Search Results (181)

Background: The rapid advancement in artificial intelligence (AI) has fundamentally reshaped gut microbiome research by enabling high-resolution analysis of complex, high-dimensional microbial communities and their functional interactions with the human host. Objective: This narrative review aims to synthesize recent methodological advances in AI-driven gut microbiome research and to evaluate their translational relevance for therapeutic optimization, personalized nutrition, and precision medicine. Methods: A narrative literature review was conducted using PubMed, Google Scholar, Web of Science, and IEEE Xplore, focusing on peer-reviewed studies published between approximately 2015 and early 2025. Representative articles were selected based on relevance to AI methodologies applied to gut microbiome analysis, including machine learning, deep learning, transformer-based models, graph neural networks, generative AI, and multi-omics integration frameworks. Additional seminal studies were identified through manual screening of reference lists. Results: The reviewed literature demonstrates that AI enables robust identification of diagnostic microbial signatures, prediction of individual responses to microbiome-targeted therapies, and design of personalized nutritional and pharmacological interventions using in silico simulations and digital twin models. AI-driven multi-omics integration—encompassing metagenomics, metatranscriptomics, metabolomics, proteomics, and clinical data—has improved functional interpretation of host–microbiome interactions and enhanced predictive performance across diverse disease contexts. For example, AI-guided personalized nutrition models have achieved AUC exceeding 0.8 for predicting postprandial glycemic responses, while community-scale metabolic modeling frameworks have accurately forecast individualized short-chain fatty acid production. Conclusions: Despite substantial progress, key challenges remain, including data heterogeneity, limited model interpretability, population bias, and barriers to clinical deployment. Future research should prioritize standardized data pipelines, explainable and privacy-preserving AI frameworks, and broader population representation. Collectively, these advances position AI as a cornerstone technology for translating gut microbiome data into actionable insights for diagnostics, therapeutics, and precision nutrition. Full article

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis. Full article

Overwinter Syndrome (OWS) affects grass carp (Ctenopharyngodon idellus) aquaculture in China, causing high mortality and economic losses under low temperatures. Failure of antibiotic therapies shows limits of the ‘low–temperature–pathogen’ model and shifts focus to mucosal barrier dysfunction and host–microbiome interactions in OWS. We compared healthy and diseased grass carp collected from the same pond using histopathology, transcriptomics, proteomics, and metagenomics. This integrated approach was used to characterize intestinal structure, microbial composition, and host molecular responses at both taxonomic and functional levels. Results revealed a three-layer barrier failure in OWS fish: the physical barrier was compromised, with structural damage and reduced mucosal index; microbial dysbiosis featured increased richness without changes in diversity or evenness, and expansion of the virobiota, notably uncultured Caudovirales phage; and mucosal immune dysregulation indicated loss of local immune balance. Multi-omics integration identified downregulation of lysosome-related and glycosphingolipid biosynthesis pathways at transcript and protein levels, with disrupted nucleotide metabolism. Overall gut microbial richness, rather than individual taxa abundance, correlated most strongly with host gene changes linked to immunity, metabolism, and epithelial integrity. Although biological replicates were limited by natural outbreak sampling, matched high-depth multi-omics datasets provide exploratory insights into OWS-associated intestinal dysfunction. In summary, OWS entails a cold-triggered breakdown of intestinal barrier integrity and immune homeostasis. This breakdown is driven by a global restructuring of the gut microbiome, which is marked by increased richness, viral expansion, and functional shifts, ultimately resulting in altered host–microbe crosstalk. This ecological perspective informs future mechanistic and applied studies for disease prevention. Full article

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite advances in screening and therapeutic strategies, early detection and individualized treatment remain major challenges. In recent years, an expanding repertoire of biomarkers has emerged, spanning genomic, transcriptomic, proteomic, and metabolomic signatures. Epigenetic features, such as DNA methylation panels, as well as non-coding RNAs and the gut microbiome, hold potential not only for improving early diagnosis but also for refining prognosis and predicting therapeutic responses within the framework of precision oncology. This narrative review provides an updated, integrative overview of CRC diagnostic, prognostic, and predictive biomarkers. We distinguish established markers already in clinical practice, such as RAS and BRAF mutations, HER2 amplification, microsatellite instability/mismatch repair deficiency (MSI/dMMR), and widely investigated molecular alterations including TP53 mutations and immune-checkpoint-related markers, from novel biomarkers with growing translational potential. We also discuss the implementation challenges of these biomarkers in clinical practice, including issues related to validation, standardization, and cost-effectiveness, as well as the multi-modal approach for the development of composite diagnostic panels. Full article

Fermentation, one of the oldest food processing techniques, is known to play a pivotal role in improving the nutritional and functional characteristics of cereals, with positive implications for gut health and overall well-being. The present study aims to examine the phenolic acids, peptides, and potential bioactive properties of 2 novel sorghum-based fermented beverages, Niselo and Delishe. A total of 48 phenolic compounds were identified through targeted and untargeted Ultra-High Performance Liquid Chromatography coupled with a Quadrupole Orbitrap High-Resolution Mass Spectrometer (UHPLC–Q-Orbitrap HRMS) analyses, revealing a higher content of phenolic acids in Niselo and a prevalence of flavonoids in Delishe. Niselo exhibited enhanced in vitro cytoprotective and reactive oxygen species (ROS)-scavenging activity and displayed a clear cytoprotective effect against hydrogen peroxide-induced oxidative stress in Caco-2 cells. Proteomic profiling using tryptic digestion revealed that Niselo has a substantial abundance of fragments of peptides matching several stress-related and antioxidant proteins, indicating a superior stress-response and/or defense capability. Overall, these findings highlight the functional potential of sorghum-based fermented beverages, supporting their role as health-promoting products. Full article

Background: Unhealthy diets characterized by high salt, fat, and fructose content are established risk factors for metabolic and cardiovascular disorders and may have indirect effects on cognitive function. However, the combined impact of a high-salt, high-fat, and high-fructose diet (HSHFHFD) on systemic physiology and brain health remains to be fully elucidated. Methods: Sprague-Dawley (SD) rats received a customized high-salt, high-fat diet supplemented with 30% fructose water for 18 weeks. Physiological and brain parameters were assessed, in combination with multi-omics analyses including brain proteomics and metabolomics, serum metabolomics, and gut microbiota profiling. Results: HSHFHFD significantly elevated blood glucose, blood pressure, and serum levels of TG, TC, and LDL in rats. Serum metabolomic profiling identified over 100 differentially abundant metabolites in the Model group. Proteomics, metabolomics, and gut microbiome integration revealed pronounced alterations in both brain proteomic and metabolomic profiles, with 155 differentially expressed proteins associated with glial cell proliferation and 65 differential metabolites linked to fatty acid and amino acid metabolism, among others. Experimental validation confirmed marked upregulation of GFAP and Bax protein, concomitant with downregulation of ZO-1 and occludin. Furthermore, HSHFHFD perturbed the CREB signaling pathway, leading to diminished BDNF expression. The levels of inflammatory factors, including IL-6, IL-10, IL-1β and TNFα, were significantly elevated in the brain. Oxidative stress was evident, as indicated by elevated malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and altered NAD⁺/NADH ratio. Additionally, HSHFHFD significantly reduced the abundance of beneficial gut bacteria, including Lactobacillus, Romboutsia, and Monoglobus. Conclusions: HSHFHFD-induced depletion of gut Lactobacillus spp. may disrupt the linoleic acid metabolic pathway and gut–brain axis homeostasis, leading to the impairment of neuroprotective function, blood–brain barrier dysfunction, and exacerbated neuroinflammation and oxidative stress in the brain. These effects potentially increase the susceptibility of rats to neurodegenerative disorders. Full article

Background: The arsenic-responsive repressor, ArsR, has long been understood as a canonical regulator of the arsRBC operon, which confers resistance to arsenic stress. However, recent studies suggest a broader regulatory scope for ArsR. Here, we investigated the proteomic landscape of Escherichia coli strains with and without ArsR to elucidate ArsR as an activator in both non-stressing and arsenic-stressing conditions. Methods: Using mass-spectrometry-based shotgun proteomics and statistical analyses, we characterized the differential abundance of proteins across AW3110 (ΔarsRBC), AW3110 complemented with arsR, and wild-type K-12 strains under control and arsenite-stressed conditions. Results: Our study shows that ArsR influences proteomic networks beyond the ars operon, integrating metabolic and redox responses crucial for cellular adaptation and survival. This suggests that ArsR has a significant role in gut microbiome metabolomic profiles in response to arsenite. Proteins involved in alanine, lactaldehyde, arginine, thioredoxin, and proline pathways were significantly elevated in strains where ArsR was detected, both with and without arsenite. We identified proteins exhibiting an “ArsR-dependent” activation pattern, highlighting ArsR’s potential role in redox balance and energy metabolism. Conclusions: These findings challenge the classical view of ArsR as a repressor and position it as a pleiotropic regulator, including broad activation. Full article

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are microbial metabolites with recognised roles in gut and immune homeostasis, but their therapeutic relevance in gastric cancer, particularly in combination with chemotherapeutics, remains unclear. This study investigated the antiproliferative synergy between a combined SCFA mixture (APB) and doxorubicin (Dox) in AGS gastric adenocarcinoma cells using integrated cellular, molecular, and proteomic approaches. APB and Dox each inhibited cell proliferation, with IC₅₀ values of 568.33 ± 82.56 μg/mL and 0.22 ± 0.04 μg/mL, respectively, and their combination (3000 + 0.27 μg/mL) enhanced cytotoxicity, achieving 103.46% inhibition and reducing the APB IC₅₀ to 512.80 ± 18.37 μg/mL. Combination index values confirmed synergistic interactions (CI₅₀ = 0.61; CI₉₅ = 0.13). APB+Dox significantly increased apoptosis (94.83%) with minimal necrosis (4.64%) and induced strong ROS generation comparable to APB alone, while Dox showed limited oxidative effects. Proteomic profiling revealed downregulation of ribosomal proteins and cell cycle regulators in Dox and APB+Dox groups, with the combination further enhancing apoptosis-related pathways and stress responses. Overall, these findings indicate that SCFA-based interventions, exemplified by APB+Dox, may offer a low-toxicity strategy to potentiate chemotherapy efficacy in gastric cancer through apoptosis induction, redox disruption, and attenuation of drug resistance. Full article

The acute gouty arthritis (AGA) to chronic gouty arthritis (CGA) transition is a critical phase leading to irreversible joint damage and systemic complications. However, current molecular mechanism investigations have remained limited to single-omics approaches that lack comprehensive multi-omics explorations. We integrate high-depth data-independent acquisition (DIA) proteomics and untargeted metabolomics to analyze serum samples from healthy controls (n =28), AGA (n = 31), and CGA (n = 14) patients to address this gap. Through differential expression analysis, we identified nine persistently dysregulated pivotal proteins with robust discriminative capacity, including the urate excretion regulator ZBTB20 and inflammation/immune-related proteins (GUCY1A2, CNDP1, LYZ, SERPINA5, GSN). Additionally, 11 consistently altered core metabolites with diagnostic potential were detected, indicating perturbations in sex hormones, thyroid hormones, gut microbiota-derived metabolites, environmental exposures, and nutritional factors. Multi-omics KEGG enrichment analysis highlighted thyroid hormone synthesis, AMPK signaling pathway, and taurine and hypotaurine metabolism as central pathways. Correlation network analysis further revealed significant immune dysregulation, illustrating an evolution from acute immune activation to chronic inflammation during AGA-to-CGA progression. Our study establishes that a coordinated disruption of the thyroid hormone–AMPK–taurine metabolic axis and concomitant immune microenvironment remodeling is associated with chronic gout development. These findings provide critical targets for developing early diagnostic indicators and targeted interventions for CGA. Full article

The gut-brain axis is a complex communication network linking the gastrointestinal tract and the central nervous system, in which the gut microbiota plays a pivotal role in regulating intestinal homeostasis, immune responses and neuroendocrine functions. This review summarizes current knowledge on the role of the porcine gut microbiota in the functioning of the gut-brain axis and examines nutritional strategies aimed at its modulation. Key production-related stressors, such as weaning, transport and handling, disrupt microbiota composition, increase intestinal permeability and activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to heightened stress responses, impaired immunity and behavioral disturbances. Evidence indicates that supplementation with probiotics, prebiotics, or postbiotics stabilizes the gut microbiota, enhances the production of bioactive metabolites, supports intestinal barrier integrity and alleviates oxidative stress. Such interventions improve adaptation to environmental stress, animal welfare and performance, while potentially reducing the need for antibiotics. Maintaining a balanced gut microbiota is therefore essential for the proper functioning of the neuroendocrine and immune systems in pigs. An integrated approach utilizing omics technologies (metagenomics, metabolomics, proteomics) may further elucidate microbiota-brain interactions and support the development of sustainable and ethical swine production strategies. Full article

Major Depressive Disorder (MDD) poses a significant global health burden, characterized by a complex and heterogeneous pathophysiology insufficiently targeted by conventional single-treatment approaches. This review presents an integrative framework incorporating network pharmacology, artificial intelligence (AI), and multi-omics technologies to advance a systems-level understanding and management of MDD. Its central contribution lies in moving beyond reductionist methods by embracing a holistic perspective that accounts for dynamic interactions within biological networks. The primary objective is to demonstrate how AI-powered integration of multi-omics data—spanning genomics, proteomics, and metabolomics—can enable the construction of predictive network models. These models are designed to uncover fundamental disease mechanisms, identify clinically relevant biotypes, and reveal novel therapeutic targets tailored to specific pathological contexts. Methodologically, the review examines the microbiota–gut–brain (MGB) axis as an illustrative case study, detailing its pathogenic roles through neuroimmune alterations, metabolic dysfunction, and disrupted neuro-plasticity. Furthermore, we propose a translational roadmap that includes AI-assisted biomarker discovery, computational drug repurposing, and patient-specific “digital twin” models to advance precision psychiatry. Our analysis confirms that this integrated framework offers a coherent route toward mechanism-based personalized therapies and helps bridge the gap between computational biology and clinical practice. Nevertheless, important challenges remain, particularly pertaining to data heterogeneity, model interpretability, and clinical implementation. In conclusion, we stress that future success will require integrating prospective longitudinal multi-omics cohorts, high-resolution digital phenotyping, and ethically aligned, explainable AI (XAI) systems. These concerted efforts are essential to realize the full potential of precision psychiatry for MDD. Full article

Whiteleg shrimp (Penaeus vannamei) is currently facing significant challenges related to severe disease outbreaks. As the importance of the host–microbiota relationship is being revealed, modulating this relationship has become a key strategy in disease management. Xylooligosaccharides (XOS)—short-chain sugar molecules—have been gaining attention for their potential health benefits in the prebiotics field. In this study, an XOS-rich extract from Salicornia ramosissima was incorporated into shrimp feeds to evaluate its impact on gut health, with the main focus on gut proteomics and microbiota. XOS were incorporated at 0.1% (XOS_0.1) and 1% (XOS_1) concentrations, and a 14-day feeding trial, followed by a bacterial challenge with Vibrio harveyi, was performed. The effects of XOS were evaluated by assessing zootechnical parameters, gene expression in the hepatopancreas, and gut microbiota and proteome. The results showed no significant differences in zootechnical parameters and gene expression after the 14-day trial between animals fed XOS diets and control. However, shrimp fed XOS_1 showed an increased diversity of the microbial communities in the gut when compared with those fed control. Also, known shrimp gut symbionts, such as Ruegeria, Leisingera, and Demequina, were significantly enriched in groups fed XOS after the feeding trial. XOS also modulated the regulation of proteins in the gut. Nevertheless, stressful conditions appear to alter the effects of XOS and the dynamics of gut bacteria. Further studies are warranted to understand the impacts of long-term inclusion of XOS extracts, especially on health-related parameters and disease resistance. Full article

The gut microbiota has emerged as a critical immune–metabolic interface, orchestrating a complex network of interactions that extend well beyond digestion. This highly diverse community of bacteria, viruses, archaea, and eukaryotic microbes modulates host immunometabolism, metabolic reprogramming, and systemic inflammatory responses, thereby shaping human health and disease trajectories. Dysbiosis, or disruption of microbial homeostasis, has been implicated in inflammatory bowel disease, cardiometabolic disorders, neurodegeneration, dermatological conditions, and tumorigenesis. Through the biosynthesis of short-chain fatty acids (SCFAs), bile acid derivatives, tryptophan metabolites, and microbial-derived indoles, the gut microbiota regulates epigenetic programming, barrier integrity, and host–microbe cross-talk, thereby influencing disease onset and progression. In oncology, specific microbial taxa and oncomicrobiotics (cancer-modulating microbes) are increasingly recognized as key determinants of immune checkpoint inhibitor (ICI) responsiveness, chemotherapeutic efficacy, and resistance mechanisms. Microbiota-targeted strategies such as fecal microbiota transplantation (FMT), precision probiotics, prebiotics, synbiotics, and engineered microbial consortia are being explored to recalibrate microbial networks and enhance therapeutic outcomes. At the systems level, the integration of multi-omics platforms (metagenomics, transcriptomics, proteomics, and metabolomics) combined with network analysis and machine learning-based predictive modeling is advancing personalized medicine by linking microbial signatures to clinical phenotypes. Despite remarkable progress, challenges remain, including the standardization of microbiome therapeutics, longitudinal monitoring of host–microbe interactions, and the establishment of robust ethical and regulatory frameworks for clinical translation. Future directions should prioritize understanding the causal mechanisms of microbial metabolites in immunometabolic regulation, exploring microbial niche engineering, and developing precision microbiome editing technologies (CRISPR, synthetic biology). Full article

Post-weaning diarrhea caused by Enterotoxigenic Escherichia coli (ETEC) is a major disease in piglets and leads to substantial economic losses in the swine industry. Compared to conventional lysozyme, yak stomach lysozyme (YSL) demonstrates distinctive resistance to pepsin, trypsin, high temperature, and acidic conditions. This study investigated the effects of dietary YSL supplementation on intestinal health in weaned piglets challenged with ETEC, utilizing metabolomics and proteomics. A total of 18 weaned piglets were randomly divided into three groups: control (C), diarrhea (D), and YSL treatment (YLT). Groups C and D were fed a basal diet, while the YLT group received the basal diet supplemented with YSL at a dosage of 100,000 U/kg following ETEC challenge. Following an acclimation period, piglets in groups D and YLT were orally challenged with ETEC, while group C received the same volume of sterile LB broth. The feeding trial lasted for 21 days before sample collection. The results demonstrated that dietary supplementation with YSL significantly reduced the diarrhea rate (p < 0.05). Compared with the D group, the YLT group exhibited significantly increased serum albumin levels (p < 0.05), along with a tendency toward greater villus height (p = 0.085) and higher serum glucose levels (p = 0.052), indicating an improvement in nutritional and metabolic status Metabolomic analysis identified 260 differentially abundant metabolites between the YLT and D groups (81 upregulated, 179 downregulated), which were predominantly enriched in pathways related to amino acid biosynthesis and metabolism, purine metabolism, and nucleic acid metabolism. Proteomic profiling revealed 571 differentially expressed proteins (237 upregulated, 334 downregulated). Upregulated proteins were mainly involved in arginine biosynthesis and base excision repair, while downregulated proteins were associated with the PPAR signaling pathway and Salmonella infection. In summary, dietary YSL supplementation alters the metabolic and proteomic profiles in the intestines of diarrheic piglets, potentially improving gut barrier function and nutrient utilization. This study offers novel insights into the potential of YSL as a promising feed additive for prevention of post-weaning diarrhea in pigs. Full article