PubMed

J Transl Med. 2023 Oct 19;21(1):740. doi: 10.1186/s12967-023-04570-0.ABSTRACTBACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction.METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed.RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05).CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.PMID:37858192 | DOI:10.1186/s12967-023-04570-0

J Transl Med. 2023 Oct 19;21(1):739. doi: 10.1186/s12967-023-04564-y.ABSTRACTBACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous.METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2.RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate).CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.PMID:37858181 | DOI:10.1186/s12967-023-04564-y

Eur Respir J. 2023 Oct 19;62(4):2301547. doi: 10.1183/13993003.01547-2023. Print 2023 Oct.NO ABSTRACTPMID:37857433 | DOI:10.1183/13993003.01547-2023

Environ Sci Technol. 2023 Oct 19. doi: 10.1021/acs.est.3c04561. Online ahead of print.ABSTRACTPrenatal exposure to single chemicals belonging to the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in the mother, fetus, and placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed to multiple PFAS, the potential joint effects of PFAS on the metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics to identify metabolites and metabolic pathways perturbed by exposure to a PFAS mixture during pregnancy. Targeted assessment of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS), along with untargeted metabolomics profiling, were conducted on nonfasting serum samples collected from pregnant African Americans at 6-17 weeks gestation. We estimated the overall mixture effect and partial effects using quantile g-computation and single-chemical effects using linear regression. All models were adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, and gestational weeks at sample collection. Our analytic sample included 268 participants and was socioeconomically diverse, with the majority receiving public health insurance (78%). We observed 13.3% of the detected metabolic features were associated with the PFAS mixture (n = 1705, p < 0.05), which was more than any of the single PFAS chemicals. There was a consistent association with metabolic pathways indicative of systemic inflammation and oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, and vitamins A, C, D, and E metabolism) across all metabolome-wide association studies. Twenty-six metabolites were validated against authenticated compounds and associated with the PFAS mixture (p < 0.05). Based on quantile g-computation weights, PFNA contributed the most to the overall mixture effect for γ-aminobutyric acid (GABA), tyrosine, and uracil. In one of the first studies of its kind, we demonstrate the feasibility and utility of using methods designed for exposure mixtures in conjunction with metabolomics to assess the potential joint effects of multiple PFAS chemicals on the human metabolome. We identified more pronounced metabolic perturbations associated with the PFAS mixture than for single PFAS chemicals. Taken together, our findings illustrate the potential for integrating environmental mixture analyses and high-throughput metabolomics to elucidate the molecular mechanisms underlying human health.PMID:37857362 | DOI:10.1021/acs.est.3c04561

Food Chem. 2023 Oct 11;436:137737. doi: 10.1016/j.foodchem.2023.137737. Online ahead of print.ABSTRACTGanoderma lingzhi is an important medicinal fungus, which is widely used as dietary supplement and for pharmaceutical industries. However, the spatial distribution and dynamic accumulation pattern of active components such as ganoderic acids (GAs) among different parts of G. lingzhi fruiting body are still unclear. In this study, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with untargeted metabolomics analysis was applied to investigate the metabolites distribution within G. lingzhi fruiting body at four different maturity stages (squaring, opening, maturation and harvesting stage). A total of 132 metabolites were characterized from G. lingzhi, including 115 triterpenoids, 11 fatty acids and other component. Most of the GAs content in the cap was significantly higher than that in the stipe, with six components such as ganoderic acid B being extremely significant. GAs in the cap was mainly present in the bottom edge of the mediostratum layer, such as ganoderic A-I and ganoderic GS-1, while in the stipe, they were mainly distributed in the shell layer and the context layer, such as ganoderic A-F. Most ganoderic acids content in both the stipe and the cap of G. lingzhi was gradually decreased with the development of G. lingzhi. The GAs in the stipe was gradually transferred from the shell layer to the content layer, while the distribution of GAs among different tissues of the cap was not significantly changed. In addition, linoleic acid, 9-HODE, 9-KODE and other fatty acids were mainly accumulated in the opening and maturing stage of the caps. This study further clarifies the spatial dynamic distribution of GAs in G. lingzhi fruiting body at four different maturity stages (squaring, opening, maturation and harvesting stage), which provides a basis for the rational utilization of the medicinal parts of G. lingzhi. Furthermore, mass spectrometry imaging combined with non-target metabolome analysis provides a powerful tool for the spatial distribution of active substances in the different regions of the medicinal edible fungi.PMID:37857205 | DOI:10.1016/j.foodchem.2023.137737

Food Chem. 2023 Oct 14;436:137759. doi: 10.1016/j.foodchem.2023.137759. Online ahead of print.ABSTRACTAdjunct cultures strongly determined the distinguishing sensorial and nutritional characteristics of cheeses. Metabolites, flavor profiles and ripening characteristics of Monascus-ripened cheese enhanced by the co-fermentation of Ligilactobacillus salivarius AR809 were investigated. The AR809 significantly increased the contents of soluble nitrogen, small peptides (<1200 Da), free amino acids, and casein degradation degree in the resulting cheese. Furthermore, AR809 significantly promoted the formation of methyl ketones during cheese maturation. Based on untargeted metabolomics analysis, metabolites related to fatty acids metabolism and lysine degradation were highly enriched in Monascus-rich region of cheese. AR809 was primarily engaged in amino acid metabolism, promoting the synthesis of amino acids and dipeptide. L. salivarius and Monascus co-fermentation produced more beneficial bioactive metabolites involved in amino acids and lipid metabolisms than Monascus used alone in cheese ripening. Therefore, as adjunct culture, L. salivarius AR809 exhibited tremendous potential in improving nutrition and flavor quality during cheese ripening.PMID:37857204 | DOI:10.1016/j.foodchem.2023.137759

Microbiol Res. 2023 Oct 12;278:127516. doi: 10.1016/j.micres.2023.127516. Online ahead of print.ABSTRACTSignal-mediated cell fusion is vital for colony development in filamentous fungi. Arthrobotrys oligospora is a representative nematode-trapping (NT) fungus that produces adhesive networks (traps) to capture nematodes. Here, we characterized Aoadv-1, Aoso, Aoham-6, and Aoham-5 of A. oligospora, homologs of proteins involved in cellular communication and fusion in the model fungus Neurospora crassa. The deletion of four genes resulted in the complete loss of cell fusion, and traps produced by mutants did not close to form mycelial rings but were still capable of capturing nematodes. The absence of these genes inhibits aerial mycelial extension, slows colony growth, and increases mycelial branching. In addition, the mutants showed reduced sporulation capacity and tolerance to oxidative stress, increased sensitivity to SDS, and disturbed lipid droplet accumulation and autophagy. In addition, transcriptome and metabolomic analyses suggested that Aoadv-1 and Aoso are involved in multiple cellular processes and secondary metabolism. Our results revealed that Aoadv-1, Aoso, Aoham-6, and Aoham-5 regulate mycelial growth and trap morphogenesis through cell fusion, which contributed to elucidating the molecular mechanisms of cellular communication regulating mycelial development and trap morphogenesis in NT fungi.PMID:37857124 | DOI:10.1016/j.micres.2023.127516

BMC Neurol. 2023 Oct 19;23(1):373. doi: 10.1186/s12883-023-03414-0.ABSTRACTBACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and, according to the Global Burden of Disease estimates in 2015, was the fastest growing neurological disorder globally with respect to associated prevalence, disability, and deaths. Information regarding the awareness, diagnosis, phenotypic characteristics, epidemiology, prevalence, risk factors, treatment, economic impact and lived experiences of people with PD from the African perspective is relatively sparse in contrast to the developed world, and much remains to be learned from, and about, the continent.METHODS: Transforming Parkinson's Care in Africa (TraPCAf) is a multi-faceted, mixed-methods, multi-national research grant. The study design includes multiple sub-studies, combining observational (qualitative and quantitative) approaches for the epidemiological, clinical, risk factor and lived experience components, as appropriate, and interventional methods (clinical trial component). The aim of TraPCAf is to describe and gain a better understanding of the current situation of PD in Africa. The countries included in this National Institute for Health and Care Research (NIHR) Global Health Research Group (Egypt, Ethiopia, Ghana, Kenya, Nigeria, South Africa and Tanzania) represent diverse African geographies and genetic profiles, with differing resources, healthcare systems, health and social protection schemes, and policies. The research team is composed of experts in the field with vast experience in PD, jointly led by a UK-based and Africa-based investigator.DISCUSSION: Despite the increasing prevalence of PD globally, robust data on the disease from Africa are lacking. Existing data point towards the poor awareness of PD and other neurological disorders on the continent and subsequent challenges with stigma, and limited access to affordable services and medication. This multi-site study will be the first of its kind in Africa. The data collected across the proposed sub-studies will provide novel and conclusive insights into the situation of PD. The selected country sites will allow for useful comparisons and make results relevant to other low- and middle-income countries. This grant is timely, as global recognition of PD and the public health challenge it poses builds. The work will contribute to broader initiatives, including the World Health Organization's Intersectoral global action plan on epilepsy and other neurological disorders.TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN77014546 .PMID:37858118 | DOI:10.1186/s12883-023-03414-0

BMC Plant Biol. 2023 Oct 20;23(1):503. doi: 10.1186/s12870-023-04467-6.ABSTRACTBACKGROUND: Quinoa is an important economic crop, drought is one of the key factors affecting quinoa yield. Clarifying the adaptation strategy of quinoa to drought is conducive to cultivating drought-tolerant varieties. At present, the study of quinoa on drought stress-related metabolism and the identification of related metabolites are still unknown. As a direct feature of biochemical functions, metabolites can reveal the biochemical pathways involved in drought response.RESULT: Here, we studied the physiological and metabolic responses of drought-tolerant genotype L1 and sensitive genotype HZ1. Under drought conditions, L1 had higher osmotic adjustment ability and stronger root activity than HZ1, and the relative water content of L1 was also higher than that of HZ1. In addition, the barrier-to- sea ratio of L1 is significantly higher than that of HZ1. Using untargeted metabolic analysis, a total of 523, 406, 301 and 272 differential metabolites were identified in L1 and HZ1 on day 3 and day 9 of drought stress. The key metabolites (amino acids, nucleotides, peptides, organic acids, lipids and carbohydrates) accumulated differently in quinoa leaves. and HZ1 had the most DEMs in Glycerophospholipid metabolism (ko00564) and ABC transporters (ko02010) pathways.CONCLUSION: These results provide a reference for characterizing the response mechanism of quinoa to drought and improving the drought tolerance of quinoa.PMID:37858063 | DOI:10.1186/s12870-023-04467-6

Lab Anim (NY). 2023 Oct 19. doi: 10.1038/s41684-023-01268-0. Online ahead of print.ABSTRACTType 2 diabetes is a challenge in modern healthcare, and animal models are necessary to identify underlying mechanisms. The Nile rat (Arvicanthis niloticus) develops diet-induced diabetes rapidly on a conventional rodent chow diet without genetic or chemical manipulation. Unlike common laboratory models, the outbred Nile rat model is diurnal and has a wide range of overt diabetes onset and diabetes progression patterns in both sexes, better mimicking the heterogeneous diabetic phenotype in humans. While fasted blood glucose has historically been used to monitor diabetic progression, postprandial blood glucose is more sensitive to the initial stages of diabetes. However, there is a long-held assumption that ad libitum feeding in rodent models leads to increased variance, thus masking diabetes-related metabolic changes in the plasma. Here we compared repeatability within triplicates of non-fasted or fasted plasma samples and assessed metabolic changes relevant to glucose tolerance in fasted and non-fasted plasma of 8-10-week-old male Nile rats. We used liquid chromatography-mass spectrometry lipidomics and polar metabolomics to measure relative metabolite abundances in the plasma samples. We found that, compared to fasted metabolites, non-fasted plasma metabolites are not only more strongly associated with glucose tolerance on the basis of unsupervised clustering and elastic net regression model, but also have a lower replicate variance. Between the two sampling groups, we detected 66 non-fasted metabolites and 32 fasted metabolites that were associated with glucose tolerance using a combined approach with multivariable elastic net and individual metabolite linear models. Further, to test if metabolite replicate variance is affected by age and sex, we measured non-fasted replicate variance in a cohort of mature 30-week-old male and female Nile rats. Our results support using non-fasted plasma metabolomics to study glucose tolerance in Nile rats across the progression of diabetes.PMID:37857753 | DOI:10.1038/s41684-023-01268-0

Nat Metab. 2023 Oct 19. doi: 10.1038/s42255-023-00908-6. Online ahead of print.ABSTRACTMetabolic regulation is integral to the proper functioning of innate lymphoid cells, yet the underlying mechanisms remain elusive. Here, we show that disruption of exogenous proline uptake, either through dietary restriction or by deficiency of the proline transporter Slc6a7, in lymphoid tissue inducer (LTi) cells, impairs LTi activation and aggravates dextran sodium sulfate-induced colitis in mice. With an integrative transcriptomic and metabolomic analysis, we profile the metabolic characteristics of various innate lymphoid cell subsets and reveal a notable enrichment of proline metabolism in LTi cells. Mechanistically, defective proline uptake diminishes the generation of reactive oxygen species, previously known to facilitate LTi activation. Additionally, LTi cells deficient in Slc6a7 display downregulation of Cebpb and Kdm6b, resulting in compromised transcriptional and epigenetic regulation of interleukin-22. Furthermore, our study uncovers the therapeutic potential of proline supplementation in alleviating colitis. Therefore, these findings shed light on the role of proline in facilitating LTi activation and ultimately contributing to gut homeostasis.PMID:37857730 | DOI:10.1038/s42255-023-00908-6

ISME J. 2023 Oct 19. doi: 10.1038/s41396-023-01532-8. Online ahead of print.ABSTRACTAdvances in bioanalytical technologies are constantly expanding our insights into complex ecosystems. Here, we highlight strategies and applications that make use of non-targeted metabolomics methods in aquatic chemical ecology research and discuss opportunities and remaining challenges of mass spectrometry-based methods to broaden our understanding of environmental systems.PMID:37857709 | DOI:10.1038/s41396-023-01532-8

Nat Commun. 2023 Oct 19;14(1):6607. doi: 10.1038/s41467-023-42432-x.ABSTRACTObesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.PMID:37857661 | DOI:10.1038/s41467-023-42432-x

Nat Commun. 2023 Oct 19;14(1):6611. doi: 10.1038/s41467-023-42472-3.NO ABSTRACTPMID:37857625 | DOI:10.1038/s41467-023-42472-3

J Agric Food Chem. 2023 Oct 19. doi: 10.1021/acs.jafc.3c04460. Online ahead of print.ABSTRACTHuanglongbing (HLB) is a highly destructive disease that inflicts significant economic losses on the citrus industry worldwide but with no cure available. However, microbiomes formulated by citrus plants may serve as disease antagonists, increasing the level of HLB tolerance. This study established an integrated analysis of untargeted metabolomics and microbiomics data for different citrus cultivars, providing critical insights into the interactions between plant metabolism and plant-associated bacteria in the development of HLB. Machine learning models were applied to screen important metabolites and bacteria in multiple citrus materials, and the selected metabolites were then analyzed to identify essential pathways enriched in the plant and to correlate with the selected bacteria. Results demonstrated that the regulation of plant pathways, especially ABC transporters and ubiquinone and other terpene-ubiquinone biosynthesis pathways, could affect the microbial community structure, indicating potential solutions for controlling HLB by modulating bacteria in citrus plants or breeding tolerant citrus cultivars.PMID:37857602 | DOI:10.1021/acs.jafc.3c04460

Oral Dis. 2023 Oct 19. doi: 10.1111/odi.14774. Online ahead of print.ABSTRACTOBJECTIVE: Emerging evidence suggests that glucose depletion (GD)-induced cell death depends on system Xc- , a glutamate/cystine antiporter extensively studied in ferroptosis. However, the underlying mechanism remains debated. Our study confirmed the correlation between system Xc- and GD-induced cell death and provided a strategic treatment for oral squamous cell carcinoma (OSCC).METHODS: qPCR and Western blotting were performed to detect changes in xCT and CD98 expression after glucose withdrawal. Then, the cell viability of OSCCs under the indicated conditions was measured. To identify the GD-responsible transcriptional factors of SLC7A11, we performed a luciferase reporter assay and a ChIP assay. Further, metabolomics was conducted to identify changes in metabolites. Finally, mitochondrial function and ATP production were evaluated using the seahorse assay, and NADP+ /NADPH dynamics were measured using a NADP+ /NADPH kit.RESULTS: In OSCCs, system Xc- promoted GD-induced cell death by increasing glutamate consumption, which promoted NADPH exhaustion and TCA blockade. Moreover, GD-induced xCT upregulation was governed by the p-eIF2α/ATF4 axis.CONCLUSIONS: System Xc- overexpression compromised the metabolic flexibility of OSCC under GD conditions, and thus, glucose starvation therapy is effective for killing OSCC cells.PMID:37856618 | DOI:10.1111/odi.14774

Metabolomics. 2023 Oct 19;19(11):88. doi: 10.1007/s11306-023-02050-6.ABSTRACTINTRODUCTION: Microbicidal violet-blue light in the visible spectrum (405 nm) has been under evaluation for pathogen inactivation in ex vivo human plasma and platelets (PLTs) stored in plasma. Results to date have demonstrated that several blood-borne infectious disease-causing pathogens can be successfully reduced to significantly low levels in the light-treated plasma and PLTs.METHOD: In order to evaluate whether the microbicidal 405 nm light is safe for the treatment of PLT concentrates for pathogen inactivation, LC/MS-based metabolomics analyses were performed to evaluate the overall impact of 405 nm violet-blue light treatment on ex vivo PLT concentrates suspended in plasma and on plasma itself, and to identify metabolome changes in intra-platelet and extra-cellular medium (i.e., plasma).RESULTS: The metabolomics data identified that platelet activating factors (PAFs), agonists and prostaglandins, which can influence PLT basic functions such as integrity, activation, and aggregation potential were unaltered, suggesting that 405 nm light illumination is safe regarding PLT basic functions. Distinct increases in hydroxyl fatty acids and aldehydes, as well as decreases in antioxidant metabolites indicated that reactive oxygen species (ROS) were generated at high levels after only one hour of exposure to 405 nm light. Distinctly changed endogenous photosensitizer metabolites after 1 h of light exposure provided good evidence that 405 nm light was an effective microbicide acting through ROS mechanism and no external additive photosensitizers were required.PMID:37855954 | DOI:10.1007/s11306-023-02050-6

mSystems. 2023 Oct 19:e0033123. doi: 10.1128/msystems.00331-23. Online ahead of print.ABSTRACTHigh-fructose intake is one of the high-risk factors for hypertension. Several probiotics have been reported to reduce high blood pressure (BP) via modulating gut microbiota, but the mechanism of the antihypertensive effect of probiotics is insufficiently understood. Herein, we investigated the antihypertensive effect of Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 based on the integrative analysis of gut metagenome and serum metabolome in high-fructose-treated mice. After 16-week intervention, M8 and M9 significantly reduced the median blood pressure by 16.92% and 15.39% in SBP, and 18.56% and 20.62% in DBP, respectively. Metagenomic analysis revealed that the increased Lawsonia and Pyrolobus, and reduced Alistipes and Alloprevotella levels were tightly correlated with lowered BP. Functionally, the decreased pathways of "base excision repair" (BER) and "D-glutamine and D-glutamate metabolism" were associated with BP reduction. Metabolomics data analysis further revealed that the probiotic interventions regulated vascular smooth muscle contraction, serotonergic synapse, cholinergic synapse, and lipid and vitamin metabolism in BP control. Additionally, association analyses indicated a strong negative correlation between Alistipes and "steroid hormone biosynthesis," suggesting that Alistipes could affect blood pressure by changing steroid hormone levels. In conclusion, our findings indicate that the probiotic efficacies in alleviating hypertension are linked to specific gut microbes and metabolic pathways, which provide a potential mechanistic understanding of probiotics modulated blood pressure, paving the way for future assessment of the therapeutic potential of probiotics in hypertension management. Elevated blood pressure affects 40% of the adult population, which accounts for high cardiovascular disease risk and further high mortality yearly. The global understanding of the gut microbiome for hypertension may provide important insights into the prevention. Bifidobacterium lactis M8 and Lactobacillus rhamnosus M9 originated from human breast milk, were able to decrease blood pressure, and modified metabolites in a high fructose-induced elevated blood pressure mouse model. Moreover, we found there was a close relationship between unexplored gut microbes and elevated blood pressure. Also, subsequently, the cross-link was explored among gut microbes, metabolites, and some metabolic pathways in gut microbial environment through introducing novel prediction methodology and bioinformatic analysis. It allowed us to hypothesize that probiotics can prevent elevated blood pressure via gut microbiota and related metabolism.Thus, utilization of dietary strategies (such as probiotics) to maintain the blood pressure level is of crucial importance.PMID:37855616 | DOI:10.1128/msystems.00331-23

Microbiol Spectr. 2023 Oct 19:e0228123. doi: 10.1128/spectrum.02281-23. Online ahead of print.ABSTRACTAttenuating the expression of fungal camptothecin biosynthetic genes with subculturing is the challenge that halts their further implementation. The camptothecin productivity of the subcultured Aspergillus terreus has been restored upon addition of Ficus elastica indigenous microbiome; however, the identity of triggering signals of A. terreus camptothecin biosynthesis remains ambiguous. In this study, differential proteomics and metabolomics analyses were implemented to unravel the differentially abundant proteins and metabolites associated with the weakening/restoration of the biosynthetic machinery of camptothecin by A. terreus. The functional proteins, namely, ribosomal proteins, ATP, metal ion, and GTP binding proteins, were abolished by the seventh culture of A. terreus; however, the expression of these proteins was completely restored upon addition of F. elastica microbiome. Among the proteins of highly altered abundance, Pleckstrin homology (PH) domain-containing protein, peptidylprolyl cis/trans isomerase, 60S ribosomal protein, and So-Cu domain-containing proteins were significantly decreased with subculturing of A. terreus and strikingly restored upon addition of F. elastica microbiome. The metabolites 5,7-dihydroxy-2-(4-hydroxyphenyl)-3,6-dimethoxy-4H-chromen and glutaric acid of A. terreus were significantly decreased with subculturing and completely restored upon addition of F. elastica microbiome. The most differentially abundant metabolites were involved in glycolysis, TCA cycle, mevalonate pathway, terpenoids and shikimate synthesis, and ultimately with camptothecin biosynthesis. Thus, overexpression of PH domain-containing protein and peptidylprolyl cis/trans isomerase could be a new avenue for a metabolically stable camptothecin producing A. terreus. IMPORTANCE Decreasing the camptothecin productivity by fungi with storage and subculturing is the challenge that halts their further implementation to be an industrial platform for camptothecin (CPT) production. The highest differentially abundant proteins were Pleckstrin homology (PH) domain-containing proteins and Peptidyl-prolyl cis/trans isomerase that fluctuated with the subculturing of A. terreus with a remarkable relation to CPT biosynthesis and restored with addition of F. elastica microbiome.PMID:37855596 | DOI:10.1128/spectrum.02281-23

Microbiol Spectr. 2023 Oct 19:e0270423. doi: 10.1128/spectrum.02704-23. Online ahead of print.ABSTRACTBacterial metabolism in oral biofilms is comprised of complex networks of nutritional chains and biochemical regulations. These processes involve both intraspecies and interspecies networks as well as interactions with components from host saliva, gingival crevicular fluid, and dietary intake. In a previous paper, a large salivary glycoprotein, mucin MUC5B, was suggested to promote a dental health-related phenotype in the oral type strain of Streptococcus gordonii DL1, by regulating bacterial adhesion and protein expression. In this study, nuclear magnetic resonance-based metabolomics was used to examine the effects on the metabolic output of monospecies compared to dual species early biofilms of two clinical strains of oral commensal bacteria, S. gordonii and Actinomyces naeslundii, in the presence of MUC5B. The presence of S. gordonii increased colonization of A. naeslundii on salivary MUC5B, and both commensals were able to utilize MUC5B as a sole nutrient source during early biofilm formation. The metabolomes suggested that the bacteria were able to release mucin carbohydrates from oligosaccharide side chains as well as amino acids from the protein core. Synergistic effects were also seen in the dual species biofilm metabolome compared to the monospecies, indicating that A. naeslundii and S. gordonii cooperated in the degradation of salivary MUC5B. A better understanding of bacterial interactions and salivary-mediated regulation of early dental biofilm activity is meaningful for understanding oral biofilm physiology and may contribute to the development of future prevention strategies for biofilm-induced oral disease.IMPORTANCEThe study of bacterial interactions and salivary-mediated regulation of early dental biofilm activity is of interest for understanding oral microbial adaptation to environmental cues and biofilm maturation. Findings in oral commensals can prove useful from the perspectives of both oral and systemic health of the host, as well as the understanding of general microbial biofilm physiology. The knowledge may provide a basis for the development of prognostic biomarkers, or development of new treatment strategies, related to oral health and disease and possibly also to other biofilm-induced conditions. The study is also an important step toward developing the methodology for similar studies in other species and/or growth conditions.PMID:37855449 | DOI:10.1128/spectrum.02704-23