PubMed

Microb Cell Fact. 2023 Mar 15;22(1):52. doi: 10.1186/s12934-023-02054-w.ABSTRACTBACKGROUND: Thraustochytrids accumulate lipids with a high content of docosahexaenoic acid (DHA). Although their growth and DHA content are significantly affected by the dissolved oxygen (DO) supply, the role of DO on the transcriptional regulation of metabolism and accumulation of intracellular metabolites remains poorly understood. Here we investigate the effects of three different DO supply conditions (10%, 30%, and 50%) on the fed-batch culture of the Aurantiochytrium PKU#Mn16 strain to mainly reveal the differential gene expressions and metabolite profiles.RESULTS: While the supply of 10% DO significantly reduced the rates of biomass and DHA production in the early stages of fermentation, it achieved the highest amounts of biomass (56.7 g/L) and DHA (6.0 g/L) on prolonged fermentation. The transcriptome analyses of the early stage (24 h) of fermentation revealed several genes involved in the central carbon, amino acid, and fatty acid metabolism, which were significantly downregulated at a 10% DO level. The comparative metabolomics results revealed the accumulation of several long-chain fatty acids, amino acids, and other metabolites, supporting the transcriptional regulation under the influence of a low oxygen supply condition. In addition, certain genes involved in antioxidative systems were downregulated under 10% DO level, suggesting a lesser generation of reactive oxygen species that lead to oxidative damage and fatty acid oxidation.CONCLUSIONS: The findings of this study suggest that despite the slow growth and metabolism in the early stage of fermentation of Aurantiochytrium sp. PKU#Mn16, a constant supply of low dissolved oxygen can yield biomass and DHA content better than that with high oxygen supply conditions. The critical information gained in this study will help to further improve DHA production through bioprocess engineering strategies.PMID:36918882 | DOI:10.1186/s12934-023-02054-w

BMC Microbiol. 2023 Mar 14;23(1):67. doi: 10.1186/s12866-023-02807-y.ABSTRACTBACKGROUND: The present study aimed to investigate the changes in volatile components and metabolites of Dendrobium officinale (D. officinale) juice fermented with starter cultures containing Saccharomycopsis fibuligera and Lactobacillus paracasei at 28 ℃ for 15 days and post-ripened at 4 ℃ for 30 days using untargeted metabolomics of liquid chromatography-mass spectrometry (LC-MS) and headspace solid-phase microextraction-gas chromatography (HS-SPME-GC-MS) before and after fermentation.RESULTS: The results showed that the alcohol contents in the S. fibuligera group before fermentation and after fermentation were 444.806 ± 10.310 μg/mL and 510.999 ± 38.431 μg/mL, respectively. Furthermore, the alcohol content in the fermentation broth group inoculated with the co-culture of L. paracasei + S. fibuligera was 504.758 ± 77.914 μg/mL, containing a significant amount of 3-Methyl-1-butanol, Linalool, Phenylethyl alcohol, and 2-Methyl-1-propanol. Moreover, the Ethyl L (-)-lactate content was higher in the co-culture of L. paracasei + S. fibuligera group (7.718 ± 6.668 μg/mL) than in the L. paracasei (2.798 ± 0.443 μg/mL) and S. fibuligera monoculture groups (0 μg/mL). The co-culture of L. paracasei + S. fibuligera significantly promoted the metabolic production of ethyl L (-)-lactate in D. officinale juice. The differential metabolites screened after fermentation mainly included alcohols, organic acids, amino acids, nucleic acids, and their derivatives. Twenty-three metabolites, including 11 types of acids, were significantly up-regulated in the ten key metabolic pathways of the co-culture group. Furthermore, the metabolic pathways, such as pentose and glucuronate interconversions, the biosynthesis of alkaloids derived from terpenoid and polyketide, and aminobenzoate degradation were significantly up-regulated in the co-culture group. These three metabolic pathways facilitate the synthesis of bioactive substances, such as terpenoids, polyketides, and phenols, and enrich the flavor composition of D. officinale juice.CONCLUSIONS: These results demonstrate that the co-culture of L. paracasei + S. fibuligera can promote the flavor harmonization of fermented products. Therefore, this study provides a theoretical basis for analyzing the flavor of D. officinale juice and the functional investigation of fermentation metabolites.PMID:36918762 | DOI:10.1186/s12866-023-02807-y

Nat Cell Biol. 2023 Mar;25(3):381-389. doi: 10.1038/s41556-023-01095-y. Epub 2023 Mar 13.ABSTRACTCOVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens1,2. This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities of infection for lung airway organoids, lung alveolar organoids and cardiomyocytes, and identified several genes that are generally implicated in controlling SARS-CoV-2 infection, including CIART, the circadian-associated repressor of transcription. Lung airway organoids, lung alveolar organoids and cardiomyocytes derived from isogenic CIART-/- human pluripotent stem cells were significantly resistant to SARS-CoV-2 infection, independently of viral entry. Single-cell RNA-sequencing analysis further validated the decreased levels of SARS-CoV-2 infection in ciliated-like cells of lung airway organoids. CUT&RUN, ATAC-seq and RNA-sequencing analyses showed that CIART controls SARS-CoV-2 infection at least in part through the regulation of NR4A1, a gene also identified from the multi-organoid analysis. Finally, transcriptional profiling and pharmacological inhibition led to the discovery that the Retinoid X Receptor pathway regulates SARS-CoV-2 infection downstream of CIART and NR4A1. The multi-organoid platform identified the role of circadian-clock regulation in SARS-CoV-2 infection, which provides potential therapeutic targets for protection against COVID-19 across organ systems.PMID:36918693 | DOI:10.1038/s41556-023-01095-y

Sci Rep. 2023 Mar 14;13(1):4210. doi: 10.1038/s41598-023-31096-8.ABSTRACTThe aim of the study was to report the burden of type one diabetes mellitus (T1DM) by sex, age, year, and province in Iran over the past 30 years, according to data provided by the global burden of disease (GBD) study. Incidence, prevalence, death, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability due to T1DM by age groups and sex was reported for 31 provinces of Iran from 1990 to 2019 with their 95% uncertainty intervals (UI). In 2019, national age-standardized incidence (11.0 (95% UI: 8.9-13.5)), prevalence (388.9 (306.1-482.1)), death (0.7 (0.6-0.8)), and DALYs (51.7 (40.9-65.1)) rates per 100,000 wre higher than 1990 except for death. Also, the mortality to incidence ratio reduced in all provinces over time particularly after 2014 as well. GBD data analysis showed that age-standardized incidence and prevalence rates of T1DM have increased, the death rate reduced, and DALYs remained unchanged during the past 30 years in Iran and its 31 provinces. death rate reduced and DALYs remained unchanged during the past 30 years in Iran and its 31 provinces.PMID:36918650 | DOI:10.1038/s41598-023-31096-8

Biomed Pharmacother. 2023 Feb;158:114176. doi: 10.1016/j.biopha.2022.114176. Epub 2023 Jan 9.ABSTRACTBACKGROUND: Cancer-associated fibroblasts (CAFs) are major players in tumor-stroma communication, and participate in several cancer hallmarks to drive tumor progression and metastatic dissemination. This study investigates the driving effects of tumor-secreted factors on CAF biology, with the ultimate goal of identifying effective therapeutic targets/strategies for head and neck squamous cell carcinomas (HNSCC).METHODS: Functionally, conditioned media (CM) from different HNSCC-derived cell lines and normal keratinocytes (Kc) were tested on the growth and invasion of populations of primary CAFs and normal fibroblasts (NFs) using 3D invasion assays in collagen matrices. The changes in MMPs expression were evaluated by RT-qPCR and kinase enrichment was analyzed using mass spectrometry phosphoproteomics.RESULTS: Our results consistently demonstrate that HNSCC-secreted factors (but not Kc CM) specifically and robustly promoted pro-invasive properties in both CAFs and NFs, thereby reflecting the plasticity of fibroblast subtypes. Concomitantly, HNSCC-secreted factors massively increased metalloproteinases levels in CAFs and NFs. By contrast, HNSCC CM and Kc CM exhibited comparable growth-promoting effects on stromal fibroblasts. Mechanistically, phosphoproteomic analysis predominantly revealed phosphorylation changes in fibroblasts upon treatment with HNSCC CM, and various promising kinases were identified: MKK7, MKK4, ASK1, RAF1, BRAF, ARAF, COT, PDK1, RSK2 and AKT1. Interestingly, pharmacologic inhibition of RAF1/BRAF using sorafenib emerged as the most effective drug to block tumor-promoted fibroblast invasion without affecting fibroblast viability CONCLUSIONS: Our findings demonstrate that HNSCC-secreted factors specifically fine tune the invasive potential of stromal fibroblasts, thereby generating tumor-driven pro-invasive niches, which in turn to ultimately facilitate cancer cell dissemination. Furthermore, the RAF/BRAF inhibitor sorafenib was identified as a promising candidate to effectively target the onset of pro-invasive clusters of stromal fibroblasts in the HNSCC microenvironment.PMID:36916400 | DOI:10.1016/j.biopha.2022.114176

Rapid Commun Mass Spectrom. 2023 Mar 14:e9504. doi: 10.1002/rcm.9504. Online ahead of print.ABSTRACTRATIONAL: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a prevalent complication of cardiac surgery, which may be associated with a great risk of developing chronic kidney disease and mortality. This study aimed to investigate the possible links between gut microbiota metabolism and CSA-AKI.METHODS: A prospective cohort of patients who underwent cardiac surgery was continuously recruited, who were further divided into CSA-AKI group and Non-AKI group based on the clinical outcomes. Their faecal and plasma samples were collected before the surgery and were separately analysed by non-targeted and targeted metabolomics. The differential metabolites related to CSA-AKI were screened out using statistical methods, and altered metabolic pathways were determined by examining the Kyoto Encyclopedia of Genes and Genomes database.RESULTS: Nearly 1000 faecal metabolites were detected through high-resolution mass spectrometry (MS) and bioinformatics at high and mid confidence levels, and 49 differential metabolites at high confidence level may perform essential biological functions and provide potential diagnostic indicators. Compared with the Non-AKI group, the patients in the CSA-AKI group displayed dramatic changes in gut microbiota metabolism, including amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and ABC transporters. Meanwhile, 188 plasma metabolites were identified and quantified by tandem MS, and 34 differential plasma metabolites were screened out between the two groups using univariate statistical analysis. These differential plasma metabolites were primarily enriched in the following metabolic pathways: sulphur metabolism, amino acid biosynthesis, tryptophan metabolism, and ABC transporters. Furthermore, the content of indole metabolites in the faecal and plasma samples of the CSA-AKI group was higher than that of the Non-AKI group.CONCLUSIONS: Patients with CSA-AKI may have dysbiosis of their intestinal microbiota and metabolic abnormalities in their gut system before cardiac surgery. Thus, some metabolites and related metabolic pathways may be potential biomarkers and new therapeutic targets for the disease.PMID:36918294 | DOI:10.1002/rcm.9504

J Pharmacol Exp Ther. 2023 Mar 14:JPET-AR-2022-001493. doi: 10.1124/jpet.122.001493. Online ahead of print.ABSTRACTType 2 diabetes (T2D) is a rising pandemic worldwide. Diet and lifestyle changes are typically the first intervention for T2D. When this intervention fails, the biguanide, metformin, is the most common pharmaceutical therapy. Yet, it's full mechanisms of action remain unknown. In this work, we applied an ultrahigh resolution, mass spectrometry-based platform for untargeted plasma metabolomics to human plasma samples from a case-control observational study of non-diabetic and well-controlled T2D subjects, the latter treated conservatively with metformin or diet and lifestyle changes only. No statistically significant differences existed in baseline demographic parameters, glucose control, or clinical markers of cardiovascular disease risk between the two T2D groups, which we hypothesized would allow the identification of circulating metabolites independently associated with treatment modality. Over 3000 blank-reduced metabolic features were detected, with the majority of annotated features being lipids or lipid-like molecules. Altered abundance of multiple fatty acids and phospholipids were found in T2D subjects treated with diet and lifestyle changes as compared to non-diabetic subjects: changes that were often reversed by metformin. Our findings provide direct evidence that metformin monotherapy alters the human plasma lipidome independent of T2D disease control and support a potential cardioprotective effect of metformin worthy of future study. Significance Statement This work provides important new information on the systemic effects of metformin in type 2 diabetic subjects. We observed significant changes in the plasma lipidome with metformin therapy, with metabolite classes previously associated with cardiovascular disease risk significantly reduced as compared to diet and lifestyle changes. While cardiovascular disease risk was not a primary outcome of our study, our results provide a jumping-off point for future work into the cardioprotective effects of metformin, even in well-controlled type 2 diabetes.PMID:36918276 | DOI:10.1124/jpet.122.001493

RMD Open. 2023 Mar;9(1):e002741. doi: 10.1136/rmdopen-2022-002741.ABSTRACTOBJECTIVES: Muscle soreness occurs after exercise and also in musculoskeletal diseases, such as fibromyalgia (FM). However, the nosography and pathoetiology of morbid soreness in FM remain unknown. This study aimed to investigate the morbid soreness of FM, evaluate its therapeutic responses and probe its pathophysiology with metabolomics profiling.METHODS: Patients with newly diagnosed FM were prospectively recruited and completed self-report questionnaires pertaining to musculoskeletal symptoms. The phenotypes and metabotypes were assessed with variance, classification and correlation analyses.RESULTS: Fifty-one patients and 41 healthy controls were included. Soreness symptoms were prevalent in FM individuals (92.2%). In terms of manifestations and metabolomic features, phenotypes diverged between patients with mixed pain and soreness symptoms (FM-PS) and those with pain dominant symptoms. Conventional treatment for FM did not ameliorate soreness severity despite its efficacy on pain. Moreover, despite the salient therapeutic efficacy on pain relief in FM-PS cases, conventional treatment did not improve their general disease severity. Metabolomics analyses suggested oxidative metabolism dysregulation in FM, and high malondialdehyde level indicated excessive oxidative stress in FM individuals as compared with controls (p=0.009). Contrary to exercise-induced soreness, lactate levels were significantly lower in FM individuals than controls, especially in FM-PS. Moreover, FM-PS cases exclusively featured increased malondialdehyde level (p=0.008) and a correlative trend between malondialdehyde expression and soreness intensity (r=0.337, p=0.086).CONCLUSIONS: Morbid soreness symptoms were prevalent in FM, with the presentation and therapeutic responses different from FM pain conditions. Oxidative stress rather than lactate accumulation involved phenotype modulation of the morbid soreness in FM.TRIAL REGISTRATION NUMBER: NCT04832100.PMID:36918228 | DOI:10.1136/rmdopen-2022-002741

Anal Chem. 2023 Mar 14. doi: 10.1021/acs.analchem.2c05145. Online ahead of print.ABSTRACTMyxobacteria are fascinating prokaryotes featuring a potent capacity for producing a wealth of bioactive molecules with intricate chemical topology as well as intriguing enzymology, and thus it is critical to developing an efficient pipeline for bioprospecting. Herein, we construct the database MyxoDB, the first public compendium solely dedicated to myxobacteria, which enabled us to provide an overview of the structural diversity and taxonomic distribution of known myxobacterial natural products. Moreover, we demonstrated that the cutting-edge NMR-based metabolomics was effective to differentiate the biosynthetic priority of myxobacteria, whereby MyxoDB could greatly streamline the dereplication of multifarious known compounds and accordingly speed up the discovery of new compounds. This led to the rapid identification of a class of linear di-lipopeptides (archangimins) and a rare rearranged sterol (corasterol) that were endowed with unique chemical architectures and/or biosynthetic enzymology. We also showcased that NMR-based metabolomics, MyxoDB, and genomics can also work concertedly to accelerate the targeted discovery of a polyketidic compound pyxipyrrolone C. All in all, this study sets the stage for the discovery of many more novel natural products from underexplored myxobacterial resources.PMID:36917632 | DOI:10.1021/acs.analchem.2c05145

PLoS One. 2023 Mar 14;18(3):e0282700. doi: 10.1371/journal.pone.0282700. eCollection 2023.ABSTRACTThe main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.PMID:36917582 | DOI:10.1371/journal.pone.0282700

Hum Mol Genet. 2023 Mar 14:ddad041. doi: 10.1093/hmg/ddad041. Online ahead of print.ABSTRACTBarth syndrome is an X-linked disorder caused by loss-of-function mutations in Tafazzin (TAZ), an acyltransferase that catalyzes remodeling of cardiolipin, a signature phospholipid of the inner mitochondrial membrane. Patients develop cardiac and skeletal muscle weakness, growth delay, and neutropenia, although phenotypic expression varies considerably between patients. Taz knockout mice recapitulate many of the hallmark features of the disease. We used mouse genetics to test the hypothesis that genetic modifiers alter the phenotypic manifestations of Taz inactivation. We crossed TazKO/X females in the C57BL6/J inbred strain to males from 8 inbred strains and evaluated the phenotypes of first generation (F1) TazKO/Y progeny, compared to TazWT/Y littermates. We observed that genetic background strongly impacted phenotypic expression. C57BL6/J and CAST/EiJ[F1] TazKO/Y mice developed severe cardiomyopathy, whereas A/J[F1] TazKO/Y mice had normal heart function. C57BL6/J and WSB/EiJ[F1] TazKO/Y mice had severely reduced treadmill endurance, whereas endurance was normal in A/J[F1] and CAST/EiJ[F1] TazKO/Y mice. In all genetic backgrounds, cardiolipin showed similar abnormalities in knockout mice, and transcriptomic and metabolomic investigations identified signatures of mitochondrial uncoupling and activation of the integrated stress response. TazKO/Y cardiac mitochondria were small, clustered, and had reduced cristae density in knockouts in severely affected genetic backgrounds but were relatively preserved in the permissive A/J[F1] strain. Gene expression and mitophagy measurements were consistent with reduced mitophagy in knockout mice in genetic backgrounds intolerant of Taz mutation. Our data demonstrate that genetic modifiers powerfully modulate phenotypic expression of Taz loss-of-function and act downstream of cardiolipin, possibly by altering mitochondrial quality control.PMID:36917259 | DOI:10.1093/hmg/ddad041

J Agric Food Chem. 2023 Mar 14. doi: 10.1021/acs.jafc.2c08738. Online ahead of print.ABSTRACTPunicalagin (PA) is a key ellagitannin abundant in pomegranate with wide-ranging biological activities. In this study, we examined the biological processes by which PA regulates bacterial growth and inflammation in human cells using multiomics and molecular docking approaches. PA promoted macrophage-mediated bacterial killing and inhibited the growth of Citrobacter rodentium by inducing a distinct metabolome pattern. PA acted as a selective regulator of histone deacetylases (HDACs) and affected 37 pathways in macrophages, including signaling mediated by pattern recognition receptors, such as Toll-like and NOD-like receptors. In silico simulation showed that PA can bind with high affinity to HDAC7. PA downregulated HDAC7 at both mRNA and protein levels and resulted in a decrease in the level of histone 3 lysine 27 acetylation. Our findings provide evidence that PA exerts its biological effects via multiple pathways, which can be exploited in the development of this bioactive food ingredient for disease management.PMID:36917202 | DOI:10.1021/acs.jafc.2c08738

Physiol Plant. 2023 Mar 14:e13891. doi: 10.1111/ppl.13891. Online ahead of print.ABSTRACTAs a fungicide, oxathiapiprolin has excellent effects on diseases caused by oomycetes. Fungicides generally protect crops by inhibiting pathogens, but little research has addressed the effects of fungicides on crops. This study combined transcriptomic and metabolomic analyses to systematically analyze the physiological regulatory mechanisms of oxathiapiprolin on tobacco under Phytophthora nicotianae infection. The results showed that under Phytophthora nicotianae infection, tobacco's photosynthetic rate and antioxidant enzyme activity increased after the application of oxathiapiprolin. Omics results showed that the genes related to carbon metabolism, disease-resistant proteins, and amino acid synthesis were highly expressed, and the amino acid content increased in tobacco leaves. This study is the first comprehensive investigation of the physiological regulatory effects of oxathiapiprolin on tobacco in response to Phytophthora nicotianae infection. These findings provide a basis for the balance between regulating tobacco growth and development and enhancing disease resistance under the stimulation of oxathiapiprolin and provide new research and development opportunities for identifying new disease-resistance genes and the development of high-yielding disease-resistant crop varieties.PMID:36917080 | DOI:10.1111/ppl.13891

Microbiol Spectr. 2023 Mar 14:e0383122. doi: 10.1128/spectrum.03831-22. Online ahead of print.ABSTRACTPlants recruit beneficial microbes to enhance their ability to fight pathogens. However, the current understanding of microbial recruitment is largely limited to belowground systems (root exudates and the rhizosphere). It remains unclear whether the changes in leaf metabolites induced by infectious pathogens can actively recruit beneficial microbes to mitigate the growth of foliar pathogens. In this study, we integrated microbiome and metabolomic analyses to systematically explore the dynamics of phyllosphere fungal and bacterial communities and key leaf metabolites in two crabapple species (Malus sp. "Flame" and Malus sp. "Kelsey") at six stages following infection with Gymnosporangium yamadae. Our results showed that the phyllosphere microbiome changed during lesion expansion, as highlighted by a reduction in bacterial alpha-diversity and an increase in fungal alpha-diversity; a decreasing and then an increasing complexity of the microbial co-occurrence network was observed in Kelsey and a decreasing complexity occurred in Flame. In addition, nucleotide sugars, diarylheptanoids, and carboxylic acids with aromatic rings were more abundant in early stages of collection, which positively regulated the abundance of bacterial orders Pseudomonadales (in Kelsey), Acidimicrobiales, Bacillales, and Flavobacteriales (in Flame). In addition, metabolites such as flavonoids, lignin precursors, terpenoids, coumarins, and quaternary ammonium salts enriched with the expansion of lesions had a positive regulatory effect on fungal families Rhynchogastremataceae and Golubeviaceae (in Flame) and the bacterial order Actinomycetales (in Kelsey). Our findings highlight that plants may also influence phyllosphere microorganisms by adjusting leaf metabolites in response to biotic stress. IMPORTANCE Our findings demonstrate the response patterns of bacterial and fungal communities in the Malus phyllosphere to rust fungus G. yamadae infection, and they also reveal how the phyllosphere microbiome changes with the expansion of lesions. We identified several metabolites whose relative abundance varied significantly with lesion expansion. Using a framework for assessing the role of leaf metabolites in shaping the phyllosphere microbiome of the two Malus species, we identified several specific metabolites that have profoundly selective effects on the microbial community. In conclusion, our study provides new evidence of the ecological niche of the phyllosphere in supporting the "cry for help" strategy for plants.PMID:36916990 | DOI:10.1128/spectrum.03831-22

Microbiol Spectr. 2023 Mar 14:e0398022. doi: 10.1128/spectrum.03980-22. Online ahead of print.ABSTRACTEmerging evidence confirms using probiotics in promoting growth and immunity of farmed fish. However, the molecular mechanisms underlying the host-microbiome interactions mediated by probiotics are not fully understood. In this study, we used rainbow trout (Oncorhynchus mykiss) as a model to investigate the internal mechanisms of host-microbiome interactions influenced by two probiotic bacteria, Bacillus velezensis and Lactobacillus sakei. We carried out experiments, including intestinal histology, serum physiology, and transcriptome and combined intestinal microbiome and metabolite profiling. Our results showed that both probiotics had a positive effect on growth, immunity, serum enzyme activity, the gut microbiome, and resistance to Aeromonas salmonicida in rainbow trout. Moreover, the intestinal microbial structure was reshaped with increased relative abundance of potential beneficial bacteria, such as Ruminococcus, Lachnospiraceae ucg-004, Leptotrichia, Bacillus coagulans, Porphyromonadaceae, Anaerococcus, and Photobacterium in the B. velezensis group and Paenibacillaceae and Eubacterium hallii in the L. sakei group. Metabolomic profiling and transcriptome analysis revealed upregulated metabolites as biomarkers, i.e., sucrose and l-malic acid in the B. velezensis group, and N-acetyl-l-phenylalanine, N-acetylneuraminic acid, and hydroxyproline in the L. sakei group. Additionally, a multiomics combined analysis illustrated significant positive correlations between the relative abundance of microflora, metabolites, and gene expression associated with immunity and growth. This study highlights the significant role of probiotics as effectors of intestinal microbial activity and shows that different probiotics can have a species-specific effect on the physiological regulation of the host. These findings contribute to a better understanding of the complex host-microbiome interactions in rainbow trout and may have implications for the use of probiotics in aquaculture. IMPORTANCE Probiotics are kinds of beneficial live microbes that impart beneficial effects on the host. Recent studies have proven that when given supplementation with probiotics, farmed fish showed improved disease prevention and growth promotion. However, the underlying metabolic functions regarding their involvement in regulating growth phenotypes, nutrient utilization, and immune response are not yet well understood in the aquaculture field. Given the active interactions between the gut microbiota and fish immune and growth performance, we conducted the supplementation experiments with the probiotics Bacillus velezensis and Lactobacillus sakei. The results showed that probiotics mediated intestinal microbiome- and microbiota-derived metabolites regulating the growth and immunity of fish, and different probiotics participated in the species-specific physiological regulation of the host. This study contributed to a better understanding of the functional interactions associated with host health and gut microbiota species.PMID:36916965 | DOI:10.1128/spectrum.03980-22

Microb Biotechnol. 2023 Mar 14. doi: 10.1111/1751-7915.14245. Online ahead of print.ABSTRACTGut microbiota plays important roles in host metabolism. Whether and how much the gut microbiota in different gut locations contributes to the variations of host serum metabolites are largely unknown, because it is difficult to obtain microbial samples from different gut locations on a large population scale. Here, we quantified the gut microbial compositions using 16S rRNA gene sequencing for 1070 samples collected from the ileum, cecum and faeces of 544 F6 pigs from a mosaic pig population. Untargeted metabolome measurements determined serum metabolome profiles. We found 1671, 12,985 and 103,250 significant correlations between circulating serum metabolites and bacterial ASVs in the ileum, cecum, and faeces samples. We detected nine serum metabolites showing significant correlations with gut bacteria in more than one gut location. However, most metabolite-microbiota pairwise associations were gut location-specific. Targeted metabolome analysis revealed that CDCA, taurine, L-leucine and N-acetyl-L-alanine can be used as biomarkers to predict porcine fatness. Enriched taxa in fat pigs, for example Prevotella and Lawsonia intracellularis were positively associated with L-leucine, while enriched taxa in lean pigs, such as Clostridium butyricum, were negatively associated with L-leucine and CDCA, but positively associated with taurine and N-acetyl-L-alanine. These results suggested that the contributions of gut microbiota in each gut location to the variations of serum metabolites showed spatial heterogeneity.PMID:36916818 | DOI:10.1111/1751-7915.14245

Cancer Control. 2023 Jan-Dec;30:10732748231154711. doi: 10.1177/10732748231154711.ABSTRACTBACKGROUND: The overall poor prognosis in pancreatic cancer is related to late clinical detection. Early diagnosis remains a considerable challenge in pancreatic cancer. Unfortunately, the onset of clinical symptoms in patients usually indicate advanced disease or presence of metastasis.ANALYSIS AND RESULTS: Currently, there are no designated diagnostic or screening tests for pancreatic cancer in clinical use. Thus, identifying risk groups, preclinical risk factors or surveillance strategies to facilitate early detection is a target for ongoing research. Hereditary genetic syndromes are a obvious, but small group at risk, and warrants close surveillance as suggested by society guidelines. Screening for pancreatic cancer in asymptomatic individuals is currently associated with the risk of false positive tests and, thus, risk of harms that outweigh benefits. The promise of cancer biomarkers and use of 'omics' technology (genomic, transcriptomics, metabolomics etc.) has yet to see a clinical breakthrough. Several proposed biomarker studies for early cancer detection lack external validation or, when externally validated, have shown considerably lower accuracy than in the original data. Biopsies or tissues are often taken at the time of diagnosis in research studies, hence invalidating the value of a time-dependent lag of the biomarker to detect a pre-clinical, asymptomatic yet operable cancer. New technologies will be essential for early diagnosis, with emerging data from image-based radiomics approaches, artificial intelligence and machine learning suggesting avenues for improved detection.CONCLUSIONS: Early detection may come from analytics of various body fluids (eg 'liquid biopsies' from blood or urine). In this review we present some the technological platforms that are explored for their ability to detect pancreatic cancer, some of which may eventually change the prospects and outcomes of patients with pancreatic cancer.PMID:36916724 | DOI:10.1177/10732748231154711

EMBO Rep. 2023 Mar 14:e55747. doi: 10.15252/embr.202255747. Online ahead of print.ABSTRACTMetabolic processes play a critical role in immune regulation. Metabolomics is the systematic analysis of small molecules (metabolites) in organisms or biological samples, providing an opportunity to comprehensively study interactions between metabolism and immunity in physiology and disease. Integrating metabolomics into systems immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. Here, we provide an overview on recent technological developments of metabolomic applications in immunological research. To begin, two widely used metabolomics approaches are compared: targeted and untargeted metabolomics. Then, we provide a comprehensive overview of the analysis workflow and the computational tools available, including sample preparation, raw spectra data preprocessing, data processing, statistical analysis, and interpretation. Third, we describe how to integrate metabolomics with other omics approaches in immunological studies using available tools. Finally, we discuss new developments in metabolomics and its prospects for immunology research. This review provides guidance to researchers using metabolomics and multiomics in immunity research, thus facilitating the application of systems immunology to disease research.PMID:36916532 | DOI:10.15252/embr.202255747

Mol Omics. 2023 Mar 14. doi: 10.1039/d2mo00288d. Online ahead of print.ABSTRACTColorectal cancer (CRC) is a multifactorial heterogeneous disease largely due to both genetic predisposition and environmental factors including the gut microbiota, a dynamic microbial ecosystem inhabiting the gastrointestinal tract. Elucidation of the molecular mechanisms by which the gut microbiota interacts with the host may contribute to the pathogenesis, diagnosis, and promotion of CRC. However, deciphering the influence of genetic variants and interactions with the gut microbial ecosystem is rather challenging. Despite recent advancements in single omics analysis, the application of multi-omics approaches to integrate multiple layers of information in the microbiome and host to introduce effective prevention, diagnosis, and treatment strategies is still in its infancy. Here, we integrate host- and microbe-based multi-omics studies, respectively, to provide a strategy to explore potential causal relationships between gut microbiota and colorectal cancer. Specifically, we summarize the recent multi-omics studies such as metagenomics combined with metabolomics and metagenomics combined with genomics. Meanwhile, the sample size and sample types commonly used in multi-omics research, as well as the methods of data analysis, were also generalized. We highlight multiple layers of information from multi-omics that need to be verified by different types of models. Together, this review provides new insights into the clinical diagnosis and treatment of colorectal cancer patients.PMID:36916422 | DOI:10.1039/d2mo00288d

Anim Biosci. 2023 Feb 26. doi: 10.5713/ab.23.0001. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to evaluate the physicochemical, metabolomic, and sensory qualities of Chikso and Hanwoo beef during 28 days of wet aging.METHODS: Rump and loins from Hanwoo and Chikso were obtained and wet-aged for 28 days at 4°C. The samples were collected at 7-day interval (n = 3 for each period). Physicochemical qualities including pH, meat color, shear force value, and myofibrillar fragmentation index, metabolomic profiles, and sensory attributes (volatile organic compounds and relative taste intensities) were measured.RESULTS: Chikso showed a significantly higher shear force value than Hanwoo on day 0; however, no differences between breeds were found after day 14, regardless of the cuts. Overall, Chikso had abundant metabolites than Hanwoo, especially L-carnitine and tyrosine. Among the volatiles, the ketone ratio was higher in the Chikso rump than the Hanwoo rump; however, Chikso had fewer alcohols and aldehydes than Hanwoo. Chikso rump showed higher taste intensities than the Hanwoo rump on day 0, and sourness decreased in Chikso, but increased in the Hanwoo rump on day 14. Wet aging for 14 days intensified the taste of Chikso loin but reduced the umami intensity of Hanwoo loin.CONCLUSION: Chikso had different metabolomic and sensory characteristics compared to Hanwoo cattle, and 14 days of wet aging could improve its tenderness and flavor traits.PMID:36915929 | DOI:10.5713/ab.23.0001