Benzoate Metabolism Research Articles

DOP33 Distinct perturbances in metabolic pathways associate with disease progression in patients with Inflammatory Bowel Disease

Abstract Background Patients with inflammatory bowel diseases (IBD) exhibit distinct shifts in circulating metabolite levels that have been associated with clinical disease activity and disease phenotype. However, there are limited data on the impact of metabolomic changes on disease progression in IBD. We aimed to understand the association of circulating metabolite levels and related pathways with the risk of disease progression in patients with IBD. Methods We conducted an observational cohort study using the Mount Sinai Crohn’s and Colitis Registry (MSCCR). Patients were prospectively enrolled with baseline questionnaires and biospecimens that were then linked to longitudinal electronic health record data. A total of 1,456 serum metabolites were measured in 277 patients with UC and 375 patients with CD using untargeted metabolomics. Disease progression was defined as any new steroid or biological prescriptions, IBD-related hospitalizations, or surgery. Multivariable Cox proportional hazards regression models, adjusted for age, sex, smoking, biologic use, and surgery were used to explore metabolite associations with risk of disease progression. Metabolite set enrichment analysis (MSEA) was performed to identify underlying metabolic pathways associated with disease progression. Results During a median 2-year follow-up time (IQR 0.3-5.1 years), 375 patients (57.5%) had a disease progression event. Among CD, 151 metabolites significantly correlated with the composite outcome (FDR<0.1). Of these, 81 (53.6%) were linked to higher risk, mainly enriched in amino acids, purine, and pyrimidine metabolism, fibrinogen cleavage peptides, and bile acid pathways. Additionally, 70 (46.4%) metabolites associated with lower risk with enrichment in fatty acid metabolism, steroid biosynthesis, histidine, tryptophan, and antioxidant pathways. In CD, aspartate metabolism was most significantly associated with increased risk and linoleic metabolism with decreased risk. In UC, 84 metabolites were significantly associated with disease progression (FDR<0.1), with 29 (34.5%) associated with increased and 55 (65.5%) with decreased risk. Metabolic pathways linked to higher risk were sphingolipid, benzoate, hydrogen sulfide, polyamine, and tyrosine metabolism, while protective metabolites were enriched in branched-chain amino acid (BCAA), steroid biosynthesis, histidine, and phenylalanine pathways. In UC, sphingolipid metabolism was prominently associated with increased risk and BCAA metabolism with decreased risk. Conclusion Specific metabolites and metabolic pathways are associated with risk of disease progression in patients with IBD, highlighting potential prognostic metabolite biomarkers and pathways that may be important in modulating risk of disease progression.

An integrated metagenomic model to uncover the cooperation between microbes and magnetic biochar during microplastics degradation in paddy soil

The free radicals released from the advanced oxidation processes can enhance microplastics degradation, however, the existence of microbes acting synergistically in this process is still uncertain. In this study, magnetic biochar was used to initiate the advanced oxidation process in flooded soil. paddy soil was contaminated with polyethylene and polyvinyl chloride microplastics in a long-term incubation experiment, and subsequently subjected to bioremediation with biochar or magnetic biochar. After incubation, the total organic matter present in the samples containing polyvinyl chloride or polyethylene, and treated with magnetic biochar, significantly increased compared to the control. In the same samples there was an accumulation of “UVA humic” and “protein/phenol-like” substances. The integrated metagenomic investigation revealed that the relative abundance of some key genes involved in fatty acids degradation and in dehalogenation changed in different treatments. Results from genome-centric investigation suggest that a Nocardioides species can cooperate with magnetic biochar in the degradation of microplastics. In addition, a species assigned to the Rhizobium taxon was identified as a candidate in the dehalogenation and in the benzoate metabolism. Overall, our results suggest that cooperation between magnetic biochar and some microbial species involved in microplastic degradation is relevant in determining the fate of microplastics in soil.

0030 Insomnia is associated with lower serum antioxidants in the Hispanic Community Health Study/Study of Latinos

Abstract Introduction Insomnia is associated with neurodegenerative diseases. Concentration levels of some metabolites are associated with pathophysiologic changes, possibly in a sex-specific manner. Thus, serum metabolite levels are useful for understanding insomnia-related pathophysiological changes and how they potentially relate to neurodegenerative disease. Methods The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a longitudinal cohort study following self-reported Hispanic/Latino individuals in the U.S. At baseline, insomnia symptoms were captured using the Women Health Initiative Insomnia Rating Scale (WHIIRS), insomnia being defined as WHIIRS≥9. Metabolites were measured using blood serum from the baseline exam in independent discovery and replication datasets. In discovery, metabolite associations with WHIIRS and with insomnia were estimated in linear regression. Significant associations (FDR p-values< 0.05) were tested in the replication dataset and considered replicated if their p-value< 0.05 and the direction of association matched with the discovery analysis. Associations were further studied for gender interaction. All analyses were adjusted for age, self-reported gender, study center, and Hispanic/Latino background. Results 3,895 individuals participated in the discovery analysis, and 2,121 in replication analysis. Female individuals were aged 46.5 on average (SD 15.1) and 35% had insomnia, while male individuals were aged 44.8 (14.8) and 24% had insomnia. After quality control, 767 metabolites were tested for association. Six metabolites were associated with WHIIRS (FDR< 0.05) in the gender-combined analysis. Three were xenobiotics which were on the benzoate or salicylic acid metabolism pathway. Of the 6 metabolite associations, two replicated (p-value< 0.05): hydrocinnamate and indolepropionate. These two metabolites had spearman correlation of 0.44. Higher levels of both metabolites were associated with lower WHIIRS, showing stronger associations in females (interaction p-value =0.04 for hydrocinnamate and p-value=0.13 for indolepropionate). Associations remained essentially unchanged in a model further adjusting for hypertension and diabetes. When removing 534 individuals who self-reported using sleeping pills at least once a week, the associations attenuated slightly: from an effect estimates of -0.0075 to -0.0069 (hydrocinnamate) and from -0.0082 to -0.0068 (indolepropionate). Conclusion Among the HCHS/SOL target population, insomnia symptom severity is associated with a lower concentrations of some plasma metabolite levels which are important antioxidant needed in preventing oxidative stress and neurodegeneration. Support (if any) R01HL161012.

Rats with Long-Term Cholestasis Have a Decreased Cytosolic but Maintained Mitochondrial Hepatic CoA Pool.

Previous studies showed that rats with long-term bile duct ligation have reduced coenzyme A stores per g of liver but maintained mitochondrial CoA stores. Based on these observations, we determined the CoA pool in the liver homogenate, liver mitochondria, and liver cytosol of rats with bile duct ligation for 4 weeks (BDL rats, n = 9) and sham-operated control rats (CON rats, n = 5). In addition, we tested the cytosolic and mitochondrial CoA pools by assessing the metabolism of sulfamethoxazole and benzoate in vivo and of palmitate in vitro. The hepatic total CoA content was lower in BDL than CON rats (mean ± SEM; 128 ± 5 vs. 210 ± 9 nmol/g), affecting all subfractions equally (free CoA (CoASH), short- and long-chain acyl-CoA). In BDL rats, the hepatic mitochondrial CoA pool was maintained, and the cytosolic pool was reduced (23.0 ± 0.9 vs. 84.6 ± 3.7 nmol/g liver; CoA subfractions were affected equally). The urinary excretion of hippurate after i.p. benzoate administration (measuring mitochondrial benzoate activation) was reduced in BDL rats (23.0 ± 0.9 vs. 48.6 ± 3.7% of dose/24 h), whereas the urinary elimination of N-acetylsulfamethoxazole after i.p. sulfamethoxazole administration (measuring the cytosolic acetyl-CoA pool) was maintained (36.6 ± 3.0 vs. 35.1 ± 2.5% of dose/24 h BDL vs. CON rats). Palmitate activation was impaired in the liver homogenate of BDL rats but the cytosolic CoASH concentration was not limiting. In conclusion, BDL rats have reduced hepatocellular cytosolic CoA stores, but this reduction does not limit sulfamethoxazole N-acetylation or palmitate activation. The hepatocellular mitochondrial CoA pool is maintained in BDL rats. Impaired hippurate formation in BDL rats is explained best by mitochondrial dysfunction.

Evaluating the influence of gradient applied voltages on electro-enhanced sequence batch reactor treating aniline wastewater: System performance, microbial community and functional genes

Aniline is an important industrial raw material. Its complex structure makes it difficult to be chemically oxidized and its intense biological toxicity also increases the difficulty of biodegradation. Therefore, electro-biological system based on biological processing have become a new direction in the field of environmental governance. Comparative evaluation of the performance differences of reactors at gradient external voltages (1.5, 3.0, 4.5 and 6.0 V) was investigated to seek the optimal applied voltage in the electro-enhanced sequence batch reactor treating aniline wastewater. Results showed that all reactors degraded aniline effectively, the aniline degradation rate of five reactors was about 100%. However, the highest removal efficiency of total nitrogen was obtained at 1.5 V, up to 88.89%. Compared with control, high applied voltage (>3.0 V) deteriorated the nitrification performance and the removal efficiency of TN was descended along with the increase of applied voltages. Besides, proper applied voltage promoted the secretion of extracellular polymeric substance. The sludge activity such as specific oxygen utilization rate (SOUR), dehydrogenase (DHA) was highly increased under the applied voltage of 1.5V, so did the Ammonia monooxygenase (AMO) and nitrate reductase (NAR). Based on the high-throughput sequencing analysis, introducing applied voltages altered the microbial diversity and community structure. Particularly, several functional genera such as autotrophic nitrifying bacteria and denitrifying bacteria were enriched in the system at 1.5V. Network analysis also found that the cooperative/competitive relationship between key functional genus became simpler under the higher voltage. Additionally, the contribution of the functional flora to key metabolic pathways (benzoate and nitrogen metabolism) and the expression of various functional genes was augmented at the 1.5V applied voltage.

Draft Genome Sequence and Annotation of Priestia aryabhattai Strain BD1 Isolated from a Dye Sediment

The 5,079,658-bp genome of Priestia aryabhattai strain BD1 isolated from a dye waste sediment consists of 5,185 protein-coding genes, of which 790 were hypothetical proteins, 63 were RNAs, and 54 were pseudogenes. Putative genes involved in oxygen/redox potential sensing, dye degradation, metal toxicity, antibiotic tolerance, and benzoate metabolism were found.

Gut microbiota on admission as predictive biomarker for acute necrotizing pancreatitis.

BackgroundAcute necrotizing pancreatitis (NP), a severe form of acute pancreatitis (AP), has higher mortality and worse outcome than non-necrotizing pancreatitis (non-NP). Infected NP is a devastating subgroup of NP. To date neither NP nor infected NP has robust prediction strategies, which may delay early recognition and timely intervention. Recent studies revealed correlations between disturbed gut microbiota and AP severity. Some features of intestinal microbiota have the potential to become biomarkers for NP prediction.MethodsWe performed 16S rRNA sequencing to analyze gut microbiota features in 20 healthy controls (HC), and 58 AP patients on hospital admission. The AP patients were later classified into NP and non-NP groups based on subsequent diagnostic imaging features. Random forest regression model and ROC curve were applied for NP and infected NP prediction. PIRCUSt2 was used for bacterial functional pathway prediction analysis.ResultsWe found that the three groups (HC, NP, and non-NP) had distinct microorganism composition. NP patients had reduced microbial diversity, higher abundance of Enterobacteriales, but lower abundance of Clostridiales and Bacteroidales compared with the non-NP group. Correlation analyses displayed that intestine bacterial taxonomic alterations were related to severity, ICU admission, and prognosis. By pathway prediction, species more abundant in NP patients had positive correlation with synthesis and degradation of ketone bodies, and benzoate degradation. Enterococcus faecium (ASV2) performed best in discriminating NP and non-NP patients. Finegoldia magna (ASV3) showed the maximal prediction capacity among all ASVs and had comparable accuracy with Balthazar CT to detect patients with infected NP.ConclusionsOur study suggests that NP patients have distinct intestinal microbiota on admission compared to non-NP patients. Dysbiosis of intestinal microbiota might influence NP progression through ketone body or benzoate metabolism. Enterococcus faecium and Finegoldia magna are potential predictors for NP and infected NP. Our findings explore biomarkers which may inform clinical decision-making in AP and shed light on further studies on NP pathophysiology and management.

Gender-based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum-fermented rice bran diet against inflammation-associated colon tumorigenesis.

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross-feeding between the host and RB-modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RBresponsive microbe Bifidobacterium longum), and non-fermented RBwere fed as 10% w/w (diet) to gut microbiota-intactspf or germ-free micegf to investigate comparative efficacy against inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC. Results indicated both microbiota-dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local-mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid-4 sulfate, trigonelline, and salicylate) were correlated with anti-CRC efficacy. Germ-free studies revealed gender-specific physiological variables could differentially impact CRC growth and progression. In the germ-free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB-fed micegf . Ex vivo fermentation of RB did not parallel the localized-protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation-associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).

Biodegradation Pathway and Detoxification of β-cyfluthrin by the Bacterial Consortium and Its Bacterial Community Structure.

In the process of microbial degradation of pyrethroid pesticides, the synergistic effect of the microbial community is more conducive to the complete degradation of toxic compounds than a single strain. At present, the degradation pathway of pyrethroids in a single strain has been well revealed, but the synergistic metabolism at the community level has not been well explained. This study elucidated the bacterial community succession, metabolic pathway, and phytotoxicity assessment during β-cyfluthrin biodegradation by a novel bacterial consortium enriched from contaminated soil. The results showed that the half-life of β-cyfluthrin at different initial concentrations of 0.25, 0.5, 0.75, and 1.0 mg mL-1 were 4.16, 7.34, 12.81, and 22.73 days, respectively. Enterobacter was involved in β-cyfluthrin degradation metabolism in the initial stage, and other bacterial genera (Microbacterium, Ochrobactrum, Pseudomonas, Hyphomicrobiaceae, Achromobacter, etc.) significantly contribute to the degradation of intermediate metabolites in the later stages. Functional gene prediction and metabolite analysis showed that xenobiotic biodegradation and metabolism, especially benzoate degradation and metabolism by cytochrome P450 were the major means of β-cyfluthrin degradation. Further, two degradation pathways of β-cyfluthrin were proposed, which were mainly ester hydrolysis and oxidation to degrade β-cyfluthrin through the production of carboxylesterase and oxidoreductase. In addition, the inoculated bacterial consortium could degrade β-cyfluthrin residues in water and soil and reduce its phytotoxicity in Medicago sativa. Hence, this novel bacterial consortium has important application in the remediation environments polluted by β-cyfluthrin.

Plasma and Urine Metabolomic Response to an Ultra-Processed Dietary Pattern: A Biomarker Discovery Analysis in a Domiciled Randomized Controlled Crossover Feeding Trial

ObjectivesTo identify metabolomic markers that differed between dietary patterns (DP) that are either high in or void of ultra-processed foods (UPFs) according to NOVA. MethodsA secondary analysis of a randomized, crossover, controlled feeding trial in which 20 domiciled, healthy participants (mean ± SD: 31 ± 7 years, BMI 22 ± 11.6, 50% female) consumed a UPF-DP (80% UPFs) and an unprocessed DP (UN-DP; 0% UPFs) for two weeks with no washout. DPs were matched for energy, macronutrients, total fiber, total sugar, and sodium; presented at 200% of energy requirements; and consumed ad libitum. Metabolite levels were measured in EDTA plasma at the end of each DP (wk 2) and in 24-hr and spot urine at wk 1 and 2, using untargeted liquid chromatography with high resolution/tandem mass spectrometry and annotated using Metabolon’s reference library and authentic standards. Metabolites (n = 1000 plasma, n = 1272 24-hr urine, and n = 1281 spot urine) with <80% missing data and coefficients of variation <30% were assigned minimum detected values, scaled to median of 1, and log2-transformed. Linear mixed models in SAS identified metabolites that differed between UPF-DP and UN-DP adjusted for trial, DP sequence, timepoint, and body weight changes, with a subject-specific random intercept and Benjamini-Hochberg multiple comparison correction. ResultsFor plasma, 183 metabolites differed between UPF-DP and UN-DP at wk 2. For 24-hr urine, 461 metabolites differed between UPF-DP and UN-DP at wk 1 and 2, 68 of which also differed at wk 1 and 2 for spot urine. Twenty metabolites consistently differed between UPF-DP and UN-DP at each timepoint and for each sample type. The sub pathways for these 20 metabolites included glutamate metabolism (n = 1 metabolite); ascorbate and aldarate metabolism (n = 1); benzoate metabolism (n = 2); methionine, cysteine, SAM and taurine metabolism (n = 2); secondary bile acid metabolism (n = 2); fatty acid dicarboxylate (n = 1); and plant-food components (n = 2); 9 could not be annotated. ConclusionsWe identified exogenous and endogenous metabolites, representing a range of metabolic pathways, that consistently differed between a UPF-DP and UN-DP. These candidate biomarkers of UPF intake require investigation in larger samples with dietary data sufficient for NOVA classification. Funding SourcesNCI, NIDDK.

NMR Metabolomics Reveal Urine Markers of Microbiome Diversity and Identify Benzoate Metabolism as a Mediator between High Microbial Alpha Diversity and Metabolic Health.

Microbial metabolites measured using NMR may serve as markers for physiological or pathological host–microbe interactions and possibly mediate the beneficial effects of microbiome diversity. Yet, comprehensive analyses of gut microbiome data and the urine NMR metabolome from large general population cohorts are missing. Here, we report the associations between gut microbiota abundances or metrics of alpha diversity, quantified from stool samples using 16S rRNA gene sequencing, with targeted urine NMR metabolites measures from 951 participants of the Study of Health in Pomerania (SHIP). We detected significant genus–metabolite associations for hippurate, succinate, indoxyl sulfate, and formate. Moreover, while replicating the previously reported association between hippurate and measures of alpha diversity, we identified formate and 4-hydroxyphenylacetate as novel markers of gut microbiome alpha diversity. Next, we predicted the urinary concentrations of each metabolite using genus abundances via an elastic net regression methodology. We found profound associations of the microbiome-based hippurate prediction score with markers of liver injury, inflammation, and metabolic health. Moreover, the microbiome-based prediction score for hippurate completely mediated the clinical association pattern of microbial diversity, hinting at a role of benzoate metabolism underlying the positive associations between high alpha diversity and healthy states. In conclusion, large-scale NMR urine metabolomics delivered novel insights into metabolic host–microbiome interactions, identifying pathways of benzoate metabolism as relevant candidates mediating the beneficial health effects of high microbial alpha diversity.

Human gray and white matter metabolomics to differentiate APOE-dependent metabolic changes in early and late Alzheimer's disease.

Many have suggested that irregularities in metabolism play an underlying role in the progression of Alzheimer's Disease (AD). A detailed knowledge of the biochemical composition of AD brain tissue vs normal brain tissue will be key in understanding the metabolic processes underlying AD, especially as they relate to APOE genotype. Here we perform a metabolomics analysis on the brain tissue of a large cohort of community-based participants in the UK-ADC brain bank to characterize the biochemical profiles of brains with and without Alzheimer's disease and other mixed pathologies based on APOE genotype and disease stage. The global biochemical profiles of post-mortem human brain tissue from the gray matter of Brodmann area 9 was determined using mass spectroscopy. Brain tissue from 158 community-based older adult volunteers was analyzed. Metabolites were quantified using global untargeted metabolomics (HD4) and compared between cohorts using Welch's two-sample t-test to approximate fold change of metabolites between disease stage and APOE genotype. Random forest was used to rank metabolites in order of importance for predicting AD presence in tissue. Late stage disease in the APOE E4 genotype has decreases in lysophospholipids, long chain polyunsaturated fatty acids, endocannabinoids, and branched fatty acids as well as N-acetylserine in the gray matter. Late stage disease in the APOE E4 genotype has increases in phospholipid metabolism and decreases in amino acid metabolism and Vitamin B6. The APOE E4 genotype is associated with increases in gamma-glutamyl amino acids, lysophospholipid, and amino acid metabolism and decreases in urea cycle, sterol, stachydrine, and benzoate metabolism during early stages of disease, but that there are few metabolic differences between genotypes in later disease. Alzheimer's disease has increases in phospholipid metabolism and decreases in amino acid metabolism compared to normal. Early stage disease showed many metabolic differences between genotypes and late stage tissues looked remarkably similar across genotype. This suggests there may be metabolically distinct pathways that each genotype takes to produce a tissue with common endpoint of disease characterized by an AD biochemical profile. Further studies are needed to examine whether these metabolites are consistently altered in Alzheimer's disease.

Plasma Metabolomics and Lipidomics Differentiate Obese Individuals by Peripheral Neuropathy Status.

Peripheral neuropathy (PN) is a frequent prediabetes and type 2 diabetes (T2D) complication. Multiple clinical studies reveal that obesity and dyslipidemia can also drive PN progression, independent of glycemia, suggesting a complex interplay of specific metabolite and/or lipid species may underlie PN. This work aimed to identify the plasma metabolomics and lipidomics signature that underlies PN in an observational study of a sample of individuals with average class 3 obesity. We performed plasma global metabolomics and targeted lipidomics on obese participants with (n = 44) and without PN (n = 44), matched for glycemic status, vs lean nonneuropathic controls (n = 43). We analyzed data by Wilcoxon, logistic regression, partial least squares-discriminant analysis, and group-lasso to identify differential metabolites and lipids by obesity and PN status. We also conducted subanalysis by prediabetes and T2D status. Lean vs obese comparisons, regardless of PN status, identified the most significant differences in gamma-glutamyl and branched-chain amino acid metabolism from metabolomics analysis and triacylglycerols from lipidomics. Stratification by PN status within obese individuals identified differences in polyamine, purine biosynthesis, and benzoate metabolism. Lipidomics found diacylglycerols as the most significant subpathway distinguishing obese individuals by PN status, with additional contributions from phosphatidylcholines, sphingomyelins, ceramides, and dihydroceramides. Stratifying the obese group by glycemic status did not affect discrimination by PN status. Obesity may be as strong a PN driver as prediabetes or T2D in a sample of individuals with average class 3 obesity, at least by plasma metabolomics and lipidomics profile. Metabolic and complex lipid pathways can differentiate obese individuals with and without PN, independent of glycemic status.

Metabolites Associated with Coffee Consumption and Incident Chronic Kidney Disease.

Moderate coffee consumption has been associated with lower risk of CKD; however, the exact biologic mechanisms underlying this association are unknown. Metabolomic profiling may identify metabolic pathways that explain the association between coffee and CKD. The goal of this study was to identify serum metabolites associated with coffee consumption and examine the association between these coffee-associated metabolites and incident CKD. Using multivariable linear regression, we identified coffee-associated metabolites among 372 serum metabolites available in two subsamples of the Atherosclerosis Risk in Communities study (ARIC; n=3811). Fixed effects meta-analysis was used to pool the results from the two ARIC study subsamples. Associations between coffee and metabolites were replicated in the Bogalusa Heart Study (n=1043). Metabolites with significant associations with coffee in both cohorts were then evaluated for their prospective associations with incident CKD in the ARIC study using Cox proportional hazards regression. In the ARIC study, mean (SD) age was 54 (6) years, 56% were daily coffee drinkers, and 32% drank >2 cups per day. In the Bogalusa Heart Study, mean (SD) age was 48 (5) years, 57% were daily coffee drinkers, and 38% drank >2 cups per day. In a meta-analysis of two subsamples of the ARIC study, 41 metabolites were associated with coffee consumption, of which 20 metabolites replicated in the Bogalusa Heart Study. Three of these 20 coffee-associated metabolites were associated with incident CKD in the ARIC study. We detected 20 unique serum metabolites associated with coffee consumption in both the ARIC study and the Bogalusa Heart Study, and three of these 20 candidate biomarkers of coffee consumption were associated with incident CKD. One metabolite (glycochenodeoxycholate), a lipid involved in primary bile acid metabolism, may contribute to the favorable kidney health outcomes associated with coffee consumption. Two metabolites (O-methylcatechol sulfate and 3-methyl catechol sulfate), both of which are xenobiotics involved in benzoate metabolism, may represent potential harmful aspects of coffee on kidney health.

Mapping of the benzoate metabolism by human gut microbiome indicates food-derived metagenome evolution

Sodium benzoate is one of the widely used food preservatives and its metabolism in the human body has been studied only with the host perspective. Despite the human gut microbiome being considered as a virtual human organ, its role in benzoate metabolism is yet to be elucidated. The current study uses a multi-omic approach to rationalize the role of human gut microbes in benzoate metabolism. Microbial diversity analysis with multiple features synchronously indicates the dominance of Bacteroidetes followed by Firmicutes, Actinobacteria, and Proteobacteria. Metagenomic exploration highlights the presence of benzoate catabolic protein features. These features were mapped on to the aerobic and anaerobic pathways of benzoate catabolism. Benzoate catabolism assays identified statistically significant metabolites (P < 0.05) associated with the protocatechuate branch of the beta-ketoadipate pathway of the benzoate metabolism. Analysis of the 201 human gut metagenomic datasets across diverse populations indicates the omnipresence of these features. Enrichment of the benzoate catabolic protein features in human gut microbes rationalizes their role in benzoate catabolism, as well as indicates food-derived microbiome evolution.

Untargeted metabolomics yields insight into ALS disease mechanisms

ObjectiveTo identify dysregulated metabolic pathways in amyotrophic lateral sclerosis (ALS) versus control participants through untargeted metabolomics.MethodsUntargeted metabolomics was performed on plasma from ALS participants (n=125) around 6.8 months after diagnosis...

Genome-Wide Analysis Reveals Genetic Potential for Aromatic Compounds Biodegradation of Sphingopyxis.

Members of genus Sphingopyxis are frequently found in diverse eco-environments worldwide and have been traditionally considered to play vital roles in the degradation of aromatic compounds. Over recent decades, many aromatic-degrading Sphingopyxis strains have been isolated and recorded, but little is known about their genetic nature related to aromatic compounds biodegradation. In this study, bacterial genomes of 19 Sphingopyxis strains were used for comparative analyses. Phylogeny showed an ambiguous relatedness between bacterial strains and their habitat specificity, while clustering based on Cluster of Orthologous Groups suggested the potential link of functional profile with substrate-specific traits. Pan-genome analysis revealed that 19 individuals were predicted to share 1,066 orthologous genes, indicating a high genetic homogeneity among Sphingopyxis strains. Notably, KEGG Automatic Annotation Server results suggested that most genes pertaining aromatic compounds biodegradation were predicted to be involved in benzoate, phenylalanine, and aminobenzoate metabolism. Among them, β-ketoadipate biodegradation might be the main pathway in Sphingopyxis strains. Further inspection showed that a number of mobile genetic elements varied in Sphingopyxis genomes, and plasmid-mediated gene transfer coupled with prophage- and transposon-mediated rearrangements might play prominent roles in the evolution of bacterial genomes. Collectively, our findings presented that Sphingopyxis isolates might be the promising candidates for biodegradation of aromatic compounds in pollution sites.

Abstract P191: Metabolites Associated With Coffee Consumption and Incident Chronic Kidney Disease

Introduction: Several studies have found moderate coffee consumption to be inversely associated with chronic kidney disease (CKD), however the biological mechanisms underlying this benefit are unclear. Metabolomic studies allow for the characterization of metabolites in biological specimens and are useful for detecting biomarkers of coffee consumption and metabolic pathways underlying the association between coffee and CKD. Hypothesis: We hypothesized that metabolites altered by coffee consumption would be associated with CKD incidence. Methods: A total of 3,809 African-American and Caucasian ARIC study participants had measurements of serum metabolites: 373 metabolites in sample 1 and 758 metabolites in sample 2. Linear regression models were used to estimate cross-sectional associations between metabolites and average cups of coffee consumed per day. Cox regression models were used to estimate associations between coffee metabolites and incident CKD. Results: In sample 1, 13 metabolites were significantly and positively associated with coffee consumption (p&lt;0.05/373=1.3х10 -4 ), one of which (hippurate) was inversely associated with incident CKD ( Table ). In sample 2, 29 metabolites were positively associated and 20 were negatively associated with coffee consumption (p&lt;0.05/758=6.6х10 -5 ). All 13 metabolites detected in sample 1 were also significantly associated with coffee in sample 2. Higher levels of three metabolites (O-sulfo-L-tyrosine, erythritol, and N-acetylserine) were associated with lower intake of coffee and higher risk of incident CKD. Conclusions: We detected 13 candidate biomarkers of coffee consumption that replicated across two samples. Four metabolites, consisting of a food component (erythritol), chemical (O-sulfo-L-tyrosine), and compounds that are involved in the metabolism of benzoate (hippurate), glycine, serine, and threonine (N-acetylserine), may play contribute to the favorable health outcomes observed with coffee consumption.

Abstract P211: Association Between Urbanization-related Change in Diet, the Gut Microbiota and Microbiome-related Metabolites in a Rapidly Urbanizing Environment in China

Introduction: Numerous studies suggest that there are rural-urban differences in gut microbial community, partially due the Westernization of diet. However, most studies are based on short-term follow-up and cannot assess how the transition from traditional to Western diets over time shapes human gut microbiota and whether these microbiota changes subsequently impact the metabolomic profile of the host. Hypothesis: We hypothesize that trajectories in diet shape components of the gut microbial community, with strong associations for microbiota and microbiome-mediated metabolites. Methods: We used growth mixture models to estimate individual-specific intercepts (current % calories from animal source food in 2015) and slopes (change in % calories from animal source food from 1991-2015) in 1,468 adults from the population-based China Health and Nutrition Survey (CHNS) across 20 years of urbanization-related change. We then tested the association between the gut microbiota genera in 2015 with these intercepts and slopes in linear regression models, allowing for interactions between the intercepts and slopes. In the subset of the sample with metabolomic measures collected (n = 500), we then tested whether bacteria associated with change in diet (FDR corrected p-values &lt; 0.05 from the joint test of both main effect and interaction) were associated with microbiome-related metabolites using linear regression models. Results: Controlling for current % calories from animal source food, we found 57 gut microbiota measures that were significantly associated with the rate of change in % animal source calories, with the majority (19%) coming from the order Clostridiales. For 55 gut microbiota measures, we found evidence that the association between current diet and gut microbiota was modified by the rate of change in diet. Thirty-two microbiome-related metabolites, over 50% of which were involved in the benzoate metabolism or food component pathways, were associated with these gut microbiota measures. Conclusions: Our findings suggest that long-term change in calories consumed from animal source foods may shape the composition of the gut microbial community. Further, our metabolome findings suggest that pathways linking diet and the microbiome through microbial metabolites may be particularly relevant.

Dissipation of Emamectin Benzoate Residues in Rice and Rice-Growing Environments

The experiment developed the ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS) method for testing emamectin benzoate, and studied the metabolism of emamectin benzoate in rice plants and rice-growing environments via application of this testing method. The dissipation curve of emamectin benzoate standard substance was good at 0.5–200 μg L−1, and its correlation coefficient was greater than 0.99. In the concentration range of 0.1–50 μg kg−1, the average recovery rate of plants, soil, and field water was 82 %–102 %, and relative standard deviation (RSD) was between 0.3 % and 15.9 %. Half-lives in rice plants and soil were 0.8–2.8 days and 1.9–3.8 days, respectively, and emamectin benzoate was not detected in rice or rice hull. The experiment showed that emamectin benzoate is harmless to human health at the concentration recommended by the manufacturer.