Search Results (194)

Cardiovascular–kidney–metabolic (CKM) syndrome encompasses the convergent pathophysiology of obesity, insulin resistance, type 2 diabetes, chronic kidney disease, and cardiovascular disease, conditions whose interactions account for a substantial proportion of cardiovascular morbidity and mortality despite contemporary guideline-directed therapy. Nitric oxide (NO) pathway dysfunction constitutes a unifying mechanism across this continuum, linking endothelial dysfunction, impaired insulin signaling, and multiorgan injury through endothelial NO synthase (eNOS) uncoupling, increased arginase activity, asymmetric dimethylarginine (ADMA) accumulation, and paradoxical inducible NO synthase (iNOS)-driven nitrosative stress. Established cardiometabolic therapies—sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), renin–angiotensin–aldosterone system (RAAS) inhibitors, statins, and metformin—improve NO signaling indirectly through reductions in oxidative stress and inflammation yet fail to fully restore NO bioavailability and leave substantial residual cardiovascular and renal risk unaddressed. Direct NO-restoring strategies, including soluble guanylate cyclase (sGC) modulators, arginase inhibition, ADMA-lowering approaches, and microbiome-targeted interventions, demonstrate mechanistic promise in preclinical and early translational studies but currently lack outcome-level evidence. Biomarkers of NO pathway dysfunction—ADMA, flow-mediated dilation (FMD), the tetrahydrobiopterin–dihydrobiopterin (BH4/BH2) ratio, cyclic guanosine monophosphate (cGMP), and endothelial microparticles (EMPs)—offer a foundation for patient phenotyping but remain insufficiently standardized for clinical use. A NO-centered framework provides a biologically coherent model for understanding residual cardiometabolic risk; its translation into personalized therapy will require validated biomarker panels and biomarker-guided outcome trials. Full article

Background: Coronary artery disease (CAD) frequently coexists with cardiometabolic and hepatic dysfunction, yet accessible biomarkers capturing this convergence remain limited. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, has been proposed as an integrative marker of endothelial and metabolic impairment. This study aimed to evaluate the diagnostic value of ADMA as a unified biomarker of endothelial dysfunction (ED), cardiometabolic burden, and metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with stable CAD. Methods: In this cross-sectional study, 298 patients with stable CAD (functional class I–II) were enrolled at two centers in Tashkent, Uzbekistan. Serum ADMA was measured by ELISA; endothelial function was assessed by flow-mediated dilation (FMD). Associations between ADMA, metabolic indices, MASLD, and CAD severity were analyzed. Results: MASLD was present in 48.3% of CAD patients and metabolic syndrome (MetS) in 62.4%. Patients with MASLD had more severe angina, reduced exercise tolerance, and greater ischemic burden than those without. ADMA correlated positively with BMI, waist circumference, TyG index, and TG/HDL-C ratio (all p < 0.001), with the TyG index showing the strongest predictive value for elevated ADMA (AUC 0.76). A dose–response relationship linked rising ADMA to worsening FMD; concentrations >160 ng/mL conferred markedly increased odds of overt ED (OR 114.8, 95% CI 6.8–1935.0) and were disproportionately prevalent in patients with MASLD (93.1% vs. 61.0%, p < 0.001). Conclusions: ADMA is markedly elevated in stable CAD and closely tracks endothelial, metabolic, and hepatic dysfunction. These cross-sectional associations position ADMA as a promising, hypothesis-generating integrative biomarker; prospective longitudinal studies are needed before its use for risk stratification in primary and cardiovascular care can be recommended. Full article

Biomarker, the short form of “biological marker”, appeared in the scientific literature in the 1940s. Since then, many different definitions have been suggested, but a generally applicable explanation of the term biomarker in science is extremely challenging. The word biomarker is found in 1.3 million articles in the scientific database PubMed^® that currently comprises more than 39 million citations for biomedical literature. Biomarkers are closely associated with human health and disease. The present article attempts to approach and evaluate the multifaceted term “biomarker” from a clinical perspective by searching the PubMed database. The search term biomarker was combined with other search terms related to medicine, physiology, biochemistry, and chemistry. Currently generally accepted clinical biomarkers, such as the high-molecular-mass N-terminal prohormone of brain natriuretic peptide (NT-proBNP, 60%), prostate-specific antigen (PSA, 67%), and troponin (37%), serve as a kind of positive control. The combination of the search term biomarker with selected low-molecular substances of clinically non-validated and hence rather experimental character yielded surprisingly high fractions of 41% for 8-iso-prostaglandin F_2α, 39% for symmetric dimethylarginine (SDMA), and 28% for asymmetric dimethylarginine (ADMA). The results of our survey are presented and discussed in detail for a wide spectrum of diseases. We focused on mechanisms that are assumed to underlie the biological activity and specificity of biomarkers. We also considered potential roles of the analytical chemistry of biomarkers including the emerging metabolomics and proteomics. Reliable analytical methods have been used for the quantification of the isomeric low-molecular-mass ADMA and SDMA in human biological samples. ADMA, but not SDMA, is considered an endogenous inhibitor of the endothelium-derived nitric oxide (NO) synthesis, one of the most potent endogenous vasodilators. Paradoxically, the utility of ADMA and SDMA as biomarkers in the renal and cardiovascular systems seems to contradict their main biological activity. This prominent pair is representative of many biomarkers and reveals that the supposed biomarker utility is likely to be predicated on not yet considered biological activity. The majority of human diseases are heterogenic, affect many organs and seem to include different and overlapping biochemical pathways. In recent years, especially proteomic studies provided a series of new potential candidate biomarkers. However, such biomarkers must still be validated in the clinic before they can be introduced into clinical practice. This is perhaps the most critical phase in the discovery of disease biomarkers. Our analysis reveals that the area of biomarker research is highly challenging. With minor exceptions, there is no specific biomarker for a single disease. In addition to clinical examinations, a combination of several biomarkers seems to be needed for reliable diagnosis and therapy. Analytical chemistry, especially proteomics, delivers a huge amount of data, which may complicate and even hinder progress in this area. Specific quantitative analysis of candidate biomarkers observed by proteomics (and metabolomics) is highly recommended to proceed with the same biological samples from studies in which the biomarkers were discovered. Full article

A key mechanism in the pathogenesis of cerebral small vessel disease (CSVD) is endothelial dysfunction associated with impaired metabolism of nitric oxide (NO) and its main substrate, L-arginine. The aim of the study was to assess parameters of L-arginine metabolism and their association with MRI-defined brain damage in CSVD patients. A total of 100 CSVD patients (according to MRI STRIVE standards) and cognitive impairment (CI) of varying severity, as well as 20 healthy volunteers, were analyzed. Levels of L-arginine and its metabolites—L-ornithine, L-citrulline, and asymmetric dimethylarginine (ADMA)—were measured; diffusion tensor MRI, MRI volumetry, and morphometry were performed. A threshold level of L-arginine (51.25 μmol/L) was identified, above which an association with CI was observed. Patients with L-arginine ≥ 51.25 μmol/L demonstrated poorer performance on cognitive tests (Stroop test, trail-making test (TMT)-B, TMT B–A, 10-word test) and more severe brain damage, reflected by greater severity of MRI markers (white matter hyperintensities, microbleeds), changes in brain component volumes, cortical atrophy in specific regions, and impairment of white matter microstructural integrity. The obtained data indicate a pathogenetic link between disturbances in L-arginine homeostasis and the development of CSVD with CI and support the need for further studies aimed at refining approaches to their correction. Full article

Asthma is a heterogeneous inflammatory airway disease with variable clinical phenotypes. Dysregulation of the arginine–nitric oxide (NO) pathway contributes to airway hyperresponsiveness and endothelial dysfunction, but its role across stages of pediatric asthma remains unclear. In order to replicate real-world clinical heterogeneity, this investigation assessed serum levels of L-arginine, symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA), L-citrulline, and the SDMA/ADMA ratio in children with managed asthma, asthma exacerbation, upper respiratory tract infections (URTIs), pneumonia, COVID-19, and healthy controls. Discovering stage-specific arginine pathway changes and evaluating their ability to distinguish asthma and asthma exacerbations from other clinically similar respiratory disorders was the primary aim of our research study. Receiver operating characteristic (ROC) analysis demonstrated that the SDMA/ADMA ratio achieved the strongest individual discriminative performance for distinguishing asthma exacerbation from controlled asthma (AUC: 0.917), while the combined multimarker model incorporating all four metabolites yielded an AUC of 0.983 with a sensitivity of 87.5% and specificity of 95.5%. These results indicate that arginine pathway metabolites, especially the SDMA/ADMA ratio, may merit additional research as possible markers of acute disease activity in asthma, even though they are exploratory and need external confirmation. Full article

Background/Objectives: Cardiovascular complications remain the leading cause of mortality among patients with end-stage renal disease (ESRD) treated with maintenance hemodialysis (HD). Global longitudinal strain (GLS) is a sensitive echocardiographic marker of left ventricular systolic dysfunction that enables the detection of transient contractile abnormalities consistent with intradialytic myocardial stunning. This study aimed to assess intradialytic GLS dynamics during a single HD session and to identify predictors of GLS deterioration. Methods: Forty-three patients were enrolled. Transthoracic echocardiography, electrocardiography, and pulse wave analysis were performed before HD, at mid-session, and after HD. Biochemical assessment included, among others, plasma osmolality, electrolytes, and biomarkers of oxidative stress and endothelial dysfunction. Results: Three distinct intradialytic GLS trajectories were identified: GLS worsening (GLSw, 46.5%), GLS stable (GLSs, 34.9%), and GLS improvement (GLSi, 18.6%). In the GLSw group, independent predictors of GLS deterioration included a decrease in left atrial volume index (LAVI, p = 0.0002), an increase in left ventricular end-systolic volume index (LVESVI, p = 0.0067), diabetes mellitus (p = 0.0094), and an increase in the malondialdehyde-to-creatinine ratio (MDA/CREA, p = 0.0055). In the GLSi group, GLS improvement was associated with a decrease in plasma osmolality (p = 0.0326) and asymmetric dimethylarginine (ADMA, p = 0.0279), as well as an increase in the subendocardial viability ratio index (SEVRI, p = 0.0004) and caspase-1 (p = 0.0005). Conclusions: Intradialytic GLS trajectories are heterogeneous and reflect individual susceptibility to GLS deterioration. Modifiable adverse factors likely include oxidative stress, osmotic stress, fluid overload, uremic toxin- and ion-disturbance-related stress, and impaired coronary microvascular reserve. Future prospective studies are needed. Full article

Hepatic ischemia–reperfusion injury (IRI) is a major cause of liver damage and is characterized by oxidative stress, inflammatory signaling, and hepatocellular apoptosis. Aim: This study investigated the hepatoprotective effects of agomelatine (AGO) administered before ischemia or at the onset of reperfusion in a hepatic IRI model. Rats were allocated into four experimental groups: Sham, IRI, IRI+AGO, and AGO+IRI. Hepatic ischemia was induced by clamping the hepatic pedicle for 1 h followed by 1 h of reperfusion. AGO (20 mg/kg) was administered orally either before ischemia or at the onset of reperfusion. Oxidative stress markers, antioxidant enzymes, nitric-oxide-related parameters, cytokines, liver injury enzymes, and histopathological changes were evaluated. IRI increased oxidant markers and reduced antioxidant defenses. AGO treatment improved redox balance and antioxidant parameters in both treatment groups, with stronger antioxidant responses observed in the AGO+IRI group. Nitric oxide (NO)-related markers differed among groups, including changes in L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels, and interleukin-6 (IL-6) levels decreased following AGO administration, particularly in the AGO+IRI group. Histopathological injury and caspase-3 expression were also attenuated in AGO-treated animals. AGO attenuates hepatic IRI by improving redox balance, modulating NO metabolism, and reducing IL-6–associated signaling and apoptosis, with stronger protection when administered before ischemia. Full article

Nitric oxide (NO) functions as a master integrative regulator of cardiovascular–kidney–metabolic (CKM) homeostasis, yet it displays a profound Janus face, defined by concentration- and context-dependent roles in both health and disease. This narrative review examines NO signaling from a life-course perspective, beginning with fetal programming, during which the NO–asymmetric dimethylarginine (ADMA) axis orchestrates placental development and nephron endowment. Perturbations during this critical window—such as maternal ADMA elevation—can imprint a maladaptive trajectory toward adult-onset hypertension and chronic kidney disease. In adulthood, this initially silent dysregulation of NO signaling is amplified by Western dietary patterns and environmental pollutants, culminating in the clinical manifestation of the CKM triad. This pathological transition is driven by eNOS uncoupling and ADMA accumulation, which shift redox balance toward peroxynitrite formation and precipitate mitochondrial bioenergetic failure. Moreover, while constitutive NO production is essential for vascular homeostasis, pathological induction of inducible NOS generates excessive NO fluxes that promote insulin resistance and tissue injury. With advancing age, a progressive loss of NO resilience further exacerbates multi-organ vulnerability. To mitigate the cumulative burden of CKM disease, this review highlights developmental reprogramming strategies—such as perinatal L-citrulline supplementation and ADMA-lowering interventions—as interventions to restore physiological NO signaling. Integrating such early-life strategies with contemporary pharmacological therapies offers a coherent framework for maintaining NO bioavailability and extending health span across the life course. Full article

Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article

Asthma is increasingly recognized as a heterogeneous syndrome where traditional management fails, particularly given spirometry’s limitations in assessing small airway dysfunction. This review synthesizes the transition from clinical phenotyping to deep molecular endotyping, establishing a framework for precision medicine. We highlight the insufficiency of absolute eosinophil counts, proposing eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) as superior activation metrics. Furthermore, we explore Type 2 drivers (IL-4/IL-13, periostin) and epithelial alarmins like TSLP. Beyond classical immunology, the text describes metabolic dysregulation, specifically asymmetric dimethylarginine (ADMA) in obese-asthma phenotypes where nitric oxide synthase uncoupling promotes oxidative stress. We also analyze YKL-40 and surfactant protein D (SP-D) as markers of remodeling and barrier permeability, alongside microRNAs—specifically miR-21—in corticosteroid resistance. We conclude that managing refractory asthma requires shifting from reactive symptom control to an integrated analysis of multi-omic biomarkers. Establishing this comprehensive molecular profile via specialized centers is fundamental for addressing current diagnostic limitations, selecting biological therapies, and modifying the disease trajectory through an endotype-driven strategy addressing inflammatory, metabolic, and structural pathologies. Full article

Background: Haemodialysis (HD) superimposes additional circulatory stress on the microvasculature, leading to endothelial dysfunction, which plays a key role in the development of haemodialysis-associated multiorgan dysfunction. This study was undertaken to evaluate the effect of a single HD session on retinal and choroidal microcirculation, using optical coherence tomography angiography (OCTA) in relation to changes in the blood levels of selected biochemical modulators of endothelial function. Methods: The vessel density (VD) of 35 patients was evaluated before and after a single HD session, using OCTA in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC). Retinal thickness (RT) and choroidal thickness (CT) were also assessed. Asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1) and malondialdehyde (MDA) levels, oxidative stress (OS) status and systemic parameters were assessed before and after a single HD session. The correlation between changes in these parameters and changes in selected OCTA parameters was tested. Results: A single HD session resulted in a significant increase in RT and a decrease in CT. In addition to increased oxidative and osmotic stress resulting from a significant reduction in plasma osmolality, the HD session was associated with a significant increase in ET-1 levels and a decrease in ADMA levels. These biochemical changes correlated with changes in RT and CT, as well as with changes in VD in the retinal capillary plexuses and the CC. Increased ET-1 levels and decreased plasma osmolality were identified as predictors of RT increase, whereas increased MDA levels corrected serum creatinine-predicted CT reduction. Conclusions: Changes in ADMA and ET-1 and OS, as well as osmotic stress induced by a single HD session, affect the eye microcirculation and morphology of the retina and choroid. OCTA examination is a promising method for assessing microcirculation in HD patients. Full article

Background: Manganese (Mn) exposure is common in welding and metal-processing occupations and has been implicated in both thyroid disruption and endothelial dysfunction through oxidative and nitric-oxide–related pathways. However, endocrine and vascular biomarkers have rarely been examined together in occupational settings. Methods: In this cross-sectional study, 95 Mn-exposed workers and 95 non-exposed controls were evaluated. Whole-blood Mn, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine and citrulline were measured using validated Inductively Coupled Plasma—Mass Spectrometer and chemiluminescent immunoassays. Group differences were assessed using independent samples t-tests, and exposure–biomarker associations were evaluated using Pearson correlations (p < 0.05). Results: Mn-exposed workers had significantly higher blood Mn levels than controls (19.82 ± 4.54 vs. 10.22 ± 3.07 µg/L; p < 0.001). Thyroid hormones (T3, T4, and TSH) were significantly lower among Mn workers, representing a non-classical hormonal pattern, including T3 (2.47 ± 0.31 vs. 3.14 ± 0.42 ng/L; p < 0.001), T4 (1.02 ± 0.13 vs. 1.21 ± 0.18 ng/L; p < 0.001), and TSH (1.75 ± 0.53 vs. 2.88 ± 0.37 mIU/L; p < 0.001). Endothelial biomarkers also differed: ADMA (0.26 ± 0.14 vs. 0.19 ± 0.08 µmol/L; p < 0.001) and SDMA (0.24 ± 0.06 vs. 0.20 ± 0.03 µmol/L; p < 0.001) were higher, while citrulline was lower (18.77 ± 10.23 vs. 22.82 ± 6.70 µmol/L; p = 0.002). In Mn workers, blood Mn showed negative correlations with T3 (r = –0.535, p < 0.01), T4 (r = –0.331, p < 0.01), and TSH (r = –0.652, p < 0.01), and positive correlations with ADMA (r = 0.205, p < 0.05) and SDMA (r = 0.193, p < 0.05). Conclusions: These findings indicate measurable differences in thyroid hormones and dimethylarginine-related endothelial markers among Mn-exposed workers. While the cross-sectional design precludes causal inference, the combined pattern suggests a possible unusual biological response involving both endocrine regulation and nitric-oxide–related pathways. Further longitudinal studies incorporating oxidative stress markers, co-exposure assessment, and functional endothelial testing are needed to clarify the biological relevance of these associations. Full article

Cadmium (Cd) is a persistent toxic metal that bioaccumulates in human tissues and may disrupt redox and endocrine pathways, yet the metabolic mechanisms linking Cd exposure to both endothelial and prostate dysfunctions remain insufficiently defined. This study investigated whether chronic occupational Cd exposure alters methylated arginine metabolism and prostate-specific antigen (PSA) levels, indicating a shared toxicometabolic axis. A total of 150 male workers were enrolled, including 75 metallurgical employees with documented Cd exposure and 75 matched controls. All participants were non-smokers, eliminating confounding from tobacco-related oxidative or endocrine effects. Urinary Cd concentrations were quantified using Inductively Coupled Plasma–Mass Spectrometry (ICP–MS), and serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, citrulline, and PSA were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and electrochemiluminescence. The use of Inductively Coupled Plasma–Mass Spectrometry for cadmium quantification and LC-MS/MS for methylated arginine profiling provided high analytical specificity and sensitivity, strengthening the validity of biomarker measurements. Correlation and multivariable analyses adjusted for age and body mass index. Cd-exposed workers demonstrated significantly elevated urinary Cd, PSA, ADMA, and SDMA levels, alongside reduced arginine/ADMA ratios, consistent with impaired nitric oxide bioavailability. Urinary Cd strongly correlated with PSA and ADMA levels. These findings indicate that Cd may disrupt the nitric oxide pathway and elevates PSA, supporting a mechanistic link between vascular and prostate stress. Combined ADMA, SDMA, and PSA profiling may serve as an early biomarker panel for Cd-related metabolic injury in occupational settings. Full article

In recent years, the L-arginine/nitric oxide (NO) pathway has garnered increasing attention across a range of pathological conditions, including skin diseases. NO is an important modulator of skin homeostasis, being actively involved in numerous processes such as vasodilation, keratinocyte proliferation, melanogenesis and cell signaling. Under inflammatory conditions, post-translational changes in L-arginine take place, resulting in the synthesis of methylarginines including monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). Once ADMA and MMA are generated, they compete with L-arginine to bind to the active site of NO synthase, which reduces the production of NO. Additionally, SDMA inhibits the transport of L-arginine, leading to a lower concentration of this amino acid within cells. Consequently, by impacting both the availability of L-arginine and the production of NO, conditions favoring oxidative stress and endothelial dysfunction are created. Dysregulation of L-arginine/NO pathway is closely related to inflammation and oxidative stress, two events that play a cardinal role in the pathogenesis of chronic inflammatory skin diseases. We conducted a narrative review that synthesizes current evidence on methylarginine levels in patients with chronic inflammatory skin diseases. Our aim was to enhance our knowledge about the role of these compounds in pathogenesis and provide new insights into the mechanisms underlying these conditions that can be the basis for novel diagnostic biomarkers and therapies. Full article

Gut-derived uremic toxins may play a key role in neurodevelopmental conditions such as autism spectrum disorder (ASD) via host-microbe metabolic interactions. We evaluated five uremic toxins—p-cresyl sulfate (PCS), indoxyl sulfate (IS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in urine samples of 97 children with ASD and 71 neurotypical controls, stratified by Bristol Stool Chart (BSC) consistency types. Four of these toxins (PCS, IS, TMAO, ADMA) were integrated into a novel composite biomarker called the Metabolic Index of Gut Dysfunction (MIGD), while SDMA was measured as a complementary renal function marker. While individual metabolite levels showed no statistically significant differences, group-wise analysis by stool phenotype revealed distinct trends. ASD children with hard stools (BSC 1–2) showed elevated PCS levels and the MIGD score (median 555.3), reflecting phenolic fermentation dominance with reduced indolic detoxification. In contrast, children with loose stools (BSC 6–7) had the lowest MIGD values (median 109.8), driven by higher IS and lower ADMA concentrations, suggestive of enhanced indole metabolism. These findings indicate that MIGD may serve as a novel biomarker to stratify metabolic phenotypes in ASD, linking urinary metabolite patterns to gut function. Further validation in larger and longitudinal cohorts is warranted to confirm its potential utility in precision microbiota-targeted interventions. Full article