Serum Metabolomic Profiles Research Articles

The Role of Serum Metabolomics in Distinguishing Chronic Rhinosinusitis With Nasal Polyp Phenotypes.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by different clinical features and treatment responsiveness. This study aimed to compare the serum metabolomics profiles between eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) and healthy controls (HC) and explore objective biomarkers for distinguishing eCRSwNP before surgery.Methods: Serum samples were collected from 33 neCRSwNP patients, 37 eCRSwNP patients, and 29 HC. Serum metabolomics profiles were investigated by ultra-high-performance liquid chromatography–mass spectrometry.Results: The analysis results revealed that neCRSwNP, eCRSwNP, and HC exhibited distinctive metabolite signatures. In addition, eCRSwNP could be distinguished from neCRSwNP referring to their serum metabolic profiles, and the top ten different metabolites were citrulline, choline, linoleic acid, adenosine, glycocholic acid, L-serine, triethanolamine, 4-guanidinobutyric acid, methylmalonic acid, and L-methionine, which were related to several most important pathways including arginine and proline metabolism; glycine, serine, and threonine metabolism; linoleic acid metabolism; and purine metabolism. Among these distinctive metabolites, citrulline, linoleic acid, adenosine, and 4-guanidinobutyric acid showed good predictabilities, and the serum levels of citrulline, linoleic acid, and adenosine were significantly correlated with tissue eosinophil (T-EOS) percentage and T-EOS count.Conclusion: eCRSwNP patients exhibited discriminative serum metabolic signatures in comparison with neCRSwNP patients and HC. These results suggested that metabolomics profiles contributed to understanding the pathophysiological mechanisms of CRSwNP and distinguishing its phenotypes

Metabolomic assessment of mechanisms underlying anti-renal fibrosis properties of petroleum ether extract from Amygdalus mongolica

Context The petroleum ether extract (PET) of Amygdalus mongolica (Maxim.) Ricker (Rosaceae) has an ameliorative effect on renal fibrosis (RF). Objective To evaluate the antifibrotic effects of A. mongolica seeds PET on RF by serum metabolomics, biochemical and histopathological analyses. Materials and methods Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, RF model, benazepril hydrochloride-treated model (1.5 mg/kg) and PET-treated (1.75, 1.25, 0.75 g/kg) groups, and the respective drugs were administered intragastrically for 21 days. Biochemical indicators including BUN, Scr, HYP, SOD, and MDA were measured. Haematoxylin and eosin and Masson staining were used for histological examination. The serum metabolomic profiles were determined by UPLC-Q-TOF/MS and metabolism network analysis. Acute toxicity test was performed to validate biosafety. Results The PET LD50 was >23.9 g/kg in rats. PET significantly alleviated fibrosis by reducing the levels of Scr (from 34.02 to 32.02), HYP (from 403.67 to 303.17) and MDA (from 1.84 to 1.73), and increasing that of SOD (from 256.42 to 271.85). Metabolomic profiling identified 10 potential biomarkers, of which three key markers were significantly associated with RF-related pathways including phenylalanine, tyrosine and tryptophan biosynthesis, amino sugar and nucleotide sugar metabolism and tyrosine metabolism. In addition, three key biomarkers were restored to baseline levels following PET treatment, with the medium dose showing optimal effect. Conclusions These findings revealed the mechanism of A. mongolica PET antifibrotic effects for RF rats on metabolic activity and provided the experimental basis for the clinical application.

Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis.

We aimed to use serum metabolomics to discriminate infants with severe respiratory syncytial virus (RSV) bronchiolitis who later developed subsequent recurrent wheezing from those who did not and to investigate the relationship between serum metabolome and host immune responses with regard to the subsequent development of recurrent wheezing. Fifty-one infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6months of age or less were included and followed for up to the age of 3years. Of them, 24 developed subsequent recurrent wheezing and 27 did not. Untargeted serum metabolomics was performed by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS/MS). Cytokines were measured by multiplex immunoassay. Difference in serum metabolomic profiles was observed between infants who developed recurrent wheezing and those who did not. L-lactic acid level was significantly higher in infants with recurrent wheezing than those without. Pyrimidine metabolism, glycerophospholipid metabolism, and arginine biosynthesis were identified as the most significant changed pathways between the two groups. Moreover, L-lactic acid level was positively associated with serum CXCL8 level. This exploratory study showed that differential serum metabolic signatures during severe RSV bronchiolitis in early infancy were associated with the development of subsequent recurrent wheezing in later childhood.

Identification of novel diagnostic biomarkers in endometrial cancer using targeted metabolomic profiling

PurposeEndometrial cancer (EC) is the most common gynecological malignancy with high disease burden especially in advanced stages of the disease. Our study investigated the metabolomic profile of EC patient’s serum with the aim of identifying novel diagnostic biomarkers that could be used especially in early disease detection. Material and methodsUsing targeted metabolomic serum profiling based on HPLC-TQ/MS, women with EC (n ​= ​15) and controls (n ​= ​21) were examined for 232 endogenous metabolites. ResultsTop performing biomarkers included ceramides, acylcarnitines and 1-methyl adenosine. Top 4 biomarkers combined achieved 94% sensitivity with 75% specificity with AUC 92.5% (CI 90.5–94.5%). Individual markers also provided significant predictive values: C16-ceramide achieved sensitivity 73%, specificity 81%, AUC 0.83, C22-ceramide sensitivity 67%, specificity 81%, AUC 0.77, hydroxyhexadecenoylcarnitine sensitivity 60%, specificity 96%, AUC 0.76 and 1-methyladenosine sensitivity 67%, specificity 81%, AUC 0.75. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination. ConclusionsUsing mass spectrometry targeted metabolomic profiling, ceramides, acylcarnitines and 1-methyladenosine were identified as potential diagnostic biomarkers for EC. Additionally, these identified metabolites may provide additional insight into cancer cell metabolism.

Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Disease: A Case-Control Study.

Objectives: Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers.Methods: Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry.Results: A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate Q = 1.87 × 10−11 and 7.09 × 10−6, respectively), and glycerol was higher (Q = 1.20 × 10−6), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867–0.968, sensitivity 0.880, specificity 0.780).Conclusions: Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.

Serum Metabolomics Profiling of Commercially Mixed Functional Foods-Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy.

Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer’s disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aβ-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aβ-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta–MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aβ-42 injection) and Abeta–NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aβ-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aβ-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.

Serum Metabolomic Profiling of Patients with Non-Infectious Uveitis

The activities of various metabolic pathways can influence the pathogeneses of autoimmune diseases, and intrinsic metabolites can potentially be used to diagnose diseases. However, the metabolomic analysis of patients with uveitis has not yet been conducted. Here, we profiled the serum metabolomes of patients with three major forms of uveitis (Behҫet’s disease (BD), sarcoidosis, and Vogt-Koyanagi-Harada disease (VKH)) to identify potential biomarkers. This study included 19 BD, 20 sarcoidosis, and 15 VKH patients alongside 16 healthy control subjects. The metabolite concentrations in their sera were quantified using liquid chromatography with time-of-flight mass spectrometry. The discriminative abilities of quantified metabolites were evaluated by four comparisons: control vs. three diseases, and each disease vs. the other two diseases (such as sarcoidosis vs. BD + VKH). Among 78 quantified metabolites, 24 kinds of metabolites showed significant differences in these comparisons. Four multiple logistic regression models were developed and validated. The area under the receiver operating characteristic (ROC) curve (AUC) in the model to discriminate disease groups from control was 0.72. The AUC of the other models to discriminate sarcoidosis, BD, and VKH from the other two diseases were 0.84, 0.83, and 0.73, respectively. This study provides potential diagnostic abilities of sarcoidosis, BD, and VKH using routinely available serum samples that can be collected with minimal invasiveness.

Altered exosomal microRNA profiles in bronchoalveolar lavage fluid can mediate metabolism in patients with Acinetobacter baumannii ventilator-associated pneumonia.

BackgroundVentilator-associated pneumonia (VAP) is a major public health problem and is most commonly caused by Acinetobacter baumannii (Ab) infection. In our study, we investigated the profiles of exosomal microRNAs (miRNAs) extracted from the bronchoalveolar lavage fluid (BALF) and serum of patients with Acinetobacter baumannii ventilator-associated pneumonia (Ab-VAP). We also examined the serum metabolomic profiles of these patients. Our aim was to study the associations between lung tissue-derived exosomal miRNAs and changes in global metabolism in patients with Ab-VAP.MethodsConsecutively sampled patients admitted to an intensive care unit (ICU) for pulmonary infection treatment were enrolled in this study. Demographic information and biochemical measurements were collected. Serum samples were obtained following overnight fasting on admission. Bronchoscopies were performed and BALF samples were collected from each patient. Exosomes were extracted using kits from System Biosciences (SBI) and miRNA sequencing was performed. Non-targeted metabolomics were used to express metabolic profiles.ResultsWe found significant changes in the miRNA profiles of patients with Ab-VAP; these changes occurred in both BALF exosomal miRNA and serum exosomal miRNA. Gene Ontology analysis further identified the function of miRNA in system metabolism. Serum metabolomic profiles and ratios of biological significance were found to be differentially regulated in Ab-VAP patients. This differential regulation was correlated with the differential expression of miRNAs.ConclusionsOur data summarizes the dysregulation of serum metabolism and exosomal miRNA excretion that occurs in Ab-VAP patients. The correlation found between BALF exosomal miRNA and dysregulated metabolism, as indicated by the irregular expression of metabolites in the cellular metabolic pathway, highlights potential biomarkers for the diagnosis and treatment of Ab infection.

Prediction of sublingual immunotherapy efficacy in allergic rhinitis by serum metabolomics analysis

BackgroundAllergen-specific immunotherapy (ASIT) is currently the only therapy for allergic rhinitis (AR) that can induce immune tolerance to allergens. However, the course of ASIT is long and there is no objective biomarker to predict treatment efficacy. The present study aimed to explore potential biomarkers predictive of efficacy of AIT based on serum metabolomics profiles. MethodsThis prospective study recruited 72 consecutive eligible patients who were assigned to receive sublingual immunotherapy (SLIT). Serum samples were collected prior to SLIT and utilized to obtain metabolomics profiling by applying ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Treatment response was determined 3 years after SLIT, and patients were divided into effective group and ineffective group. Orthogonal partial least square-discriminate analysis (OPLS-DA) was performed to evaluate the metabolite differences between two groups. ResultsSixty-eight patients completed the whole SLIT, 39 patients were categorized into effective group and 29 patients were classified into ineffective group. A total of 539 metabolites were obtained, and 197 of which were identified as known substances. Using these 197 known metabolites, the OPLS-DA results showed that effective group and ineffective group exhibited distinctive metabolite signatures and metabolic pathways. Six metabolites including lactic acid, ornithine, linolenic acid, creatinine, arachidonic acid and sphingosine were identified to exhibit good performance in predicting the efficacy of SLIT, and these metabolite changes mainly involved glycolysis and pyruvate metabolism, arginine and proline metabolism and fatty acid metabolism pathways. ConclusionBy metabolomics analysis, we identified several serum biomarkers that can reliably and accurately predict the efficacy of SLIT in AR patients. The discriminative metabolites and related metabolic pathways contributed to better understand the mechanisms of SLIT in AR patients.

Untargeted Metabolomics and Polyamine Profiling in Serum before and after Surgery in Colorectal Cancer Patients

Colorectal cancer is one of the most prevalent cancers in Korea and globally. In this study, we aimed to characterize the differential serum metabolomic profiles between pre-operative and post-operative patients with colorectal cancer. To investigate the significant metabolites and metabolic pathways associated with colorectal cancer, we analyzed serum samples from 68 patients (aged 20–71, mean 57.57 years). Untargeted and targeted metabolomics profiling in patients with colorectal cancer were performed using liquid chromatography-mass spectrometry. Untargeted analysis identified differences in sphingolipid metabolism, steroid biosynthesis, and arginine and proline metabolism in pre- and post-operative patients with colorectal cancer. We then performed quantitative target profiling of polyamines, synthesized from arginine and proline metabolism, to identify potential polyamines that may serve as effective biomarkers for colorectal cancer. Results indicate a significantly reduced serum concentration of putrescine in post-operative patients compared to pre-operative patients. Our metabolomics approach provided insights into the physiological alterations in patients with colorectal cancer after surgery.

Serum Metabolomic Profiling Reveals the Amelioration Effect of Methotrexate on Imiquimod-Induced Psoriasis in Mouse.

Background:The imiquimod (IMQ)-induced psoriasis mouse model has been used as a model for pathogenic mechanism research, and methotrexate (MTX) is widely employed to treat various clinical manifestations of psoriasis. We explored the underlying pathogenesis of psoriasis and the treatment mechanism of the conventional drugs from the metabolic perspective of the psoriasis mouse model.Methods:Male BALB/c mice were smeared IMQ for 7 days to induce treatment-resistant psoriasis and intragastrically administered 1 mg/kg MTX. We evaluated inflammation of psoriasis-like lesions and therapeutic effects of MTX based on histological changes and immunohistochemistry. Based on gas chromatography-mass spectrometer detection of serum samples, a comprehensive metabolomics analysis was carried out to identify alterations of metabolites.Results:It was found that MTX ameliorated psoriatic lesions (representative erythema, scaling, and thickening) by inhibiting proliferation and differentiation of keratinocytes. Using multivariate statistical analysis to process metabolomics data, the results displayed alterations in serum metabolites among mice of the control group, IMQ group, and MTX group. Compared with group, psoriasis mice had the higher level of d-galactose and lower expression of myo-inositol, 9,12-octadecadienoic acid, and cholesterol. In contrast with the model set, serum levels of glycine, pyrrolidone carboxylic acid, d-galactose, and d-mannose were significantly decreased in the MTX group.Conclusion:The differential metabolites, reflecting the perturbation in the pathways of inositol phosphate metabolism; galactose metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and glutathione metabolism, may lead to the pathogenesis of psoriasis, and they are also related to the pharmacological treatment effect of MTX on psoriasis. This study established the foundation for further research on the mechanism and therapeutic targets of psoriasis.

Hypoglycemic Effect of Prolamin from Cooked Foxtail Millet (Setaria italic) on Streptozotocin-Induced Diabetic Mice.

Millet proteins have been demonstrated to possess glucose-lowering and lipid metabolic disorder modulation functions against diabetes; however, the molecular mechanisms underlying their anti-diabetic effects remain unclear. The present study aimed to investigate the hypoglycemic effect of prolamin from cooked foxtail millet (PCFM) on type 2 diabetic mice, and explore the gut microbiota and serum metabolic profile changes that are associated with diabetes attenuation by PCFM. Our diabetes model was established using a high-fat diet combined with streptozotocin before PCFM or saline was daily administrated by gavage for 5 weeks. The results showed that PCFM ameliorated glucose metabolism disorders associated with type 2 diabetes. Furthermore, the effects of PCFM administration on gut microbiota and serum metabolome were investigated. 16S rRNA gene sequencing analysis indicated that PCFM alleviated diabetes-related gut microbiota dysbiosis in mice. Additionally, the serum metabolomics analysis revealed that the metabolite levels disturbed by diabetes were partly altered by PCFM. Notably, the decreased D-Glucose level caused by PCFM suggested that its anti-diabetic potential can be associated with the activation of glycolysis and the inhibition of gluconeogenesis, starch and sucrose metabolism and galactose metabolism. In addition, the increased serotonin level caused by PCFM may stimulate insulin secretion by pancreatic β-cells, which contributed to its hypoglycemic effect. Taken together, our research demonstrated that the modulation of gut microbiota composition and the serum metabolomics profile was associated with the anti-diabetic effect of PCFM.

Identification of Novel Diagnostic Biomarkers in Breast Cancer Using Targeted Metabolomic Profiling

IntroductionBreast cancer (BC) is the most common cancer in women, with a high disease burden, especially in the advanced disease stages. Our study investigated the metabolomic profile of breast cancer patients’ serum with the aim of identifying novel diagnostic biomarkers that could be used, especially for early disease detection. Materials and MethodsUsing targeted metabolomic serum profiling based on high-performance liquid chromatography mass spectrometry, women with BC (n = 39) and a control group (n = 21) were examined for 232 endogenous metabolites. ResultsThe top performing biomarkers included acylcarnitines (ACs) and 9,12-linoleic acid. A combined panel of the top 4 biomarkers achieved 83% sensitivity and 81% specificity, with an area under the curve (AUC) of 0.839 (95% confidence interval, 0.811-0.867). Individual markers also provided significant predictive values: AC 12:0, sensitivity of 72%, specificity of 67%, and AUC of 0.71; AC 14:2, sensitivity of 74%, specificity of 71%, and AUC of 0.73; AC 14:0: sensitivity of 67%, specificity of 81%, and AUC of 0.73; and 9,12-linoleic acid, sensitivity of 69%, specificity of 67%, and AUC of 0.71. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination. ConclusionUsing mass spectrometry-targeted metabolomic profiling, ACs and 9,12-linoleic acid were identified as potential diagnostic biomarkers for breast cancer. Additionally, these identified metabolites could provide additional insight into cancer cell metabolism.

Multiomic Profiling of Iron Deficient Infant Monkeys Detects Biochemical Signatures of Inflammatory and Neural Dysfunction in Blood and CSF Prior to Anemia

Background: Pre-anemic iron deficiency (ID) and ID anemia in infancy is associated with long-term effects on brain development. Iron is an essential micronutrient needed for multiple neurodevelopmental processes, including energy production, myelination and neurotransmission. Serum and cerebrospinal fluid (CSF) metabolomic and proteomic analyses can potentially characterize the metabolic and protein signatures of aberrant iron-dependent brain development pathways. A better understanding of the timing and course of the biochemical signatures of ID-induced dysfunction in the heme and intrathecal compartments may help with early diagnosis and treatment of iron deficiency prior to onset of anemia. Objective: To determine proteomic and metabolomic signatures of ID-induced dysfunction in serum and CSF of infant monkeys prior to the onset of iron deficiency anemia (IDA). Methods: Hematological parameters were determined in rhesus monkey infants (Macaca mulatta) at 4 and 6 months of age as they progressed from preanemic ID to IDA (ID group; n=6) or remained iron-sufficient(IS group; n=12). Blood and CSF were collected at 4 and 6 months and metabolically profiled using HPLC/MS with isobaric standards for identification and quantification. Proteomic quantification utilized a custom TMT-labeled workflow with an Orbitrap Fusion Tribrid mass spectrometer. Serum and CSF metabolomic and proteomic profiles of the ID and IS groups were compared, along with a a third group of infants that became IDA earlier at 4 months of age (IDA group; n=3). Results: Evidence of pre-anemic ID was apparent in some infant at 4 months of age with clinical IDA evident at 6 months A (Hgb <10 g/dL and MCV <60 fL). A total of 1,128 CSF proteins and 251 serum proteins were identified and quantified. Over 4,000 metabolite features were observed in serum and CSF across three modalities including reverse phase positive, reverse phase negative and HILIC mode. Pathway analyses provided evidence of increased inflammatory activity, impacts on neural pathways, and bioindicators of acute phase responses in ID and IDA groups. Signs of these metabolic changes were already present in the preanemic ID? period (4 months). Conclusions: Biomarkers indicating indicative of increased inflammatory activity with downstream effects on pathways involved in normal neural function were detectable in both the CSF and serum of ID monkeys prior to the onset of clinical anemia. Brain-specific proteomic and metabolomic profiling of novel analytes in circulation can facilitate earlier diagnosis and treatment of infantile ID to reduce neurodevelopmental risk. Funded by NIH/NICHD Grant HD089989, this abstract is sponsored by ASH member Zohar Sachs MD, PhD Disclosures No relevant conflicts of interest to declare.

Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice

Berberine compounds (BC), consisting of berberine (BBR), oryzanol and vitamin B6, have been used to treat diabetes and hyperlipidemia in recent years, but the potential mechanisms under the effects have not been well determined. In this study, we evaluated the effect of BC in db/db mice, and found that BC treatment reversed the increased levels of fasting glucose and hemoglobin A1c in db/db mice, which was superior to BBR treatment. Fecal 16S rRNA gene sequencing indicated that BC increased relative abundance of microbiomes Bacteroidaceae and Clostridiaceae, which may promote conversion of primary bile acid cholic acid (CA) into secondary bile acid deoxycholic acid (DCA). Gas chromatography/mass spectrometry (GC/MS)-based metabolomics revealed that BC treatment increased fecal DCA level. Since DCA processes the potential to activate bile acid receptor-takeda G protein-coupled receptor 5 (TGR5) and induce glucagon-like peptide (GLP) secretion, we detected TGR5 expression, and found that BC-treatment significantly increased the colonic TGR5 and serum GLP-1/-2 levels in db/db mice. Modulation of TGR5-GLP pathway may also affect metabolomic profiles of serum and liver, and BC treatment showed effects on restoring the altered carbohydrate, lipid, amino acid and nucleotide metabolism. Our study suggested that BC improved hyperglycemia, the effect might attribute to the increased microbiome mediated DCA production, which up-regulated colonic TGR5 expression and GLP secretion, and improved glucose, lipid and energy metabolism in db/db mice.

Multiomics Study of Gut Bacteria and Host Metabolism in Irritable Bowel Syndrome and Depression Patients.

Background and AimsIrritable bowel syndrome (IBS) and depression have high tendencies of comorbidity. In particular, diarrhea-predominant IBS (IBS-D) and depression exhibit similar fecal microbiota signatures, yet little is known about their pathogenic mechanism. Here, we propose that the differences in structure and composition of IBS-D and depression gut microbiota give rise to different downstream functions, which lead to distinct clinical phenotypes via host metabolism and further influence the interaction of brain–gut axis.MethodsWe performed multiomics study, including fecal metagenome-wide sequencing and serum metabolomics profiling in 65 individuals with IBS-D (n=22), depression (n=15), comorbid patients (n=13), and healthy controls (n=15). We analyzed functional genes contributed by the primary genus and evaluated their correlations with clinical indices and host metabolites.ResultsMetagenomic analysis revealed 26 clusters of orthologous groups of protein (COG) categories consisting of a total of 4,631 functional genes. Trehalose and maltose hydrolase (COG1554) and fucose permease (COG0738) were the most relevant and enriched functional genes in the IBS-D patients; urease accessory proteins UreE (COG2371) was that in the depression patients. Context based genome annotation suggest that an alteration of Escherichia coli and Enterobacter cloacae in IBS-D and depression respectively may be responsible for the enrichment described above. Correlation with host metabolites, such as maltotriose and isomaltose in carbohydrate metabolism and anandamide in neuroactive metabolism, drew further connections between these findings.ConclusionsThese changes led us to propose a connection between genomic signatures and clinical differences observed in IBS-D and depression. Our findings provide further insights into the involvement of gut microbiota in diseases related to brain–gut disorder.

1H NMR serum metabolomic profiling of patients at risk of cardiovascular diseases performing stress test

Cardiovascular diseases are the leading cause of death worldwide. Changes in lifestyle and/or pharmacological treatment are able to reduce the burden of coronary artery diseases (CAD) and early diagnosis is crucial for the timely and optimal management of the disease. Stress testing is a good method to measure the burden of CAD but it is time consuming and pharmacological testing may not fully mimic exercise test. The objectives of the present project were to characterize the metabolic profile of the population undergoing pharmacological and exercise stress testing to evaluate possible differences between them, and to assess the capacity of 1H NMR spectroscopy to predict positive stress testing. Pattern recognition was applied to 1H NMR spectra from serum of patients undergoing stress test and metabolites were quantified. The effects of the stress test, confounding variables and the ability to predict ischemia were evaluated using OPLS-DA. There was an increase in lactate and alanine concentrations in post-test samples in patients undergoing exercise test, but not in those submitted to pharmacological testing. However, when considering only pharmacological patients, those with a positive test result, showed increased serum lactate, that was masked by the much larger amount of lactate associated to exercise testing. In conclusion, we have established that pharmacological stress test does not reproduce the dynamic changes observed in exercise stress. Although there is promising evidence suggesting that 1H NMR based metabolomics could predict stress test results, further studies with much larger populations will be required in order to obtain a definitive answer.

Association of the serum metabolomic profile by nuclear magnetic resonance spectroscopy with sperm parameters: a cross-sectional study of 325 men

To determine whether 155 circulating metabolic measures relevant to lifestyle and metabolic health are associated with sperm parameters, as measured by concentration, motility, and total motile sperm count (TMSC). Cross sectional. University hospital. Three hundred twenty-five men prospectively recruited between April 1, 2017 and March 31,2019. Detailed demographic, lifestyle, fertility, medical history, and semen analysis with quantification of nonfasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis, and inflammatory markers) by nuclear magnetic resonance (NMR) spectroscopy. Association of serum metabolic profiles with sperm parameters. The age of the participants was mean 37.2 years, with a median sperm concentration of 35 million/mL and median motility of 53%. Of these men, 76% had a TMSC >15 million, 10% had 5-15 million, and 14% had <5 million. In both univariate and confounder adjusted analyses, an extensive range of lipids and lipoproteins, glycolysis-related metabolites, amino acids, ketone bodies, creatinine, or albumin showed no strong statistically significant association with sperm concentration, motility, or the odds of having a reduced or low TMSC. Higher levels of glycolysis metabolites and ketone bodies were associated with an increased odds of TMSC <15 million compared with ≥15 million (odds ratios of ∼1.2-1.3), and several lipids/lipoprotein concentrations appeared to protect against very low TMSC (<5 million compared with ≥5 million) with odds ratios of ∼0.8 or greater. Several metabolites exhibited potentially clinically relevant strength of association with the odds of a low TMSC and warrant replication.

Tongue Coating Bacteria as a Potential Stable Biomarker for Gastric Cancer Independent of Lifestyle.

Gastric cancer (GC) is one of the most common cancers, and the noninvasive diagnostic methods for monitoring GC are still lacking. Growing evidence shows that human microbiota has potential value for identifying digestive diseases. The present study aimed to explore the association of the tongue coating microbiota with the serum metabolic features and inflammatory cytokines in GC patients and seek a potential, noninvasive biomarker for diagnosing GC. The tongue coating microbiota was profiled by 16S rRNA and 18S rRNA genes sequencing technology in the original population with 181 GC patients and 112 healthy controls (HCs). Propensity score matching method was used to eliminate potential confounders including age, gender, and six lifestyle factors and a matching population with 66 GC patients and 66 HCs generated. Serum metabolomics profiling was performed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) in the matching population. Random forest model was constructed for the diagnosis of GC. Linear discriminant analysis effect size (LEfSe) revealed that the differential bacterial taxa between GC patients and HCs in the matching population were similar to that in the original population, while the differential fungal taxa between GC patients and HCs dramatically changed before and after PSM. By random forest analysis, the combination of six bacterial genera (Peptostreptococcus, Peptococcus, Porphyromonas, Megamonas, Rothia, and Fusobacterium) was the optimal predictive model to distinguish GC patients from HCs effectively, with an area under the curve (AUC) value of 0.85. The model was verified with a high predictive potential (AUC = 0.76 to 0.96). In the matching population, eighteen specific HCs-enriched bacterial genera (Porphyromonas, Parvimonas, etc.) had negative correlations with lysophospholipids metabolites, and three of them had also negative correlations with serum IL-17α. The alteration of tongue coating microbiota had a possible linkage with the inflammations and metabolome, and the tongue coating bacteria could be a potential noninvasive biomarker for diagnosing GC, which might be independent of lifestyle.

Association of the functional ovarian reserve with serum metabolomic profiling by nuclear magnetic resonance spectroscopy: a cross-sectional study of ~\u2009400 women

BackgroundWomen with diminished ovarian reserve are known to have increased cardiovascular risk, whether there is a continuous association between the ovarian reserve biomarkers; anti-Müllerian hormone (AMH), antral follicle count (AFC) and cardio-metabolic risk factors are unknown.MethodsA cross-sectional study of 398 women intending to undergo IVF with pre-treatment early follicular AMH and AFC measurements. Serum lipids, lipoprotein subclasses and low-molecular-weight metabolites were quantified by NMR spectroscopy (155 metabolic measures). Associations were analysed using multivariable regression.ResultsParticipants were mean 35.5 (SD 4.43) years old and had a median AMH of 16 pmol/l (IQR 8.8, 28.0 pmol/l) and a median AFC of 12 (IQR 7.16). AMH showed positive associations with HDL, omega-6 and polyunsaturated fatty acids and the amino acids isoleucine, leucine and tyrosine, with effects ranging from 0.11 (95%CI 0.004 to 0.21) for total lipids in small HDL to 0.16 (0.06 to 0.26) for isoleucine, for a mean difference of one SD of metabolite per one SD increment in AMH, and negatively with acetate: − 0.31(− 0.22, − 0.004) SD per 1 SD AMH. AFC was positively associated with alanine, glutamine and glycine. Results were consistent, though less precisely estimated, when restricted to those women who were preparing for treatment because of their partner’s infertility.ConclusionsIn women intending to have IVF, AMH and AFC were not associated with traditional lipid measured but were associated with a number of novel cardiovascular risk factors. Prospective studies will be required for replication, determination of causality and confirmation that ovarian reserve is impacting on metabolism rather than variation in metabolism is influencing ovarian reserve.