ABSTRACT
BACKGROUND: High glucose levels are key factors and key contributors to several cardiovascular diseases associated with cardiomyocyte injury. Ferroptosis, which was identified in recent years, is a mode of cell death caused by the iron-mediated accumulation of lipid peroxides. Neuregulin-4 (Nrg4) is an adipokine that has protective effects against metabolic disorders and insulin resistance. Our previous study revealed that Nrg4 has a protective effect against diabetic myocardial injury, and the aim of this study was to investigate whether Nrg4 could attenuate the occurrence of high glucose-induced ferroptosis in cardiomyocytes. METHODS: We constructed an in vivo diabetic myocardial injury model in which primary cardiomyocytes were cultured in vitro and treated with Nrg4. Changes in ferroptosis-related protein levels and ferroptosis-related indices in cardiomyocytes were observed. In addition, we performed back-validation and explored signalling pathways that regulate ferroptosis in primary cardiomyocytes. RESULTS: Nrg4 attenuated cardiomyocyte ferroptosis both in vivo and in vitro. Additionally, the AMPK/NRF2 signalling pathway was activated during this process, and when the AMPK/NRF2 pathway was inhibited, the beneficial effects of Nrg4 were attenuated. CONCLUSION: Nrg4 antagonizes high glucose-induced ferroptosis in cardiomyocytes via the AMPK/NRF2 signalling pathway.
Subject(s)
AMP-Activated Protein Kinases , Ferroptosis , Glucose , Myocytes, Cardiac , NF-E2-Related Factor 2 , Neuregulins , Signal Transduction , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/drug effects , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Neuregulins/metabolism , Neuregulins/genetics , Animals , Ferroptosis/drug effects , Glucose/metabolism , Signal Transduction/drug effects , AMP-Activated Protein Kinases/metabolism , AMP-Activated Protein Kinases/genetics , Mice , Male , RatsABSTRACT
Approximately two-thirds of patients with asthma, a common inflammatory airway disease, are thought to present with allergies. Probiotics and tryptophan metabolites are becoming increasingly important in treating allergic asthma. This study aimed to identify potential probiotic strains and tryptophan metabolites that could alleviate asthma symptoms. Based on in vitro fermentation experiments, we evaluated variations in probiotic capacity to metabolize tryptophan. Of the eight tested strains, Bifidobacterium animalis subsp. lactis CCFM1274 produced relatively high levels of indole-3-carboxaldehyde (I3C). A mouse model of allergic asthma was established by oral administration of ovalbumin (OVA) and was subjected to oral administration of probiotics. The results demonstrated that treatment with CCFM1274 reduced the tendency for body weight loss and mortality in OVA-induced asthmatic mice. Ingestion of CCFM1274 improved the infiltration of perivascular and peribronchial inflammatory cells in the lung sections stained with hematoxylin and eosin (H&E). This outcome was accompanied by a reduction in the serum levels of OVA-specific immunoglobulin E (OVA-sIgE) and in the levels of IL-10 and IL-17 in the bronchoalveolar lavage fluid (BALF). The linear discriminant analysis effect size (LEfSe) of the gut microbiota showed that CCFM1274 increased the relative abundance of Bifidobacterium. In conclusion, CCFM1274 remodeled intestinal tryptophan metabolism in mice and contributed to the improvement of allergic asthma.
ABSTRACT
Microbial aggregation mainly occurs on the intestinal epithelium, mucosal layer and undigested food particles in the gastrointestinal tract (GIT). Undigested food particles are usually insoluble dietary fiber (IDF), which can be easily obtained through daily diet, but there are few studies investigating whether the gut bacteria adhering to undigested food particles can form multi-species biofilms. In this study, we prepared mono- and multi-species biofilms using 18 core gut bacteria via a dynamic fermentation method, and it was found that multi-species composed of nine core gut bacteria (M9) showed the best biofilm formation ability. Cell counts of the nine bacteria in multi-species biofilms were 9.36, 11.85, 10.17, 9.93, 12.88, 11.39, 10.089, 9.06, and 13.21 Log10 CFU mL-1. M9 was tightly connected and regularly stacked on wheat fiber and had larger particle sizes than mono-species biofilms. M9 retained biofilm formation ability under pH and bile salt stresses. A human feces invasion experiment demonstrated that M9 can stably adhere to wheat fiber under the interference of complex gut bacteria, and the M9 multi-species biofilm had positions that can be filled by various gut bacteria. Metabolome results indicated that the M9 multi-species biofilm had more metabolic productions and more complex interspecies interactions than mono-species biofilms. This study provides a dynamic fermentation method to prepare multi-species biofilms on wheat fiber in vitro. It will also offer a research basis for clarifying whether gut bacteria can utilize IDF to form biofilm structures in vivo and the possible interspecific interactions and physiological functions of bacteria in biofilms.
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Herein, we report the assembly behavior of triptycenes with aldehyde (Trip-1) and amino (Trip-2) groups on pristine and iodine-passivated Au(111) surfaces by a combination of scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and density functional theory (DFT) calculation. On Au(111) surface, Trip-1 forms long trimer chains and two-dimensional islands via aldehyde-aldehyde hydrogen bonding in one dimension and π-π stacking of adjacent benzene rings in the other dimension. In contrast, Trip-2 lies as individuals or in disorderly stacked islands. Trip-2 and Trip-1 can be mixed in an arbitrary ratio. And Trip-2 molecules disrupt the ordered self-assembly structure of Trip-1 due to the formation of stronger aldehyde-amino hydrogen bonding. DFT, XPS, and Raman spectra confirm the conformational difference of Trip-1 and -2, as well as the aldehyde-amino hydrogen bonding formation in Trip-1 and Trip-2 mixture. On the iodine-passivated Au(111) surface, Trip-1 forms single-molecule chains and a hexagonal closely packed structure due to iodine interlayer mediation. Trip-2 molecules disrupt the hexagonal closely packed structure of Trip-1.
ABSTRACT
SnTe, as a potential medium-temperature thermoelectric material, reaches a maximum power factor (PF) usually above 750 K, which is not conducive to continuous high-power output in practical applications. In this study, PF is maintained at high values between 18.5 and 25 µW cm-1 K-2 for Sn0.99In0.01Te-x wt% tourmaline samples within the temperature range of 323 to 873 K, driving the highest PFeng of 1.2 W m-1 K-1 and PFave of 22.5 µW cm-1 K-2, over 2.5 times that of pristine SnTe. Such an extraordinary PF is attributed to the synergy of resonant levels and Sn vacancy suppression. Specifically, the Seebeck coefficient increases dramatically, reaching 88 µV K-1 at room temperature. Meanwhile, by Sn vacancy suppression, carrier concentration, and mobility are optimized to ≈1019 cm-3 and 740 cm2 V-1 s-1, respectively. With the tourmaline compositing, Sn vacancies are further suppressed and the thermal conductivity simultaneously decreases, with the minimum lattice thermal conductivity of 0.9 W m-1 K-1. Finally, the zT value ≈0.8 is obtained in the Sn0.99In0.01Te sample. The peak of the power output density reaches 0.89 W cm-2 at a temperature difference of 600 K. Such SnTe alloys with high and "temperature-independent" PF will offer an option for realizing high output power in thermoelectric devices.
ABSTRACT
Asthma is a prevalent respiratory disease. The present study is designed to determine whether gut microbiota-derived tryptophan metabolites alleviate allergic asthma inflammation in ovalbumin (OVA)-induced mice and explore the effect and potential mechanism therein. Asthma model mice were constructed by OVA treatment, and kynurenine (KYN), indole-3-lactic acid (ILA), in-dole-3-carbaldehyde (I3C), and indole acetic acid (IAA) were administered by intraperitoneal injection. The percent survival, weight and asthma symptom score of mice were recorded. The total immunoglobulin E and OVA-specific (s)IgE in the serum and the inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) were detected by the corresponding ELISA kits. The composition of the gut microbiota and tryptophan-targeted metabolism in mouse feces were analyzed using 16S rRNA gene sequencing and targeted metabolomics, respectively. The four tryptophan metabolites improved the percent survival, weight and asthma symptoms of mice, and reduced the inflammatory cells in lung tissues, especially I3C. I3C and IAA significantly (p < 0.05) downregulated the levels of OVA-IgE and inflammatory cytokines. KYN was observed to help restore gut microbiota diversity. Additionally, I3C, KYN, and ILA increased the relative abundance of Anaeroplasma, Akkermansia, and Ruminococcus_1, respectively, which were connected with tryptophan metabolic pathways. IAA also enhanced capability of tryptophan metabolism by the gut microbiota, restoring tryptophan metabolism and increasing production of other tryptophan metabolites. These findings suggest that tryptophan metabolites may modulate asthma through the gut microbiota, offering potential benefits for clinical asthma management.
ABSTRACT
Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and ß-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.
Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Animals , Mice , Humans , Machine LearningABSTRACT
For decades, soft sensors have been extensively renowned for their efficiency in real-time tracking of expensive variables for advanced process control. However, despite the diverse efforts lavished on enhancing their models, the issue of label sparsity when modeling the soft sensors has always posed challenges across various processes. In this paper, a fledgling technique, called co-training, is studied for leveraging only a small ratio of labeled data, to hone and formulate a more advantageous framework in soft sensor modeling. Dissimilar to the conventional routine where only two players are employed, we investigate the efficient number of players in batch processes, making a multiple-player learning scheme to assuage the sparsity issue. Meanwhile, a sliding window spanning across both time and batch direction is used to aggregate the samples for prediction, and account for the unique 2D correlations among the general batch process data. Altogether, the forged framework can outperform the other prevalent methods, especially when the ratio of unlabeled data is climbing up, and two case studies are showcased to demonstrate its effectiveness.
ABSTRACT
BACKGROUND AND PURPOSE: The habenula is a key node in the regulation of emotion-related behavior. Accurate visualization of the habenula and its reliable quantitative analysis is vital for the assessment of psychiatric disorders. To obtain high-contrast habenula images and allow them to be compatible with clinical applications, this preliminary study compared 3T MP2RAGE and quantitative susceptibility mapping with MPRAGE by evaluating the habenula segmentation performance. MATERIALS AND METHODS: Ten healthy volunteers were scanned twice with 3T MPRAGE and MP2RAGE and once with quantitative susceptibility mapping. Image quality and visibility of habenula anatomic features were analyzed by 3 radiologists using a 5-point scale. Contrast assessments of the habenula and thalamus were also performed. The reproducibility of the habenula volume from MPRAGE and MP2RAGE was evaluated by manual segmentation and the Multiple Automatically Generated Template brain segmentation algorithm (MAGeTbrain). T1 values and susceptibility were measured in the whole habenula and habenula geometric subregion using MP2RAGE T1-mapping and quantitative susceptibility mapping. RESULTS: The 3T MP2RAGE and quantitative susceptibility mapping demonstrated clear boundaries and anatomic features of the habenula compared with MPRAGE, with a higher SNR and contrast-to-noise ratio (all P < .05). Additionally, 3T MP2RAGE provided reliable habenula manual and MAGeTbrain segmentation volume estimates with greater reproducibility. T1-mapping derived from MP2RAGE was highly reliable, and susceptibility contrast was highly nonuniform within the habenula. CONCLUSIONS: We identified an optimized sequence combination (3T MP2RAGE combined with quantitative susceptibility mapping) that may be useful for enhancing habenula visualization and yielding more reliable quantitative data.
Subject(s)
Habenula , Humans , Habenula/diagnostic imaging , Reproducibility of Results , Algorithms , Magnetic Resonance Imaging/methods , Healthy Volunteers , BrainABSTRACT
Antibiotic treatment often causes collateral damage to the gut microbiota, including changes in its diversity and composition. Dietary fiber helps maintain intestinal health, regulate short-chain fatty acids, and promote the recovery of the intestinal microbiome. However, it is currently unknown which specific plant-based dietary fiber is optimal as a dietary supplement for restoring the intestinal microbiota after antibiotic disturbance. Previously, we proposed predictive recovery-associated bacterial species (p-RABs) and identified the most important interventions. This study aimed to identify an optimal form of dietary fiber to recover the gut microbiome after antibiotic treatment. Therefore, we examined the types of dietary fibers associated with p-RABs through a p-RAB-metabolite bilayer network constructed from prior knowledge; we searched for dietary fiber that could provide nutritional support for Akkermansia muciniphila and Bacteroides uniformis. C57BL/6J mice were fed with 500 mg kg-1 of different types of dietary fibers daily for one week after being treated with ampicillin. The results showed that mannan-oligosaccharides could better promote the diversity of intestinal microbial growth, enhance the recovery of most genera, including Akkermansia and Bacteroides, and inhibit certain pathogenic bacteria, such as Proteus, compared to the other fiber types. Furthermore, mannan-oligosaccharides could regulate the levels of short-chain fatty acids, especially butyric acid. Functional predictions showed that starch metabolism, galactose metabolism, and the metabolism of other carbohydrates played key roles in the early recovery process. In conclusion, mannan-oligosaccharides could enhance the recovery of the intestinal microbiome after antibiotic treatment, offering valuable insights for targeted dietary strategies.
Subject(s)
Anti-Bacterial Agents , Mannans , Animals , Mice , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/metabolism , Mannans/metabolism , Mice, Inbred C57BL , Oligosaccharides/pharmacology , Dietary Fiber/metabolism , Bacteria , Fatty Acids, Volatile/metabolismABSTRACT
The development of antibiotics was a turning point in the history of medicine; however, their misuse and overuse have contributed to the current global epidemic of antibiotic resistance. According to epidemiological studies, early antibiotic exposure increases the risk of immunological and metabolic disorders. This study investigated the effects of exposure to different doses of sulfamethazine (SMZ) on offspring mice and compared the effects of exposure to SMZ on offspring mice in prenatal and early postnatal periods and continuous periods. Furthermore, the effects of SMZ exposure on the gut microbiota of offspring mice were analyzed using metagenome. According to the results, continuous exposure to high-dose SMZ caused weight gain in mice. IL-6, IL-17A, and IL-10 levels in the female offspring significantly increased after high-dose SMZ exposure. In addition, there was a significant gender difference in the impact of SMZ exposure on the gut microbiota of offspring: Continuous high-dose SMZ exposure significantly decreased the relative abundance of Ligilactobacillus murinus, Limosilactobacillus reuteri, Lactobacillus johnsonii, and Bifidobacterium pseudolongum (p < 0.05) in female offspring mice; however, these significant changes were not observed in male offspring mice.
ABSTRACT
Accumulating evidence has revealed the anti-inflammatory properties of Lactobacillus-derived exopolysaccharides (EPSs). However, interspecific differences among these Lactobacillus-derived anti-inflammatory EPSs have not been investigated. Cell experiments showed that Limosilactobacillus fermentum, Lacticaseibacillus rhamnosus, and Lactiplantibacillus plantarum-derived EPSs exhibited excellent anti-inflammatory efficacy in vitro. Subsequently, we used Lactobacillus-derived EPSs to treat colitis in mice. There was no significant difference in EPS's repair of the intestinal barrier from the five Lactobacillus species. However, Ligilactobacillus salivarius-derived EPSs and L. plantarum-derived EPSs more potently reduced proinflammatory cytokines (TNF-α, IL-1ß, IL-6, TNF-γ, and IL-17), increasing IL-10 concentrations in the colon. Lactobacillus-derived EPS moieties from five species regulate intestinal bacteria at the strain level. Immunofluorescence staining revealed that owing to the different infiltration and polarization effects of Lactobacillus-derived EPSs on macrophages, the in vitro and in vivo anti-inflammatory effects of Lactobacillus-derived EPSs were inconsistent. The structure-activity relationship showed that Lactobacillus-derived EPSs with high fructose content had excellent anti-inflammatory activity in vivo. The results mentioned above revealed that the anti-inflammatory activity of Lactobacillus-derived EPSs had interspecific variability, and the mechanism of anti-inflammatory action in vitro and in vivo was different.
Subject(s)
Lactobacillus , Probiotics , Animals , Mice , Polysaccharides, Bacterial/pharmacology , Cytokines , Intestines , Anti-Inflammatory Agents/pharmacologyABSTRACT
Age-related changes in the microbiome have been reported in previous studies; however, direct evidence for their association with frailty is lacking. Here, we introduce biological age based on gut microbiota (gAge), an integrated prediction model that integrates gut microbiota data from different perspectives with potential background factors for aging assessment. Simulation results show that, compared with a single model, the ensemble model can not only significantly improve the prediction accuracy, but also make full use of the data in unpaired samples. From this, we identified markers associated with age development and grouped markers into accelerated aging and mitigated aging according to their effect on the prediction. Importantly, the application of gAge to an elderly cohort with different frailty levels confirmed that gAge and its predictive residuals are closely related to the individual's health status and frailty stage, and age-related markers overlap significantly with disease and frailty characteristics. Furthermore, we applied the gAge prediction model to another independent cohort of the elderly population for aging assessment and found that gAge could effectively represent the aging population. Overall, our study explains the association between the gut microbiota and frailty, providing potential targets for the development of gut microbiota-based targeted intervention strategies for aging.
Subject(s)
Frailty , Gastrointestinal Microbiome , Microbiota , Aged , Humans , Frail Elderly , AgingABSTRACT
Tryptophan (TRP) contributes to individual immune homeostasis and good condition via three complex metabolism pathways (5-hydroxytryptamine (5-HT), kynurenine (KP), and gut microbiota pathway). Indole propionic acid (IPA), one of the TRP derivatives of the microbiota pathway, has raised more attention because of its impact on metabolic disorders. Here, we retrospect increasing evidence that TRP metabolites/IPA derived from its proteolysis impact host health and disease. IPA can activate the immune system through aryl hydrocarbon receptor (AHR) and/or Pregnane X receptor (PXR) as a vital mediator among diet-caused host and microbe cross-talk. Different levels of IPA in systemic circulation can predict the risk of NAFLD, T2DM, and CVD. IPA is suggested to alleviate cognitive impairment from oxidative damage, reduce gut inflammation, inhibit lipid accumulation and attenuate the symptoms of NAFLD, putatively enhance the intestinal epithelial barrier, and maintain intestinal homeostasis. Now, we provide a general description of the relationships between IPA and various physiological and pathological processes, which support an opportunity for diet intervention for metabolic diseases.
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The electrocatalytic 5-hydroxymethylfurfural (HMF) oxidation reaction coupling with hydrogen evolution reaction (HER) serves as a promising strategy to generate both high-value-added products and clean energy, which is limited by the poor catalytic efficiency of bifunctional electrocatalysts and unclear electrocatalytic mechanism for HMF oxidation reaction. Herein, we fabricate a bifunctional NiSe2-NiMoO4 heterostructure nanowire electrocatalyst for the conversion of HMF to 2,5-furandicarboxylic acid (FDCA) and simultaneous H2 production. As expected, the NiSe2-NiMoO4 exhibits outstanding activity and selectivity toward HMF oxidation reaction. In particular, at a potential of 1.50 V, the yield of FDCA could reach 98 % with a faradaic efficiency of 96.5 %, as well as excellent stability. Density functional theory calculation results demonstrate that the NiSe2-NiMoO4 heterostructure could tune the adsorption energy of HMF, facilitate high-valence active species formation, and enhance electronic conductivity. Furthermore, a two-electrode electrolyzer assembled using NiSe2-NiMoO4 as a bifunctional catalyst requires 1.53 V to acquire a current density of 50 mA cm-2, which is 201 mV lower than that of water electrolysis. This work provides new insights for designing multifunctional catalysts for biomass upgrading coupled with hydrogen evolution.
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The habenula (Hb) is involved in many natural human behaviors, and the relevance of its alterations in size and neural activity to several psychiatric disorders and addictive behaviors has been presumed and investigated in recent years using magnetic resonance imaging (MRI). Although the Hb is small, an increasing number of studies have overcome the difficulties in MRI. Conventional structural-based imaging also has great defects in observing the Hb contrast with adjacent structures. In addition, more and more attention should be paid to the Hb's functional, structural, and quantitative imaging studies. Several advanced MRI methods have recently been employed in clinical studies to explore the Hb and its involvement in psychiatric diseases. This review summarizes the anatomy and function of the human Hb; moreover, it focuses on exploring the human Hb with noninvasive MRI approaches, highlighting strategies to overcome the poor contrast with adjacent structures and the need for multiparametric MRI to develop imaging markers for diagnosis and treatment follow-up. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
Subject(s)
Habenula , Mental Disorders , Multiparametric Magnetic Resonance Imaging , Humans , Habenula/anatomy & histology , Magnetic Resonance Imaging/methodsABSTRACT
Objective: This study was carried out to evaluate the clinical efficacy of proprotein convertase chymotrypsin 9 (PCSK9) inhibitors in multi-branch lesions in coronary artery disease with substandard lipid-lowering effects. Methods: This retrospective study collected the clinical data of 100 patients with multiple coronary artery diseases admitted to our hospital between May 2020 and August 2022 for analysis. The eligible patients were assigned to either a PCSK9 inhibitor group or a control group at a ratio of 1:1 by their dosing regimens, with 50 cases in each group. Outcome measures for the clinical efficacy of PCSK9 inhibitors included lipid levels, low-density lipoprotein cholesterol (LDL-C) changes, serum concentrations of coronary artery disease-related inflammatory factors, improvement of angina questionnaire scores, adverse reactions, and major cardiovascular adverse events. Results: PCSK9 inhibitors resulted in significantly lower serum concentrations of total cholesterol (TC), LDL-C, and ApoB and higher high-density lipoprotein cholesterol (HDL-C) levels versus conventional lipid-lowering medication (P < .05). The two arms exhibited similar serum concentrations of triglyceride (TG) and ApoA1 after treatment (P > .05). With LDL-C<1.4 mmol/L as the cut-off for desirable blood lipid levels, 47 (94%) patients reached the standard after in the PCSK9 inhibitors group, while no eligible cases were reported in the control group (P < .05). PCSK9 inhibitors provided a marked reduction in the serum concentrations of high-sensitivity C-reactive protein in the patients. Patients had higher angina stability (AS), angina flare (AF), physical limitation (PL), and treatment satisfaction (TS) scores after PCSK9 inhibitor administration versus after conventional medication (P < .05). PCSK9 inhibitors were associated with a significantly lower incidence of adverse cardiovascular events (10%) versus conventional medication (42%) (P < .05). Conclusion: PCSK9 inhibitors significantly improve the LDL-C concentrations of patients with multiple lesions of coronary artery disease who have failed to meet lipid-lowering targets, this enables physicians to more effectively manage patients' cholesterol levels, consequently reducing their cardiovascular risk. Moreover, these inhibitors have the potential to enhance patients' quality of life by alleviating relieve angina symptoms. These findings offer valuable insights into managing multi-branch coronary artery disease.
ABSTRACT
The gut microbiome has been regarded as one of the fundamental determinants regulating human health, and multi-omics data profiling has been increasingly utilized to bolster the deep understanding of this complex system. However, stemming from cost or other constraints, the integration of multi-omics often suffers from incomplete views, which poses a great challenge for the comprehensive analysis. In this work, a novel deep model named Incomplete Multi-Omics Variational Neural Networks (IMOVNN) is proposed for incomplete data integration, disease prediction application and biomarker identification. Benefiting from the information bottleneck and the marginal-to-joint distribution integration mechanism, the IMOVNN can learn the marginal latent representation of each individual omics and the joint latent representation for better disease prediction. Moreover, owing to the feature-selective layer predicated upon the concrete distribution, the model is interpretable and can identify the most relevant features. Experiments on inflammatory bowel disease multi-omics datasets demonstrate that our method outperforms several state-of-the-art methods for disease prediction. In addition, IMOVNN has identified significant biomarkers from multi-omics data sources.
Subject(s)
Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Humans , Multiomics , Biomarkers , Inflammatory Bowel Diseases/genetics , Neural Networks, ComputerABSTRACT
Bacterial biofilm is an emerging form of life that involves cell populations living embedded in a self-produced matrix of extracellular polymeric substances (EPS). Currently, little is known about the molecular mechanisms of Bifidobacterium biofilm formation. We used the Bifidobacterium biofilm fermentation system to preparation of biofilms on wheat fibers, and multi-omics analysis of both B. pseudocatenulatum biofilms and planktonic cells were performed to identify genes and metabolites involved in biofilm formation. The average diameter of wheat fibers was around 50 µm, while the diameter of particle in wheat fibers culture of B. pseudocatenulatum was over 260 µm at 22 h with 78.96% biofilm formation rate (BR), and the field emission scanning electron microscopy (FESEM) results showed that biofilm cells on the surface of wheat fibers secreted EPS. Transcriptomic analysis indicated that genes associated with stress response (groS, mntH, nth, pdtaR, pstA, pstC, radA, rbpA, whiB, ybjG), quorum sensing (dppC, livM, luxS, sapF), polysaccharide metabolic process (rfbX, galE, zwf, opcA, glgC, glgP, gtfA) may be involved in biofilm formation. In addition, 17 weighted gene co-expression network analysis (WGCNA) modules were identified and two of them positively correlated to BR. Metabolomic analysis indicated that amino acids and amides; organic acids, alcohols and esters; and sugar (trehalose-6-phosphate, uridine diphosphategalactose, uridine diphosphate-N-acetylglucosamine) were main metabolites during biofilm formation. These results indicate that stress response, quorum sensing (QS), and EPS production are essential during B. pseudocatenulatum biofilm formation.
ABSTRACT
The occurrence of obesity and related metabolic disorders is rising, necessitating effective long-term weight management strategies. With growing interest in the potential role of gut microbes due to their association with responses to different weight loss diets, understanding the mechanisms underlying the interactions between diet, gut microbiota, and weight loss remains a challenge. This study aimed to investigate the potential impact of a multiphase dietary protocol, incorporating an improved ketogenic diet (MDP-i-KD), on weight loss and the gut microbiota. Using metagenomic sequencing, we comprehensively analyzed the taxonomic and functional composition of the gut microbiota in 13 participants before and after a 12-week MDP-i-KD intervention. The results revealed a significant reduction in BMI (9.2% weight loss) among obese participants following the MDP-i-KD intervention. Machine learning analysis identified seven key microbial species highly correlated with MDP-i-KD, with Parabacteroides distasonis exhibiting the highest response. Additionally, the co-occurrence network of the gut microbiota in post-weight-loss participants demonstrated a healthier state. Notably, metabolic pathways related to nucleotide biosynthesis, aromatic amino acid synthesis, and starch degradation were enriched in pre-intervention participants and positively correlated with BMI. Furthermore, species associated with obesity, such as Blautia obeum and Ruminococcus torques, played pivotal roles in regulating these metabolic activities. In conclusion, the MDP-i-KD intervention may assist in weight management by modulating the composition and metabolic functions of the gut microbiota. Parabacteroides distasonis, Blautia obeum, and Ruminococcus torques could be key targets for gut microbiota-based obesity interventions.