among QP groups, and performed pathway enrichment analysis to comparatively analyze the effects of QP on fever-related metabolic pathways by ultra-performance liquid chromatography-mass spectrometry. The results showed that the antipyretic effect of QP was superior to that of each disassembled prescription, with Gypsum Fibrosum primarily contributing to the efficacy, followed by Indigo Naturalis and Junci Medulla. QP had an effective antipyretic effect, which was related to lowering the levels of TNF-α, IL-6, IL-1β, and calcium in rabbit serum, lowering the levels of PGE2 and cAMP in rabbit cerebrospinal fluid, and increasing the level of calcium in rabbit cerebrospinal fluid. A total of 27 endogenous biomarkers were screened by serum metabolomics for the treatment of fever with QP. It is hypothesized that the antipyretic mechanism of QP may be related to regulating α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. In summary, QP exhibited a significant antipyretic effect in rabbits with lipopolysaccharide-induced fever. [Display omitted] • The significant antipyretic activity of the classical formula Qingwanzi Pills was discovered. • It can exert antipyretic effects by modulating inflammatory factors TNF-α, IL-6, IL-1β, and central mediators PGE2 and cAMP. • Its antipyretic mechanisminvolves the regulation of α-linolenic acid, sphingolipid, tryptophan, and bile acid metabolism. [ABSTRACT FROM AUTHOR]

Li Bao,1,2 Chunjing Yang,1,2 Zhengyuan Shi,1,2 Zhanrong Wang,3 Dechun Jiang1,2 1Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Biocharacteristic Profiling for Evaluation of Rational Drug Use, Beijing, People’s Republic of China; 3Department of Traditional Chinese Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Zhanrong WangDepartment of Traditional Chinese Medicine, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing 100038, People’s Republic of China, Tel +86-10-6392-6405Email dor_j@163.comDechun JiangDepartment of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing 100038, People’s Republic of China, Tel +86-10-6392-6723Email jiangdechun@sina.comBackground: Obesity is a public health problem all over the world, and dietary habits are considered one of the important reasons.Methods: In this study, serum metabolites of mice fed a normal or high-fat diet (HFD) were analyzed using UPLC-QTOF-MS.Results: A significant increase in body weight was noted in HFD mice. The HFD and control groups were significantly different from each other on OPLS-DA scores. The major metabolites contributing to obesity were lipid metabolites (phosphatidylcholines, phosphatidylethanolamine, and lysophosphatidylcholines). In addition, this study revealed that glycerophospholipid metabolism, α-linolenic acid metabolism, and linoleic acid metabolism were related to obesity and obesity-associated diseases.Conclusion: These results can be used to better understand obesity and assess its risk, which will provide new ideas for treatment.Keywords: obesity, serum metabolomics, high-fat diet, UPLC-QTOF-MS technique

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWDon CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions. [ABSTRACT FROM AUTHOR]

Grazing (G) yaks (Bos grunniens) are generally of low fertility, which severely limits the income of local pastoralists. However, we recently found that yaks had a 52% higher estrus rate in house feeding (HF) than in G. Gas chromatography-mass spectrometry (GC-MS) and 16S rRNA gene sequencing were used to analyze serum metabolites and fecal microbiota of 20 rutting yaks in the G and HF systems, respectively, to explain this phenomenon. The results showed that 73 total metabolites differed significantly (p < 0.05 and VIP > 1) between the G and HF systems. In the HF system, 53 were upregulated and 20 were downregulated compared with the G system. Organic oxygen compounds, organic acids and their derivatives, and lipids and lipid-like molecules were the most common differential metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapper revealed that 25 metabolic signaling pathways differed significantly between the two systems. The top three enriched pathways included central carbon metabolism in cancer, aminoacyl--tRNA biosynthesis, and ABC transporters. The 16S rRNA gene sequencing data showed no significant differences in Chao 1 index between the two systems. According to principal component analysis (PCA), the HF and G systems were distinctly and separately clustered in terms of fecal microbiota distribution. The G system showed significantly higher abundances of Firmicutes. The HF system showed significantly higher abundances of Alistipes, Treponema, and Rikenellaceae_ RC9_ gut_ group. Pearson's correlation analysis and core network analysis revealed that Rikenellaceae_RC9_ gut_ group, Alistipes, and Treponema were positively correlated with myo-inositol and formed the core bacteria. In summary, the HF system promoted the estrus rate and changed the composition of yak fecal microbiota and serum metabolites. Increased estrus rate might be obtained due to enhanced myo-inositol content in yak serum via the HF system. Correlation analysis suggested that myo-inositol content might also be partly increased via yak-specific fecal microbiota, contributing to the estrus rate. These findings could lead to a novel therapeutic strategy for G yaks due to their low estrus rate. [ABSTRACT FROM AUTHOR]

In in vitro fertilization (IVF), it is meaningful to find novel biomarkers predicting ovarian response in advance. The aim of the study was to identify serum metabolomics predicting ovarian response after controlled ovarian stimulation (COS). Blood samples collected at the start of pituitary downregulation and on the fifth day after COS using Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were analyzed to quantify metabolites. Demographic data were calculated with SPSS version 22.0 software. Multivariate statistics were used to analyze metabolomics dataset. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic model. Analyses revealed 50 different metabolomics between the pre- and post-COS groups. Compared with baseline, amino acids increased significantly following COS. At baseline, acetylglycine was more abundant in FOI<1 group, while glycine and lipids increased in FOI≥1 group. After COS, glycine, N-acetyl-L-alanine, D-alanine, and 2-aminomuconic acid were higher in those with FOI≥1, but L-glutamine was abundant in FOI<1. ROC curves indicated that combination of glycine, acetylglycine, and lipids predicts different responses to COS (AUC=0.866). Serum metabolism might reflect the response to ovarian stimulation. Higher glycine and PC may be a good predictor for response to COS. [ABSTRACT FROM AUTHOR]

Inonotus hispidus (Bull.: Fr.) P. Karst. spore powder (IHS) contains polyphenols and triterpenoids with pharmacological effects. Here, we analyzed its composition, and we investigated the effects of IHS on colorectal cancer (CRC) in B6/JGpt-Apcem1Cin(min)/Gpt (ApcMin/+) mice and its potential mechanisms by analyzing gut microbiota and serum metabolomics. The enzyme-linked immunosorbent assays and Western blotting were used to confirm the changes in the cytokine and protein levels associated with IHS administration. The IHS affected the abundance of gut microbiota and the level of L-arginine (L-Arg). Furthermore, the IHS influenced T cells in ApcMin/+ mice by increasing the interleukin (IL)-2 and decreasing the IL-5, -6, and -10 levels, thus suppressing tumor development. Overall, IHS showed anti-CRC properties in ApcMin/+ mice by affecting the gut microbiota and serum metabolites, which in turn affected the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling, and regulated the abundance of CD8+ T cells. These results provide experimental support for the potential future treatment of CRC with IHS. [ABSTRACT FROM AUTHOR]

The ameliorating effects and mechanisms of Morchella esculenta polysaccharides (MEP-1) on lipid metabolism were investigated in high-fat diet (HFD) mice. The results showed that MEP-1 intervention significantly reduced serum TC, TG, LDL-C, and inflammatory factors (TNF-α, IL-1β and IL-6) in HFD mice in a dose-dependent manner, and high-dose (400 mg/kg/d) exhibited the most significant reductive effects. In addition, MEP-1 significantly recovered the gut microbiota disorders caused by HFD, especially decreasing the ratio of Firmicutes and Bacteroidetes (F/B) and increasing the dominant bacterial of Muribaculaceae&#95;genus, Bacteroides, Alistipes and Enterococcus. Moreover, MEP-1 promoted the production of SCFAs and increased the expression levels of Occludin, Claudin and Muc2, also regulated lipid metabolism disorder and inflammation by inhibiting TLR4/MyD88/NF-κB via the gut-liver axis. In addition, serum metabolomic analysis revealed that l-phenylalanine, l-arginine and acetylcholine were significantly upregulated with MEP-1 intervention, and were negatively correlated with blood lipid level, in which l-arginine could activate NO/PPARα/CPT1A pathway to ameliorate lipid metabolism disorders. Such results demonstrated that gut microbiota, amino acid metabolic and insulin secretion pathways might be the important factors that mediated the regulation of MEP-1 in lipid metabolism. The results also provided new evidence and strategies for the application of MEP-1 as functional foods., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Long-term use of rhubarb (RH) can cause adverse gastrointestinal reactions (such as diarrhea), whereas RH steaming with wine (PRH) can alleviate RH-induced diarrhea. However, the potential material basis and mechanisms by which wine steaming alleviates diarrhea caused by RH remain unclear., Purpose: To reveal the potential material basis and underlying mechanisms of wine steaming in alleviating diarrhea caused by RH from the perspective of small intestinal flora and immune function., Methods: The major anthraquinone/anthrone components were detected using high-performance liquid chromatography (HPLC). Constipation model mice were replicated using loperamide hydrochloride and were administered RH and PRH for six consecutive weeks. Histopathological observation (duodenum, jejunum, and ileum) was performed using hematoxylin-eosin (HE) staining, and the serum levels of inflammatory cytokines, immunoglobulin G (IgG), and immunoglobulin A (IgA) were examined. CD4 + , CD8 + , and Treg cells counts in peripheral blood were determined using flow cytometry; The protein expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) was determined using immunohistochemistry (IHC) and western blot (WB). The small intestine contents and feces were analyzed by 16 S rRNA sequencing and the contents of short chain fatty acids (SCFAs) in feces were determined using gas chromatography-mass spectrometry (GC-MS). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the blood absorption compounds and endogenous metabolites., Results: The levels of the major anthraquinone/anthrone components were decreased in PRH. RH and PRH both increased the wet fecal weight at 12 h (WFW-12) and fecal water rate (FWR), alleviated the dry and black fecal morphology, and relieved small intestine injuries in the second week. In the fourth week, although RH and PRH alleviated the abnormal levels of indicators in the model mice (fecal water rate, immune cells percentage, and TLR4/NF-κB expression), minor small intestinal damage was observed. Compared to that at the fourth week, RH and PRH increased the levels of WFW-12, FWR, inflammatory cytokines, and TLR4/NF-κB expression, and decreased the levels of IgG/IgA and immune cells with extended administration (sixth week). Further, damage to the small intestine worsened (severe ileal damage) and different degrees of loose stools were observed in RH- and PRH-administered mice in the sixth week. Compared with those in the control group, the levels of WFW-12, FWR, inflammatory cytokines, TLR4/NF-κB expression, IgG/IgA, and immune cell percentage were significantly different in the RH-H and PRH-H mice at the sixth week (except for CD8 + in PRH-H). Further, RH and PRH disturbed the gut microbiota (GM) (Lactobacillus and Dubosiella decreased, Aerococcus and Corynebacterium increased) and obviously reduced the content of SCFAs (acetic acid, butyric acid, and isobutyric acid). However, almost all the results indicated a lower impact of PRH than that of RH. Metabolic pathways mainly involved in glycerophospholipid metabolism were identified along with a total of 21 blood absorption components, including anthraquinones, anthrones, flavanols, and tannins. The correlation analysis showed a positive correlation of pathogenic bacteria (Aerococcus and Corynebacterium) with inflammatory cytokines, TLR4/NF-κB, LysoPC(20:0/0:0), and PE (16:0/20:4(8Z,11Z,14Z,17Z)) and a negative correlation with immune cells and SCFAs (acetic acid and isobutyric acid); however, the opposite results were observed for beneficial bacteria (Lactobacillus and Dubosiella)., Conclusion: Overall, PRH can alleviate RH-induced diarrhea by recovering the GM imbalance and abnormal levels of GM-mediated SCFAs, alleviating the decrease in cellular immune function and abnormal expression of TLR4/NF-κB, thereby suppressing the release of inflammatory factors, possibly, through its lower content of anthraquinones. This study explored for the first time the processing mechanism of wine steaming in alleviating RH-induced diarrhea from the aspects of small intestinal flora and small intestinal immune function., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Trichosanthes kirilowii-Allium macrostemon (Chinese name Gualou and Xiebai, GLXB), a classical herb pair, has significant clinical efficacy in the treatment of myocardial ischemia (MI). In this study, network pharmacology combined with RNA-seq strategy was employed to predict the targets and pathways of GLXB for MI. GLXB significantly modulated signaling pathways related to the pathology of MI, such as anti-inflammatory and anti-apoptotic signaling pathways such as WNT, PI3K/AKT, and AMPK. GSEA showed that GLXB administration downregulated these key pathways. In addition, Metabolomic analysis demonstrated that GLXB treatment reversed metabolic disorder. Integrative analysis demonstrated three key metabolites (pyruvate, lactate, and palmitate) and three differential genes (Pck1, Cdo1, and Cth) that affected glycolysis or gluconeogenesis and cysteine and methionine metabolism. The results of molecular docking showed that chrysin-7-O-glucuronide and diosmetin-7-O-rutinoside may be the crucial components that exert myocardial protective activity. Western blot showed that GLXB administration reversed the expression levels of Pck1, Cdo1, Cth, Alb, Bcl2, and Ccnd1. This study has elucidated that GLXB could alleviate MI in rats by modulating WNT and PI3K/AKT signaling pathways, thereby reducing inflammation and apoptosis as well as improving energy metabolism., (© 2024 John Wiley & Sons Ltd.)

This study investigated the impact of Glycyrrhiza polysaccharides (GPS) on the respiratory health of broilers. Specifically, 240 one-day-old male Arbor Acres (AA) broilers were randomly assigned to two groups: basal diet (CON) and GPS (supplemented with 150 mg/kg of Glycyrrhiza polysaccharides). When compared with the CON group, the GPS group significantly increased the broiler average daily gain, serum immunoglobulin A, immunoglobulin M, immunoglobulin G, antioxidant capacity, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and tracheal messenger RNA (mRNA) expression levels of SOD1, SOD2, and GSH-Px. The GPS group also had a reduced feed conversion ratio, reduced lung IL-1β and IL-6 levels, and upregulated tracheal mRNA expression of Occludin, Claudin1, and Mucin-2. Additionally, the GPS group had alterations in lung microbial diversity and composition. Transcriptomic and metabolomic analyses revealed the activation of the T cell receptor (TCR) signaling pathway and linoleic acid metabolic pathway in the GPS group. Correlation analysis demonstrated significant associations between differential bacteria, genes, serum metabolites, and phenotypic indicators. In conclusion, Glycyrrhiza polysaccharide supplementation positively influenced the respiratory health of broilers by modulating the lung microbiota, activating the TCR signaling pathway, and affecting the linoleic acid metabolism pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Constitution is a valuable part of traditional Chinese medicine theory; it is defined as the internal foundation for the occurrence, development, transformation and outcome of diseases, and has its characteristic gut microbiota. Previous study showed that deficiency constitution was related to lower Hb counts. However, no research has examined how alterations in the gut microbiome induced by deficiency constitution may increase the tendency for anemia., Methods: We used a multiomics strategy to identify and quantify taxonomies and compounds found under deficient constitution individuals and further explore the possible pathological factors that affect red blood cell indices., Results: ① People with deficient constitution showed lower hemoglobin (Hb), more Firmicutes, less Bacteroidetes, and higher α diversity. ② We identified Escherichia coli , Clostridium bolteae , Ruminococcus gnavus , Streptococcus parasanguinis and Flavonifractor plautii as potential biomarkers of deficient constitution. ③ Slackia piriformis , Clostridium&#95;sp&#95;L2&#95;50 and Bacteroides plebeius were enriched in balanced-constitution individuals, and Parabacteroides goldsteinii was the key bacterial marker of balanced constitution. ④ Flavonifractor plautii may be a protective factor against the tendency for anemia among deficient individuals. ⑤ Ruminococcus gnavus may be the shared microbe base of deficiency constitution-related the tendency for anemia. ⑥ The microorganism abundance of the anaerobic phenotype was lower in deficient constitution group. ⑦ Alterations in the microbiome of deficient-constitution individuals were associated with worse health status and a greater risk of anemia, involving intestinal barrier function, metabolism and immune responses, regulated by short-chain fatty acids and bile acid production., Conclusion: The composition of the gut microbiome was altered in people with deficient constitution, which may explain their poor health status and tendency toward anemia., Competing Interests: LHa and XJ is employed by Kangmeihuada GeneTech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Chen, Lin, Huang, Qiu, Sun, Yuan, Xu, Chen, Xu, Shang, Deng, Liu, Tan, He, Li, Deng, Zhang, Guan, Liang, Fang, Jiang, Han, Huang and Yang.)

Supercritical carbon-dioxide (SC-CO2) is a promising two-phase technology for flavor components (volatile oil and alkylamides) extract from Zanthoxylum bungeanum pericarp. However, the gastric protective effect of SC-CO2 extract from Z. bungeanum (SZB) have not been systematically investigated. In this study, response surface methodology (RSM) was employed to optimize the yield of SZB, and the average yield of 11.07 % were obtained under optimal parameters (30 MPa, 43 °C and time 75 min). Here, limonene, linalool and hydroxy-α-sanshool were identified as the main compounds of SZB by GC–MS and UPLC-Q-Extractive Orbitrap/MS analysis. When the gastric protective effect of SZB (5, 10 and 20 mg/kg, p.o.) were evaluated, significant increase in body weight and organ indexes of rat, and decreased gastric lesion were observed. Furthermore, nineteen serum metabolites were regarded as the potential biomarkers for the gastric protective effect of SZB. Collectively, this study provides a comprehensive perspective into the chemical composition analysis and gastric protective effect of Z. bungeanum SC-CO2 extract.

BackgroundProbiotics have shown potential antidepressant effects. This study evaluated the effect and probable mechanisms of bifid triple viable capsules (BTVCs) on a rat model of chronic unpredictable mild stress (CUMS).Materials and methodsRats were randomly divided into Normal, CUMS model, fluoxetine hydrochloride (FLX), BTVCs, and FLX+BTVCs groups. Depressive-like behaviours, pathological changes in the hippocampus, changes in serum metabolites and potential biomarkers, and metabolic pathways were detected via behavioural tests, haematoxylin-eosin staining, nissl staining, non-targetted metabolomics, and ingenuity pathway analysis (IPA).ResultsThe rats displayed depressive-like behaviours after CUMS exposure, but BTVCs ameliorated the depressive-like behaviours. In addition, the pathological results showed that the hippocampal tissue was damaged in rats after CUMS exposure and that the damage was effectively alleviated by treatment with BTVCs. A total of 20 potential biomarkers were identified. Treatment with BTVCs regulated D-phenylalanine, methoxyeugenol, (±)-myristoylcarnitine, 18:3 (6Z, 9Z, 12Z) /P-18:1 (11Z), propionyl-L-carnitine, and arachidonic acid (AA) concentrations, all compounds that are involved with biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, linoleic acid metabolism and AA metabolism. The IPA demonstrated that endothelin-1 signalling and cyclic adenosine monophosphate response element binding protein (CREB) signalling in neurons may be involved in the development of depression.ConclusionOur findings suggest that BTVCs can alleviate depressive-like behaviours, restore damage to the hippocampus in CUMS rats and regulate serum metabolism, which may be related to endothelin-1 signalling or CREB signalling in neurons.

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by skip intestinal lesions that can occur in any part of the gastrointestinal tract. Currently, the diagnosis of CD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in metabolites in CD serum and identify potential predictive biomarkers of CD diagnosis. We collected serum samples from 316 subjects, including patients with CD and healthy controls (HCs). Serum metabolomics was conducted using liquid chromatography coupled to mass spectrometry. Potential biomarkers were screened and evaluated by univariate and multivariate analyses. A panel of two metabolites (deoxycholic acid and palmitic amide) was identified as a specific biomarker of CD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 80.25% with a specificity of 95.54% in discriminating CD patients from healthy controls. The biomarkers identified are increased in CD compared with healthy controls. Our approach successfully identified serum biomarkers associated with CD patients. The potential biomarkers indicated that CD metabolic disturbance might be associated with bile acid biosynthesis, fatty acids and energy metabolism.

(1) Background: Fecal microbiota transplantation (FMT) is an effective treatment for ulcerative colitis (UC). Metabolomic techniques would assist physicians in clinical decision-making. (2) Methods: Patients with active UC undergoing FMT were enrolled in the study and monitored for 3 months. We explored short-term changes in the serum metabolic signatures of groups and the association between baseline serum metabolomic profiles and patient outcomes. (3) Results: Forty-four eligible patients were included in the analysis. Of them, 50.0% and 29.5% achieved clinical response and clinical remission, respectively, 3 months post-FMT. The top two significantly altered pathways in the response group were vitamin B6 metabolism and aminoacyl-tRNA biosynthesis. Both the remission and response groups exhibited an altered and enriched pathway for the biosynthesis of primary bile acid. We found a clear separation between the remission and non-remission groups at baseline, characterized by the higher levels of glycerophosphocholines, glycerophospholipids, and glycerophosphoethanolamines in the remission group. A random forest (RF) classifier was constructed with 20 metabolic markers selected by the Boruta method to predict clinical remission 3 months post-FMT, with an area under the curve of 0.963. (4) Conclusions: FMT effectively induced a response in patients with active UC, with metabolites partially improving post-FMT in the responsive group. A promising role of serum metabolites in the non-invasive prediction of FMT efficacy for UC demonstrated the value of metabolome-informed FMT in managing UC.

The effects of vitamin E supplementation on cancer and other chronic diseases are not clear. We compared the serum metabolomic profile of differing vitamin E dosages in order to re-examine the previously observed changes in a novel C22 lactone sulfate compound, androgenic steroids, and other metabolites. A total of 3409 women and men previously selected for metabolomics studies in the PLCO Cancer Screening Trial were included in this investigation. Serum metabolites were profiled using ultrahigh-performance liquid and gas chromatography/tandem mass spectrometry. Seventy known metabolites including C22 lactone sulfate and androgens were significantly associated with vitamin E supplementation. In the sex-stratified analysis, 10 cofactors and vitamins (e.g., alpha-CEHC sulfate and alpha-CEHC glucuronide), two carbohydrates (glyceric and oxalic acids), and one lipid (glycocholenate sulfate) were significantly associated with vitamin E dose in both males and females (FDR-adjusted p-value < 0.01). However, the inverse association between C22 lactone sulfate and daily vitamin E supplementation was evident in females only, as were two androgenic steroids, 5-androstenediol and androsterone glucuronide. Our study provides evidence of distinct steroid hormone pathway responses based on vitamin E dosages. Further studies are needed to gain biological insights into vitamin E biochemical effects relevant to cancer and other chronic diseases.

Background: Rheumatoid arthritis (RA) is a chronic and refractory autoimmune disease. Deficiency pattern (DP) and excess pattern (EP), as crucial types of Chinese medicine pattern diagnoses published by International Classification of Diseases 11th Revision (ICD-11), could provide new strategies for RA diagnosis. However, the biological basis of DP and EP of RA is not explicit. Methods: 19 female RA DP patients, 41 female RA EP patients and 30 female healthy participants were included in the study. The serums of participants were collected and analyzed by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to profile metabolic characteristics of RA DP and EP. Furthermore, bioinformatics analysis results were obtained by using Ingenuity Pathway Analysis (IPA) and statistical analysis was performed by SAS version 9.4 for further identification of potential biomarkers. Results: Serum metabolic profiling revealed 25 and 24 differential metabolites in RA DP and EP respectively, and 19 metabolites were common to RA DP and EP. Compared with DP group, L-Homocysteic acid, LysoPE(P-16:0/0:0), N(omega)-Hydroxyarginine and LysoPC(16:0/0:0) decreased (P < 0.05), and Pyruvic acid, D-Ribose, Gamma-Glutamylserine, PE(22:0/24:1(15Z)), Inosinic acid increased (P < 0.05) in EP group. Menawhile, S-Nitrosoglutathione, 5-Thymidylic acid, SN38 glucuronide, PE(22:0/24:0), PC(24:0/24:1(15Z)) and Bisdiphosphoinositol tetrakisphosphate increased significantly in DP group compared to EP group (P < 0.05). For the unique metabolites, bioinformatics analysis results showed that 5-Methoxytryptamine involved in Melatonin Degradation II and Superpathway of Melatonin Degradation is the key metabolite to RA DP. Meanwhile, GABA is the key metabolite in EP group, which involved in Glutamate Dependent Acid Resistance, GABA Receptor Signaling, Glutamate Degradation III (via 4-aminobutyrate) and 4-aminobutyrate Degradation I. Bioinformatics analysis between unique metabolites of RA DP and EP groups with human target genes for RA showed that 5-methoxytryptamine and LysoPC(18:1(9Z)/0:0), the unique metabolites of RA DP, might participate in colorectal cancer metastasis signaling, tumor microenvironment pathway, apoptosis signaling, MYC mediated apoptosis signaling, erythropoietin signaling pathway and LXR/RXR activation. Simultaneously, GABA, LysoPA(18:1(9Z)/0:0) and L-Targinine, the unique metabolites of RA EP, might participate in neuroinflammation signaling pathway, osteoarthritis pathway, glucocorticoid receptor signaling, ILK signaling, IL-17 signaling and HIF1α signaling. Conclusions: The study indicates that serum metabolomics preliminarily revealed the biological basis of RA DP and EP. 5-methoxytryptamine, LysoPC(18:1(9Z)/0:0) and GABA, LysoPA(18:1(9Z)/0:0), L-Targinine might be the predictors to distinguish the DP and EP of RA respectively. These interesting results provide thoughts for further study of traditional medicine patterns of ICD-11. It also contributes to provide strategy for personalized precision treatment of RA and further validation is needed. [ABSTRACT FROM AUTHOR]

Introduction: Closed head injury (CHI) causes neurological disability along with systemic alterations that can activate neuro-endocrine response through hypothalamic–pituitary–adrenal (HPA) axis activation. A dysregulated HPA axis function can lead to relocation of energy substrates and alteration in metabolic pathways and inflammation at the systemic level. Objectives: Assessment of time-dependent changes in serum metabolites and inflammation after both mild and moderate CHI. Along with this, serum corticosterone levels and hypothalamic microglial response were observed. Methods: Rats underwent mild and moderate weight-drop injury and their serum and hypothalamus were assessed at acute, sub-acute and chronic timepoints. Changes in serum metabolomics were determined using high resolution NMR spectroscopy. Serum inflammatory cytokine, corticosterone levels and hypothalamic microglia were assessed at all timepoints. Results: Metabolites including lactate, choline and branched chain amino acids were found as the classifiers that helped distinguish between control and injured rats during acute, sub-acute and chronic timepoints. While, increased αglucose: βglucose and TMAO: choline ratios after acute and sub-acute timepoints of mild injury differentiated from moderate injured rats. The injured rats also showed distinct inflammatory profile where IL-1β and TNF-α levels were upregulated in moderate injured rats while IL-10 levels were downregulated in mild injured rats. Furthermore, injury specific alterations in serum metabolic and immunologic profile were found to be associated with hyperactive HPA axis, with consistent increase in serum corticosterone concentration post injury. The hypothalamic microglia showed a characteristic activated de-ramified cellular morphology in both mild and moderate injured rats. Conclusion: The study suggests that HPA axis hyperactivity along with hypothalamic microglial activation led to temporal changes in the systemic metabolism and inflammation. These time dependent changes in the metabolite profile of rats can further strengthen the knowledge of diagnostic markers and help distinguish injury related outcomes after TBI. [ABSTRACT FROM AUTHOR]

The metabolic alterations associated with the increase in milk production make the transition period critical to the health of dairy cows, usually leading to a higher incidence of disease in periparturient animals. In this manuscript, we describe the use of NMR-based untargeted metabolomics to follow how these changes impact the serum metabolome in a group of 28 transition dairy cows with no initial clinical diseases. Principal component analysis (PCA) of serum 1H NMR data from four weeks before calving to 8 weeks after parturition allowed us to clearly identify four stages during the transition period. Pairwise comparisons using orthogonal partial least square discriminant analysis (OPLS-DA) and univariate data analysis led to the identification of 18 metabolites that varied significantly through these stages. Species such as acetate, betaine, and creatine are observed early after calving, while other markers of metabolic stress, including acetone, β-hydroxybutyrate (BHB), and choline, accumulate significantly at the height of milk production. Furthermore, marked variations in the levels of lactate, allantoin, alanine, and other amino acids reveal the activation of different gluconeogenic pathways following parturition. Concomitant with a return to homeostasis, a gradual normalization of the serum metabolome occurs 8 weeks after calving. Correlations of metabolite levels with dietary and metabolic adaptations based on animal parity could also be identified. Overall, these results show that NMR-based chemometric methods are ideally suited to monitor manifestations of metabolic diseases throughout the transition period and to assess the impact of nutritional management schemes on the metabolism of dairy cows.

Honglei Zhao,1 Hongyan Wu,2 Meitao Duan,2 Ruixuan Liu,2 Quanhong Zhu,1 Kai Zhang,2 Lili Wang1 1Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 2Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, People’s Republic of ChinaCorrespondence: Kai ZhangResearch Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technologies, Chinese Academy of Sciences, Shenzhen, People’s Republic of ChinaTel +86-13076878540Email kai.zhang@siat.ac.cnLili WangFuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of ChinaEmail 1248532808@qq.comPurpose: The aim of the present study was to examine the protective effects of cinnamaldehyde (CA) on type 1 diabetes mellitus (T1DM) and explore the underlying molecular mechanisms by using multiple omics technology.Methods: T1DM was induced by streptozotocin in the mice. Immunostaining was performed to evaluate glycogen synthesis in the liver and morphological changes in the heart. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. The serum metabolomics were determined by liquid chromatography–mass spectrometry. The relevant gene expression levels were determined by quantitative real-time PCR.Results: CA treatment significantly improved the glucose metabolism and insulin sensitivity in T1DM mice. CA increased glycogen synthesis in the liver and protected myocardial injury in T1DM mice. CA affected the gut microbiota particularly by increasing the relative abundance of Lactobacillus johnsonii and decreasing the relative abundance of Lactobacillus murinus in T1DM mice. The glucose level was positively correlated with 88 functional pathways of gut microbiota and negatively correlated with 2 functional pathways of gut microbiota. Insulin resistance was positively correlated with 11 functional pathways. The analysis of serum metabolomics showed that CA treatment significantly increased the levels of taurochenodeoxycholic acid, tauroursodeoxycholic acid, tauro-α-muricholic acid and tauro-β-muricholic acid, taurodeoxycholic acid, taurocholic acid and taurohyodeoxycholic acid in T1DM mice. Taurohyodeoxycholic acid level was highly correlated with the blood glucose levels. Furthermore, the abundance of Faecalibacterium prausnitzii was positively correlated with AKT2, insulin like growth factor 1 receptor, E2F1 and insulin receptor substrate 1 mRNA expression levels, while taurohyodeoxycholic acid level was negatively correlated with IRS1 mRNA expression level.Conclusion: Our results indicated that CA may interfere with gut microbiota to affect host metabolomics, especially the bile acids, so as to directly or indirectly modulate the expression levels of glucose metabolism-related genes, thus subsequently reducing the blood glucose level in the T1DM mice.Keywords: cinnamaldehyde, type 1 diabetes, glucose, insulin, gut microbiota, serum metabolomics

Animal aggression is one of the most conserved behaviors. Excessive and inappropriate aggression was a serious social concern across species. After long-term selection under strict stress conditions, Henan gamecock serves as a good model for studying aggressive behavior. In this research, we constructed a Henan game chicken backcross population containing 25% Rhode Island Red (RIR), and conducted brain transcriptomics and serum metabolomics analyses on Henan gamecock (HGR) through its comparison with its female encounters (HGH) and the male backcross birds (BGR). The study revealed that seven differential metabolites in serum and 172 differentially expressed genes in the brain were commonly shared in both HGR vs. HGH and HGR vs. BGR comparisons. They exhibited the same patterns of modulation in Henan gamecocks, following either HGH < HGR > BGR or HGH > HGR < BGR style. Therein, some neurological genes involving in serotonergic and dopaminergic signaling were upregulated, while the levels of many genes related with neuro-immune function were decreased in Henan gamecock. In addition, many unknown genes specifically or highly expressed in the brain of the Henan gamecock were identified. These genes are potentially key candidates for enhancing the bird's aggression. Multi-omics joint analysis revealed that tyrosine metabolism and neuroactive ligand-receptor interaction were commonly affected. Overall, our results propose that the aggressiveness of Henan gamecocks can be heightened by the activation of the serotonergic-dopaminergic metabolic process in the brain, which concurrently impairs the neuroimmune system. Further research is needed to identify the function of these unknown genes on the bird's aggressive behavior. [ABSTRACT FROM AUTHOR]

Di Zhang,1,* Yafei Guo,2,* Yingli Wang2 1Department of Basic Medicine, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Traditional Chinese Medicine and Food Engineering, Shanxi University of Traditional Chinese Medicine, Jinzhong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di Zhang Email zhangdi0801@live.cnIntroduction: Astragalus is a commonly used traditional Chinese medicine in China, which has been widely applied to enhance the immunomodulatory function of the body. The main bioactive components are complicated. To explore the role of the components, various techniques have been applied in Astragalus extraction. Membrane separation technique featured with green processing condition and high efficiency is of signification interest in the application of Astragalus treatment.Methods: In this study, a new ingredients group A4 was separated from Astragalus using membrane separation technique. The quantification and identification of A4 were achieved by UV-vis spectrometry and UPLC-MS measurements. Pathological approaches along with serum metabolomics were utilized to study the immunoprotective effects of the extracts and explore the underlying mechanisms on metabolic activity.Results: It was observed that A4 could promote the secretion of IL-2 and IFN-γ, stimulate the activated CD4+CD25+ and CD8+ CD25+ T lymphocytes in splenocytes and protect rat spleen to some extent. Seven crucial biomarkers that related to immunity regulations were screened out and identified through serum metabonomic analysis coupled with nuclear magnetic resonance. The enrichment analysis revealed that A4 alleviated the immune dysfunction by modulating amino acid metabolism and energy metabolism for the first time.Conclusion: The new ingredients group A4 isolated from the Astragalus membrane can reduce the immune dysfunction by regulating the amino acid metabolism and energy metabolism of rats.Keywords: Astragalus, membrane separation, immunomodulatory, serum metabolomics

[Display omitted] • A total of 50 chemical compounds were identified from the aqueous decoction of oven-dried (DCF) and shade-dried Chrysanthemi Flos (SCF). • Chrysanthemi Flos showed hypotensive, lipid-regulating, and liver and kidney damage-reducing effects in MetS disease. • The eight metabolites considered as potential biomarkers for the treatment of MetS. • No significant difference between DCF and SCF for the treatment of MetS. As an important medicinal and dietary flower tea, Chrysanthemi Flos has hypotensive, hypolipidemic and hypoglycaemic benefits. This study investigated the effects of two types of processed Chrysanthemi Flos products—oven-dried Chrysanthemi Flos (DCF) and shade-dried Chrysanthemi Flos (SCF)—on rats with metabolic syndrome (MetS) and their potential mechanisms of action. The pharmacodynamic analysis showed that DCF and SCF improved hypertension, regulated lipid profiles, and reduced liver and kidney damage. Metabolomics analysis revealed eight metabolites, including L-serine, oxaloacetate and succinate as potential biomarkers for mitigating metabolic disorders in MetS rats. Our findings provide scientific evidence for the integration of Chrysanthemi Flos -based products into clinical dietary interventions, offering insights into the mechanisms through which these products can ameliorate MetS. These results have important implications for the development of functional foods that can improve metabolic health. [ABSTRACT FROM AUTHOR]

In the present work, a neutral polysaccharide (DHP-2W) with attenuating cognitive disorder was identified from Dendrobium huoshanense and its structure was clarified. The polysaccharide was successfully purified from D. huoshanense by column chromatography and its activity was evaluated. With a molecular weight of 508.934 kDa, this polysaccharide is composed of mannose and glucose at a molar ratio of 75.81: 24.19. Structural characterization revealed that DHP-2W has a backbone consisting of 4)- β -D-Manp-(1 and 4)- β -D-Glcp-(1. In vivo experiments revealed that DHP-2W improved cognitive disorder in D-galactose treated mice and relieved oxidative stress and inflammation. DHP-2W attenuates D-galactose-induced cognitive disorder by inhibiting the BCL2/BAX/CASP3 pathway and activating the AMPK/SIRT pathway, thereby inhibiting apoptosis. Furthermore, DHP-2W had a significant effect on regulating the serum levels of Flavin adenine dinucleotide, Shikimic acid, and Kynurenic acid in aged mice. These, in turn, had a positive impact on AMPK/SIRT1 and BCL2/BAX/CASP3, resulting in protective effects against cognitive disorder. • Dendrobium huoshanense homogeneous polysaccharide (DHP-2W) was studied to slow down inflammation and improve cognitive disorder in ageing mice. • The anti-aging mechanism of Dendrobium huoshanense homogeneous polysaccharide (DHP-2W) was verified to be the Bcl2/Bax/Caspase3 and AMPK/SIRT1 signaling pathways. • To explore the material basis of improving cognitive disorder of Dendrobium huoshanense homogeneous polysaccharide by using serum non-targeted metabolome for the first time. [ABSTRACT FROM AUTHOR]

Polysaccharides are important biological macromolecules in all organisms, and have recently been studied as therapeutic agents for ulcerative colitis (UC). However, the effects of Pinus yunnanensis pollen polysaccharides on ulcerative colitis remains unknown. In this study, dextran sodium sulfate (DSS) was used to induce the UC model to investigate the effects of Pinus yunnanensis pollen polysaccharides (PPM60) and sulfated polysaccharides (SPPM60) on UC. We evaluated the improvement of polysaccharides on UC by analyzing the levels of intestinal cytokines, serum metabolites and metabolic pathways, intestinal flora species diversity, and beneficial and harmful bacteria. The results show that purified PPM60 and its sulfated form SPPM60 effectively alleviated the disease progression of weight loss, colon shortening and intestinal injury in UC mice. On the intestinal immunity level, PPM60 and SPPM60 increased the levels of anti-inflammatory cytokines (IL-2, IL-10, and IL-13) and decreased the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α). On the serum metabolism level, PPM60 and SPPM60 mainly regulated the abnormal serum metabolism of UC mice by regulating the energy-related and lipid-related metabolism pathways, respectively. On the intestinal flora level, PPM60 and SPPM60 reduced the abundance of harmful bacteria (such as Akkermansia and Aerococcus) and induced the abundance of beneficial bacteria (such as lactobacillus). In summary, this study is the first to evaluate the effects of PPM60 and SPPM60 on UC from the joint perspectives of intestinal immunity, serum metabolomics, and intestinal flora, which may provide an experimental basis for plant polysaccharides as an adjuvant clinical treatment of UC.

Background: The establishment of the piglet gut microbiome has a prolonged influence on host health, as it sets the stage for establishment of the adult swine microbiome. Substantial changes in host metabolism and immunity around the time of weaning may be accompanied by alterations in the gut microbiome. In this study, we systematically evaluated differences in the gut microbiome and host metabolites among three weaning periods using shotgun metagenomic sequencing and untargeted metabolomic profiling in piglets. Results: We identified that P. copri was the most significantly different species among three weaning periods, and was the key bacterial species for mitigating piglet adaptation during the weaning transition, while Bacillus_phage_BCD7, the only differential bacteriophages, was significantly and positively correlated with P. copri enriched in day 28 group. Additionally, P. copri and Bacillus_phage_BCD7 was significantly correlated with the shifts of functional capacities of the gut microbiome and several CAZymes in day 28 group. Furthermore, the altered metabolites we observed were enriched in pathways matched to the functional capacity of the gut microbiome e.g., aminoacyl-tRNA biosynthesis. Conclusion: The results from this study indicate that the bacteria-phage interactions and host-microbial interactions during the weaning transition impact host metabolism, leading to beneficial host changes among three weaning periods. [ABSTRACT FROM AUTHOR]

Frailty is a complicated syndrome that occurs at various ages, with highest incidence in aged populations, suggesting associations between the pathogenesis of frailty and age-related changes. Gut microbiota (GM) diversity and abundance change with age, accompanied by increased levels of trimethylamine oxide (TMAO), a systemic inflammation-inducing GM metabolite. Thus, we hypothesized that TMAO may be involved in the development of frailty. We successfully established and verified a novel model of frailty in adult mice based on a 4-week intraperitoneal injection regime of TMAO followed by LPS challenge. The frailty index significantly increased in TMAO-treated mice after LPS challenge. TMAO also decreased claudin-1 immunofluorescent staining intensity in the jejunum, ileum, and colon, indicating that the destruction of intestinal wall integrity may increase vulnerability to exogenous pathogens and invoke frailty. 16S sequencing showed that TMAO significantly reduced the GM Firmicutes/Bacteroidetes (F/B) ratio, but not α-diversity. Interestingly, after LPS challenge, more genera of bacterial taxa were differently altered in the control mice than in the TMAO-treated mice. We infer that a variety of GM participate in the maintenance of homeostasis, whereas TMAO could blunt the GM and impair the ability to recover from pathogens, which may explain the continuous increase in the frailty index in TMAO-treated mice after LPS challenge. TMAO also significantly increased serum imidazole metabolites, and led to different patterns of change in serum peptide and phenylpropanoid metabolites after LPS stimulation. These changes indicate that glucose metabolism may be one mechanism by which GM inactivation causes frailty. In conclusion, TMAO leads to frailty by destroying intestinal barrier integrity and blunting the GM response. [ABSTRACT FROM AUTHOR]

Aim: At‐risk mental state (ARMS) has been recently attracting attention with respect to the improvement of the management and outcome of psychiatric diseases, such as schizophrenia. Since only a few studies have reported on biological alterations in ARMS, serum metabolomics was carried out in ARMS subjects and healthy controls using liquid chromatography with high‐resolution mass spectrometry. Methods: Serum samples were collected from ARMS subjects (n = 24; male: 12; female 12) and age‐ and sex‐matched healthy controls (n = 23 male: 11, female: 12). After serum pre‐treatment, liquid chromatography with high‐resolution mass spectrometry was performed. Multivariate analyses, such as orthogonal partial least‐squares discriminant and volcano plot analyses, were performed. Results: Serum inosine, lactate, taurine, 2,3‐dihydroxypropanoate and glutamate levels differed between the two groups. A significant increase in inosine levels was detected in the positive‐ and negative‐ion modes; however, significant differences were not observed in the levels of other purine‐related metabolites (hypoxanthine, xanthine and urate) between the two groups. Conclusion: Increased inosine levels may serve as biological markers for ARMS, in addition to alterations in the levels of lactate and certain amino acids. [ABSTRACT FROM AUTHOR]