PubMed

Front Endocrinol (Lausanne). 2026 Feb 16;17:1755982. doi: 10.3389/fendo.2026.1755982. eCollection 2026.ABSTRACTINTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a global epidemic with an unclear etiology and no effective therapeutic options. Disruption of the gut-liver axis driven by intestinal dysbiosis is closely implicated in MAFLD pathogenesis, making gut microbiota-targeted probiotic interventions promising preventive strategies.METHODS: Lacticaseibacillus rhamnosus B6, a probiotic strain isolated from homemade Bulgarian fermented milk, synthesizes immunomodulatory macromolecules and regulates the intestinal flora. In the present study, we comprehensively investigated the colonization ability and MAFLD-alleviating effects of L. rhamnosus B6 in a high-fat diet (HFD)-induced murine MAFLD model using an integrated approach encompassing metagenomics, untargeted metabolomics, serum biochemical assays, and liver histopathological analysis.RESULTS: Supplementation with L. rhamnosus B6 markedly decreased the relative abundance of Cupriavidus, Desulfovibrionaceae, and Enterobacteriacea, and inhibited the predicted lipopolysaccharide (LPS) synthesis pathway, thereby suppressing the inflammatory response. Furthermore, L. rhamnosus B6 intervention elevated unsaturated fatty acid levels by modulating lipid metabolic pathways, specifically mitochondrial β-oxidation of long-chain saturated fatty acids, α-linolenic acid, linoleic acid, and sphingolipid metabolism, while downregulating predicted myo-inositol degradation pathways, collectively contributing to MAFLD alleviation. In vitro, the metabolites of L. rhamnosus B6 exerted potent inhibitory activity against LPS-producing bacteria (e.g., Escherichia coli and Salmonella enterica).DISCUSSION: These findings demonstrate that L. rhamnosus B6 is a promising probiotic for MAFLD alleviation via dual mechanisms of attenuating inflammation and regulating lipid metabolism. This study provides compelling evidence for the specific protective effects of L. rhamnosus B6 against MAFLD and offers a novel probiotic-based therapeutic strategy for MAFLD.PMID:41778161 | PMC:PMC12950561 | DOI:10.3389/fendo.2026.1755982

Front Cell Infect Microbiol. 2026 Feb 16;16:1675560. doi: 10.3389/fcimb.2026.1675560. eCollection 2026.ABSTRACTINTRODUCTION: Gestational diabetes mellitus (GDM) affects 6% to 15% of pregnancies globally, as a severe metabolic disorder that impairs offspring health. Mounting evidence highlights the critical role of gut microbiota in metabolic regulation, yet the causal relationship between gut microbiota and GDM pathogenesis remains unclear. This study aimed to clarify this causal link and explore the underlying mechanisms.METHODS: An innovative human microbiota transplantation approach was adopted. Gut microbiota from GDM patients was transplanted into antibiotic-treated C57BL/6J mice. 16S rRNA sequencing was used to analyze the structural changes of gut microbiota in recipient mice, and metabolomics was employed to detect changes in circulating bile acid levels. For mechanism exploration, Luminex assay was used to detect multiple inflammatory factors, enzyme-linked immunosorbent assay (ELISA) was applied to measure lipopolysaccharide (LPS) levels, and Western blot (WB) was utilized to determine the expression of intestinal barrier protein.RESULTS: Transplantation of gut microbiota from GDM patients directly induced glucose intolerance in pregnant antibiotic-treated C57BL/6J mice. 16S rRNA sequencing showed significant structural reorganization of the gut microbiota in GDM microbiota recipients, characterized by decreased abundance of Lachnospiraceae_FCS020_group and increased abundance of Akkermansia, Faecalibaculum, and Bilophila. These microbiota dysregulations led to reduced expression of the intestinal barrier protein Claudin-1, elevated serum lipopolysaccharide (LPS) levels, and increased resistin and matrix metalloproteinase 9 (MMP-9) levels. Metabolomic analysis revealed decreased circulating primary bile acids (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary bile acid deoxycholic acid (DCA). Correlation analysis indicated a positive correlation between Faecalibaculum and DCA, CDCA, as well as resistin. DCA and CDCA were significantly negatively correlated with HOMA-IR, while resistin was significantly positively correlated with GTT-AUC, FINS, and HOMA-β%.CONCLUSION: These findings suggest that the imbalance in bile acid metabolism and mild inflammatory response caused by dysregulated gut microbiota is an adjustable environmental driving factor in the pathophysiological process of GDM.PMID:41778019 | PMC:PMC12950734 | DOI:10.3389/fcimb.2026.1675560

Front Mol Biosci. 2026 Feb 16;13:1760710. doi: 10.3389/fmolb.2026.1760710. eCollection 2026.ABSTRACTINTRODUCTION: Gestational diabetes mellitus (GDM) is among the most common metabolic disorders during pregnancy, and early detection is key to reducing complications for both mother and child. Mass spectrometry-based metabolomics enables detailed metabolite profiling, offering opportunities not only for early diagnosis and risk prediction but also for understanding the pathophysiological mechanisms that drive the development of GDM.METHODS: For the first time, an analysis of such a large number of metabolites was conducted: over 1,000 metabolites across 39 biochemical classes, including 912 lipids and 107 small molecules, were measured in first-trimester plasma from women with abnormal or normal fasting plasma glucose who later developed GDM, as well as from controls with normal glucose tolerance. Statistical analyses included Kruskal-Wallis ANOVA with Conover-Iman post hoc tests, Wilcoxon signed-rank tests for longitudinal changes, and ROC analysis to assess predictive and diagnostic performance. Spearman's rank correlations were used to examine relationships between metabolites and clinical parameters.RESULTS: Distinct metabolic signatures in the first trimester were associated with later GDM development. A prognostic panel, including TG (18:1_36:6), Hex2Cer(d18:1/14:0), valine, PS(36:1), TG (17:2_36:3), p-cresol sulfate, and PC(O-42:4), accurately predicted GDM (AUC = 0.934). A diagnostic panel comprising PE (P-18:0/22:4), glycine-conjugated cholic acid, LPC (20:3), carnitine esters, and arginine detected early signs of carbohydrate metabolism issues (AUC = 0.821). Women with normal fasting glucose who later developed GDM exhibited significant lipid alterations, whereas those with early fasting irregularities showed a partially GDM-like profile. Correlation analyses revealed distinct inflammatory and hormonal networks, with TNF-α-induced lipid remodelling linked to early dysglycaemia.CONCLUSION: First-trimester metabolomic signatures hold significant promise for early prediction, diagnosis, and understanding of GDM, enabling personalised risk assessment and timely intervention during pregnancy.PMID:41777670 | PMC:PMC12950703 | DOI:10.3389/fmolb.2026.1760710

Front Mol Biosci. 2026 Feb 16;13:1755542. doi: 10.3389/fmolb.2026.1755542. eCollection 2026.ABSTRACTINTRODUCTION: Rheumatoid arthritis (RA) is a complex progressive autoimmune disorder wherein chronic inflammation is tightly coupled to metabolic reprogramming. The known diagnostic markers are not sensitive and specific enough to reflect disease activity. Finding a metabolomics-based biomarker specific for established cases of RA is important. This study aimed to investigate the metabolomic profiles of patients with established RA compared to those of controls.METHODS: An untargeted high resolution mass spectrometry (MS)-based metabolomics approach with bioinformatics analysis was used to analyze 122 plasma samples, patients (n = 60), and controls (n = 62).RESULTS: A total of 300 significantly dysregulated metabolites (unpaired t-test with FDR q value < 0.05, FC cut off 1.5) were identified between RA and controls, where 147 were upregulated and 153 downregulated. From among these, 182 metabolites were identified and annotated and after excluding the exogenous metabolites 60 endogenous metabolites were successfully identified. Results from the OPLSDA model showed a clear separation between patients with RA and controls (Q2 = 0.736, R2 = 0.988), indicating significant metabolic differences between the groups. The plasma metabolomics profile revealed statistically significant changes in metabolites belonging to different classes including those involved in lipid (including Succinyladenosine, CDP- DG (PGE2/i-19: 0), PGP (i-24:0/PGD2), Octadecenoylcarnitine), amino acid (including L-Isoleucine, Cysteinyl-Serine), and nucleotide (Inosine, N6-Methyladenosine), metabolisms in RA patients, consistent with immune-metabolic dysregulation. Bioinformatics and network pathway analysis using IPA showed interconnectedness between the metabolites centered around IL-6, IL-2, IL-1, MAPK, and kininogen. The pathways most affected between RA and controls included humoral immune response, inflammatory response, hematological system development, and function. The identified metabolites influenced eicosanoid/kinin signaling, nucleic acid-mediated innate immune activation, mitochondrial dysfunction, and altered glycosylation. Subgroup analysis based on stratification using erythrocyte sedimentation rate (ESR) above 35 mm/h identified 67 metabolites that differentiated patients with high versus low ESR. Among these, three metabolites, namely, cysteinyl-serine (upregulated), tyrosyl-arginine and N2-acetyl N6-methyllysine (downregulated) overlapped with the metabolites identified in the comparison between RA and controls, suggesting links between specific metabolic changes and systemic inflammation.CONCLUSION: Our findings support the potential of plasma metabolomics for phenotyping and highlight potential candidate biomarkers for disease prognosis and monitoring in RA.PMID:41777668 | PMC:PMC12950679 | DOI:10.3389/fmolb.2026.1755542

Food Chem X. 2026 Feb 21;34:103681. doi: 10.1016/j.fochx.2026.103681. eCollection 2026 Feb.ABSTRACTThis integrated multi-omics study (metabolomics, lipidomics, proteomics) compared the compositions of bovine, caprine, ovine, porcine, and human milk. Human milk is defined by a unique microenvironment where complex human milk oligosaccharides and immune regulating small molecules act together. Components like Lnnt and Lnfp iii form interactive networks, which help modulate both gut microbiota and the immune system. Porcine milk contributes to neural development and immune function. It is rich in polar phospholipids and polyunsaturated fatty acids such as docosahexaenoic acid, important for neural structure and function. Porcine milk also contains specifically high levels of immunoglobulins, including IgM and IgG. In contrast, ruminant milks like bovine and caprine milk show a distinct composition, with high levels of certain functional proteins and active metabolites, such as xanthine dehydrogenase, osteopontin, and allantoin. These findings provide new insights for the precise development of better bovine milk based infant formula and animal milk replacers.PMID:41777635 | PMC:PMC12950474 | DOI:10.1016/j.fochx.2026.103681

Food Chem X. 2026 Feb 21;34:103692. doi: 10.1016/j.fochx.2026.103692. eCollection 2026 Feb.ABSTRACTPukeng tea (PKT), a traditional Chinese dark tea, has been consumed for centuries, yet its volatile and microbial dynamics remain unclear. This study integrated metabolomics, chemometrics, and microbiome analysis to explore PKTs with 3-20 years of storage. HS-SPME-GC-MS identified 189 volatiles, mainly alcohols, aldehydes, and ketones. PCA and PLS-DA revealed distinct metabolite patterns, with 46 differential volatiles, such as 1-butanol and 1-penten-3-ol, characterized as potential discriminants among PKT samples. Microbiota analysis showed 11 dominant bacterial genera, shifting from Firmicutes in early storage to Actinobacteriota in later stages, while Aspergillus dominated fungal communities. Correlation analysis revealed significant associations between dominant microbes such as Staphylococcus and Saccharopolyspora and aroma-active volatiles, suggesting microbial contributions to PKT's evolving flavor. This study provides the first integrated characterization of volatile and microbial diversity in PKT, offering insights into quality control, product authentication, and functional microbe discovery for the sustainable development of traditional dark teas.PMID:41777631 | PMC:PMC12950448 | DOI:10.1016/j.fochx.2026.103692

JHEP Rep. 2025 Dec 2;8(3):101703. doi: 10.1016/j.jhepr.2025.101703. eCollection 2026 Mar.ABSTRACTBACKGROUND & AIMS: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in patients with metabolic dysfunction-associated steatohepatitis (MASH). No therapy targets both diseases simultaneously, and a roadblock for discovering new treatments is the lack of animal models that recapitulate both diseases, especially in females.METHODS: Male and female Ldlr -/- mice (n = 8-13) were fed a western diet (WD), modified choline-deficient high-fat diet (mCDHFD), or modified MASH-inducing diet (mMASHD) containing equivalent physiological levels of cholesterol. Comprehensive multiomics including metabolomics, lipidomics, and transcriptomics, alongside histopathological and biochemical analyses, were integrated to characterize concurrent MASH and atherosclerosis. Transcriptomics was validated in other mouse models and integrated with human data (n = 79).RESULTS: While mCDHFD induced MASH-fibrosis in both sexes, WD was effective only in males, whereas mMASHD primarily affected females. mCDHFD induced concurrent MASH and atherosclerosis in both sexes, while WD effectively recapitulated disease co-occurrence only in males. Correlation analyses highlighted links between MASH and atherosclerosis, identifying circulating cholesterol and C-C motif chemokine ligand 2 (CCL2) as potential predictors of coexisting disease (p <0.04). Integrated metabolomic and transcriptomic analyses identified arginine-proline, glycine-serine, glutathione, and sphingolipid metabolism (p <0.03) as key dysregulated pathways, with sphinganine emerging as a predictor of disease severity. Hepatic itaconate and lactate levels were positively correlated with disease severity, whereas glycine, carnitine, 2-aminomuconic acid, and thiamine pyrophosphate were negatively associated (p <0.04). Lipidomic analyses revealed dysregulated polyunsaturated fatty acid, steryl ester, and dihexosylceramide metabolism. Integration of mouse and human transcriptomes revealed similarities in metabolic and proinflammatory/proatherogenic pathways.CONCLUSION: This sex-based multiomics analysis establishes a murine model of concurrent MASH and atherosclerosis, reveals sex-specific dietary responses, and identifies metabolic and transcriptional pathways with potential utility as biomarkers and therapeutic targets.IMPACT AND IMPLICATIONS: This study addresses the critical need for an animal model that replicates both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerotic cardiovascular disease, particularly in females, to facilitate therapeutic development. Using male and female Ldlr -/- mice, we found that different diets containing equivalent physiological levels of cholesterol induce sex-specific responses, with a modified choline-deficient high-fat diet effectively modeling both diseases in both sexes, while a western diet is effective only in males. Multiomics analyses identified key metabolic and inflammatory pathways linking MASH and atherosclerosis that mirror transcriptomic signatures found in humans, and highlight circulating cholesterol, CCL2, and sphinganine as potential biomarkers. These findings establish a translational model and reveal sex-specific metabolic pathways that will advance our understanding of the shared pathophysiology of MASH and atherosclerosis, and facilitate the development of dual therapeutic approaches, addressing an urgent unmet clinical need.PMID:41777553 | PMC:PMC12950431 | DOI:10.1016/j.jhepr.2025.101703

Food Chem X. 2025 Nov 19;32:103299. doi: 10.1016/j.fochx.2025.103299. eCollection 2025 Dec.ABSTRACTThe Bamei pig, an indigenous Chinese breed renowned for meat quality, remain poorly characterized for fermentation processing performance. The aim of this study was to compare the effects of Pure Bamei Pigs and its binary, ternary crossbred pork on physicochemical properties, microbiota, and flavor of fermented sausages. Ternary sausages exhibited the best sensory scores, the lowest water activity (Aw) and the richest profiles of olefins and esters. Metabolomics analyses showed that the most significant metabolic differences among the three groups of sausages centered on lipid metabolism. The polyunsaturated fatty acid contents, especially linoleic acid, were significantly higher in crossbred pork sausages than in Pure Bamei sausages. Microbiota analysis identified Lactobacillus and Leuconostoc were the core functional genera, was positively related to with fatty acid composition, ester alcohols, and terpenoids. Overall, ternary-cross Bamei pork is recommended as an optimal raw material for fermented Chinese sausages.PMID:41777418 | PMC:PMC12951228 | DOI:10.1016/j.fochx.2025.103299

Front Plant Sci. 2026 Feb 16;17:1766818. doi: 10.3389/fpls.2026.1766818. eCollection 2026.ABSTRACTThis study aims to investigate the pattern of dynamic leaf color changes (red-green-red) in red-leaf cotton under drought stress and rewatering, and to reveal the underlying molecular and biochemical mechanisms. Integrated transcriptomics and metabolomics analyses, combined with weighted gene co-expression network analysis (WGCNA), were employed to systematically study the physiological, gene expression, and metabolite changes in red-leaf cotton under mild drought, severe drought, and after rewatering. Under mild drought stress, red-leaf cotton accumulated higher levels of anthocyanins while maintaining relatively good photosynthetic performance, demonstrating an effective photoprotective response. In contrast, severe drought stress led to a significant decrease in anthocyanin content, accompanied by sharply reduced water retention and photosynthetic capacity, indicating a shift in physiological strategy towards survival priority. After rewatering, red-leaf cotton reactivated the flavonoid biosynthesis pathway, gradually restored anthocyanin synthesis, and showed clear phenotypic recovery. Transcriptomic analysis revealed the reprogramming of gene expression related to anthocyanin synthesis and drought tolerance pathways. Metabolomic analysis identified metabolites such as phenylalanine and 2-hydroxyquinoline, which provide precursors for anthocyanin synthesis.The research indicates that red-leaf cotton responds to drought and rewatering by dynamically regulating the flavonoid synthesis and metabolic network, demonstrating robust metabolic repair and stress memory capabilities. These mechanisms provide important theoretical support for breeding drought-resistant cotton varieties.PMID:41777400 | PMC:PMC12951637 | DOI:10.3389/fpls.2026.1766818

Front Plant Sci. 2026 Feb 16;17:1771986. doi: 10.3389/fpls.2026.1771986. eCollection 2026.ABSTRACTChemical diversity is crucial for plant ecological adaptation and nutritional value. In kiwifruit, secondary metabolites such as terpenoids influence key traits such as flavor and nutraceutical properties, however, their diversity across different species and cultivars remains poorly characterized. This study employed UPLC-MS/MS-based metabolomics to profile terpenoids in five varieties representing both Actinidia chinensis (cultivars 'Guichang', GC; 'SunGold', SG; and a wild type, WL) and Actinidia arguta (cultivars 'Maolvfeng', LC; 'Danyang', DY). We identified 309 terpenoids, revealing profound diversity. Notably, the commercial A. chinensis 'SunGold' (SG) and A. arguta 'Danyang' (DY) exhibited the highest total terpenoid content, while SG uniquely possessed a soluble sugar content 2.4 to 6 times greater than other varieties. Both varieties also showed the strongest antioxidant capacity (455.20 and 438.91 µg TE/g FW, respectively), suggesting their superior nutraceutical potential. Multivariate analysis confirmed distinct terpenoid fingerprints, with DY enriched in ursane-type triterpenes e.g., pomolic acid, 1-oxo-siaresinolic acid, camellisin B, and siegesbeckic acid, while SG was uniquely abundant in seco-iridoids like geniposide (442-fold higher than WL). Within A. chinensis, the cultivated 'Guichang' (GC) showed a significant suppression of most triterpenoids compared to its wild relative (WL), demonstrating a possible breeding or selection effect. Our findings demonstrate that terpenoid profiles are likely influenced by genetic background, both at the species and cultivar level, providing a metabolic roadmap for the targeted breeding of kiwifruit with optimized health, nutraceutical, and sensory properties.PMID:41777397 | PMC:PMC12950792 | DOI:10.3389/fpls.2026.1771986

J Multidiscip Healthc. 2026 Feb 26;19:572089. doi: 10.2147/JMDH.S572089. eCollection 2026.ABSTRACTImmune checkpoint inhibitors (ICIs) have reshaped oncology, yet overall response rates remain modest and resistance is common, driven by tumor heterogeneity and evolving tumor-immune crosstalk. Established biomarkers (PD-L1, tumor mutational burden, microsatellite instability) provide incomplete prediction. Multi-omics profiling across genomic, transcriptomic, proteomic, epigenomic, metabolomic and microbiomic layers offers a systems-level view of malignant and immune states, uncovering determinants of ICI efficacy such as lineage plasticity, stromal remodeling, immunometabolic reprogramming and microbiome-associated immune modulation. Artificial intelligence (AI) is uniquely positioned to fuse these heterogeneous data, learn non-linear cross-layer signatures, and enable interpretable predictions using approaches such as SHAP and Grad-CAM. Representative models link routine histology or imaging to molecular phenotypes, stratify patients beyond single biomarkers, and may nominate rational combinations that target oncogenic pathways, lactate-driven immune suppression, or the gut microbiome. In this narrative review, we synthesize recent AI-multi-omics advances for response modeling, immune-relevant tumor subtyping, and clinical translation, including radiomics/pathomics integration and liquid-biopsy-based monitoring, as well as emerging applications in toxicity risk prediction. We also discuss barriers to implementation-platform heterogeneity, limited prospective validation, bias, interpretability and cost-and outline future directions, including single-cell and spatial multi-omics integration, federated learning and generative modeling to improve robustness and equity of precision immunotherapy.PMID:41777263 | PMC:PMC12951862 | DOI:10.2147/JMDH.S572089

Ying Yong Sheng Tai Xue Bao. 2026 Feb;37(2):389-398. doi: 10.13287/j.1001-9332.202602.007.ABSTRACTWe simulated drought through 50% isolated rainfall exclusion and collected fine root exudates of Cunninghamia lanceolata during dry and wet seasons. Combined with total organic carbon (TOC) measurements and untargeted metabolomics (LC-MS) analysis, we investigated the seasonal responses of exudation rate and chemical composition of fine root exudates to drought stress. The results showed that there were significant seasonal variations in drought effects on root exudates. During dry season, the unit root length exudation rate and TOC concentration of root exudates decreased by 72.7% and 74.6%. In wet season, they increased by 58.0% and 35.4%, respectively. Organic acids, phenols, and amino acids were the dominant types in the root exudates under drought conditions. In dry season, defensive secondary metabolites such as phenols (e.g., phloroglucinol), flavonoids (e.g., catechin), and phenolic compounds (e.g., methyl mandelate) significantly increased, contributing to enhanced antioxidant capacity and regulation of rhizosphere microbial communities. In contrast, primary metabolites like sugars (e.g., glucose, deoxyribose) and organic acids (e.g., palmitic acid, 2-methylglutaric acid) significantly increased in wet season, promoting osmotic regulation and soil nutrient activation in C. lanceolata. Our results suggest that C. lanceolata adopts a "dry season defense, wet season attack" carbon allocation strategy to cope with drought stress, employing "conservative defense" through defensive secondary metabolites in dry season and "active adaptation" via resource-acquisitive primary metabolites in wet season.PMID:41777193 | DOI:10.13287/j.1001-9332.202602.007

Physiol Rep. 2026 Mar;14(5):e70774. doi: 10.14814/phy2.70774.ABSTRACTHuman milk contains multiple bioactive components, many of which are influenced by the mother's nutritional status. To identify the impact of maternal vitamin D status on neuroactive compounds, we conducted a post hoc analysis of breast milk and matched infant stool samples from mothers categorized as sufficient or deficient for vitamin D. Neuroactive metabolites were quantified using both targeted and nontargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS). Our findings revealed that breast milk from mothers with sufficient vitamin D levels contained significantly higher concentrations of tryptophan, phenylalanine, and tyrosine compared to milk from mothers with lower vitamin D levels. No significant differences were observed in tryptamine, kynurenine, kynurenic acid, anthranilic acid, quinolinic acid, tyramine, dopamine, epinephrine, or norepinephrine between the two groups. Among SCFAs and other acids, only hexanoic acid was significantly elevated in the breast milk of mothers with sufficient vitamin D. A nontargeted metabolomics analysis of infant stool identified distinct metabolite profiles, where oleamide, vaccenic acid, lacto-N-triaose, and N-acetyl-D-glucosamine varied according to maternal vitamin D levels, indicating that maternal nutrient status may influence the infant gut metabolome. These findings suggest that maternal vitamin D status is associated with neurotransmitter precursor levels in breast milk and a distinct metabolomic profile of infant stool.PMID:41776817 | DOI:10.14814/phy2.70774

Eur J Med Res. 2026 Mar 3. doi: 10.1186/s40001-026-04102-8. Online ahead of print.ABSTRACTBACKGROUND: The human gut mucosal microbiota is crucially involved in colorectal cancer (CRC) development. However, a comprehensive analysis of host-microbiota interactions remains limited.METHODS: Intestinal mucosal samples were collected from patients admitted to the Affiliated Suzhou Hospital of Nanjing Medical University from September 2020 to May 2021. Participants were diagnosed with colorectal cancer (n = 30), tubular adenoma with high-grade intraepithelial neoplasia (n = 25), or tubular adenoma with low-grade intraepithelial neoplasia (n = 25), or hyperplastic polyp (n = 30). Using microbiomics and metabolomics analyses, we investigated associations among intestinal mucosal microorganisms, bile acids, and short-chain fatty acids during CRC development.RESULTS: Our findings revealed gut microbial richness and diversity, as well as the relative abundances of beneficial bacteria (e.g., Lachnospiraceae, Faecalibacterium, and Blautia), decreased with increasing malignancy of mucosal lesions. During the progression from benign hyperplasia to neoplastic lesions, changes in glycocholic acid, taurocholic acid, glycoursodeoxycholic acid, and taurodeoxycholic acid, acetate, butyrate, isobutyrate, and isovalerate are correlated with alterations in the intestinal mucosal microbiota. Random forest modeling and ROC analysis in this preliminary, single-center study suggested that intestinal mucosal microorganisms and bile acids hold promise as potential combined biomarkers for CRC diagnosis. However, further validation in larger, multi-center cohorts is required to confirm their robustness and clinical utility.CONCLUSIONS: Our study initially suggests a potential association between intestinal mucosal bacteria and bile acids as well as short-chain fatty acids in the progression from benign hyperplasia to neoplastic lesions in the colon, providing new clues for understanding the role of gut microbiota in the process of colorectal cancer development.PMID:41776701 | DOI:10.1186/s40001-026-04102-8

Diabetol Metab Syndr. 2026 Mar 3. doi: 10.1186/s13098-026-02141-z. Online ahead of print.NO ABSTRACTPMID:41776572 | DOI:10.1186/s13098-026-02141-z

Biol Sex Differ. 2026 Mar 3. doi: 10.1186/s13293-026-00865-1. Online ahead of print.ABSTRACTBACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with established sex differences in incidence and progression. Epidemiological evidence suggests nicotine may confer protection against PD, but its mechanisms, particularly regarding sex-specific effects, remain unclear. This study investigated the neuroprotective mechanisms of nicotine in a rotenone-induced PD rat model, with a specific focus on evaluating sex-dependent modulation across behavioral, pathological, and gut-related outcomes.METHODS: Male and female Sprague-Dawley rats were administered rotenone (2 mg/kg/day, s.c.) for four weeks to induce PD. Nicotine (0.5 mg/kg/day, s.c.) was administered 30 min after rotenone. Motor function was assessed using rotarod and CatWalk XT gait analysis. Neuropathology in the substantia nigra was evaluated via immunofluorescence for α-synuclein and tyrosine hydroxylase (TH). Gut pathology was analyzed through colon histopathology (H&E staining) and ELISA for IL-6 and α-synuclein. Gut microbiota composition was assessed by 16 S rDNA sequencing, and serum metabolomics was performed using UPLC-MS/MS. Data were analyzed by two-way ANOVA with Tukey's post-hoc test.RESULTS: Nicotine significantly attenuated rotenone-induced motor impairments: males showed a superior response in balance-related parameters, while females exhibited enhanced efficacy in dynamic gait metrics. Pathologically, nicotine reduced nigral α-synuclein accumulation and TH depletion in both sexes, with males showing greater α-synuclein accumulation following rotenone exposure. Crucially, nicotine exclusively ameliorated colon histopathology, reduced plasma α-synuclein, and suppressed colon IL-6 in females, while attenuating intestinal α-synuclein accumulation in both sexes. Microbiota analysis revealed sex-divergent taxonomic shifts with nicotine treatment. Metabolomics showed significantly more extensive metabolic reprogramming in females, particularly affecting indole derivatives. Pearson correlations revealed significant sex-specific associations between altered serum indole derivatives and gut microbiota genera.CONCLUSIONS: Nicotine exerts neuroprotection in PD through sex-dependent modulation of multiple pathological pathways, primarily involving the gut-microbiota-metabolite axis. Females benefit from enhanced gastrointestinal protection and metabolic reprogramming, while males show preferential motor balance restoration. These findings underscore the critical importance of sex-stratified therapeutic strategies for PD.PMID:41776571 | DOI:10.1186/s13293-026-00865-1

BMC Vet Res. 2026 Mar 3. doi: 10.1186/s12917-026-05378-y. Online ahead of print.NO ABSTRACTPMID:41776562 | DOI:10.1186/s12917-026-05378-y

BMC Med. 2026 Mar 3. doi: 10.1186/s12916-026-04749-4. Online ahead of print.ABSTRACTBACKGROUND: Alterations in lipid metabolism are manifestations of amyotrophic lateral sclerosis (ALS) that contribute to the risk and rate of progression. Blood levels of triglycerides and cholesterol are altered in ALS patients and pre-symptomatic gene carriers, but mechanistic insights into these changes are lacking.METHODS: Serum samples from sporadic ALS patients (n = 118), mutated SOD1 and FUS/TARDBP (n = 20, 40, 17, respectively) with age and gender-matched controls (n = 96) were analysed for alterations in the angiopoietin-like protein (ANGPTL) system using enzyme-linked immunosorbent assays. SOD1G93A murine model was studied at pre-symptomatic (P50), early symptomatic (P90), and fully symptomatic (P110) stages, along with their wild-type (WT) littermates for ANGPTLs. Untargeted lipidomics on serum was performed using high-resolution liquid chromatography-mass spectrometry. Further, the involvement of the hypothalamus was studied using hypothalamic volumetry in patients and an antibody array spanning 308 proteins in mice.RESULTS: We show that mutation-specific patterns of systemic lipid abnormalities appear in ALS and that they correlate with reduced levels of angiopoietin-like proteins 3 and 4. ANGPTL-3/4, in turn, correlates with hypothalamic atrophy but not with corticospinal involvement, as determined by MRI volumetry and diffusion tensor imaging. Lipid phenotype and decreased ANGPTL in humans are recapitulated in two SOD1 murine ALS models, in which ANGPTL-3, -4, and -8 expression patterns are consistent with the repartitioning of lipid utilisation from muscles to the brown adipose tissue; systemic levels of ANGPTL-3 correlate with hypothalamic neuroinflammation and vascular permeability and with hypothalamic levels of agouti-related protein and neuropeptide Y.CONCLUSIONS: These data provide a molecular mechanism linking peripheral lipid metabolism to the dysfunction of a specific hypothalamic circuit through the mediation of systemic ANGPTL-3 and -4. This finding constitutes a molecularly defined entry point to manipulate lipid metabolism in ALS.PMID:41776545 | DOI:10.1186/s12916-026-04749-4

BMC Med Genomics. 2026 Mar 3. doi: 10.1186/s12920-026-02338-1. Online ahead of print.ABSTRACTPropionic acidemia (PA) is a rare autosomal recessive metabolic disorder caused by functional deficiency of propionyl-CoA carboxylase, clinically characterized by life-threatening ketoacidosis, hyperammonemia, and multiorgan dysfunction. Due to its nonspecific clinical manifestations, PA is frequently misdiagnosed or only identified during severe metabolic crises. This study reports a Chinese family with a history of offspring affected by PA. Through whole-exome sequencing and Sanger validation of fetal amniotic fluid and parental peripheral blood samples, two novel compound heterozygous variants in the PCCB gene were identified in the fetus, initially classified as variants of uncertain significance (VUS) per ACMG guidelines. Subsequent functional studies and amniotic fluid metabolomic analyses were performed. The results demonstrated that the paternal PCCB c.366_372 + 7del variant caused exon 3 skipping(p.Phe102_Gln124del) or exon 2-3 skipping (p.Gly62_Gln124del), while the maternal c.183 + 6T > G variant resulted in intron 1 retention (p.Gly62Valfs*10), both leading to protein truncation and aberrant mRNA splicing. Metabolomic analysis demonstrated significantly elevated C3 levels and an increased C3/C2 ratio, consistent with PA diagnosis. These novel PCCB splicing variants expand the mutational spectrum of PA and demonstrate the clinical utility of integrated genomic-metabolomic analysis for prenatal diagnosis and genetic counseling in high-risk PA families.PMID:41776507 | DOI:10.1186/s12920-026-02338-1

BMC Plant Biol. 2026 Mar 3. doi: 10.1186/s12870-026-08474-1. Online ahead of print.NO ABSTRACTPMID:41776417 | DOI:10.1186/s12870-026-08474-1