Disturbance Of Amino Acid Metabolism Research Articles

Insights into the molecular mechanisms of malnutrition-associated steatohepatitis: A review.

Malnutrition is a public health epidemic mainly targeting poverty-stricken people, young ones, older people, pregnant women, and individuals with metabolic disorders. Severe malnutrition is linked with several metabolic defects, such as hepatic dysfunction, hypertension, cardiovascular disease, and osteoarthritis. The proper functioning of the liver plays a crucial role in ensuring the supply of nutrients to the body. Consequently, inadequate nutrition can lead to severe periportal hepatic steatosis due to compromised mitochondrial and peroxisome functions. Reduced protein intake disrupts essential metabolic processes like the TCA cycle, oxidative phosphorylation, and β-oxidation, ultimately affecting ATP production. Furthermore, this can trigger a cascade of events, including disturbances in amino acid metabolism, iron metabolism, and gut microbiota, which activate genes involved in de novo lipogenesis, leading to the accumulation of lipids in the liver. The condition, in prolonged cases, progresses to steatohepatitis and liver fibrosis. Limited therapeutic solutions are available; however, few dietary supplements and drugs have demonstrated positive effects on the growth and health of malnourished individuals. These supplements improve parameters such as inflammatory and oxidative status, reduce triglyceride accumulation, enhance insulin sensitivity, and downregulate gene expression in hepatic lipid metabolism. This review elucidates the various mechanisms involved in malnutrition-associated steatohepatitis and provides an overview of the available approaches for treating this condition.

Lanthanum hydroxide protects kidney through gut microbiota in a rat model of chronic kidney disease.

The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine-induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.

The metabolic pathway regulation in kidney injury and repair.

Kidney injury and repair are accompanied by significant disruptions in metabolic pathways, leading to renal cell dysfunction and further contributing to the progression of renal pathology. This review outlines the complex involvement of various energy production pathways in glucose, lipid, amino acid, and ketone body metabolism within the kidney. We provide a comprehensive summary of the aberrant regulation of these metabolic pathways in kidney injury and repair. After acute kidney injury (AKI), there is notable mitochondrial damage and oxygen/nutrient deprivation, leading to reduced activity in glycolysis and mitochondrial bioenergetics. Additionally, disruptions occur in the pentose phosphate pathway (PPP), amino acid metabolism, and the supply of ketone bodies. The subsequent kidney repair phase is characterized by a metabolic shift toward glycolysis, along with decreased fatty acid β-oxidation and continued disturbances in amino acid metabolism. Furthermore, the impact of metabolism dysfunction on renal cell injury, regeneration, and the development of renal fibrosis is analyzed. Finally, we discuss the potential therapeutic strategies by targeting renal metabolic regulation to ameliorate kidney injury and fibrosis and promote kidney repair.

Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics

BackgroundDiabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PurposeThis study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. MethodsFirstly, the content determination methods of QXLZY were established with calycosin-7-O-β-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. ResultsA method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. ConclusionThis study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.

Changes in toxicity after mixing imidacloprid and cadmium: enhanced, diminished, or both? From a perspective of oxidative stress, lipid metabolism, and amino acid metabolism in mice.

Imidacloprid (IMI) and cadmium (Cd) are pollutants of concern in the environment. Although investigations about their combined toxicity to organisms such as earthworms, aquatic worms, Daphnia magna, and zebrafish have been carried out, their combined toxicity to mammals remains unknow. In this study, twenty-four 8-week-old mice were arbitrarily separated into 4 groups: CK (control group), IMI (15 mg/kg bw/day, 1/10 LD50), Cd (15 mg/kg bw/day, 1/10 LD50), and IMI + Cd (15 mg/kg bw/day IMI + 15 mg/kg bw/d Cd) and the combined toxic effects of IMI and Cd were examined with biochemical (oxidative stress testing) and omics approaches (metabolomics and lipidomics). The results revealed changes in each treatment group in terms of oxidative stress, abnormalities in lipid metabolism, and disturbances in amino acid metabolism. Co-administration had antagonistic effects on MDA accumulation and lipid metabolism disorders while acting synergistically on changes in SOD and GSH-Px activities. It is worth noting that after analysis, the changes caused by mixed administration in vivo were closer to those caused by IMI administration alone. This study provides new insights into the combined toxicity of neonicotinoids and heavy metals, which is helpful for relevant environmental governance and further investigations about their impacts on human health and the environment.

Probing the bioconcentration and metabolism disruption of bisphenol A and its analogues in adult female zebrafish from integrated AutoQSAR and metabolomics studies

Plenty of emerging bisphenol A (BPA) substitutes rise to wait for assessment of bioconcentration and metabolism disruption. Computational methods are useful to fill the data gap in chemical risk assessment, such as automated quantitative structure-activity relationship (AutoQSAR). It is not clear how AutoQSAR performs in predicting the bioconcentration factor (BCF) in adult zebrafish. Herein, AutoQSAR was used to predict the logBCFs of BPA, bisphenol AF (BPAF), bisphenol B, bisphenol F and bisphenol S (BPS). For the test set, a linear relationship was shown between the observed and predicted logBCFs with a slope of 0.97. The predicted logBCFs of these five bisphenols were quite close to their experimental data with a slope of 0.94, suggesting better performance than directed message passing neural networks and EPI Suite with a slope of 0.69 and 0.61, respectively. Thus, AutoQSAR is powerful in modeling logBCFs in fish with minimal time and expertise. To link bioconcentration with metabolic effects, female zebrafish were exposed to BPA, BPAF and BPS for metabolomics analysis. BPA caused a significant disturbance in amino acid metabolism, while BPAF and BPS significantly altered another three metabolic pathways, showing chemical-specific responses. BPAF with the highest logBCF elicited the strongest metabolomic responses reflected by the metabolic effect level index, followed by BPA and BPS. Thus, BPAF and BPS elicited higher or similar metabolism disruption compared with BPA in female zebrafish, respectively, reflecting consequences of bioconcentration.

Multi-walled carbon nanotubes enhance the toxicity effects of dibutyl phthalate on early life stages of zebrafish (Danio rerio): Research in physiological, biochemical and molecular aspects

Phthalate esters (PAEs) are widely used as plasticizers. PAEs are ubiquitous in natural water bodies, with dibutyl phthalate (DBP) being one of the most common PAEs. DBP is prone to leaching or migration into the environment, posing serious health and environmental risks. Carbon nanotubes (CNTs) have been widely used in various fields with the rapid development of nanotechnology. CNTs could alter the environmental behavior and toxicity of co-existing pollutants. CNTs have been shown to rapidly adsorb PEAs. However, current knowledge about the effects of CNTs on DBP toxicity is limited. Here we show that the toxic effects of single and combined exposure to DBP (0.1, 0.5, 1.0 mg/L) and different CNTs (MWCNTs/MWCNTs-COOH, 0.5 mg/L) on the early growth stage of zebrafish. The results suggested that a significant increase in heart rate and heart malformation rate was observed after co-exposure of DBP and MWCNTs/MWCNTs-COOH (p < 0.05). Furthermore, combined exposure increased antioxidant enzyme activity during early developmental stages in zebrafish (p < 0.05). The qRT-PCR results revealed that DBP and MWCNTs/MWCNTs-COOH co-exposure significantly interfered with the expression of genes related to oxidative stress, energy metabolism, development of cardiac function, and apoptosis (p < 0.05). In addition, for oxidative stress and cardiotoxicity, MWCNTs/MWCNTs-COOH aggravated the toxic effects of 0.5 mg/L DBP on embryos/larvae. The metabolomics results showed that co-exposure mitigated the disturbance of amino acid metabolism mediated by single DBP exposure. In general, MWCNTs/MWCNTs-COOH increased the impact of DBP in the early developmental stages of zebrafish. This study provides new insights into the toxicology of early developmental stages of aquatic organisms exposed to co-exist pollutants of DBP and CNTs.

Tandem Mass Analysis of Amino Acids and Acylcarnitine Profiles in Neonates with Congenital Hypothyroidism.

Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder. This study aimed to investigate whether disturbances in amino acid metabolism and fatty acid oxidation existed in neonates with CH compared to healthy neonates. In this case-control study, we evaluated the metabolomics of neonates with newly diagnosed CH and healthy neonates. Forty-three metabolites, including 13 amino acids and 30 acylcarnitines, were investigated. Two hundred neonates with CH and 209 healthy children were enrolled. The mean age of males and females was 4.8 ± 2.4 and 5.52 ± 3.2 days in the case group and 5.1 ± 2.6 and 4.7 ± 3.6 days in the control group, respectively. Of the metabolites, 34 were significantly different between the two groups. Five amino acids and four acylcarnitines did not differ significantly between groups. These findings pave the way for a better understanding of the relationship between alterations and the clinical manifestation of CH, which has the potential for identifying novel therapeutics.

Screening and mutation analysis of phenylalanine hydroxylase deficiency in newborns from Jiangxi province.

Background: Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase (PAH) gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time. In China, the PAHD incidence and PAH mutation spectrum vary enormously across the provinces. A total of 5,541,627 newborns from Jiangxi province were screened by NBS between 1997 and 2021. Method: One seventy one newborns from Jiangxi province were diagnosed with PAHD. By Sanger sequencing and the multiplex ligation-dependent probe amplification (MLPA) analysis, mutation analysis was performed in 123 PAHD patients. Using an arbitrary values (AV)-based model, we compared the observed phenotype with the predicted phenotype based on the genotype. Results: In this study, we speculated the PAHD incidence of Jiangxi province was about 30.9 per 1,000,000 live births (171/5,541,627). We summarized the PAH mutation spectrum in Jiangxi province for the first time. Two novel variants (c.433G > C, c.706 + 2T > A) were found. The most prevalent variant was c.728G > A (14.1%). The overall prediction rate of the genotype-phenotype was 77.4%. Conclusion: This mutation spectrum is very meaningful to improve the diagnostic rate of PAHD and to increase the accuracy genetic counseling. This study offers data for the genotype-phenotype prediction suitable for Chinese population.

Abstract C020: Identification of metabolic and molecular mechanisms contributing to ER+ cancer disparities using a machine-learning pipeline

Abstract Background: African American (AA) women are less likely to develop breast cancer but when they do, their mortality rates are 40% higher compared to Non-Hispanic White (NHW) women. This disparity is particularly striking among ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic and molecular pathways typically activated in patients with ER+ positive breast cancer. Methods: We collected plasma from AA and NHW cases and controls to conduct an untargeted metabolomics analysis using gas chromatography-mass spectrometry (GC-MS) to identify metabolites that are possibly altered in the different race groups. Statistical methods combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus on AA patients with breast cancer. The clinical significance of the findings was further examined in the PanCancer Atlas breast cancer data set. Results: We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed disturbed amino acid metabolism, while fatty acid metabolism was significant in NHW patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases, Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific histone methyltransferase NELFE was overexpressed and associated with poor survival exclusively in AA individuals. Conclusion: We employ a comprehensive and novel approach that integrates multiple machine learning methods, and statistical methods, coupled with human functional pathway analyses. This metabolic profile of serum samples might be used to assess risk progression in AA individuals with ER+ breast cancer. To our knowledge, this is a novel finding that describes metabolic alterations in AA breast cancer and emphasizes a potential biological basis for breast cancer health disparities. Citation Format: Ashlie Santaliz Casiano, Zeynep Madak-Erdogan, Dhruv Meta, Jonna Frasor, Garth Rauscher, Kent Hoskins. Identification of metabolic and molecular mechanisms contributing to ER+ cancer disparities using a machine-learning pipeline [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C020.

Solid-State NMR-Based Metabolomics Imprinting Elucidation in Tissue Metabolites, Metabolites Inhibition, and Metabolic Hub in Zebrafish by Chitosan.

In this study, we demonstrated that chitosan-applied zebrafish (Danio rerio) tissue metabolite alteration, metabolic discrimination, and metabolic phenotypic expression occurred. The spectroscopy of solid-state 1H nuclear magnetic resonance (ss 1H-NMR) has been used. Chitosan has no, or low, toxicity and is a biocompatible biomaterial; however, the metabolite mechanisms underlying the biological effect of chitosan are poorly understood. The zebrafish is now one of the most popular ecotoxicology models. Zebrafish were exposed to chitosan concentrations of 0, 50, 100, 200, and 500 mg/L, and the body tissue was subjected to metabolites-targeted profiling. The zebrafish samples were measured via solvent-suppressed and T2-filtered methods with in vivo zebrafish metabolites. The metabolism of glutamate, glutamine, glutathione (GSH), taurine, trimethylamine (TMA), and its N-oxide (TMAO) is also significantly altered. Here, we report the quantification of metabolites and the biological application of chitosan. The metabolomics profile of chitosan in zebrafish has been detected, and the results indicated disturbed amino acid metabolism, the TCA cycle, and glycolysis. Our results demonstrate the potential of comparative metabolite profiling for discovering bioactive metabolites and they highlight the power of chitosan-applied chemical metabolomics to uncover new biological insights.

Comprehensive proteomic and metabolomic analysis uncover the response of okra to drought stress.

The response of okra to drought stress is very complicated, and the molecular mechanisms underlying this process remains ambiguous up to now. In this study, different degrees of water-stress responses of okra leaf were explained by using transcriptomics and metabolomic approaches. The photosynthesis and glycometabolism in okra leaf were both adversely affected by drought stress, leading to inhibition of the carbohydrate metabolic process, and then influencing the secondary plant metabolism. Further, drought stress disturbed amino acid metabolism, especially for the tyrosine-derived pathway as well as arginine and proline metabolism, which have been shown to be significantly enriched under water withholding conditions based on multi-omics conjoint analysis (transcriptome, proteome and metabolome). In-depth analysis of the internal linkages between differentially expressed transcripts, proteins, and metabolites decidedly indicate that tyrosine metabolism could confer tolerance to drought stress by influencing carbon and nitrogen metabolism. These findings provide a whole framework of the regulation and relationships of major transcripts and peptides related to secondary metabolism, particularly, the role of critical proteins and metabolite involved in the change of amino acid metabolism in response to drought stress.

Metabolomic Profile in the Aqueous Humor of Congenital Ectopia Lentis

PurposeTo explore the metabolic profiles in the aqueous humor (AH) of patients with congenital ectopia lentis (CEL).MethodsWe conducted a comprehensive analysis of the metabolites of AH samples of patients with CEL (n = 22) and age-matched patients (n = 22) with congenital cataract by ultra-high performance liquid chromatography tandem-mass spectrometry. The metabolomic characteristics were visualized by principal component analysis, orthogonal partial least squares discriminant analysis and heat map. The levels of the differential metabolites were also compared between CEL patients with and without FBN1 mutations. Pathway enrichment analysis was performed by using Kyoto Encyclopedia of Genes and Genomes. Receiver operating characteristic analysis was performed to select potential biomarkers.ResultsThere were 175 differential metabolites identified between the two groups. Eight metabolites were found to be potential biomarkers in AH of CEL patients. The CEL group showed a significant increase in α-ketoglutarate and decrease in citrate, suggesting that the tricarboxylic acid (TCA) cycle was disturbed. l-proline, prolyl-hydroxyproline, and l-histidine were reduced, which prompted enhanced degradation of microfibrils and collagen. Insidious retinal nerve damage was implied because N-Acetyl-aspartylglutamic acid and N-Acetyl-l-aspartic acid were found to be significantly increased. Pathway enrichment analysis indicated that disturbances in amino acid metabolism and carbohydrate metabolism were the key processes in the pathogenesis of CEL and that TCA cycle disorder may be the driving force behind disease occurrence.ConclusionThese data reveal the characteristics in the metabolomic profiles of the AH of CEL patients, which help provide insights into the pathogenesis of this rare disease.

Combining fecal microbiome and metabolomics to reveal the disturbance of gut microbiota in liver injury and the therapeutic mechanism of shaoyao gancao decoction.

Chemical liver injury is closely related to gut microbiota and its metabolites. In this study, we combined 16S rRNA gene sequencing, 1H NMR-based fecal metabolomics and GC-MS to evaluate the changes in gut microbiota, fecal metabolites and Short-chain fatty acids (SCFAs) in CCl4-induced liver injury in Sprague-Dawley rats, and the therapeutic effect of Shaoyao Gancao Decoction (SGD). The results showed that CCl4-induced liver injury overexpressed CYP2E1, enhanced oxidative stress, decreased antioxidant enzymes (SOD, GSH), increased peroxidative products MDA and inflammatory responses (IL-6, TNF-α), which were ameliorated by SGD treatment. H&E staining showed that SGD could alleviate liver tissue lesions, which was confirmed by the recovered liver index, ALT and AST. Correlation network analysis indicated that liver injury led to a decrease in microbiota correlation, while SGD helped restore it. In addition, fecal metabolomic confirmed the PICRUSt results that liver injury caused disturbances in amino acid metabolism, which were modulated by SGD. Spearman’s analysis showed that liver injury disrupted ammonia transport, urea cycle, intestinal barrier and energy metabolism. Moreover, the levels of SCFAs were also decreased, and the abundance of Lachnoclostridium, Blautia, Lachnospiraceae_NK4A136_group, UCG-005 and Turicibacter associated with SCFAs were altered. However, all this can be alleviated by SGD. More importantly, pseudo germ-free rats demonstrated that the absence of gut microbiota aggravated liver injury and affected the efficacy of SGD. Taken together, we speculate that the gut microbiota has a protective role in the pathogenesis of liver injury, and has a positive significance for the efficacy of SGD. Moreover, SGD can treat liver injury by modulating gut microbiota and its metabolites and SCFAs. This provides useful evidence for the study of the pathogenesis of liver injury and the clinical application of SGD.

Changes in metabolic profiling of whiteleg shrimp (Penaeus vannamei) under hypoxic stress

Hypoxia is a common concern in shrimp aquaculture, affecting growth and survival. Although recent studies have revealed important insights into hypoxia in shrimp and crustaceans, knowledge gaps remain regarding this stressor at the molecular level. In the present study, a gas chromatography–mass spectrometry (GC–MS)-based metabolomics approach was employed to characterize the metabolic signatures and pathways underlying responses of Pacific white shrimp (Penaeus vannamei) to hypoxia and to identify associated candidate biomarkers. We compared metabolite profiles of shrimp haemolymph before (0 h) and after exposure to hypoxia (1 & 2 h). Dissolved oxygen levels were maintained above 85 % saturation in the control and before hypoxia, and 15 % saturation in the hypoxic stress treatment. Results showed 44 metabolites in shrimp haemolymph that were significantly different between before and after hypoxia exposure. These metabolites were energy-related metabolites (e.g., intermediates of citric acid cycle, lactic acid, alanine), fatty acids and amino acids. Pathway analysis revealed 17 pathways that were significantly affected by hypoxia. The changes in metabolites and pathways indicate a shift from aerobic to anaerobic metabolism, disturbance in amino acid metabolism, osmoregulation, oxidative damage and Warburg effect-like response caused by hypoxic stress. Among the altered metabolites, lactic acid was most different between before and after hypoxia exposure and had the highest accurate value for biomarker identification. Future investigations may validate this molecule as a stress biomarker in aquaculture. This study contributes to a better understanding of hypoxia in shrimp and crustaceans at the metabolic level and provides a base for future metabolomics investigations on hypoxia.

Insights into the development of pentylenetetrazole-induced epileptic seizures from dynamic metabolomic changes.

Epilepsy is often considered to be a progressive neurological disease, and the nature of this progression remains unclear. Understanding the overall and common metabolic changes of epileptic seizures can provide novel clues for their control and prevention. Herein, a chronic kindling animal model was established to obtain generalized tonic-clonic seizures via the repeated injections of pentylenetetrazole (PTZ) at subconvulsive dose. Dynamic metabolomic changes in plasma and urine from PTZ-kindled rats at the different kindling phases were explored using NMR-based metabolomics, in combination with behavioral assessment, brain neurotransmitter measurement, electroencephalography and histopathology. The increased levels of glucose, lactate, glutamate, creatine and creatinine, together with the decreased levels of pyruvate, citrate and succinate, ketone bodies, asparagine, alanine, leucine, valine and isoleucine in plasma and/or urine were involved in the development and progression of seizures. These altered metabolites reflected the pathophysiological processes including the compromised energy metabolism, the disturbed amino acid metabolism, the peripheral inflammation and changes in gut microbiota functions. NMR-based metabolomics could provide brain disease information by the dynamic plasma and urinary metabolic changes during chronic epileptic seizures, yielding classification of seizure stages and profound insights into controlling epilepsy via targeting deficient energy metabolism.

The Role of Fecal Microbiota in Liver Toxicity Induced by Perfluorooctane Sulfonate in Male and Female Mice.

Background:Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause hepatotoxicity. The underlying toxicological mechanism remains to be investigated. Given the critical role of fecal microbiota in liver function, it is possible that fecal microbiota may contribute to the liver toxicity induced by PFOS.Objectives:We aimed to investigate the role of liver-fecal microbiota axis in modulating PFOS-induced liver injury in mice.Methods:Male and female mice were exposed to PFOS or vehicle for 14 d. In this investigation, 16S rDNA sequencing and metabolomic profiling were performed to identify the perturbed fecal microbiota and altered metabolites with PFOS exposure. In addition, antibiotic treatment, fecal microbiota transplantation, and bacterial administration were conducted to validate the causal role of fecal microbiota in mediating PFOS-induced liver injury and explore the potential underlying mechanisms.Results:Both male and female mice exposed to PFOS exhibited liver inflammation and steatosis, which were accompanied by fecal microbiota dysbiosis and the disturbance of amino acid metabolism in comparison with control groups. The hepatic lesions were fecal microbiota-dependent, as supported by antibiotic treatment and fecal microbiota transplantation. Mice with altered fecal microbiota in antibiotic treatment or fecal microbiota transplantation experiments exhibited altered arginine concentrations in the liver and feces. Notably, we observed sex-specific lower levels of key microbiota, including Lactobacillus, Enterococcus, and Akkermansia. Mice treated with specific bacteria showed lower arginine levels and lower expression of the phosphorylated mTOR and P70S6K, suggesting lower activity of the related pathway and mitigation of the pathological differences observed in PFOS-exposed mice.Conclusions:Our study demonstrated the critical role of the fecal microbiota in PFOS-induced liver injury in mice. We also identified several critical bacteria that could protect against liver injury induced by PFOS in male and female mice. Our present research provided novel insights into the mechanism of PFOS-induced liver injury in mice. https://doi.org/10.1289/EHP10281

Mass spectrometry-based metabolic profiling for identification of biomarkers in serum related to the change of laying ducks in different physiological periods

Eggs are a major animal protein source for humans. Egg formation is a complex process involved in coordinating various tissues and organs, while blood is necessary for gonad differentiation and egg formation. In this study, non-targeted metabolomics technology was employed to determine the serum metabolites at the time point of 70 days (before laying period, T0), 130 days (pre-laying period, T1), 300 days (peak laying period, T2), and 340 days (post laying period, T3) in female ducks, to provide comprehensive metabolic profiling in reflecting the overall temporal changes. The results showed significant differences in the metabolites of different comparison groups (T0 vs. T1, T2 vs. T3, and T0 & T1 vs. T2& T3), supporting the main physiological responses in ducks are differential among laying periods. L-Aspartic Acid, Biotin, and Thyroxine can be considered the potential biomarkers related to sexual maturity. L-Lysine, Lumichrome, Thiamine, Riboflavin, and Pyridoxine may be biomarkers related to egg formation. Sorbitol, Isorhamnetin, Naringenin, and Hydroxykynurenine were the biomarkers associated with the decline of egg production. In addition, the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis showed that sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism. Egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. The neuroactive ligand-receptor interaction pathway may affect egg production. These findings can detect the different physiological statuses in female ducks and provide a theoretical basis for increasing egg production, and ensuring sustainable farming. Highlights The main physiological responses in ducks are differential among laying periods. 3, 6, and 4 biomarkers related to sexual maturity, the formation of the egg, and the decline of egg production, respectively. Sexual maturity was mainly involved in the biosynthesis of secondary plant metabolites, Tricarboxylic Acid Cycle, Mineral absorption, pentose phosphate pathway, and Oxocarboxylic acid metabolism, and egg formation disturbed amino acid metabolism, vitamin metabolism, and carbohydrate metabolism. while the neuroactive ligand-receptor interaction pathway may affect egg production.

The combination of thymol and cinnamaldehyde reduces the survival and virulence of Listeria monocytogenes on autoclaved chicken breast.

To reveal the antibacterial mechanism of the combination of thymol and cinnamaldehyde to Listeria monocytogenes ATCC 19115 on autoclaved chicken breast. In this study, L. monocytogenes ATCC 19115 on autoclaved chicken breast was exposed to the stress of 125μg/ml thymol and 125μg/ml cinnamaldehyde, and transcriptome analysis was used to reveal the crucial antibacterial mechanism. According to the results, 1303 significantly differentially expressed genes (DEGs) were identified. Treated by thymol and cinnamaldehyde in combination, pyrimidine and branched-chain amino acid biosynthesis of L. monocytogenes were thwarted which impairs its nucleic acid biosynthesis and intracellular metabolism. The up-regulated DEGs involved in membrane composition and function contributed to membrane repair. Besides, pyruvate catabolism and TCA cycle were restrained which brought about the disturbance of amino acid metabolism. ABC transporters were also perturbed, for instance, the uptake of cysteine, D-methionine, and betaine was activated, while the uptake of vitamin, iron, and carnitine was repressed. Thus, L. monocytogenes tended to activate PTS, glycolysis, glycerol catabolism, and pentose phosphate pathways to obtain energy to adapt to the hostile condition. Noticeably, DEGs involved in virulence factors were totally down-regulated, including genes devoted to encoding flagella, chemotaxis, biofilm formation, internalin as well as virulence gene clusters. The combination of thymol and cinnamaldehyde is effective to reduce the survival and potential virulence of L. monocytogenes on autoclaved chicken breast. This work contributes to providing theoretical information for the application and optimization of thymol and cinnamaldehyde in ready-to-eat meat products to inhibit L. monocytogenes.

Antibacterial mechanism of sucrose laurate against Bacillus cereus by attacking multiple targets and its application in milk beverage

Sucrose laurate (SL) is a promising dual-functional additive due to its emulsification and antibacterial activity. However, the knowledge on the antibacterial action of SL against Bacillus cereus was lacking, and thus it was investigated from multiple targets. The antibacterial results demonstrated that the minimum inhibitory concentration of SL was 0.3125 mg/mL, and the time-killing curve confirmed the strong antibacterial activity of SL. The alkaline phosphatase assay suggested that SL disrupted the cell wall integrity. The flow cytometry and fluorescence spectroscopy analysis indicated that SL damaged the integrity of cell membrane and dissipated the transmembrane potential, resulting in the leakage of intracellular materials, which were further supported by scanning electron microscopy and transmission electron microscopy. iTRAQ-based proteomic analysis indicated that SL down-regulated cell wall-associated hydrolase, inhibited the synthesis of fatty acids, influenced nucleic acid synthesis, disturbed amino acid metabolism, and blocked HMP pathway and TCA cycle. Finally, the promising application of SL was evidenced in milk beverage. This investigation could provide scientific basis for the practical application of SL as a dual-functional food additive.