PubMed

Nutrients. 2023 Apr 30;15(9):2161. doi: 10.3390/nu15092161.ABSTRACTRetinopathy is one of the leading causes of irreversible blindness and vision loss worldwide. Imbalanced nutrients play important roles in the pathogenesis and pathophysiology of retinal diseases. Branched-Chain Amino Acids (BCAAs), as essential amino acids, perform a variety of biological functions, including protein synthesis, glucose metabolism, lipid metabolism, inflammation, and oxidative stress in metabolic tissues of diabetes and aging-related diseases. Recently, it has been shown that BCAAs are highly related to neuroprotection, oxidative stress, inflammatory and glutamate toxicity in the retina of retinopathy. Therefore, this review summarizes the alterations of BCAA levels in retinopathy, especially diabetic retinopathy and aging-related macular disease, and the genetics, functions, and mechanisms of BCAAs in the retina as well as other metabolic tissues for reference. All of these efforts aim to provide fundamental knowledge of BCAAs for further discoveries and research on retina health based on the sensing and signaling of essential amino acids.PMID:37432261 | DOI:10.3390/nu15092161

Nutrients. 2023 Apr 26;15(9):2095. doi: 10.3390/nu15092095.ABSTRACTIntermittent fasting (IF) has been promoted as an alternative to dietary caloric restriction for the treatment of obesity. IF restricts the amount of food consumed and improves the metabolic balance by synchronizing it with the circadian rhythm. Dietary changes have a rapid effect on the gut microbiota, modulating the interaction between meal timing and host circadian rhythms. Our paper aims to review the relationships between IF and human gut microbiota. In this study, the primary area of focus was the effect of IF on the diversity and composition of gut microbiota and its relationship with weight loss and metabolomic alterations, which are particularly significant for metabolic syndrome characteristics. We discussed each of these findings according to the type of IF involved, i.e., time-restricted feeding, Ramadan fasting, alternate-day fasting, and the 5:2 diet. Favorable metabolic effects regarding the reciprocity between IF and gut microbiota changes have also been highlighted. In conclusion, IF may enhance metabolic health by modifying the gut microbiota. However additional research is required to draw definitive conclusions about this outcome because of the limited number and diverse designs of existing studies.PMID:37432222 | DOI:10.3390/nu15092095

Nutrients. 2023 Apr 25;15(9):2074. doi: 10.3390/nu15092074.ABSTRACTHypertension is closely related to metabolic dysregulation, which is associated with microbial dysbiosis and altered host-microbiota interactions. However, plasma metabolite profiles and their relationships to oral/gut microbiota in hypertension have not been evaluated in depth. Plasma, saliva, subgingival plaques, and feces were collected from 52 hypertensive participants and 24 healthy controls in a cross-sectional cohort. Untargeted metabolomic profiling of plasma was performed using high-performance liquid chromatography-mass spectrometry. Microbial profiling of oral and gut samples was determined via 16S rRNA and metagenomic sequencing. Correlations between metabolites and clinic parameters/microbiota were identified using Spearman's correlation analysis. Metabolomic evaluation showed distinct clusters of metabolites in plasma between hypertensive participants and control participants. Hypertensive participants had six significantly increased and thirty-seven significantly decreased plasma metabolites compared to controls. The plasma metabolic similarity significantly correlated with the community similarity of microbiota. Both oral and gut microbial community composition had significant correlations with metabolites such as Sphingosine 1-phosphate, a molecule involved in the regulation of blood pressure. Plasma metabolites had a larger number of significant correlations with bacterial genera than fungal genera. The shared oral/gut bacterial genera had more correlations with metabolites than unique genera but shared fungal genera and metabolites did not show clear clusters. The hypertension group had fewer correlations between plasma metabolites and bacteria/fungi than controls at species level. The integrative analysis of plasma metabolome and oral/gut microbiome identified unreported alterations of plasma metabolites in hypertension and revealed correlations between altered metabolites and oral/gut microbiota. These observations suggested metabolites and microbiota may become valuable targets for therapeutic and preventive interventions of hypertension.PMID:37432207 | DOI:10.3390/nu15092074

Nutrients. 2023 Apr 22;15(9):2026. doi: 10.3390/nu15092026.ABSTRACTBACKGROUND: Red beetroot is known to be a health-promoting food. However, little attention is placed on intestinal bioactive compound absorption. The aim of the study was to assess the urinary red beetroot juice (RBJ) intake biomarkers and possible differences in RBJ's micronutrient absorption at rest or after physical exercise.METHODS: This is a three-armed, single-blind study, involving seven healthy volunteers which were randomly divided into three groups and alternatively assigned to three experimental sessions: RBJ intake at rest, RBJ intake with physical activity, and placebo intake with physical activity. For each session, urine samples were collected before and 120, 180, and 240 min after the intake of RBJ or placebo. The same sampling times were employed for the experimental session at rest. The RBJ metabolic composition was also characterized to identify the urinary biomarkers derived from the intake.RESULTS: 4-methylpyridine-2-carboxylic acid, dopamine-3-O-sulfate, glutamine, and 3-hydroxyisobutyrate were identified as RBJ intake biomarkers. Physical activity significantly increased only the dopamine-3-O-sulfate excretion 120 min after RBJ intake.CONCLUSIONS: Urinary dopamine-3-O-sulfate is related to RBJ dopamine content, while 4-methylpyridine-2-carboxylic acid is a betanin or betalamic acid catabolite. The different excretions of these metabolites following physical activity suggest a possible effect on the RBJ uptake depending on different transport processes through the mucosa, namely diffusion-mediated transport for dopamine and saturable transcellular transport for betalamic acid derivatives. These results open new perspectives in improving the absorption of natural bioactive molecules through physical activity.PMID:37432172 | DOI:10.3390/nu15092026

Nutrients. 2023 Apr 22;15(9):2022. doi: 10.3390/nu15092022.ABSTRACTPlant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua (AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC-LTQ-Orbitrap-MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.PMID:37432154 | DOI:10.3390/nu15092022

Microbiol Spectr. 2023 Jul 11:e0085223. doi: 10.1128/spectrum.00852-23. Online ahead of print.ABSTRACTPolymyxins are last-line antibiotics employed against multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance is rapidly on the rise globally. Polymyxins initially target lipid A of lipopolysaccharides (LPSs) in the cell outer membrane (OM), causing disorganization and cell lysis. While most studies focus on how genetic variations confer polymyxin resistance, the mechanisms of membrane remodeling and metabolic changes in polymyxin-resistant strains remain unclear, thus hampering the development of effective therapies to treat severe K. pneumoniae infections. In the present study, lipid A profiling, OM lipidomics, genomics, and metabolomics were integrated to elucidate the global mechanisms of polymyxin resistance and metabolic adaptation in a polymyxin-resistant strain (strain S01R; MIC of >128 mg/L) obtained from K. pneumoniae strain S01, a polymyxin-susceptible (MIC of 2 mg/L), New Delhi metallo-β-lactamase (NDM)-producing MDR clinical isolate. Genomic analysis revealed a novel in-frame deletion at position V258 of PhoQ in S01R, potentially leading to lipid A modification with 4-amino-4-deoxy-l-arabinose (L-Ara4N) despite the absence of polymyxin B. Comparative metabolomic analysis revealed slightly elevated levels of energy production and amino acid metabolism in S01R compared to their levels in S01. Exposure to polymyxin B (4 mg/L for S01 and 512 mg/L for S01R) substantially altered energy, nucleotide, and amino acid metabolism and resulted in greater accumulation of lipids in both strains. Furthermore, the change induced by polymyxin B treatment was dramatic at both 1 and 4 h in S01 but only significant at 4 h in S01R. Overall, profound metabolic adaptation was observed in S01R following polymyxin B treatment. These findings contribute to our understanding of polymyxin resistance mechanisms in problematic NDM-producing K. pneumoniae strains and may facilitate the discovery of novel therapeutic targets. IMPORTANCE Antimicrobial resistance (AMR) is a major threat to global health. The emergence of resistance to the polymyxins that are the last line of defense in so-called Gram-negative "superbugs" has further increased the urgency to develop novel therapies. There are frequent outbreaks of K. pneumoniae infections in hospitals being reported, and polymyxin usage is increasing remarkably. Importantly, the polymyxin-resistant K. pneumoniae strains are imposing more severe consequences to health systems. Using metabolomics, lipid A profiling, and outer membrane lipidomics, our findings reveal (i) changes in the pentose phosphate pathway and amino acid and nucleotide metabolism in a susceptible strain following polymyxin treatment and (ii) how cellular metabolism, lipid A modification, and outer membrane remodeling were altered in K. pneumoniae following the acquisition of polymyxin resistance. Our study provides, for the first time, mechanistic insights into metabolic responses to polymyxin treatment in a multidrug-resistant, NDM-producing K. pneumoniae clinical isolate with acquired polymyxin resistance. Overall, these results will assist in identifying new therapeutic targets to combat and prevent polymyxin resistance.PMID:37432123 | DOI:10.1128/spectrum.00852-23

Gut Microbes. 2023 Jan-Dec;15(1):2231590. doi: 10.1080/19490976.2023.2231590.ABSTRACTThe gut microbiota affects hepatic drug metabolism. However, gut microbial factors modulating hepatic drug metabolism are largely unknown. In this study, using a mouse model of acetaminophen (APAP)-induced hepatotoxicity, we identified a gut bacterial metabolite that controls the hepatic expression of CYP2E1 that catalyzes the conversion of APAP to a reactive, toxic metabolite. By comparing C57BL/6 substrain mice from two different vendors, Jackson (6J) and Taconic (6N), which are genetically similar but harbor different gut microbiotas, we established that the differences in the gut microbiotas result in differential susceptibility to APAP-induced hepatotoxicity. 6J mice exhibited lower susceptibility to APAP-induced hepatotoxicity than 6N mice, and such phenotypic difference was recapitulated in germ-free mice by microbiota transplantation. Comparative untargeted metabolomic analysis of portal vein sera and liver tissues between conventional and conventionalized 6J and 6N mice led to the identification of phenylpropionic acid (PPA), the levels of which were higher in 6J mice. PPA supplementation alleviated APAP-induced hepatotoxicity in 6N mice by lowering hepatic CYP2E1 levels. Moreover, PPA supplementation also reduced carbon tetrachloride-induced liver injury mediated by CYP2E1. Our data showed that previously known PPA biosynthetic pathway is responsible for PPA production. Surprisingly, while PPA in 6N mouse cecum contents is almost undetectable, 6N cecal microbiota produces PPA as well as 6J cecal microbiota in vitro, suggesting that PPA production in the 6N gut microbiota is suppressed in vivo. However, previously known gut bacteria harboring the PPA biosynthetic pathway were not detected in either 6J or 6N microbiota, suggesting the presence of as-yet-unidentified PPA-producing gut microbes. Collectively, our study reveals a novel biological function of the gut bacterial metabolite PPA in the gut-liver axis and presents a critical basis for investigating PPA as a modulator of CYP2E1-mediated liver injury and metabolic diseases.PMID:37431867 | DOI:10.1080/19490976.2023.2231590

Gut Microbes. 2023 Jan-Dec;15(1):2232143. doi: 10.1080/19490976.2023.2232143.ABSTRACTThe gut microbiota and bile acid metabolism are key determinants of the response of inflammatory bowel disease to biologic therapy. However, the molecular mechanisms underlying the interactions between the response to anti-α4β7-integrin therapy and the gut microbiota and bile acid metabolism remain unknown. In this research, we investigated the role of gut microbiota-related bile acid metabolism on the response to anti-α4β7-integrin therapy in a humanized immune system mouse model with colitis induced by 2,4,6-trinitrobenzene sulfonic acid. We found that anti-α4β7-integrin significantly mitigated intestinal inflammation, pathological symptoms, and gut barrier disruption in remission-achieving colitis mice. Whole-genome shotgun metagenomic sequencing demonstrated that employing baseline microbiome profiles to predict remission and the treatment response was a promising strategy. Antibiotic-mediated gut microbiota depletion and fecal microbiome transplantation revealed that the baseline gut microbiota contained common microbes with anti-inflammatory effects and reduced mucosal barrier damage, improving the treatment response. Targeted metabolomics analysis illustrated that bile acids associated with microbial diversity were involved in colitis remission. Furthermore, the activation effects of the microbiome and bile acids on FXR and TGR5 were evaluated in colitis mice and Caco-2 cells. The findings revealed that the production of gastrointestinal bile acids, particularly CDCA and LCA, further directly promoted the stimulation of FXR and TGR5, significantly improving gut barrier function and suppressing the inflammatory process. Taken together, gut microbiota-related bile acid metabolism-FXR/TGR5 axis may be a potential mechanism for impacting the response to anti-α4β7-integrin in experimental colitis. Thus, our research provides novel insights into the treatment response in inflammatory bowel disease.PMID:37431863 | DOI:10.1080/19490976.2023.2232143

Environ Sci Technol. 2023 Jul 11. doi: 10.1021/acs.est.3c01746. Online ahead of print.ABSTRACTTriclosan (TCS), an antimicrobial compound, is known to have potential endocrine-disruptive properties, but the underlying toxic mechanisms at the metabolic level are not well understood. Here, we applied metabolomics and lipidomics combined with mass spectrometry imaging (MSI) to unveil the mechanisms of the enhanced growth of MCF-7 breast cancer cell spheroids (CCS) exposed to TCS. To obtain a wide coverage of metabolites and lipids by using MSI, we used techniques of matrix-assisted laser desorption/ionization (MALDI) and MALDI coupled with laser-postionization. The results showed that TCS and TCS sulfate penetrated into the entire area at 0-3 h and both localized in the inner area at 6 h. After 24 h, a portion of two compounds was released from CCS. Omic data indicated that TCS exposure induced alterations via several pathways, including energy metabolism and biosynthesis of glycerophospholipids and glycerolipids. Further MSI data revealed that the enhancement of energy supply in the peripheral area and the increase of energy storage in the inner area might contribute to the enhanced growth of MCF-7 breast CCS exposed to TCS. This study highlights the importance of integrating metabolite distributions and metabolic profiles to reveal the novel mechanisms of TCS-triggered endocrine disrupting effects.PMID:37431803 | DOI:10.1021/acs.est.3c01746

Alcohol (Hanover). 2023 Jul 11. doi: 10.1111/acer.15148. Online ahead of print.ABSTRACTBACKGROUND: Alcohol-associated liver disease (ALD) leads to millions of deaths worldwide annually. A few potential biomarkers have been discovered through metabolomics or proteomics. Tryptophan (Trp), one of the nine essential amino acids, has been extensively studied and has been shown to play significant roles in many mammalian physiological processes. However, Trp metabolism changes in ALD are not yet fully understood. Urine is an abundant and non-invasive source for disease biomarker discovery. The objective of the current study was to investigate whether the abundance of Trp metabolites in the urine of ALD patients is changed and if these changes in urine can serve as markers for differentiating between stages of ALD.METHOD: We quantified the concentration of Trp and its metabolites in the human urine samples of healthy controls (n = 18), patients with mild or moderate alcohol-related liver injury (n = 21), and patients with severe alcohol-associated hepatitis (AH) (n = 25) using both untargeted and targeted metabolomics.RESULTS: Eighteen Trp metabolites were identified and quantified from the untargeted metabolomics data. We then developed a targeted metabolomics method to quantify the Trp and its metabolites. Our developed method can simultaneously quantify 22 Trp metabolites within 15 mins, and 17 metabolites were quantified from the human urine samples. The data acquired in these two platforms agree and show that the Trp concentration is not affected by the severity of ALD. However, the abundance of 10 Trp metabolites is correlated with the model for end-stage liver disease (MELD) score, and the abundance of 9 metabolites have significant abundance changes between healthy control and patient groups.CONCLUSION: Our data demonstrate that Trp metabolism is altered by excessive alcohol consumption even though the concentration of Trp is not affected. Two Trp metabolites, quinolinic acid and indoxyl sulfate, correlate highly with ALD stage.PMID:37431708 | DOI:10.1111/acer.15148

Foods. 2022 Oct 20;11(20):3278. doi: 10.3390/foods11203278.ABSTRACTThe genus Hippophae (sea buckthorn) is widely cultivated and consumed in Asia and Europe. The fruit color is an important appearance and commercial trait for sea buckthorn, which is closely related to the biosynthesis and accumulation of various nutrients and pigments. The fruit colors of sea buckthorn are varied, which appear as yellow, orange, red, and brown. However, the nutrients and pigments forming different the fruit colors of sea buckthorn remain unclear. To investigate the mechanism of pigmentation of sea buckthorn fruit, integrative analyses of the transcriptome and targeted metabolome, including the carotenoids, flavonoids, and chlorophylls, were performed in five sea buckthorn varieties with different fruit colors. A total of 209 flavonoids and 41 carotenoids were identified in five sea buckthorn fruits of different colors. The types and contents of flavonoids and carotenoids in the five sea buckthorn fruits were significantly different. Interestingly, we only found a high content of chlorophyll (772.7 mg/kg) in the sea buckthorn fruit with a brown color. The quantities and relative proportions of the flavonoids, carotenoids, and chlorophyll led to the different colors of the sea buckthorn fruits. Using a weighted gene co-expression network analysis (WGCNA), the key genes related to the carotenoids and chlorophyll metabolism were identified. The high content of chlorophylls in the brown fruit was closely related to the downregulated expression of key genes in the chlorophyll degradation pathway, including SGR, SGRL, PPH, NYC1, and HCAR. Our results provide new insights into the roles of flavonoids, carotenoids, and chlorophylls in the formation of fruit color in sea buckthorn.PMID:37431026 | DOI:10.3390/foods11203278

Foods. 2022 Oct 20;11(20):3269. doi: 10.3390/foods11203269.ABSTRACTThe supercritical CO2-based decaffeination (SCD) method can be used to prepare decaffeinated tea, but its overall effect on the phytochemicals, volatiles, and sensory qualities of green and black teas is still unclear, and its suitability to prepare decaffeinated green and black teas still needs to be compared. This study revealed the effect of SCD on phytochemicals, volatiles, and sensory qualities in black and green tea prepared from the same tea leaves, and compared the suitability of preparing decaffeinated green and black teas using SCD. The results showed that the SCD could remove 98.2 and 97.1% of the caffeine in green and black tea, respectively. However, it can cause further losses of phytochemicals in green and black teas, specifically the loss of epigallocatechin gallate, epigallocatechin, epicatechin gallate, and gallocatechin gallate in green tea and the loss of theanine and arginine in green and black teas. After the decaffeination, both green and black teas lost some volatiles but also generated new volatiles. Especially, the fruit/flower-like aroma, ocimene, linalyl acetate, geranyl acetate, and D-limonene, were generated in the decaffeinated black tea, while herbal/green-like aroma, β-cyclocitral, 2-ethylhexanol, and safranal, were generated in the decaffeinated green tea. The overall acceptance of decaffeinated green tea decreased due to the substantial reduction in bitterness and astringency, while the overall acceptance of decaffeinated black tea significantly increased. Therefore, SCD is more suitable for the preparation of decaffeinated black tea.PMID:37431017 | DOI:10.3390/foods11203269

Foods. 2022 Oct 18;11(20):3248. doi: 10.3390/foods11203248.ABSTRACTFlavor is one of the most important characteristics that directly determines the popularity of a food. Moreover, the flavor of fruits is determined by the interaction of multiple metabolic components. Pepino, an emerging horticultural crop, is popular for its unique melon-like flavor. We analyzed metabolomics data from three different pepino growing regions in Haidong, Wuwei, and Jiuquan and counted the status of sweetness, acidity, flavor, and overall liking ratings of pepino fruit in these three regions by sensory panels. The metabolomics and flavor ratings were also integrated and analyzed using statistical and machine learning models, which in turn predicted the sensory panel ratings of consumers based on the chemical composition of the fruit. The results showed that pepino fruit produced in the Jiuquan region received the highest ratings in sweetness, flavor intensity, and liking, and the results with the highest contribution based on sensory evaluation showed that nucleotides and derivatives, phenolic acids, amino acids and derivatives, saccharides, and alcohols were rated in sweetness (74.40%), acidity (51.57%), flavor (56.41%), and likability (33.73%) dominated. We employed 14 machine learning strategies trained on the discovery samples to accurately predict the outcome of sweetness, sourness, flavor, and liking in the replication samples. The Radial Sigma SVM model predicted with better accuracy than the other machine learning models. Then we used the machine learning models to determine which metabolites influenced both pepino flavor and consumer preference. A total of 27 metabolites most important for pepino flavor attributes to distinguish pepino originating from three regions were screened. Substances such as N-acetylhistamine, arginine, and caffeic acid can enhance pepino's flavor intensity, and metabolites such as glycerol 3-phosphate, aconitic acid, and sucrose all acted as important variables in explaining the liking preference. While glycolic acid and orthophosphate inhibit sweetness and enhance sourness, sucrose has the opposite effect. Machine learning can identify the types of metabolites that influence fruit flavor by linking metabolomics of fruit with sensory evaluation among consumers, which conduces breeders to incorporate fruit flavor as a trait earlier in the breeding process, making it possible to select and release fruit with more flavor.PMID:37430996 | DOI:10.3390/foods11203248

Foods. 2022 Oct 11;11(20):3164. doi: 10.3390/foods11203164.ABSTRACTThe purpose of this study was to examine the effects of two different feeding systems, a control or a flaxseed and lupin diet (experimental), for a sheep flock, on the microbiota and metabolome of Kefalograviera cheese samples produced by their milk. In particular, the microbiota present in Kefalograviera cheese samples was analyzed using 16S rRNA gene sequencing, while ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was applied to investigate the chemical profile of the cheeses, considering the different feeding systems applied. The metagenomic profile was found to be altered by the experimental feeding system and significantly correlated to specific cheese metabolites, with Streptococcaceae and Lactobacillaceae establishing positive and negative correlations with the discriminant metabolites. Overall, more than 120 features were annotated and identified with high confidence level across the samples while most of them belonged to specific chemical classes. Characteristic analytes detected in different concentrations in the experimental cheese samples including arabinose, dulcitol, hypoxanthine, itaconic acid, L-arginine, L-glutamine and succinic acid. Therefore, taken together, our results provide an extensive foodomics approach for Kefalograviera cheese samples from different feeding regimes, investigating the metabolomic and metagenomic biomarkers that could be used to foresee, improve, and control cheese ripening outcomes, demonstrating the quality of the experimental Kefalograviera cheese.PMID:37430914 | DOI:10.3390/foods11203164

Foods. 2022 Oct 11;11(20):3159. doi: 10.3390/foods11203159.ABSTRACTMonascus pigments (MPs) are natural edible pigments with high safety and strong function, which have been widely used in food and health products. In this study, different types of tea extracts (rich in polyphenols) were used to regulate the biosynthesis of MPs. The results showed that 15% ethanol extract of pu-erh tea (T11) could significantly increase MPs production in liquid fermentation of Monaco's purpureus M3. Comparative transcriptomic and metabolomic analyses combined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to further explore the regulatory mechanism of T11 on the biosynthesis of MPs. Comparative transcriptomic analysis showed that there were 1503 differentially expressed genes (DEGs) between the Con group and the T11 group, which were mainly distributed in carbohydrate metabolism, amino acid metabolism, energy metabolism, lipid metabolism, metabolism of terpenoids and polyketides, etc. A total of 115 differential metabolites (DMs) identified by metabolomics between the Con and T11 groups were mainly enriched in glutathione metabolism, starch and sucrose metabolism, alanine, aspartic acid and glutamate metabolism and glycine, serine and threonine metabolism, etc. The results of metabolomics were basically consistent with those of gene transcriptomics, indicating that the regulatory effect of T11 on the biosynthesis of MPs is mainly achieved through affecting the primary metabolic pathway, providing sufficient energy and more biosynthetic precursors for secondary metabolism. In this study, tea extracts with low economic value and easy access were used as promoters of MPs biosynthesis, which may be conducive to the application of MPs in large-scale industrial production. At the same time, a more systematic understanding of the molecular regulatory mechanism of Monascus metabolism was obtained through multi-omics analysis.PMID:37430908 | DOI:10.3390/foods11203159

Integr Zool. 2023 Jul 10. doi: 10.1111/1749-4877.12749. Online ahead of print.ABSTRACTThe intestinal microbiota help regulate hibernation in vertebrates. However, it needs to be established how hibernation modulates the gut microbiome and intestinal metabolism. In the present study, we used an artificial hibernation model to examine the responses of the gut microbiota of the Strauchbufo raddei to the environmental changes associated with this behavior. Hibernation significantly lowered the diversity of the microbiota and altered the microbial community of the gut. Proteobacteria, Firmicutes, and Bacteroidota were the major bacterial phyla in the intestines of S. raddei. However, Firmicutes and Proteobacteria predominated in the gut of active and hibernating S. raddei, respectively. Certain bacterial genera such as Pseudomonas, Vibrio, Ralstonia, and Rhodococcus could serve as biomarkers distinguishing hibernating and non-hibernating S. raddei. The gut microbiota was more resistant to environmental stress in hibernating than active S. raddei. Moreover, metabolomics revealed that metabolites implicated in fatty acid biosynthesis were highly upregulated in the intestines of hibernating S. raddei. The metabolites that were enriched during hibernation enabled S. raddei to adapt to the low temperatures and the lack of exogenous food that are characteristic of hibernation. A correlation analysis of the intestinal microbiota and their metabolites revealed that the gut microbiota might participate in the metabolic regulation of hibernating S. raddei. The present study clarified the modifications that occur in the intestinal bacteria and their symbiotic relationship with their host during hibernation. These findings are indicative of the adaptive changes in the metabolism of amphibians under different environmental conditions.PMID:37430430 | DOI:10.1111/1749-4877.12749

Sci Rep. 2023 Jul 10;13(1):11156. doi: 10.1038/s41598-023-38289-1.ABSTRACTDisordered sleep is a global social problem and an established significant risk factor for psychological and metabolic diseases. We profiled non-targeted metabolites in saliva from mouse models of chronic sleep disorder (CSD). We identified 288 and 55 metabolites using CE-FTMS and LC-TOFMS, respectively, among which concentrations of 58 (CE-FTMS) and three (LC-TOFMS) were significantly changed by CSD. Pathway analysis revealed that CSD significantly suppressed glycine, serine and threonine metabolism. Arginine and proline metabolic pathways were among those that were both upregulated and downregulated. Pathways of alanine, aspartate and glutamate metabolism, genetic information processing, and the TCA cycle tended to be downregulated, whereas histidine metabolism tended to be upregulated in mice with CSD. Pyruvate, lactate, malate, succinate and the glycemic amino acids alanine, glycine, methionine, proline, and threonine were significantly decreased, whereas 3-hydroxybutyric and 2-hydroxybutyric acids associated with ketosis were significantly increased, suggesting abnormal glucose metabolism in mice with CSD. Increases in the metabolites histamine and kynurenic acid that are associated with the central nervous system- and decreased glycine, might be associated with sleep dysregulation and impaired cognitive dysfunction in mice with CSD. Our findings suggested that profiling salivary metabolites could be a useful strategy for diagnosing CSD.PMID:37429932 | PMC:PMC10333369 | DOI:10.1038/s41598-023-38289-1

Cochrane Database Syst Rev. 2023 Jul 10;7(7):CD014498. doi: 10.1002/14651858.CD014498.ABSTRACTBACKGROUND: Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32 weeks of gestation occurs in an estimated 0.4% of pregnancies. This extreme phenotype is associated with a high risk of fetal death, neonatal mortality, and neonatal morbidity. Currently, there is no causal treatment, and management is focused on indicated preterm birth to prevent fetal death. Interest has risen in interventions that aim to improve placental function by administration of pharmacological agents affecting the nitric oxide pathway causing vasodilatation.OBJECTIVES: The objective of this systematic review and aggregate data meta-analysis is to assess the beneficial and harmful effects of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or different drugs affecting this pathway against each other, in pregnant women with severe early-onset FGR.SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 July 2022), and reference lists of retrieved studies.SELECTION CRITERIA: We considered all randomised controlled comparisons of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or another drug affecting this pathway in pregnant women with severe early-onset FGR of placental origin, for inclusion in this review.DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis.MAIN RESULTS: We included a total of eight studies (679 women) in this review, all of which contributed to the data and analysis. The identified studies report on five different comparisons: sildenafil compared with placebo or no therapy, tadalafil compared with placebo or no therapy, L-arginine compared with placebo or no therapy, nitroglycerin compared with placebo or no therapy and sildenafil compared with nitroglycerin. The risk of bias of included studies was judged as low or unclear. In two studies the intervention was not blinded. The certainty of evidence for our primary outcomes was judged as moderate for the intervention sildenafil and low for tadalafil and nitroglycerine (due to low number of participants and low number of events). For the intervention L-arginine, our primary outcomes were not reported. Sildenafil citrate compared to placebo or no therapy (5 studies, 516 women) Five studies (Canada, Australia and New Zealand, the Netherlands, the UK and Brazil) involving 516 pregnant women with FGR were included. We assessed the certainty of the evidence as moderate. Compared with placebo or no therapy, sildenafil probably has little or no effect on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.80 to 1.27, 5 studies, 516 women); may reduce fetal mortality (RR 0.82, 95% CI 0.60 to 1.12, 5 studies, 516 women), and increase neonatal mortality (RR 1.45, 95% CI 0.90 to 2.33, 5 studies, 397 women), although the results are uncertain for fetal and neonatal mortality as 95% confidence intervals are wide crossing the line of no effect. Tadalafil compared with placebo or no therapy (1 study, 87 women) One study (Japan) involving 87 pregnant women with FGR was included. We assessed the certainty of the evidence as low. Compared with placebo or no therapy, tadalafil may have little or no effect on all-cause mortality (risk ratio 0.20, 95% CI 0.02 to 1.60, one study, 87 women); fetal mortality (RR 0.11, 95% CI 0.01 to 1.96, one study, 87 women); and neonatal mortality (RR 0.89, 95% CI 0.06 to 13.70, one study, 83 women). L-Arginine compared with placebo or no therapy (1 study, 43 women) One study (France) involving 43 pregnant women with FGR was included. This study did not assess our primary outcomes. Nitroglycerin compared to placebo or no therapy (1 studies, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. Sildenafil citrate compared to nitroglycerin (1 study, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups.AUTHORS' CONCLUSIONS: Interventions affecting the nitric oxide pathway probably do not seem to influence all-cause (fetal and neonatal) mortality in pregnant women carrying a baby with FGR, although more evidence is needed. The certainty of this evidence is moderate for sildenafil and low for tadalafil and nitroglycerin. For sildenafil a fair amount of data are available from randomised clinical trials, but with low numbers of participants. Therefore, the certainty of evidence is moderate. For the other interventions investigated in this review there are insufficient data, meaning we do not know whether these interventions improve perinatal and maternal outcomes in pregnant women with FGR.PMID:37428872 | PMC:PMC10332237 | DOI:10.1002/14651858.CD014498

BMJ Open. 2023 Jul 10;13(7):e070616. doi: 10.1136/bmjopen-2022-070616.ABSTRACTINTRODUCTION: Individuals with anorexia nervosa (AN) harbour distinct gut microbiomes compared with healthy individuals, which are sufficient to induce weight loss and anxiety-like behaviours when transplanted into germ-free mice. We hypothesise that faecal microbiome transfer (FMT) from healthy donors would help restore the gut microbiome of individuals with AN, which in turn, may aid patient recovery.METHODS: We aim to conduct an open-label pilot study in 20 females aged 16-32 years in Auckland, New Zealand who meet the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN and have a body mass index 13-19 kg/m2. We will recruit four healthy, lean, female donors, aged 18-32 years, who will undergo extensive clinical screening prior to stool donation. Faecal microbiota will be harvested from donors and double encapsulated in delayed release, acid-resistant capsules. All participants will receive a single course of 20 FMT capsules (five from each donor) which they can choose to take over two or four consecutive days. Stool and blood samples will be collected from participants over a period of 3 months to assess their gut microbiome profile, metabolome, levels of intestinal inflammation and nutritional status. Our primary outcome is a shift in the gut microbiome composition at 3 weeks post-FMT (Bray-Curtis dissimilarity). We will also monitor participants' body composition (whole-body dual-energy X-ray absorptiometry scans), eating disorder psychopathology, mental health and assess their views on, and tolerability of, treatment. All adverse events will be recorded and reviewed by an independent data monitoring committee.ETHICS AND DISSEMINATION: Ethics approval was provided by the Central Health and Disability Ethics Committee (Ministry of Health, New Zealand, 21/CEN/212). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.TRIAL REGISTRATION NUMBER: ACTRN12621001504808.PMID:37429676 | DOI:10.1136/bmjopen-2022-070616

J Appl Microbiol. 2023 Jul 10:lxad142. doi: 10.1093/jambio/lxad142. Online ahead of print.ABSTRACTAIMS: Study of the effect of isoleucine on the biosynthesis of FK506 and modification of its producing strain to improve the production of FK506.METHODS AND RESULTS: Metabolomics analysis was conducted to explore key changes in the metabolic processes of S. tsukubaensis Δ68 in medium with and without isoleucine. In-depth analysis revealed that the shikimate pathway, methylmalonyl-CoA and pyruvate might be the rate-limiting factors in FK506 biosynthesis. Overexpression of involved gene PCCB1 in S. tsukubaensis Δ68, a high-yielding strain Δ68-PCCB1 was generated. Additionally, the amino acids supplement was further optimized to improve FK506 biosynthesis. Finally, FK506 production was increased to 929.6 mg·L-1, which was 56.6% higher than that in the starter strain, when supplemented isoleucine and valine at 9 g·L-1 and 4 g·L-1, respectively.CONCLUSIONS: Methylmalonyl-CoA might be the key rate-limiting factors in FK506 biosynthesis and overexpression of the gene PCCB1 and further addition of isoleucine and valine could increase the yield of FK506 by 56.6%.PMID:37429605 | DOI:10.1093/jambio/lxad142