Search Results (1,144)

Background/Objectives: Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, is implicated in the pathogenesis of ulcerative colitis (UC). Tryptophan metabolism and its interaction with the aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2–related factor 2 (Nrf2) axis represent a crucial regulatory network in intestinal homeostasis. This study aimed to investigate whether the probiotic fermentation product postbiotic Nagqu4580 alleviates UC by modulating this network to inhibit intestinal epithelial ferroptosis. Methods: An acute UC model was induced in mice using 4% dextran sodium sulfate (DSS). The therapeutic effects of postbiotic Nagqu4580 were evaluated through disease activity index (DAI), colon length, histopathology, inflammatory cytokines, and intestinal barrier function. Ferroptosis was assessed by measuring lipid peroxidation (MDA, 4-HNE), antioxidant capacity (GSH/GSSG), and expression levels of GPX4 and ACSL4. Serum tryptophan metabolites were profiled using targeted metabolomics, the activation of the AhR/Nrf2 pathway was examined by Western blot, immunofluorescence, and qPCR, and gut microbiota composition was analyzed by 16S rRNA sequencing. Results: Postbiotic Nagqu4580 dose-dependently ameliorated DSS-induced UC in mice, as evidenced by reduced DAI scores, mitigated colon shortening and histological damage, decreased inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored intestinal barrier function by upregulating tight junction proteins (Claudin-1, ZO-1, Occludin). Mechanistically, postbiotic Nagqu4580 inhibited intestinal epithelial ferroptosis by reducing MDA and 4-HNE levels, restoring the GSH/GSSG balance, downregulating ACSL4, and upregulating GPX4. Serum metabolomics revealed that postbiotic Nagqu4580 reshaped tryptophan metabolism, increasing beneficial metabolites such as 5-hydroxyindoleacetic acid (5-HIAA) and decreasing potentially harmful metabolites such as 3-indoxyl sulfate (3-IS). 16S rRNA sequencing further revealed that the postbiotic Nagqu4580 partially reversed DSS-induced gut microbiota dysbiosis, with a slight increase in the abundance of beneficial genera and a significant reduction in the abundance of pro-inflammatory genera. Furthermore, postbiotic Nagqu4580 significantly activated the AhR/Nrf2 signaling pathway, enhancing the expression of AhR, Nrf2, and their downstream antioxidant genes HO-1 and GPX4. Conclusions: Postbiotic Nagqu4580 alleviates UC by inhibiting intestinal epithelial ferroptosis. Our data suggest that this protective effect is associated with the remodeling of gut microbiota-related tryptophan metabolism and subsequent activation of the AhR/Nrf2 antioxidant axis. Our findings highlight the therapeutic potential of postbiotic Nagqu4580 as a postbiotic agent for UC. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness characterised by post-exertional malaise, non-restorative sleep, and cognitive impairment, yet no objective diagnostic biomarkers have been established. Untargeted plasma metabolomics provides a broad view of the biochemical disturbances underlying ME/CFS; however, the high dimensionality of omics datasets and the limited interpretability of conventional classifiers nevertheless hinder translation into clinical practice. This study evaluates three ensemble classifiers—Explainable Boosting Machine (EBM), XGBoost, and LightGBM—for binary ME/CFS classification using plasma metabolomic and lipidomic profiles from 197 participants (106 ME/CFS; 91 healthy controls; 888 features). Feature dimensionality was reduced using a Pareto-Guided Recursive Neural Network (PRNN) pipeline. Model performance was assessed via 50-repeat stratified hold-out validation. EBM achieved the highest accuracy (0.909; 95% CI: 0.868–0.949) and area under the receiver operating characteristic curve (AUC: 0.940; 95% CI: 0.909–0.983), with XGBoost and LightGBM performing comparably. Interpretability analyses revealed that pairwise metabolite interaction terms—particularly proline & indole-3-lactate, tyrosine & N-acetylornithine, and maleic acid & arachidic acid—contributed the greatest discriminative signal. An ablation analysis comparing the full interaction-augmented EBM (AUC = 0.940) with a main-effects-only EBM (AUC = 0.882) confirmed that pairwise metabolite co-variation contributes additional discriminative value beyond individual metabolite levels, implicating amino acid catabolism, tryptophan–kynurenine pathway dysregulation, mitochondrial energy impairment, and lipid remodelling as central pathophysiological features. Global and instance-level explanations jointly demonstrated population-level metabolic signatures alongside individual heterogeneity, highlighting the added clinical value of explainable artificial intelligence (XAI) in metabolomics. These findings support EBM-based metabolomic profiling as an internally validated approach for ME/CFS classification, subject to external validation, calibration assessment, and prospective testing. Full article

Background/Objectives: This study evaluated the effects of a compound probiotic fermented feed (CPFF) containing Lactobacillus plantarum, Bacillus subtilis, yeast, and Aspergillus niger on rumen in vitro fermentation, in situ feed degradation, and growth performance in beef cattle. Methods: We established a control group (CON) and experimental groups with 2%, 4%, and 8% CPFF supplementation for in vitro fermentation. Results: The results indicated that the NH₃-N concentration in the 4% CPFF group was significantly higher than in the other groups (p < 0.001). Similarly, microbial crude protein (MCP) production was significantly greater in the 4% CPFF group compared to the CON group (p = 0.016). The molar proportions of acetate, butyrate, isobutyrate, and valerate were significantly higher in the 2% and 4% CPFF groups than in the control group (p < 0.001), while propionate levels were significantly lower (p < 0.001). After 48 h, gas production was highest in the 4% CPFF group. Based on improvements in gas production, MCP synthesis, and fermentation intensity, the 4% inclusion level was determined to be optimal for further studies. We conducted an in situ degradation trial using 4% CPFF. Results showed that at 12 h, the neutral detergent fiber (NDF) degradation rate in the 4% CPFF group was significantly higher than in the CON group at 4, 8, 12, and 48 h (p < 0.05). At 48 h, the acid detergent fiber (ADF) degradation rate in the 4% CPFF group was also significantly higher than in the CON group (p < 0.001), and this group exhibited a significant increase in crude protein (CP) degradation (p = 0.030). We analyzed rumen fluid samples from both the CON and 4% CPFF groups after in vitro fermentation using 16S rRNA sequencing and untargeted metabolomics. Microbial community analysis revealed significantly increased abundances of functional bacterial groups such as Rikenellaceae_RC9_gut_group, Christensenellaceae_R-7_group, and UCG-002 in the 4% CPFF group (p < 0.05). Differential metabolites were primarily involved in pathways related to tryptophan metabolism, and tyrosine metabolism signaling. A feeding trial was conducted by adding 4% CPFF to the diet of Angus growing cattle. The results indicated that average daily gain (ADG) (p = 0.004) and average daily feed intake (ADFI) (p = 0.001) were significantly higher in the CPFF group than in the CON group. Conclusions: In conclusion, our results demonstrate that CPFF enhances rumen fermentation activity, optimizes the microbiota and metabolic profiles of rumen fluid, and improves the average daily gain of beef cattle. This research provides a valuable theoretical basis for applying CPFF in beef cattle breeding. Full article

Cardiometabolic diseases are increasingly understood as disorders involving compartment-specific redox disruption rather than a uniform excess of reactive oxygen species. This narrative review synthesizes evidence for a proposed gut microbiota–mitochondria ferroptosis framework in which dysbiosis-derived lipopolysaccharide, trimethylamine N-oxide, short-chain fatty acids, bile acids, and tryptophan metabolites may modulate mitochondrial reactive species production, antioxidant defenses, iron handling, lipid peroxide detoxification, and inflammatory signaling. The reference set was assembled through searches of PubMed and Web of Science Core Collection, supplemented by targeted Google Scholar searches and citation chaining during manuscript preparation and revision through June 2026 and was organized around microbial metabolites, mitochondrial redox biology, ferroptosis pathways, disease-specific evidence, and redox-targeted interventions. Because this is a narrative synthesis rather than a systematic review, the framework should be interpreted as hypothesis-generating rather than as a systematically validated pathological model. Across atherosclerosis, diabetic cardiomyopathy, metabolic dysfunction-associated steatotic liver disease, obesity-associated insulin resistance, chronic kidney disease, and cardiorenal metabolic injury, the most consistent mechanistic links involve mtROS, impaired mitophagy, glutathione/GPX4 and SLC7A11 dysfunction, ACSL4-dependent lipid peroxidation, Nrf2 signaling, NLRP3 activation, and cGAS-STING-associated inflammation, although human causal evidence remains uneven. Importantly, much of the current literature supports local links within this sequence rather than a fully verified dysbiosis–metabolite–mitochondria ferroptosis–organ dysfunction chain in the same study. We therefore emphasize evidence tiers, terminology discipline, and biomarker requirements when interpreting ferroptosis-sensitive injury. Polyphenols, flavonoids, probiotics, postbiotics, melatonin, CoQ10-related strategies, mitochondria-targeted antioxidants, and ferroptosis-sensitive approaches may be most translatable when paired with microbiome, metabolomic, lipidomic, pharmacokinetic, and redox biomarkers. Full article

Background/Objectives: Probiotic interventions are widely used to improve intestinal health; however, comparative evidence on multi-strain formulations with different potencies, particularly when combined with plant-based complexes, remains limited. This study evaluated the effects of two probiotic blends containing phytonutrients: PBP1, comprising Lacticaseibacillus strains, and PBP2, comprising Lacticaseibacillus, Lactobacillus, and Bifidobacterium strains. The effects on bowel function, microbial metabolites, and gut barrier-related markers were investigated. Methods: In this randomized, double-blind, placebo-controlled trial, participants received PBP1, PBP2, or placebo for 8 weeks. Stool patterns (7-day Bristol Stool Form Scale (BSFS) diary), fecal short-chain fatty acids (SCFAs), tryptophan metabolites, zonulin, and gut microbiota were assessed at baseline and Week 8. Efficacy was evaluated by comparing each intervention group with the placebo group. Results: Both PBP1 and PBP2 significantly increased the proportion of normal stool types (BSFS types 3–5) compared with placebo (p < 0.05). Fecal SCFA levels, including acetate, propionate, and butyrate, were significantly increased in both intervention groups. Notably, butyrate levels were significantly elevated compared with placebo. Fecal tryptophan levels decreased, while indole metabolites showed increasing trends, with an inverse correlation observed between tryptophan and indole, particularly in the PBP2 group. Fecal zonulin showed a decreasing trend, with significant reductions in participants with 25.0 ≤ BMI < 30.0 kg/m². Microbiome analysis revealed preserved alpha diversity with selective compositional shifts, including enrichment of Lactobacillus-related taxa. Conclusions: Supplementation with PBP1 and PBP2 improved bowel function and was associated with changes in microbiome-derived metabolites, including SCFAs and tryptophan–indole metabolism, with BMI-dependent changes in barrier markers. These findings suggest a potential role of microbiome-mediated metabolic modulation in intestinal health. Full article

Onion peel extract (OPE) is rich in polyphenolic compounds with antimicrobial potential. Salmonella Enteritidis (SE) infection in young broiler chicks causes morbidity, reduced growth, and contributes to human gastroenteritis through contaminated poultry products. The spleen is a key secondary lymphoid organ coordinating systemic responses to pathogens in chicken. This study evaluated how dietary OPE influences spleen metabolic profiles during SE infection. Day-old Ross 708 male chicks (n = 128) were assigned to four treatments: CON, CON-SE, OPE (6 g/kg), and OPE-SE. Chicks in CON and OPE received sterile broth, whereas CON-SE and OPE-SE received 2.25 × 10⁸ CFU/mL SE at 2 d of age. At 5 and 12 dpi, spleens from six chicks per treatment were collected for untargeted HPLC-MS metabolomics. A total of 857 metabolites were identified and analyzed using MetaboAnalyst 6.0 (p < 0.05; fold change ≥ 2.0; VIP score > 1.0). In CON-SE chicks, energy generating metabolites (6-phosphogluconic acid, methylmalonic acid, propionic acid) increased, while 13,14-dihydro-15-keto-prostaglandin D2 and kynurenic acid decreased. Dietary OPE elevated several dipeptides (L-Val-Gly, L-Leu-Gly, Gly-Gly-Leu, L-Val-L-Met) and reduced ATP linked metabolites (3,6-di-O-methyl-beta-D-glucose and 3-O-beta-D-galactosyl-sn-glycerol). Enrichment analysis showed that SE infection altered valine, leucine, and isoleucine degradation and aromatic amino acid biosynthesis, whereas OPE enriched galactose and biotin metabolism in uninfected chicks, but enriched tryptophan, taurine and hypotaurine metabolism in SE-infected chicks. Overall, dietary OPE optimized response of metabolic pathways associated with immune activation, unlike corresponding pathways in CON-SE birds. Full article

Background: Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), but long-term outcomes remain limited by chronic allograft injury, infections, metabolic complications, and cardiovascular risk. Gut microbiota alterations and microbiota-derived metabolites may influence immune regulation, inflammation, drug metabolism, and graft outcomes through the gut–kidney axis. This review summarizes evidence on the gut microbiota in kidney transplantation, emphasizing immune tolerance, complications, cardiovascular risk, graft function, and perspectives. Methods: A structured search was conducted in PubMed, Scopus, and Web of Science to May 2026. Eligible publications included studies involving kidney transplant recipients (KTR), kidney disease or solid organ transplant populations, and mechanistic models. Evidence was synthesized narratively. Results: Gut microbiota alterations in KTR reflect pre-transplant dysbiosis and post-transplant exposures, including antibiotics, immunosuppression, infection, diet, hospitalization, and graft function. Dietary factors and nutrient-derived substrates may modulate microbial composition and production of relevant metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), tryptophan-derived compounds, bile acid derivatives, and uremic toxins. Microbiota-related pathways may involve barrier dysfunction, microbial translocation, innate immune activation, altered regulatory T cell/T helper 17 (Treg/Th17) balance, metabolite signaling, uremic toxin generation, and endothelial stress. Clinical studies associate dysbiosis and microbial metabolites with diarrhea, infections, delayed graft function (DGF), rejection-related shifts, tacrolimus variability, cardiovascular risk, graft dysfunction, graft failure, and mortality. Most findings need validation. Conclusions: Gut microbiota signatures and microbial metabolites are promising markers of transplant-related risk, but not established causal determinants or therapeutic targets. Clinical translation requires standardized methods, multi-omics integration, and prospective patient- and graft-centered trials. Full article

Autoimmune and immune-mediated inflammatory diseases (IMIDs) develop when genetically and environmentally susceptible hosts lose stable immune tolerance. The gut ecosystem is increasingly recognized as a biologically active interface in this process. Its bacterial, fungal, and viral components may shape mucosal and systemic immunity through antigenic stimulation, barrier regulation, and metabolite-dependent signaling, although the strength of evidence is uneven: bacteriome data are currently the most mature, whereas mycobiome, virome, and phageome findings remain more disease-specific and emerging. Dysbiosis may influence autoimmunity through overlapping routes, including epithelial barrier failure, altered short-chain fatty acid, bile acid, and tryptophan metabolism, molecular mimicry, and cross-kingdom microbial interactions. Nutrition is central to this network because dietary substrates determine microbial growth, metabolic output, epithelial integrity, and immune-cell differentiation. In this narrative review, we integrate evidence on disease-associated bacteriome, mycobiome, and virome patterns in systemic autoimmune diseases, with emphasis on rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome, systemic sclerosis, spondyloarthritis, vasculitides, and idiopathic inflammatory myopathies. COVID-19 is considered not as a proven causal driver of autoimmunity, but as an example of an environmental and infectious insult capable of perturbing microbiome–barrier–immune communication. Finally, we discuss diet-based and microbiome-targeted approaches, including probiotics, prebiotics, synbiotics, and postbiotics, as adjunctive strategies that may help restore microbial resilience and immune balance. A better understanding of the diet–microbiome–host immunity axis may support more personalized preventive and therapeutic concepts in autoimmune disease. Full article

Cognitive frailty, characterized by the coexistence of physical frailty and cognitive impairment, has emerged as a major challenge in aging populations and is closely linked to sarcopenia, neurodegeneration, and chronic inflammation. Increasing evidence suggests that the gut microbiota acts as a central regulator of neuromuscular and neurocognitive aging through the integrated gut–brain–muscle axis. This review highlights how microbial dysbiosis, reduced short-chain fatty acid (SCFA) production, systemic endotoxemia, and altered microbial metabolites contribute to mitochondrial dysfunction, neuroinflammation, anabolic resistance, and impaired neuroplasticity. Key signaling mediators, including SCFAs, bile acids, tryptophan-derived metabolites, cytokines, and myokines such as irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B, orchestrate bidirectional communication among the gut, skeletal muscle, and brain. We further discuss the role of exercise-induced microbiota remodeling and muscle endocrine signaling in promoting mitochondrial biogenesis and cognitive resilience. In addition, emerging translational strategies including probiotics, prebiotics, postbiotics, polyphenol-rich functional foods, marine bioactives, and precision nutrition are explored as potential interventions targeting this axis. Collectively, the gut–brain–muscle axis provides a novel systems biology framework for understanding cognitive frailty and developing integrated therapeutic strategies for healthy longevity. Full article

As a precious indigenous goose resource in China, the Zhedong white goose occupies an essential position in the domestic goose industry. However, this breed spontaneously enters a prolonged non-laying period of over two months per year, which greatly limits egg production capacity and restricts the economic development of the goose industry. Herein, this study systematically compared serum physiological indices and serum and fecal metabolome, as well as fecal microbial communities, between laying and non-laying Zhedong white geese, aiming to reveal the key regulatory mechanisms underlying reproductive stage transition. Physiological analyses indicated that non-laying geese had higher serum levels of GnRH, PRL, APOA, and T-AOC, whereas the concentrations of LH, E₂, TNF-α, IL-1, and calcium were significantly reduced; FSH, PROG, and BA levels showed no significant differences between the two groups. Metabolomic analysis identified 277 upregulated and 403 downregulated DAMs in feces, and 386 DAMs in serum. The shared enriched pathways across serum and fecal samples encompassed arginine biosynthesis, histidine metabolism, and pantothenate and CoA biosynthesis, as well as steroid hormone biosynthesis. A total of 120 DAMs overlapped in two specimens, and the non-laying geese presented pronounced depletion of tryptophan-derived metabolites and steroid hormone-related metabolites. Metagenomic results showed no significant difference in gut microbial alpha diversity between groups, while their microbial community structures were clearly differentiated. A total of 774 upregulated and 854 downregulated microbial species were screened in non-laying geese, and these differential microbes were primarily enriched in pathways associated with reproductive hormone signaling, steroid biosynthesis and energy metabolism. Multi-omics correlation analysis verified close associations between differential microbes and reproductive-related metabolites. Certain probiotic strains, including Pediococcus pentosaceus and Lactococcus raffinolactis, were positively correlated with steroid hormones and tryptophan metabolites, and their abundances declined obviously in the non-laying stage. Collectively, this study elaborates the holistic changes in serum biochemistry, gut metabolome and microbiome in geese at different reproductive stages. The dysregulation of amino acid and steroid hormone metabolism, combined with the loss of beneficial intestinal microbes, jointly induces the non-laying phenotype. This study provides new perspectives for understanding the gut–reproductive axis and supplies promising biomarkers to improve the laying performance of geese. Full article

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and one of the leading causes of cancer-related mortality globally, with its incidence increasingly driven not only by viral hepatitis and alcohol-related etiologies but also by metabolic dysfunction-associated steatotic liver disease. Dietary intake can modify gut microbial activity and the production of microbial metabolites, which in turn may regulate hepatic immune signaling and metabolic pathways along the gut–liver axis. Microbiota-derived metabolites have emerged as important immunometabolic mediators linking dietary factors to hepatic immune responses and metabolic reprogramming. These metabolites, which have been shown to influence hepatic immune cell function and inflammatory signaling, include short-chain fatty acids, secondary bile acids, and tryptophan-derived indoles. Changes in the production and composition of these metabolites have been associated with immune dysregulation, chronic inflammation, and metabolic reprogramming that promote hepatocellular carcinoma development. This review highlights how diet–microbiota interactions reshape hepatic immunometabolism and discusses their potential translational relevance for prevention and therapeutic strategies in hepatocellular carcinoma. Full article

Inflammatory bowel disease (IBD; Crohn’s disease and ulcerative colitis) arises from convergent dysfunction of the epithelial barrier, mucosal immunity, and gut microbiome on a background of genetic susceptibility and environmental exposures. Diet is among the most modifiable of these exposures, yet much of the diet–microbiome research in IBD remains descriptive and poorly aligned with the molecular pathways linking food to mucosal effects. This comprehensive review reframes the field around functional dysbiosis, in which altered microbial metabolic capacity (rather than taxonomic shifts alone) drives disease-relevant biology. We trace how dietary substrates and additives are converted by gut microbes into bioactive metabolites (short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, sulfur compounds, and polyphenol-derived molecules) and map these to host receptors and signaling pathways governing barrier function, mucus and antimicrobial peptide production, and Treg/Th17 balance. Defined dietary therapies (exclusive enteral nutrition, the Crohn’s disease exclusion diet plus partial enteral nutrition, and Mediterranean-style patterns) are reinterpreted as interventions that reshape microbial metabolic output, and candidate biomarkers for microbiome-informed precision nutrition are evaluated. Microbiota-derived metabolites provide the molecular interface between diet and mucosal immunity in IBD; personalized dietary algorithms remain a research goal, not a validated clinical tool, and diet is best framed as adjunctive to pharmacotherapy and dietitian care. Full article

Tryptophan (TRP) metabolism has emerged as a critical interface linking inflammation, immune regulation, oxidative stress, and cellular energetics. The kynurenine pathway, the predominant route of TRP degradation, is highly responsive to inflammatory stimuli and generates a spectrum of bioactive metabolites with divergent and context-dependent biological effects. Indoleamine 2,3-dioxygenase 1 (IDO1)-mediated TRP catabolism integrates immune activation with downstream metabolic signaling, influencing redox homeostasis, endothelial function, and mitochondrial energetics, in part by regulating nicotinamide adenine dinucleotide (NAD⁺) synthesis. Alterations in TRP metabolism are consistently observed across cardiometabolic diseases, including obesity, type 2 diabetes (T2D), atherosclerosis, myocardial infarction (MI), and heart failure with preserved ejection fraction (HFpEF), where they are associated with disease severity and adverse outcomes. Importantly, emerging data suggest that cardiometabolic phenotypes are determined not by pathway activation alone, but by the relative distribution of flux across downstream metabolic branches. Depending on the tissue compartment and stage of the disease, different biological effects may be contributed by redox-active kynurenine 3-monooxygenase (KMO)/3-hydroxykynurenine (3-HK)/quinolinic acid (QA) pathways, 3-hydroxyanthranilic acid (3-HAA)-mediated lipid and inflammasome regulation, microbiome-derived indoles, and NAD⁺-generating pathways. This review synthesizes current evidence using a branch-specific and context-dependent framework. We discuss the utility and limitations of the kynurenine-to-tryptophan ratio (KTR) as an upstream biomarker, the need for downstream metabolite panels, and therapeutic opportunities aimed at pathway modulation rather than broad inhibition. Future studies integrating temporal profiling, spatial and cell-specific approaches, large-animal models, and pathway-informed clinical trials will be essential to define causal mechanisms and enable precision therapeutic translation. Full article

Indole, a volatile metabolite produced by bacterial tryptophanase (encoded by tnaA) during tryptophan metabolism, contributes to oral malodor and may influence the progression of periodontitis. However, the genetic features underlying strain-specific indole production and its association with bacterial virulence remain unclear. Analysis of a previously published periodontitis cohort revealed that periodontitis severity was associated with salivary indole-related metabolic signatures, which were positively correlated with the abundance of Porphyromonas gingivalis (P. gingivalis). Further analysis showed that W83, a reference strain previously reported to exhibit relatively high virulence-associated characteristics, produced significantly higher levels of indole than ATCC 33277 under the experimental conditions. Comparative genomic analysis of 36 complete P. gingivalis genomes showed that the amino acid sequences of TnaA were highly conserved. However, the transposase region adjacent to tnaA differed among strains: previously reported high-virulence strains, including W83, W50, and A7436, harbored the IS5-family transposase ISPg1, whereas several low-virulence reference strains carried the IS982-family transposase IS195. In saliva samples from periodontitis patients, ISPg1 expression was positively correlated with tnaA expression, and both were associated with periodontal clinical parameters. Together, these findings indicate that transposase-associated genomic variation near tnaA is associated with strain-specific tryptophan-indole metabolism, virulence-associated gene expression, and periodontal clinical parameters, while direct causality remains to be established in future functional studies. Full article

Growing evidence indicates that the gut microbiota is not a static ecosystem but a rhythmic metabolic organ whose oscillatory activity is tightly coordinated with host circadian biology. Disruption of this temporal alignment, through irregular diet, sleep disturbance, shift work, or social jet lag, may profoundly alter microbial composition and the production of neuroactive metabolites. These alterations have emerged as potential contributors to the pathophysiology of mood disorders. This review introduces the concept of chrono-metabolic psychiatry, a framework integrating circadian rhythms, gut microbiota dynamics, and host metabolic signaling in the development and course of depressive and bipolar disorders. In this framework, the term “chrono-metabolic” refers to the integration of biological timing, host metabolic regulation, and microbiota-derived metabolic signaling. Chrono-metabolic psychiatry therefore shifts the focus from static dysbiosis or neurotransmitter imbalance alone to the time-dependent interactions among circadian misalignment, microbial rhythmicity, immune regulation, metabolite production, and affective instability. Diurnal fluctuations in short-chain fatty acids, tryptophan–kynurenine metabolites, bile acids, and microbial-derived neurotransmitters interact with clock gene regulation, hypothalamic–pituitary–adrenal axis activity, neuroinflammation, and synaptic plasticity. Chrono-disruption may represent a transdiagnostic vulnerability factor and may confirm the bidirectional relationship between mood instability and microbiota rhythmicity. Emerging therapeutic implications, including chrono-nutrition, time-restricted feeding, targeted probiotic administration (“chronobiotics”), and the microbiota-modulating effects of psychotropic medications are discussed. By shifting from a compositional to a temporal–metabolic perspective, this model highlights the importance of microbial oscillations rather than static dysbiosis alone. Integrating circadian biology into microbiota research may enable metabolomic stratification and pave the way for precision psychiatry approaches grounded in host–microbe metabolic crosstalk. Future longitudinal and time-resolved multi-omics studies are needed to validate this framework and to translate it into clinically actionable interventions. Full article