Search Results (1,767)

Acute-on-chronic liver failure (ACLF) is a rapidly progressing and highly lethal clinical syndrome characterized by multiorgan failure, driven primarily by a severe systemic inflammatory response. The pathophysiological cascade, triggered by a “cytokine storm,” subsequently evolves into profound immune paralysis. This phenomenon is driven by the dysfunction of monocytes, neutrophils, and other immune cells, compounded by their impaired cellular energetics resulting from a metabolic shift toward less efficient energy-yielding mechanisms, mainly aerobic glycolysis, with the pentose phosphate pathway contributing NADPH and biosynthetic precursors rather than ATP. This process is further exacerbated by disruptions within the gut–liver axis, wherein severe dysbiosis and impaired intestinal barrier integrity promote pathogen translocation. Beyond the gut, the liver–spleen axis constitutes a second amplification loop: the congested and immunologically remodeled spleen is proposed to sustain portal hypertension, to contribute to the circulating cytokine pool and to relay profibrogenic signals back to the liver. Coupled with generalized endothelial dysfunction, this is thought to contribute to the failure of peripheral organs. This cascade is presented as a synthesizing model of partially overlapping mechanistic hypotheses and heterogeneous evidence—much of it derived from studies in cirrhosis or animal models and still requiring deeper, ACLF-specific investigation rather than a fully established, strictly linear sequence. To date, no specific targeted therapies are available, and liver transplantation remains the sole intervention capable of substantially improving patient prognosis. Experimental immunomodulatory approaches including granulocyte colony-stimulating factor (G-CSF), intravenous albumin supplementation, therapeutic plasma exchange, mesenchymal stem cell therapy, and anti-cytokine agents represent promising therapeutic avenues. Nevertheless, appropriately tailoring these interventions to the evolving pathophysiological phases of the disease remains a significant clinical challenge, underscoring the critical need for developing precision therapies targeted at specific molecular pathways. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common chronic liver disorder in the pediatric population, closely paralleling the global rise in childhood obesity. Increasing evidence highlights the gut–liver axis as a key contributor to MASLD pathogenesis, with gut microbiota dysbiosis influencing hepatic steatosis through multiple interconnected mechanisms, including increased intestinal permeability, endotoxemia, altered bile acid metabolism, and modulation of host energy homeostasis. In children, the characterization of microbiota signatures associated with MASLD remains challenging due to heterogeneity across studies, age-related microbial dynamics, and methodological variability. This review synthesizes current evidence regarding the role of the gut microbiota in pediatric MASLD, focusing on pathogenetic pathways, reported microbial patterns, and microbiota-targeted therapeutic strategies, while incorporating relevant mechanistic evidence from adult studies where pediatric data remain limited. Although several taxa have been repeatedly associated with pediatric MASLD, findings are not yet sufficiently consistent for clinical application. Interventions such as probiotics, prebiotics, and dietary modulation show promising but still preliminary results, with limited high-quality pediatric trials available. A deeper mechanistic understanding and standardized study designs are needed to clarify causality and to support microbiota-based precision approaches in pediatric MASLD management. Full article

The gut microbiome has emerged as a critical determinant of health and disease across virtually all organ systems. In the context of chronic kidney disease (CKD) and renal transplantation, mounting evidence reveals a complex bidirectional relationship between the intestinal microbiota and kidney function—commonly referred to as the gut–kidney axis. Patients with CKD harbor a profoundly altered gut microbial ecosystem characterized by reduced diversity, depletion of beneficial commensal organisms, and expansion of pathobiont taxa capable of generating uremic toxins and pro-inflammatory mediators. These perturbations are further compounded by the uremic milieu itself, dietary restrictions, frequent antibiotic exposure, and the use of immunosuppressive agents following transplantation. The gut–liver–kidney axis adds an additional layer of complexity, linking hepatic metabolism, bile acid signaling, endotoxemia, and systemic immune activation to the progression of renal disease. Gut-derived metabolites—including short-chain fatty acids (SCFAs), bile acids, trimethylamine N-oxide (TMAO), and tryptophan-derived uremic solutes such as indoxyl sulfate and p-cresyl sulfate—serve as molecular mediators of inter-organ crosstalk and have been identified as both biomarkers and therapeutic targets. A growing body of literature supports the diagnostic and prognostic utility of microbiome composition and its metabolic signatures in patients with CKD and those undergoing renal replacement therapy. Therapeutic strategies aimed at restoring microbial homeostasis—encompassing dietary interventions, prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), bile acid–based therapies, and novel pharmacological approaches—hold considerable promise for improving outcomes in CKD and transplant recipients. Importantly, the bidirectional relationship between immunosuppressive drugs and the gut microbiota has emerged as a clinically significant determinant of both microbial ecology and drug pharmacokinetics: each major immunosuppressive agent class—corticosteroids, calcineurin inhibitors, mycophenolate mofetil, and mTOR inhibitors—induces characteristic dysbiotic patterns, while in turn, the microbiota modulates drug bioavailability through enzymatic biotransformation (notably bacterial beta-glucuronidase activity affecting mycophenolic acid enterohepatic recirculation) and modulation of host drug-metabolizing enzymes. This narrative review provides a comprehensive overview of the current understanding of microbiome dysbiosis in the setting of renal disease and transplantation, examines the mechanistic underpinnings of the gut–liver–kidney axis, details the multifaceted impact of dysbiosis on transplant outcomes—including allograft function and rejection, infection, post-transplant diabetes, and cardiovascular complications—and critically appraises the translational potential of microbiome-targeted interventions. We conclude by highlighting ongoing challenges and future directions toward personalized, microbiome-informed clinical care. Full article

The mammalian respiratory system stands as a frontline barrier, constantly exposed to environmental insults, balancing defensive immunity with gas exchange. Historically considered sterile, the lung harbors a dynamic, low-biomass microbiome that evolves continuously in response to pulmonary pathologies. Accumulating evidence underscores that respiratory health and structural recovery are not autonomous but are critically integrated with distal microbial systems, especially the intestinal tract, through the gut–lung axis (GLA). This review characterizes the GLA as a bidirectional communication highway fueled by immune pathways, microbial metabolites, and direct microbial translocations. During acute or chronic injuries, such as COVID-19, COPD, asthma, idiopathic pulmonary fibrosis (IPF) and lung cancer, the gut microbiota serves as a remote metabolic “rheostat”. It delivers pivotal signaling molecules, such as short-chain fatty acids (SCFAs) and tryptophan metabolites (indoles), that could shape the local microenvironment in which the respiratory epithelium undergoes functional repair or maladaptive, fibrotic remodeling. Mechanistically, gut-derived butyrate enhances mitochondrial activity in alveolar epithelial cells, while resident progenitors, such as Alveolar Type 2 (AT2) cells, depend on intact mitochondrial fatty acid oxidation for proper regenerative differentiation. Conversely, critical lung illness disrupts this homeostasis via a “pathological circuit,” where severe pulmonary inflammation drives gut permeability, fecal dysbiosis, and the subsequent translocation of pathogen-associated molecular patterns (PAMPs, such as LPS) or gut-associated bacteria back into the pulmonary circulation. This review highlights the systemic nature of lung regeneration, which likely depends heavily on intestinal health through the GLA. Ultimately, leveraging these remote microbial networks through precision postbiotic supplementation, dietary priming, or microbiota transplantation represents a crucial frontier in precision medicine to promote definitive alveolar repair. Full article

Background: Mung bean soup (MBS), as a common form of mung bean consumption, is widely consumed in folk to relieve summer heat. However, MBS is prone to red discoloration during cooking and storage. Furthermore, how this color change affects its phenolic compounds composition and bioactivity remains poorly understood. Objectives: Herein, this study systematically compared the phenolic profiles and heat stress (HS)-alleviating effects of normal mung bean soup (NMBS) and reddened mung bean soup (RMBS). Methods: Male C57BL/6J mice (six-week-old) were randomly assigned to four groups: control (no HS), HS, HS-NMBS, and HS-RMBS. HS was induced at 40 °C for 2 h/day for 7 days, with NMBS or RMBS provided ad libitum throughout the experiment. Phenolic analysis, oxidative stress markers, inflammatory cytokines, and gut microbiota were evaluated. Results: The results showed that reddening significantly reduced the total phenolic and flavonoid contents by 18.28% and 16.77%, respectively, accompanied by the loss of key bioactive compounds (vitexin and isovitexin). NMBS and RMBS could effectively alleviate HS-induced physiological damages in mice to varying degrees, including reduced weight loss, improved hepatic and intestinal histopathology, and lower levels of oxidative stress and inflammation (p < 0.05). However, NMBS provided superior overall protection by downregulating the expression of HS-associated genes (PPAR-γ) and pro-inflammatory cytokines (IL-1β), while upregulating the anti-inflammatory cytokine IL-10. Furthermore, supplementation with NMBS or RMBS restored the gut microbiota dysbiosis induced by HS. Especially, NMBS was more effective in restoring microbial diversity, modulating the F/B ratio, and enriching beneficial bacteria including Lactobacillus, Dubosiella, and norank_f_Muribaculaceae. Conclusions: These results highlight the importance of avoiding the occurrence of redness in MBS to maximize its efficacy. Full article

Background/Objectives: Many HIV-positive (HIV+) males receiving highly active antiretroviral therapy (HAART) experience metabolic complications, including non-alcoholic fatty liver disease (NAFLD); lipodystrophy; and intestinal dysbiosis, often characterized by a Prevotella-rich enterotype. Gut microbial fermentation produces short-chain fatty acids (SCFAs), which play important roles in host metabolism. This study investigated the relationships among HAART, anthropometrics, diet, intestinal permeability, gut microbiota composition, and lipodystrophy in HIV+ males. Methods: Forty males aged 23–60 years were enrolled, including 19 HIV+ participants recruited from the East Tennessee State University (ETSU) Health Infectious Diseases Specialty Clinic and 20 HIV-negative (HIV−) controls recruited through standard methods. Participants provided a stool sample for 16S rRNA gene sequencing, SCFA analysis by gas chromatography, and proximate analysis, and completed a food frequency questionnaire. Lipodystrophy-related measures included body mass index (BMI), hip-to-waist ratio (H:W), and liver health assessment using FibroScan. Blood samples were collected by venipuncture. Serum markers of intestinal permeability, including Claudin-21, flagellin, and intestinal fatty acid-binding protein (IFABP), were quantified by enzyme-linked immunosorbent assay (ELISA). Results: HIV+ males exhibited significantly higher H:W ratios (p = 0.001) and hepatic steatosis (p = 0.0047) than HIV− controls (Welsh’s t-test). Concentrations of isobutyrate (p = 0.0024), isovalerate (p = 0.0008), and valerate (p = 0.0329) were elevated in HIV+ participants, whereas butyrate (p = 0.0014) and total acetate/propionate/butyrate (APB) (p = 0.0046) were higher in HIV− males (Welsh’s t-test). HIV+ participants also showed greater abundances of Prevotella and Lachnospiraceae (Analysis of Compositions of Microbiomes; ANCOM). Retrospective analysis revealed that all HIV+ participants were men who have sex with men (MSM). Conclusions: HIV+ males demonstrated distinct gut microbiome profiles, altered SCFA production, and markers of disrupted lipid metabolism. These findings provide a foundation for future investigations of microbiome-metabolism interactions in HIV+ MSM. Full article

Background: Recent scientific evidence indicates that the oral–gut axis represents a critical interface in host–microbiota interactions, carrying profound implications for both periodontal and gastrointestinal diseases. This scoping review aims to evaluate the reciprocal influence between periodontitis and inflammatory bowel disease (IBD). Specifically, the underlying mechanisms of microbial translocation, immune interaction, and metabolite-mediated signaling linking the oral microbiota to gut microbial ecology are critically evaluated. Methods: Studies were selected from the PubMed, Web of Science, and Scopus databases up to May 2026. Eligible criteria included in vivo studies written in English and conducted within the last 10 years, whereas human studies involving participants under 18 years of age were excluded. The included studies analyze the effects of oral and gut dysbiosis on the opposing district. Through the database search, 2094 records were identified, and 34 articles were selected based on the eligibility criteria. Results: The included studies demonstrate the interconnection between the oral and gut microbiota. The included studies reveal that predominant oral taxa, specifically Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans, alter intestinal microbial composition. In particular, P. gingivalis colonizes the gut, exacerbating both oral and intestinal inflammation by stimulating pro-inflammatory cytokine expression via Th17 cell activation. Finally, salivary microbial composition appears to be associated with the presence and status of IBD. Conclusions: Understanding these interconnected microbial ecosystems provides valuable insights that may support the future development of integrated diagnostic and therapeutic strategies for patients suffering from periodontitis and IBD. Further large-scale studies with longer follow-up periods are required to standardize potential salivary markers and multidisciplinary therapeutic protocols for the management of periodontitis and IBD. Full article

The gut microbiome is a dynamic ecosystem that plays essential roles in host metabolism, immune regulation, colonization resistance, and maintenance of intestinal homeostasis. Antibiotic exposure profoundly disrupts this ecosystem by reducing microbial diversity, depleting beneficial commensals, reshaping microbial metabolic functions, and remodeling the gut resistome through the selection and dissemination of antibiotic resistance genes (ARGs). Increasing evidence from longitudinal metagenomic, multi-omics, and experimental studies indicates that these perturbations may persist long after antibiotic withdrawal due to incomplete ecological recovery, sustained mobile genetic element-mediated ARG dissemination, and altered microbiome resilience. Beyond antimicrobial resistance, antibiotic-induced dysbiosis has been associated with reduced short-chain fatty acid production, altered bile acid metabolism, impaired epithelial barrier function, and broader disturbances in host metabolic homeostasis, although many of these relationships remain associative rather than causal. This review provides an integrated overview of antibiotic-driven gut microbiome dysbiosis, emphasizing the ecological, functional, metabolic, and resistome-level consequences of antibiotic exposure together with the mechanisms governing microbiome recovery. Current microbiome-targeted restoration strategies, including probiotics, phage therapy, fecal microbiota transplantation, and next-generation microbiome therapeutics, are critically evaluated with particular attention to their evidence maturity, limitations, and translational potential. Finally, key knowledge gaps and future research priorities are discussed to support the development of more effective microbiome-preserving antimicrobial strategies and to limit the long-term dissemination of antimicrobial resistance. Full article

Background: Obesity and mental disorders are associated with gut microbiota dysbiosis and gut–brain axis dysfunction. This secondary analysis evaluated the effects of a 12-week weight loss program (WLP) based on a hypocaloric traditional Mexican diet (TMD) and moderate-intensity exercise on gut microbiota, body composition (BC), and metabolic parameters in Mexican adults with obesity with and without depression and anxiety symptoms. Methods: A total of 106 adults with obesity were classified based on the presence or absence of depressive and anxiety symptoms into an obesity control group without symptoms (OCG), improved symptoms (OIS), and persistent symptoms (OPS). Stool samples were analyzed by sequencing the V3–V4 region of the 16S rRNA gene. Longitudinal changes in serum biochemistry, BC, intestinal permeability markers, and gut microbiota were analyzed using linear mixed-effects models. Differential taxa were identified using linear discriminant analysis effect size (LEfSe), and associations between bacterial genera, biochemical variables, and dietary components were explored using MaAsLin 2. Results: The WLP significantly improved metabolic, inflammatory, intestinal permeability, and BC markers, as well as depressive and anxiety symptoms, although participants remained in WHO grade I obesity. These improvements were accompanied by selective, group-dependent modulation of bacterial genera rather than broad microbiota restructuring. LEfSe identified 22 taxonomic biomarkers: 16 in OPS, 5 in OIS, and 1 in OCG. Conclusions: The culturally adapted WLP, which combined a hypocaloric TMD with exercise, promoted improvements in metabolism and BC in all participants, along with group-specific gut microbiota remodeling that may be associated with differential changes in depressive and anxiety symptoms in the context of persistent obesity. Full article

Intestinal microbiome dysbiosis has been associated with transplant-related mortality and graft-versus-host disease in allo-HSCT patients. We assessed how pre-transplant antibiotic and antineoplastic exposures, together with multidrug-resistant colonization, are associated with baseline gut microbiome diversity at allo-HSCT. We conducted a prospective, single-center cohort study at Fundeni Clinical Institute (Bucharest, Romania) between August 2024 and June 2025, enrolling 52 allo-HSCT recipients and 27 healthy controls. Fecal samples were collected before conditioning. Gut microbiome composition was assessed via 16S rRNA gene sequencing and analyzed using QIIME2 and R. Associations were evaluated using Wilcoxon test, multivariable linear regression, and PERMANOVA. Shannon diversity was significantly lower in patients (median 4.71, IQR 3.97–5.44) than in healthy controls (median 6.09, IQR 5.87–6.28; p < 0.001). In bivariate analyses, carbapenem (p adj = 0.02) and oxazolidinone exposure (p adj = 0.005) were associated with reduced diversity, while immunotherapy was associated with higher diversity (p adj = 0.042). Broad-spectrum penicillin (p adj = 0.062) and ESBL colonization (p adj = 0.066) did not reach significance. In the multivariable antibiotic model, although the overall model was statistically significant (model p = 0.039), no individual antibiotic class remained significantly associated with Shannon diversity after adjustment for co-exposures. Beta diversity differed modestly with carbapenem exposure (R² = 0.033, p = 0.019). Pre-transplant antibiotic exposures were associated with lower gut microbiome diversity at allo-HSCT admission, with patterns consistent with a cumulative rather than a class-specific association. These findings support antibiotic stewardship in pre-transplant care. Full article

Chemotherapy-induced gastrointestinal toxicity represents a major clinical challenge, with accumulating evidence implicating gut microbiota dysbiosis in reduced treatment tolerance. Ifosfamide is a widely used alkylating agent; however, its effects on gut microbial community structure remain incompletely understood. This preclinical study investigated ifosfamide-associated microbiota alterations and evaluated the microbiota-modulating potential of gallic acid as a supportive intervention. Male rats were assigned to control, ifosfamide, gallic acid, and combined ifosfamide + gallic acid groups. Fecal samples were collected longitudinally and analyzed using full-length 16S rRNA gene sequencing for high-resolution taxonomic profiling. At the phylum level, ifosfamide exposure induced a marked decrease in Bacillota accompanied by a significant expansion of Bacteroidota, reflecting a dysbiotic shift associated with intestinal stress. Genus-level analysis revealed substantial reductions in beneficial taxa, including Lactobacillus, Ligilactobacillus, and Blautia, alongside enrichment of stress-adaptive and opportunistic genera such as Romboutsia and Segatella. Species-level profiling demonstrated significant depletion of mucosa-associated lactic acid bacteria, including Lactobacillus johnsonii, Lactobacillus intestinalis, and Ligilactobacillus murinus, following ifosfamide treatment. Conversely, opportunistic taxa such as Romboutsia ilealis and Segatella copri and transient increases in Escherichia coli were observed, consistent with chemotherapy-induced intestinal perturbation. Gallic acid administration partially preserved microbial diversity, attenuated the expansion of opportunistic taxa, and supported recovery of beneficial bacteria, resulting in an intermediate microbial profile under combination treatment. These findings provide preclinical evidence that gallic acid mitigates ifosfamide-associated gut dysbiosis and highlight gut microbiota modulation as a potential adjunctive strategy to improve chemotherapy tolerance. Further translational and clinical investigations are warranted. Full article

Background/Objectives: Clostridioides difficile infection (CDI) is an increasingly recognised nosocomial complication in patients hospitalised with coronavirus disease 2019 (COVID-19), driven by broad-spectrum antibiotic exposure, corticosteroid use, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related intestinal dysbiosis. The contribution of underlying cardiovascular comorbidities, particularly heart failure, to CDI susceptibility in hospitalised COVID-19 patients remains insufficiently characterised. We aimed to evaluate the prevalence, risk factors, and clinical impact of CDI in hospitalised COVID-19 patients at a tertiary Romanian infectious diseases centre, with a specific focus on cardiovascular disease and modifiable antimicrobial-prescribing factors. Methods: This single-centre retrospective observational cohort study enrolled 395 consecutive adult patients hospitalised with SARS-CoV-2 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) at the “Victor Babeș” Clinical Hospital for Infectious Diseases and Pneumophthisiology, Timișoara, Romania, between 1 March 2020 and 31 December 2024. Patients were stratified into a CDI group (n = 24) and a non-CDI group (n = 371) on the basis of hospital-onset CDI. Demographic, clinical, laboratory, therapeutic, and outcome variables were extracted from electronic medical records. Continuous variables were compared using Student’s independent-samples t-test, categorical variables using Fisher’s exact test; odds ratios (ORs) with exact 95% confidence intervals (CIs) were computed for all binary comparisons, and a parsimonious multivariable logistic regression was used to adjust the antibiotic-exposure effect for age. Temporal relationships between CDI onset and sepsis documentation were also analysed. A two-sided p-value < 0.05 was considered statistically significant. Results: CDI was identified in 24 patients (prevalence 6.1%). The CDI and non-CDI groups were comparable in age (71.1 ± 10.2 vs. 71.7 ± 11.4 years; p = 0.817), sex distribution (50.0% vs. 45.8% female; p = 0.833), and vaccination status (p = 0.383). Heart failure prevalence did not differ between groups (29.2% vs. 26.7%; OR 1.13, 95% CI 0.46–2.81; p = 0.813). Any antibiotic therapy was strongly associated with CDI (95.8% vs. 70.6%; OR 9.57, 95% CI 1.28–71.74; p = 0.004), as was longer duration of antibiotic therapy (8.1 ± 2.2 vs. 5.2 ± 3.7 days; p < 0.001). In the multivariable model, each additional day of antibiotic therapy was independently associated with a 13.6% increase in the odds of CDI (adjusted OR 1.14 per day, 95% CI 1.03–1.26; p = 0.013) after adjustment for age. Piperacillin/tazobactam accounted for 65.2% (15/23) of the recorded pre-CDI broad-spectrum antibiotic regimens among antibiotic-exposed CDI patients. Documented sepsis was substantially more frequent in CDI patients (95.8% vs. 15.4%; p < 0.001) and length of hospitalisation was prolonged (15.6 ± 8.2 vs. 12.0 ± 8.1 days; p = 0.038). In-hospital mortality did not differ significantly (4.2% vs. 7.5%; p = 1.000). Conclusions: Hospital-onset CDI complicated 6.1% of hospitalised COVID-19 admissions and was independently associated with the cumulative duration of antibiotic therapy. Heart failure was not significantly associated with CDI in this cohort; however, given the limited number of CDI events, this should be interpreted as absence of evidence rather than evidence of absence. CDI was also associated with prolonged hospitalisation and high co-occurrence of documented sepsis, although causality cannot be inferred from the retrospective design. These findings support strengthened antibiotic stewardship and targeted CDI surveillance in COVID-19 inpatient wards. Full article

Intestinal dysbiosis is a hallmark of both inflammatory bowel conditions and colorectal cancer, yet the mechanisms by which inflammatory mediators alter microbial communities and may contribute to tumor development remain poorly understood. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in innate immunity and the progression of inflammatory and neoplastic disorders. In this study, sequencing of the microbial 16S rRNA gene was performed to characterize the fecal microbiota profiles of wild-type (WT) and MIF-knockout (MIF-KO) BALB/c mice subjected to AOM/DSS-induced colitis-associated colorectal cancer (CAC). CAC induction resulted in marked microbial shifts, including increases in Muribaculaceae and Bacteroidota, in both WT and MIF-KO mice. Notably, MIF-KO CAC mice developed more severe disease compared with WT CAC mice. Furthermore, FMT experiments revealed that the fecal microbiota from MIF-KO donors was associated with increased tumor burden in WT recipients under CAC-inducing conditions compared with that in recipients colonized with WT-derived microbiota. Together, these findings suggest that MIF deficiency is associated with gut microbiota remodeling during CAC and support a potential relationship between the MIF-dependent host context, microbial composition and colorectal cancer severity. Full article

Background: Immune dysregulation and gut dysbiosis are increasingly implicated in autism spectrum disorder (ASD), but compartment-specific intestinal cytokine profiles remain poorly defined. Aim: To characterize stool cytokine profiles and pro-/anti-inflammatory balance in children with ASD across development. Methods: We analyzed stool samples from 283 children (109 controls, 104 mild ASD, 70 severe ASD; age 0.9–21.5 years) recruited at a tertiary centre. Nine cytokines (IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, TNF-α) were measured using a Luminex multi-plex assay; IL-15 was excluded due to >70% missing values. Group comparisons used Mann–Whitney U tests, with age stratification at the cohort median (≤9.5 vs. >9.5 years). A composite pro-/anti-inflammatory ratio (IL-1α + IL-1β + IL-6 + IL-8 + IL-17 + TNF-α + IFN-γ divided by IL-4 + IL-10) was calculated. Results: In the overall cohort, stool IL-8 and IL-4 were significantly decreased in ASD versus controls (IL-8: median 0.36 vs. 0.49 ng/L, p = 0.0041; IL-4: 0.28 vs. 0.30 ng/L, p = 0.0316), with a graded reduction from controls to mild and severe ASD. Age-stratified analysis revealed that IL-8 reduction was confined to younger children (≤9.5 years; p = 0.0025) and absent in older children, while IL-1β was significantly reduced in younger ASD children and tended to reverse in older ASD children. The pro-/anti-inflammatory ratio was markedly elevated in severe ASD (median 491 vs. 209 in controls; p = 0.059), particularly in older children. Stool IL-8 and IL-1β correlated inversely with CARS scores within the ASD group. Conclusions: Children with ASD show decreased stool IL-8 and IL-4 and a shift toward a pro-inflammatory cytokine balance, with the strongest alterations during early childhood. These findings are consistent with the hypothesis of a developmental window of intestinal immune dysregulation in ASD, with stool IL-8 as the primary FDR-corrected finding. The present cross-sectional data do not establish causality and independent replication is required before clinical conclusions are drawn. Full article

Non-celiac gluten sensitivity (NCGS), even though it is a term defined for more than four decades, is still an enigmatic clinical entity. This is primarily due to the absence of specific diagnostic criteria, with most reports relying on patients’ self-diagnosis. Individuals with NCGS experience intestinal (abdominal pain, bloating, diarrhea, or constipation) and extraintestinal symptoms (“foggy mind,” depression, anxiety, and deterioration of psychiatric conditions) after gluten consumption. Frequent disregard and oversight of extraintestinal manifestations, such as psychiatric symptoms, further complicates NCGS. The lack of understanding about NCGS causes individuals living with this condition to experience distress, frustration, and stigmatization. An impaired intestinal barrier, gut dysbiosis, and alterations in the gut–brain axis are proposed as key factors in the NCGS and psychiatric symptoms associated with NCGS. None of these links are yet definitive, and the methodological limitations of existing studies—small samples, self-reported diagnoses, and insufficient blinding—demand that conclusions be drawn with appropriate restraint. The purpose of this review is to provide an up-to-date understanding of the pathophysiology of NCGS and psychiatric symptoms associated with NCGS. Future studies should focus on development of reliable, objective diagnostic markers for NCGS and on the design of adequately powered, double-blind, placebo-controlled trials that incorporate validated psychiatric outcome measures alongside intestinal indices. Full article