Search Results (138)

Functional pet foods are increasingly being developed to support host metabolism and intestinal health. Lycium barbarum polysaccharide (LBP), a major bioactive component of goji berries, has been reported to possess antioxidant, anti-inflammatory, immunomodulatory, and gut microbiota-regulatory activities; however, its effects in domestic cats remain unclear. This study investigated the effects of dietary LBP supplementation on serum metabolomic profiles and gut microbiota in adult cats. Twenty-four healthy adult Chinese domestic cats (1.50 ± 0.50 years old; 3.70 ± 0.80 kg) were allocated to four groups using a body-weight-balanced procedure (n = 6 per group): a basal diet group (C) and basal diet supplemented with 0.2% (L), 0.3% (M), or 0.4% (H) LBP. After a 1-week adaptation period, the formal feeding trial lasted 8 weeks. Growth-related indices, health scores, hematological and serum biochemical parameters, untargeted serum metabolomics, and fecal 16S rRNA sequencing were evaluated. LBP supplementation did not significantly affect body weight, average daily feed intake, body condition score, fecal score, coat score, hematological indices, or serum biochemical parameters. Metabolomic analysis showed that LBP mainly affected lipid metabolism, unsaturated fatty acid biosynthesis, branched-chain amino acid metabolism, lysine degradation, and protein digestion and absorption-related pathways. Microbiota analysis showed changes in alpha diversity, community structure, and the relative abundance of taxa such as Olsenella, Bifidobacterium, Catenibacterium, Peptoclostridium, Collinsella, and Clostridium. Correlation analysis suggested potential associations between key bacterial genera and serum metabolites related to fatty acid and amino acid metabolism. Overall, dietary LBP altered serum metabolic signatures and gut microbial composition without causing adverse effects in adult cats, These exploratory findings require confirmation in larger feline studies and do not establish an optimal supplementation level. Full article

Diarrhea-predominant irritable bowel syndrome (IBS-D) frequently occurs alongside depression, greatly impairing patients’ life quality, with limited targeted treatments. Low-molecular-weight peptides (LMWPs) from Musca domestica larvae exert gut-protective bioactivities, but their efficacy and molecular mechanisms for comorbid IBS-D and depression remain unelucidated. A chronic–acute combined stress (CACS)-induced rat model of IBS-D complicated with depression was established and treated with LMWPs. The study evaluated intestinal and depressive behavioral phenotypes, and integrated 16S rRNA sequencing, untargeted serum metabolomics and quantitative detection of fecal SCFAs for multi-omics correlation analysis. 1. CACS triggered typical comorbid symptoms, which LMWPs alleviated with effects similar to trimebutine maleate. 2. LMWP treatment was associated with reshaped gut microbiota, restored metabolic pathways, altered levels of 27 disease-associated serum metabolites, and increased fecal SCFA levels. 3. Multi-omics correlation analyses suggested that the therapeutic benefits may involve crosstalk among gut microbiota, SCFAs, and tryptophan metabolites. Larva-derived LMWP relieves IBS-D combined with depression by modulating gut microecology, SCFA generation and serum metabolic balance through the gut–brain axis, which can serve as a novel promising therapeutic candidate. Full article

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host metabolism using a multi-omics approach. Male C57BL/6J mice were exposed to six weeks of CIH or normoxia. Colonic barrier integrity was assessed by histological and molecular analyses. Gut microbiota was profiled by full-length 16S rRNA gene sequencing. Untargeted metabolomics was performed on fecal and serum samples, followed by integrated microbiome–metabolome analysis. CIH markedly impaired colonic barrier integrity, as evidenced by disrupted crypt architecture, reduced goblet cell abundance, and decreased expression of ZO-1, Occludin, and Claudin-5. CIH also induced gut microbial dysbiosis, characterized by depletion of the beneficial mucin-associated bacterium Akkermansia muciniphila and enrichment of several anaerobic taxa. Metabolomic analysis revealed opposite alterations of PC (20:2/0:0) and LysoPE (20:5/0:0) between feces and serum, whereas melatonin was consistently decreased in both compartments. Integrated multi-omics analysis further revealed close associations between microbial dysbiosis and metabolic remodeling. Collectively, these findings demonstrate that CIH disrupts intestinal homeostasis through coordinated alterations in barrier integrity, gut microbiota composition, and host metabolism, providing new insights into the intestinal mechanisms underlying OSA-associated systemic dysfunction. Full article

A total of 96 26-day-old weaned piglets were randomly assigned to four groups with three replicates per group: (1) CON group (basal diet), (2) PRS group (protease supplementation), (3) AMS group (amylase supplementation), and (4) combined protease and amylase group (PAS group) (protease and amylase supplementation). Compared to the CON group, AMS group reduced feed-to-gain ratio (p < 0.05). Additionally, all treatments increased ether extract digestibility (p < 0.05). The PRS and AMS groups reduced serum urea nitrogen level (p < 0.01). PAS group increased total protein, and decreased total cholesterol (p < 0.05). PRS and/or AMS supplementation increased serum glutathione peroxidase. IgM and IgG were higher in the AMS group. Furthermore, levels of D-Lactate and diamine oxidase were reduced (p < 0.05). PRS group exhibited increased fecal acetic acid and valeric acid levels (p < 0.05). Microbiota analysis showed that PRS or/and AMS supplementation enriched bacteria, including Anaerovoracaceae and Blautia. Metabolomics analysis revealed that health-promoting differential metabolites, including S-nitrosoglutathione and kynurenic acid, were further enriched, indicating enhanced immune regulation and intestinal homeostasis. Taken together, PRS or/and AMS supplementation can effectively promote nutrient digestion, intestinal microbiota structure and metabolism, and enhance intestinal barrier, thereby improving growth performance in weaned piglets. Full article

Yeast hydrolysate (YH) is a yeast-derived functional feed ingredient containing bioactive peptides, amino acids, nucleotides, β-glucans, and mannan oligosaccharides, which may exert prebiotic-like effects by regulating nutrient metabolism, host health, and intestinal microbial homeostasis. However, its effects on lactating Dezhou jennies remain largely unclear. This study investigated the effects of dietary YH supplementation on body weight change, serum biochemical parameters, serum metabolomic profiles, and fecal microbiota composition in lactating Dezhou jennies. Sixteen healthy lactating Dezhou jennies were randomly assigned to a control group fed a basal diet (MCON, n = 8) or a YH supplementation group fed the basal diet supplemented with YH (MYE, n = 8) for 60 days. Compared with the MCON group, the MYE group showed numerically higher final body weight and body weight change. Serum biochemical analysis showed that YH supplementation significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and increased triglyceride (TG) concentrations, while all measured biochemical parameters remained within physiological reference ranges. Serum metabolomic profiling identified 193 differential metabolites between the two groups, including 55 upregulated and 138 downregulated metabolites in the MYE group. These metabolites were mainly associated with amino acid metabolism, lipid metabolism, bile acid metabolism, steroid hormone biosynthesis, mineral absorption, ABC transporters, and protein digestion and absorption, indicating that YH supplementation reshaped nutrient-related metabolic pathways in lactating Dezhou jennies. Fecal microbiota analysis showed no significant changes in α-diversity or overall community structure; however, the MYE group displayed numerically higher microbial richness indices, more unique ASVs and genera, a lower relative abundance of Bacteroidota, and a higher relative abundance of Bacillota. LEfSe analysis further revealed enrichment of specific bacterial taxa in the MYE group, including Christensenellaceae_R-7_group, Anaerovorax, and UCG-related taxa. Collectively, these preliminary findings suggest that dietary YH supplementation may alter selected serum biochemical indices and circulating metabolites and may selectively affect the relative abundance of certain fecal bacterial taxa in lactating Dezhou jennies. However, given the limited sample size, these results should be interpreted cautiously, and larger-scale studies are needed to confirm their reproducibility and practical significance. Full article

Obesity is a chronic metabolic disorder closely associated with dyslipidemia, insulin resistance, low-grade inflammation, and gut microbiota dysbiosis. Mulberry leaves are rich in bioactive proteins, but whether mulberry leaf albumin-type protein can improve diet-induced obesity remains unclear. In this study, ultrafiltered mulberry leaf albumin-type protein (UMP) was prepared and its anti-obesity effects were evaluated in high-fat diet (HFD)-fed C57BL/6J mice. UMP contained 87.12 ± 0.52 g/100 g protein, 2.52 ± 0.00 g/100 g polyphenols, and 8.21 ± 1.49 g/100 g polysaccharides, with two major albumin-type protein bands of approximately 14 and 52 kDa. Structural analysis showed that UMP was mainly composed of β-turns and α-helices. In HFD-fed mice, daily administration of UMP for 16 weeks reduced body weight gain by 3.85 g and 5.63 g in the low- and high-dose groups, respectively, without affecting food intake. Biochemical assays, glucose and insulin tolerance tests, and histological analysis showed that UMP improved insulin responsiveness, alleviated serum dyslipidemia, reduced hepatic lipid accumulation, and decreased circulating alanine aminotransferase, aspartate aminotransferase, and lipopolysaccharide levels. Histological analysis and nuclear magnetic resonance-based short-chain fatty acid quantification further showed that UMP protected colonic morphology and increased colonic short-chain fatty acid levels. Gut microbiota analysis showed that UMP restored microbial diversity, reduced the Firmicutes/Bacteroidota ratio, and enriched potentially beneficial genera, including Ileibacterium and norank_f_Muribaculaceae. Fecal biochemical assays suggested that UMP promoted fecal free fatty acid excretion and partially improved bile acid-related metabolic alterations. Untargeted serum metabolomics revealed that UMP reshaped metabolic pathways related to lipid turnover, bile acid signaling, glucose utilization, and glucuronidation. Correlation analysis linked UMP-enriched bacterial taxa with key metabolites involved in fatty acid and energy metabolism. Together, these findings indicate that UMP attenuates HFD-induced obesity through coordinated regulation of gut microbiota, intestinal metabolites, and systemic metabolic homeostasis. UMP may therefore represent a promising functional dietary protein for the prevention of obesity-related metabolic disorders. Full article

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to Western dietary patterns. Yet, preclinical studies rely on continuous high-fat feeding, overlooking the intermittent nature of human eating. Whether dietary periodicity itself influences the gut–liver axis and MASLD pathogenesis remains unknown. We compared continuous and intermittent high-fat, high-cholesterol (HFHC) diets in guinea pigs, a model that mirrors human lipoprotein metabolism, hepatic cholesterol handling, and hindgut fermentation. Methods: Integrated multi-omics analyses (serum metabolomics, fecal 16S rRNA sequencing, and liver transcriptomics) were employed in a guinea pig model, stratified into normal diet (ND), intermittent HFHC diet (IHD), and IHD with flaxseed lignan supplementation, to compare the effects of dietary regimens and the therapeutic efficacy of lignan on hepatic pathology. Results: Both diets induced hallmark hepatic features of MASLD; however, the intermittent regimen provoked significantly more severe hepatic steatosis, inflammation, oxidative stress, and fibrosis. Hepatic transcriptomic analysis identified the PI3K-Akt signaling pathway as the most significantly enriched pathway in the IHD group. Mechanistically, this aggravated liver injury was linked to gut microbiota dysbiosis and a marked depletion of the microbial metabolite enterolactone. Fecal microbiota transplantation confirmed that the dysbiotic microbiota directly transmits the aggravated liver injury phenotype. Supplementation with flaxseed lignan, the dietary precursor of enterolactone, restored enterolactone production, corrected the dysregulated gut microbiota–enterolactone axis, and largely normalized the expression of PI3K-Akt downstream targets, thereby alleviating hepatic pathology. Conclusions: These findings suggest that alterations in the gut microbiota–enterolactone axis may contribute to diet-periodicity-driven liver injury and highlight its potential involvement in disease progression. Modulating this axis through dietary interventions, such as flaxseed lignan supplementation, may represent a promising nutritional strategy for mitigating MASLD associated with cyclical dietary exposure. Full article

Background: Postpartum depression (PPD) is a prevalent and debilitating disorder, with increasing evidence implicating the gut microbiota–brain axis. However, integrated alterations in gut microbiota and circulating metabolites in PPD remain insufficiently characterized. Methods: Fecal and serum samples were collected from patients with PPD and healthy controls (HC). Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17). Gut microbiota was analyzed by 16S rRNA sequencing, and serum metabolites were profiled using untargeted LC–MS-based metabolomics. Spearman correlation and receiver operating characteristic (ROC) analyses were performed. Results: A total of 63 participants (42 PPD, 21 HC) were included. Significant alterations in gut microbial composition were observed in PPD, including decreased Faecalibacterium and Akkermansia and increased Ralstonia and Fusobacterium. Candidate differential serum metabolic features, including LPE-related and energy-metabolism-related features, were identified. Exploratory correlation analyses suggested distinct microbiota–metabolite association patterns, and several microbial taxa and serum metabolic features were associated with HAMD-17 scores. ROC analysis showed that several taxa and metabolic features exhibited preliminary discriminative performance with this cohort, although further validation is required. Conclusions: PPD was associated with alterations in gut microbiota composition and exploratory circulating metabolite profiles, potentially involving lipid dysregulation, neuroinflammation, steroid-related metabolism, and neurotoxicity-related pathways. The identified taxa and putatively annotated metabolites should be regarded as exploratory PPD-associated candidates rather than validated biomarkers or mechanistic mediators. Further validation in larger, independent cohorts is warranted. These findings may also inform future microbiota- and nutrition-oriented strategies for postpartum mental health management. Full article

This study investigated the effects of dietary protein levels and arginine supplementation on growth performance, nitrogen metabolism, serum biochemical indices, inflammatory markers, gut microbiota, and fecal metabolomic profiles in growing beagles. Sixty healthy beagles were assigned to six dietary treatments in a 2 × 3 factorial design: two crude protein levels (normal, 22%; low, 18%) and three arginine supplementation levels (0%, 0.266%, 0.532%) over 45 days. Growth performance and nutrient digestibility were not significantly affected by diet. Low-protein diets reduced nitrogen intake and excretion while increasing biological value, indicating improved nitrogen utilization. Serum total cholesterol, blood urea nitrogen, and creatinine were influenced by protein and arginine levels, and inflammatory markers TNF-α and IL-6 were modulated by their interaction. Gut microbiota composition was altered at the taxonomic level but not at the level of the overall structure; arginine supplementation increased microbial richness under normal protein conditions. Fecal metabolomic analysis showed that arginine mainly affected amino acid metabolism, mineral absorption, and bile acid pathways, whereas protein reduction impacted lipid metabolism, bile secretion, and energy-related pathways. Overall, reducing dietary protein to 18% improved nitrogen utilization without impairing growth. Among the six dietary treatments, the normal-protein diet supplemented with moderate arginine (22% CP + 0.266% L-arginine, 1.10% total arginine) was associated with the most balanced overall physiological response. Metabolomic findings from the four selected dietary groups provided additional evidence that dietary protein and arginine modulated distinct metabolic pathways, although these findings should be interpreted within the scope of the selected-group comparison. These results provide a practical basis for optimizing amino acid balance and nitrogen utilization in growing dogs and may contribute to the development of more precise and sustainable pet food formulations. Full article

The ABE classification is crucial for the management of stable chronic obstructive pulmonary disease (COPD), reflecting disease symptom burden and exacerbation risk. Although gut microbiota is intimately linked to COPD pathogenesis, associations among the gut microbiota, its derived metabolites, and exacerbation risk in stable COPD patients remain poorly understood. We recruited 74 stable COPD patients (Group A, n = 18; Group B, n = 26; Group E, n = 30) for cross-sectional multi-omics profiling via fecal metagenomic sequencing and untargeted serum metabolomic analyses. Group E exhibited a decreasing trend in alpha diversity compared to Groups A and B. In addition, Group A displayed the most complex bacterial cooperative network, showing lower complexity and connectivity as symptom burden and risk of exacerbations increased. Taxonomically, the family Prevotellaceae was significantly enriched in Group A, while Streptococcaceae and Lactobacillaceae were more abundant in Groups B and E. Among 51 species displaying progressive trends with increasing exacerbation risk, 35 increased (e.g., Clostridium ljungdahlii) and 16 decreased (e.g., Prevotella dentalis). Furthermore, metabolomics analysis revealed that serum O-phosphoethanolamine levels were markedly elevated in Group E and showed a positive correlation with the COPD Assessment Test and modified Medical Research Council dyspnea scale scores. Exploratory mediation analysis suggested that elevated systemic O-phosphoethanolamine levels partially mediated the association between Clostridium ljungdahlii and COPD exacerbation risk. This study establishes significant associations between gut microbiota and phenotypic stratification in stable COPD patients. The identified Clostridium ljungdahlii/O-phosphoethanolamine axis may be associated with symptom burden and COPD exacerbation risk, provide a basis for further mechanistic studies. Full article

Oral lichen planus (OLP) is a chronic inflammatory oral disease associated with immune dysregulation and malignant transformation risk. Vitamin D and probiotics may modulate immune and microbial pathways involved in OLP. In this study, we evaluated their effects on clinical outcomes and multi-omics profiles in 25 adult OLP patients (median age: 68 years). Vitamin D-deficient patients received 2000 IU/day vitamin D3, and all participants received a probiotic blend (Limosilactobacillus reuteri LRE11, Lacticaseibacillus rhamnosus LR04, and Lacticaseibacillus casei LC04) for 16 weeks. Clinical assessments and analyses of saliva, serum, oral swabs, and stool samples were performed before and after treatment. Clinical outcomes improved significantly, with reductions in lesion number (p < 0.001), lesion size (p = 0.004), and bleeding lesions (p = 0.014); 76% of patients were classified as in remission. Vitamin D levels increased significantly among deficient patients receiving correction (p < 0.01). Salivary and fecal metabolomics showed significant remodeling of amino acid and carbohydrate pathways, including decreases in branched-chain amino acids in saliva and modulation of nicotinamide- and amino acid-related metabolites in feces. Microbiome α-diversity remained stable, whereas β-diversity shifted significantly across oral and fecal sites, with enrichment of Lacticaseibacillus and other context-dependent commensals. Multi-omics integration identified three latent factors linking salivary cytokines, microbial taxa, metabolites, and systemic lipid profiles, suggesting coordinated mucosal–metabolic–immune remodeling across the oral–gut axis. Full article

Probiotics are promising alternatives to antibiotics in calf rearing, but effects of Lactobacillus species combined with Bacillus subtilis on preweaning development remain unclear. Two probiotic consortia—L. plantarum + B. subtilis (TG1) vs. L. acidophilus + B. subtilis (TG2)—were compared in Holstein calves. Forty-eight newborn calves (initial BW 37.0 ± 2.7 kg) were randomly assigned to control (CG) or probiotic groups (TG1, TG2) from day 3 for 60 days. Growth, fecal scores, serum biochemistry, antioxidant/immune indices, rumen fermentation, 16S rRNA, and untargeted metabolomics were measured. Compared with CG, TG1 increased final body weight (p = 0.002) and average daily gain (ADG, p = 0.002), whereas TG2 did not differ from CG in either parameter. Both TG1 and TG2 decreased feed conversion ratio (FCR, p < 0.001), with TG1 showing a lower value than TG2. At day 60, TG1 had greater body oblique length than TG2 (p = 0.030), whereas neither TG1 nor TG2 differed from CG. Serum analysis: TG1 decreased ALT (p = 0.039) and increased CAT (p = 0.024) and HDL-C (p = 0.047) compared with CG, while TG2 did not differ from CG in these parameters. Both TG1 and TG2 decreased CRE compared with CG (p < 0.001). TG2 increased GSH-Px compared with CG and TG1 (p = 0.044), whereas TG1 did not differ from CG. Rumen fermentation: both TG1 and TG2 increased BCP compared with CG (p = 0.009); TG1 elevated isobutyrate compared with CG (p = 0.030), whereas TG2 did not differ from CG; TG2 reduced NH₃-N compared with CG (p = 0.026), whereas TG1 did not differ from CG. No α/β-diversity differences were observed, but taxa were modulated: TG1 enriched Actinobacteria and Olsenella; TG2 enriched Bacteroidetes, Prevotella, and Ruminococcus. Metabolomics: TG1 upregulated steroid hormone and phenylalanine metabolism; TG2 enhanced unsaturated fatty acid biosynthesis. Correlation networks linked Ruminococcus and UCG-005 to antioxidant status and VFA profiles. These findings indicate that different probiotic consortia are associated with distinct physiological outcomes in preweaning calves, supporting consortium selection for targeted feeding. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder associated with gut dysbiosis and tryptophan metabolism disturbance, but the mechanisms of probiotic action are unclear. We orally administered Lactobacillus reuteri DSM 17938 live bacteria (1.0 × 10⁹ CFU/mL, 0.2 mL) or its fermentation supernatant lyophilized powder at three concentrations to MPTP-induced PD male C57BL/6J mice. Treatments increased locomotor distance and speed, elevated serum SOD and GSH, reduced MDA, TNF-α, IL-6, and IL-1β, promoted neuronal survival, and tended to increase TH expression in the substantia nigra. 16S rRNA sequencing showed that treatments altered gut microbiota composition. PD mice had increased Lactobacillus and Allobaculum but decreased Oscillospira and Helicobacter; treatments restored Oscillospira. Fecal untargeted metabolomics revealed disturbed tryptophan metabolism in PD, with elevated indoleacetic acid and reduced kynurenic acid, xanthurenic acid, indole-3-ethanol, and α-oxo-1H-indole-3-propanoic acid. Treatments significantly restored neuroprotective metabolites including kynurenic acid, xanthurenic acid, and serotonin. PICRUSt2 predicted tryptophan synthesis pathway-associated microbes (Oscillospira, Ruminococcus, Coprococcus). Treatments ameliorated motor deficits, oxidative stress, inflammation, and dopaminergic neuron death, correlating with gut microbiota modulation and accumulation of microbiota-derived tryptophan metabolites. Live bacteria showed superior antioxidant and neuroprotective efficacy compared to supernatant, likely due to sustained colonization and continuous metabolic activity. These findings suggest that targeting key tryptophan-metabolizing bacteria or their metabolites may be a potential PD therapy. Full article

Background/Objectives: Metabolomics has emerged as a tool to gain insight into the body’s biological responses to therapeutic interventions. Bariatric surgery remains the most effective treatment for severe obesity and associated comorbidities, leading to significant weight and metabolic improvements. Using a multi-platform, multi-compartment metabolomics approach, this study systematically characterizes longitudinal changes in fecal and serum metabolomes of 45 patients following sleeve gastrectomy (SG). Participants were stratified by weight loss outcomes to identify metabolic signatures associated with differential responses, which may serve as predictors of weight loss and provide mechanistic insights in developing targeted therapeutic strategies. Methods: Metabolomic and lipidomic responses to SG were analyzed using multivariable linear mixed-effects models based on data collected pre-operatively and at 3 and 12 months post-operatively. Results: The percentage total weight loss for the highest versus lowest weight loss tertiles (T₃ vs. T₁) at twelve months was 35.81 + 5.4% and 19.49 + 2.62%, p < 0.001, respectively. Substantial alterations in fecal metabolites and lipid species were observed among T3 after twelve months, including aspartate, tyrosine, carnitine, glycine, PC.ae.C36.4, PC.aa.C38.0, PC.ae.C44.4, PC.ae.C40.2, and PC.aa.C40:5. Specifically, changes in serum lipid species including SM.OH.C22:1, PC.ae.C32:1, PC.aa.C34:4, PC.aa.C36:6, PC.ae.C34:3, PC.ae.C34:1, and PC.ae.C32:2, support serum lipidomics as a minimally invasive marker of gut remodeling and adaptation following SG. Sex-stratified analysis revealed unique fecal and serum metabolic changes, highlighting the significance of personalized metabolic monitoring and obesity treatment. Conclusions: Our findings identify metabolic alterations associated with response variability following SG and highlight the potential utility of machine learning to predict weight-loss trajectories and inform personalized interventions. Full article

Background: Febrile seizures (FSs) are the most common neurological emergency in early childhood; however, the biological basis of disease heterogeneity remains poorly understood. Although growing evidence suggests that gut–brain axis dysregulation contributes to seizure susceptibility, it remains unclear whether gut microbiota-associated metabolic disturbances are linked to clinical phenotypes, particularly simple FS (SFS) and complex FS (CFS). Methods: An integrated multiomics study was conducted in clinically characterized pediatric cohorts, comprising 50 children with FS and 50 healthy controls, and their gut microbiota was profiled via 16S rRNA sequencing. As some pediatric serum specimens did not meet the minimum volume requirement of the analytical platform, serum amino acid profiling was performed in a subset of samples using an equal-volume pooling strategy. In brief, two individual serum samples from the same study group were combined into one composite sample, yielding 25 pooled samples in the FS group and 25 in the control group. Subsequently, untargeted fecal metabolomics was performed in an expanded cohort of 53 healthy controls, 50 children with SFS, and 42 children with CFS. Additionally, the central metabolic profiles of the CFS and SFS groups were compared using untargeted cerebrospinal fluid metabolomics. Given the variation in sample sizes across omics platforms, each dataset was analyzed within its corresponding eligible subset, and cross-omics integration was interpreted primarily at the pathway and phenotype levels. Results: Children with FS exhibited reduced gut microbial diversity and altered microbial composition, characterized by the enrichment of Streptococcus, Enterococcus, and Escherichia–Shigella, along with the depletion of beneficial taxa, including Faecalibacterium, Lachnoclostridium, and Parasutterella. Functional prediction indicated significant changes in amino acid-related pathways, especially arginine and proline metabolism, amino acid metabolism, and glutathione metabolism. Serum profiling showed elevated levels of phenylalanine, kynurenine, and γ-aminobutyric acid, along with reduced levels of tryptophan, threonine, lysine, glutamine, taurine, citrulline, 3-methylhistidine, α-aminobutyric acid, hydroxyproline, and phosphoethanolamine. Correlation analysis identified Lachnoclostridium and Parasutterella as key taxa associated with neuroactive metabolites. Additionally, fecal metabolomics revealed that both SFS and CFS samples exhibited significant metabolic divergence from the controls, with arginine biosynthesis emerging as a shared altered pathway and L-arginine reduced in both phenotypes. Notably, cerebrospinal fluid metabolomics demonstrated clear metabolic separation between CFS and SFS, signifying phenotype-specific central metabolic signatures. Conclusions: FS is related to gut microbiota dysbiosis, systemic amino acid remodeling, and phenotype-associated metabolic stratification. Arginine metabolism may represent a shared mechanistic hub across FS phenotypes, while central metabolic divergence may contribute to the biological distinction between SFS and CFS. These findings establish a multiomics framework for understanding FS pathogenesis and identifying potential biomarkers and therapeutic targets. Full article