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Povzetek: Autism spectrum disorder (ASD) has been associated with alterations in the gut microbiota and its metabolites, particularly short-chain fatty acids (SCFAs) and microbiota-derived tryptophan catabolites, which may influence neurodevelopment through immune and epigenetic mechanisms. We investigated whether stool SCFAs and tryptophan-pathway metabolites differ between children with ASD and typically developing controls, and whether these metabolites associate with ASD severity and systemic biochemical signatures. In this cross-sectional study, we analyzed stool samples from 229 children (160 with ASD, 69 controls) with complete SCFA and tryptophan-metabolite data, while urine metabolomics data were available for a subset and were used for exploratory stool–urine integration analyses. Children with ASD and controls were similar in age, but the ASD group had a higher proportion of males. Absolute concentrations of individual SCFAs, total SCFAs, and derived indices were broadly comparable between groups; nominal differences in propionate/acetate ratio and caproate did not remain significant after false discovery rate correction. Similarly, stool tryptophan-pathway metabolites reported as ng/a.u. based on the NanoDrop-derived proxy (tryptophan, kynurenine, indole-3-acetic, indole-3-lactic, indole-3-propionic, indole-3-aldehyde, N-acetyl-tryptophan, serotonin, melatonin, tryptamine) and functional ratios (kynurenine/tryptophan, indole-derived/tryptophan, serotonin/tryptophan) showed no robust ASD–control differences; N-acetyl-tryptophan was nominally higher in ASD but did not survive multiple-testing correction. In the ASD subgroup with available Childhood Autism Rating Scale (CARS) data (n = 34), SCFA and tryptophan indices showed only weak, non-significant correlations with global ASD severity. In contrast, correlation analyses revealed two coherent metabolic modules, i.e., an SCFA block with very strong internal correlations among individual SCFAs and total SCFAs and a tryptophan block with strong correlations between metabolites and their normalized ratios, while cross-module correlations were modest. These results indicate that stool SCFA and microbiota-derived tryptophan profiles do not robustly distinguish ASD from controls in this cohort, but they form stable metabolic modules compatible with microbiome–epigenome frameworks.
Ključne besede: autism spectrum disorder, gut microbiota, short-chain fatty acids, tryptophan metabolism, indole metabolites, kynurenine pathway, epigenetics, microbiome–epigenome interaction, metabolomics, pediatrics
Objavljeno v DiRROS: 05.05.2026; Ogledov: 76; Prenosov: 51
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Povzetek: Background/Objectives: Protein-bound uremic toxins (PBUTs), particularly p-cresyl sulfate (PCS) and indoxyl sulfate (IS), are associated with cardiovascular toxicity and increased mortality. Conventional hemodialysis (HD) removes PBUTs poorly, and the efficacy of medium cut-off (MCO) dialyzer membranes remains uncertain. Furthermore, PBUT production is influenced by gut microbial metabolism and can be modified through diet. We hypothesized that MCO dialysis would provide superior clearance of PCS and IS compared with online hemodiafiltration (OL-HDF), and that combining MCO dialysis with increased dietary fiber and short-chain fatty acid (SCFA) intake would further reduce PBUT levels. Methods: In this prospective randomized trial, 62 maintenance HD patients underwent a 2-week wash-in period with high-flux HD (HF-HD) and were then randomized to MCO-HD (EXP) or OL-HDF (CON). After a 4-week intervention with the assigned dialysis modality, both groups continued with the same dialysis treatment and received an 8-week dietary intervention consisting of 19 g/day fiber and 1 g/day sodium propionate. The study concluded with a 4-week wash-out period on HF-HD. Primary outcomes were total serum PCS and IS levels measured at four timepoints. Results: Fifty-two patients completed the study. No significant changes in PCS or IS were observed after the dialysis-only intervention. PCS levels remained stable throughout the study. When the aligned dialysis regimen was combined with the dietary intervention, IS levels were significantly lower in the CON than in the EXP group (31.5 ± 10.3 vs. 42.0 ± 15.8 µmol/L; p = 0.006), with a partial rebound after wash-out in the CON group (39.6 ± 20.9 µmol/L; p = 0.003). Conclusions: While MCO-HD and OL-HDF had a similar effect on serum PCS and IS concentrations, only OL-HDF combined with the dietary intervention significantly reduced IS levels.
Ključne besede: fiber supplementation, indoxyl sulfate, medium cut-off dialyzer, p-cresyl sulfate, protein-bound uremic toxins
Objavljeno v DiRROS: 24.04.2026; Ogledov: 144; Prenosov: 156
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Povzetek: Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition often accompanied by gastrointestinal (GI) symptoms. Inflammatory proteins in stool have been proposed as potential biomarkers, but evidence remains inconsistent. We compared fecal levels of a1-antitrypsin (A1AT), immunoglobulin A (IgA), and calprotectin (Cal) in 57 children with ASD and 57 biological siblings without ASD. Sibling designs are now preferred to disentangle ASD-specific biology from shared environmental and microbiome factors. Participants were carefully screened to exclude recent antibiotic use, digestive problems, gastrointestinal infections, and abnormal dietary patterns, thereby controlling for major factors known to influence gut inflammatory markers. Methods: Stool samples were thawed, freeze-dried, and proteins extracted using ammonium bicarbonate buffer with sodium deoxycholate. After BCA quantification, samples were reduced, alkylated, spiked with stable isotope– labelled peptides, and digested with trypsin. Peptides were purified and analyzed by UHPLC–MS/MS (Agilent 6495A) in dynamic SRM mode. Quantification used internal standards and normalization to total protein. Ratios of IgA1/IgA2 and S100A8/S100A9 were calculated. ASD severity was evaluated using the Childhood Autism Rating Scale (CARS). Results: Children with ASD showed trends toward higher IgA and calprotectin and lower a1-antitrypsin compared with siblings, but differences were not statistically significant. Subgroup analysis suggested different distribution patterns in moderate versus severe ASD, including higher IgA in the moderate group and altered S100A8/S100A9 ratio in the severe group. These subgroup findings were exploratory, derived from critically underpowered post-hoc analyses (severe subgroup: n = 11 pairs, ~18% power for medium effects), and should be considered hypothesis-generating only, pending validation in adequately powered pre-registered studies. Conclusions: The results are consistent with recent meta-analyses reporting no consistent evidence of gut inflammation in ASD. Larger, sex-matched studies with full assay validation are needed to clarify the role of stool proteins in ASD.
Ključne besede: autism, inflammation, protein biomarkers
Objavljeno v DiRROS: 16.04.2026; Ogledov: 158; Prenosov: 106
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Povzetek: 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.
Ključne besede: autism spectrum disorder, uremic toxins, microbiota–host interactions, p-cresyl sulfate, indoxyl sulfate, gut metabolic dysfunction, urinary biomarkers, Bristol stool chart
Objavljeno v DiRROS: 14.04.2026; Ogledov: 161; Prenosov: 108
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Povzetek: Autism spectrum disorder (ASD) has been associated with disruptions in tryptophan (TRP) metabolism, affecting the production of key neuroactive metabolites. Investigating these metabolic pathways could yield valuable biomarkers for ASD severity and progression. We included 44 children with ASD and 44 healthy children, members of the same family. The average age in the ASD group was 10.7 years, while the average age in the control group was 9.4 years. Urinary tryptophan metabolites were quantified via liquid chromatography—mass spectrometry operating multiple reaction monitoring (MRM). Urinary creatinine was analyzed on an Advia 2400 analyzer using the Jaffe reaction. Statistical comparisons were made between ASD subgroups based on CARS scores. Our findings indicate that children with ASD have higher TRP concentrations (19.94 vs. 16.91; p = 0.04) than their siblings. Kynurenine (KYN) was found at higher levels in children with ASD compared to children in the control group (82.34 vs. 71.20; p = 0.86), although this difference was not statistically significant. The ASD group showed trends of higher KYN/TRP ratios and altered TRP/ indole-3-acetic acid (IAA) and TRP/5-hydroxyindoleacetic acid (5-HIAA) ratios, correlating with symptom severity. Although the numbers of the two groups were different, our findings suggest that mild and severe illnesses involve separate mechanisms. However, further comprehensive studies are needed to validate these ratios as diagnostic tools for ASD.
Ključne besede: autism spectrum disorder, tryptophan, kynurenine, CARS
Objavljeno v DiRROS: 14.04.2026; Ogledov: 109; Prenosov: 79
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