Search Results (5,339)

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/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which gut–skin axis dysregulation is increasingly implicated. We conducted a prospective pilot study to describe the clinical evolution of pediatric AD following individualized, stool-guided microbiota-targeted therapy and to explore whether baseline dysbiosis markers predict outcomes beyond baseline disease severity. Methods: Twenty-one children with AD and laboratory-confirmed gut dysbiosis were enrolled consecutively at a tertiary pediatric center in Romania in a single-arm prospective pilot study. Gut microbiota was assessed using targeted culture-based stool analysis, generating a Flora Index and a binary High Putrefaction Flora classification. Individualized treatment consisted of strain-specific probiotics, prebiotics, and antifungals when indicated. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) at baseline, 30 days, and 90 days. Longitudinal changes were evaluated using repeated-measures ANOVA and hierarchical regression models. Results: High Putrefaction Flora was present in 71.4% of participants. Mean POEM decreased from 14.67 ± 5.22 at baseline to 7.10 ± 3.82 at 90 days, while mean SCORAD decreased from 41.66 ± 15.28 to 17.93 ± 11.68 (both p < 0.001). Approximately 76% of participants achieved a ≥50% reduction in POEM, and 71% achieved a ≥50% reduction in SCORAD. Individualized microbiota-targeted therapy was associated with substantial improvements in both clinical and patient-reported disease severity over the 90-day follow-up. Although children with High Putrefaction Flora exhibited higher disease severity scores in unadjusted analyses, baseline disease severity was the only significant predictor of 90-day outcomes. The Flora Index provided no independent explanatory value. Conclusions: In this exploratory single-arm pilot study, individualized microbiota-targeted therapy was associated with substantial and clinically meaningful improvement in AD severity over 90 days. Dysbiosis markers were associated with disease burden but did not independently predict outcomes, suggesting that they may function primarily as indicators of baseline severity rather than prognostic biomarkers. Because of the uncontrolled study design, causal inferences regarding treatment effects cannot be made, and these findings should be considered hypothesis-generating. Adequately powered randomized controlled trials are required to determine the efficacy of individualized microbiota-targeted interventions in pediatric atopic dermatitis. Full article

Lameness is a major welfare and economic disorder in dairy production and a clinical sign with multiple causes. This review focuses on claw horn disruption lesions (CHDL), a major cause of periparturient lameness. Although hoof-centered prevention and treatment remain essential, preclinical systemic alterations, recurrence, and clustering with other transition-period disorders suggest that CHDL may sometimes represent the local expression of broader pathophysiology. We propose the Lameness Triad, in which three mechanisms converge: sustained endotoxemic pressure and TLR4-mediated innate immune activation, endothelial glycocalyx degradation and vascular dysfunction, and metabolic triage that reallocates resources from production toward defense. Their combined pathogenic pressure is proposed to produce clinical disease when it exceeds a cow-specific Susceptibility–Resilience Gate comprising mucosal barrier integrity, hepatic endotoxin clearance, immune calibration, redox reserve, hoof structural reserve, and prior damage. Ruminal dysbiosis, mammary involution, and postpartum uterine contamination may contribute to inflammatory and endotoxemic pressure, whereas the confined, continuously loaded digital corium may become a principal site of clinical expression. Longitudinal multi-omics studies identified inflammatory, urinary, and milk-metabolite alterations before diagnosis, with within-cohort serum and urine models discriminating cows that later became lame as early as eight weeks prepartum. These findings require prospective validation and do not establish the complete causal sequence. The framework extends, rather than replaces, established hoof-health programs and provides testable hypotheses for earlier detection, prevention, and selection for resilience. Full article

Persistent HIV-1 reservoirs remain a major barrier to a durable functional cure despite long-term suppressive antiretroviral therapy. Although resting memory CD4⁺ T cells constitute the best-characterized cellular reservoir, tissue microenvironments shape viral persistence and immune clearance. The rectal mucosa represents a specialized tissue niche containing HIV-susceptible target cells, antigen-presenting cells, microbial products, inflammatory cues, and local metabolic signals. Within this setting, myeloid-lineage cells, particularly tissue-resident macrophages and dendritic cells, may contribute to HIV-1 persistence through mechanisms distinct from classical T-cell latency. Here, we review how rectal mucosal macrophages may support HIV-1 persistence through longevity, resistance to apoptosis, metabolic adaptation, epigenetic regulation, and sequestration of virions within virus-containing compartments. We also discuss the dual role of mucosal dendritic cells as sentinels that capture and transfer HIV-1 to CD4⁺ T cells, while considering the limited evidence for inducible proviral persistence in selected anatomical and cellular contexts. Importantly, we further distinguish bona fide reservoir-bearing cells from reservoir-supportive mechanisms, including viral capture, trans-infection, immune suppression, and niche-mediated protection. We also highlight how mucosal dysbiosis, barrier disruption, microbial metabolites, chronic interferon signaling, and immunoregulatory myeloid programs may stabilize HIV-1 persistence in rectal tissues. Integrating intact proviral assays, functional measurements, single-cell profiling, multiplex imaging, and spatial transcriptomics will be critical for defining myeloid-associated persistence and guiding tissue-targeted HIV-1 cure strategies. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by immune dysregulation, microbiota imbalance, and intestinal barrier damage. Unconjugated bilirubin (UCB) shows promise in treating UC due to its anti-inflammatory properties but is limited by poor solubility and potential toxicity. This study developed a chitosan-based controlled-release microsphere (CBMS) treatment to overcome these issues. CBMS utilizes the mucoadhesive properties of chitosan to achieve targeted, controlled UCB release in the colon, enhancing its stability and bioavailability. In a DSS-induced UC mouse model, CBMS alleviated clinical symptoms, reduced colon shortening, and improved histological outcomes, including reduced inflammation and enhanced mucosal repair. The mechanism involves CBMS retention in the intestinal lumen, UCB inactivation of digestive proteases, and restoration of microbiota balance, suppressing pro-inflammatory pathways. CBMS offers a promising new therapeutic strategy for UC and insights into polysaccharide-based drug delivery systems. Full article

Histamine plays an essential role in gastrointestinal physiology and immune control, while its balance in the intestinal environment is largely maintained through degradation by diamine oxidase (DAO), a copper-dependent enzyme mainly produced by differentiated enterocytes. Impaired DAO activity reduces the intestinal barrier to luminal histamine, leading to increased local and systemic exposure and contributing to altered motility, permeability, visceral sensitivity, and immune activation. Accumulating research suggests that disturbances in diamine oxidase regulation contribute to the development of various gastrointestinal diseases, including histamine intolerance, inflammatory and functional bowel disorders, intestinal ischemia, and liver pathology. This review summarizes current knowledge on the biochemistry, localization, and regulation of DAO, as well as histamine signalling via H1–H4 receptors in the gastrointestinal tract. We highlight the interaction between epithelial injury, immune activation, dysbiosis, and histamine accumulation, and discuss the divergent interpretation of mucosal versus circulating DAO activity. Finally, we critically assess the diagnostic limitations of serum DAO and explore emerging therapeutic strategies targeting impaired histamine degradation. Although DAO represents a promising adjunctive biomarker and therapeutic target, its clinical utility requires standardized measurement methods and integrative diagnostic approaches. Full article

Gut microbiota dysbiosis has been associated with ischemic stroke (IS), myocardial infarction (MI), and aging, but whether these contexts share reproducible microbial features remains unclear. We conducted an exploratory and hypothesis-generating descriptive study of genus-level microbiota patterns across an internal IS cohort and publicly available external IS, MI, and age-stratified or longevity-associated datasets. Analyses were performed within predefined age strata and interpreted cautiously because of the small internal cohort, cross-cohort heterogeneity, and the absence of direct metabolite, intestinal barrier, inflammatory, or microbial activity measurements. No taxon in the internal cohort remained statistically significant after false-discovery-rate correction; therefore, all taxonomic observations were treated as descriptive. Candidate overlapping features included repeated detection of Escherichia-Shigella and Klebsiella and non-uniform patterns among genera previously associated with short-chain fatty acid metabolism, including Faecalibacterium, Blautia, and Roseburia. Lachnoclostridium and Bacteroides showed opposite abundance gradients in selected cross-dataset comparisons. These observations suggest possible ecological overlap across ischemic disease and age-associated microbiome contexts, but they do not establish causality, disease-specific biomarkers, or shared microbial function. The mechanistic models discussed in this manuscript are literature-informed hypotheses based on exploratory compositional data and require future validation in larger, harmonized longitudinal cohorts using metagenomic, metabolomic, clinical, and experimental measurements. Full article

Background/Objectives: Psoriatic disease (PsD) is a chronic, systemic inflammatory disorder characterized by a wide spectrum of clinical manifestations extending beyond skin and joint involvement. Increasing evidence suggests a relevant role of the gut microbiota in the pathogenesis of psoriatic arthritis (PsA), although a clear causal relationship remains to be fully established. The aim of this review is to summarize current evidence on the role of the gut microbiome in PsD, with a focus on immune modulation, disease pathogenesis and potential therapeutic implications. Methods: A narrative review of the literature was conducted, focusing on studies investigating gut microbiota composition, dysbiosis patterns, and microbiome-related mechanisms in PsD and PsA, as well as emerging microbiota-targeted interventions. Results: Recent advances in high-throughput sequencing technologies have identified distinct microbial signatures associated with PsA onset and progression. Dysbiosis appears to influence immune system regulation, contributing to systemic inflammation through mechanisms involving intestinal barrier dysfunction and immune activation. Patients with PsA exhibit specific alterations in gut microbial composition compared to healthy controls. Emerging therapeutic strategies targeting the microbiota—including dietary interventions, probiotics, and fecal microbiota transplantation—show potential as adjunctive approaches in disease management, although clinical evidence remains limited. Conclusions: The gut microbiome represents a promising area of research in PsD, offering novel insights into disease mechanisms and potential therapeutic targets. Further studies are needed to clarify causal relationships and to define the clinical applicability of microbiota-based interventions. Full article

Background/Objectives: Alcohol-associated liver disease (ALD) is driven by gut-liver axis dysfunction, including intestinal barrier disruption, dysbiosis, microbial translocation, inflammation, metabolic dysfunction, and malnutrition. Fermented dairy foods may modulate several of these domains, yet whether sheep yogurt, as an intact fermented dairy matrix, is relevant in ALD is unknown. This scoping review mapped evidence relevant to sheep yogurt, ALD, and gut-liver axis biology. Methods: A PRISMA-ScR-guided scoping review searched PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar from January 2006 to February 2026. Eligible sources were charted using a prespecified framework classifying evidence as direct, indirect, or mechanistic inference. Mapped domains included ALD pathophysiology; intestinal barrier integrity; bacterial and fungal microbial ecology; bile acid and tryptophan-aryl hydrocarbon receptor signaling; nutritional vulnerability; fermented dairy interventions; and ovine dairy-matrix characteristics. Results: Of 1388 records identified, 121 sources were included after duplication and screening. No eligible study directly tested sheep yogurt or a defined sheep yogurt preparation in ALD-relevant experimental or clinical settings. Indirect evidence supported the relevance of gut-liver axis dysfunction to ALD and indicated that selected fermented dairy products, probiotics, postbiotics, and microbial preparations may influence intestinal permeability, inflammatory signaling, microbial ecology, oxidative stress, and liver-injury outcomes. Compositional data supported sheep yogurt as a distinct food matrix. However, findings from isolated components, probiotic-only interventions, and non-ALD models could not be interpreted as evidence of sheep yogurt efficacy in ALD. Conclusions: The current literature supports a hypothesis-driven research framework rather than any therapeutic claim for sheep yogurt in ALD. Any potential benefit of sheep yogurt in ALD remains hypothetical and cannot support clinical or dietary recommendations until validated experimentally. Future direct, comparator-controlled studies of intact sheep yogurt should assess liver injury, barrier integrity, microbial translocation, relevant metabolites, and nutrition-related outcomes. Full article

Background/Objectives: The skin microbiome maintains barrier integrity, immune homeostasis, and pathogen defense; dysbiosis contributes to acne vulgaris, dandruff, seborrheic dermatitis, atopic dermatitis, psoriasis, and alopecia. This scoping review critically appraised evidence on prebiotics, probiotics, synbiotics, postbiotics, and paraprobiotics in dermo-cosmetics for acne vulgaris and scalp disorders. Methods: A scoping search (2006–2026) covered SciELO, PubMed/PMC, Google Scholar, CAPES Portal, Scopus, Heliyon, Frontiers, Nature, Wiley, and MDPI, following PRISMA 2020 guidelines. Results: Of 1665 records, 66 were included. For acne, effective prebiotics included blackcurrant, grape seed, ginseng, trehalose, and glucomannan hydrolysate; effective probiotic strains included Streptococcus thermophilus, Bifidobacterium longum, Staphylococcus epidermidis, and Streptococcus salivarius. A synbiotic (B. breve BR03, Lacticaseibacillus casei LC03, Ligilactobacillus salivarius LS03) reduced inflammatory lesions by 56.67% in an 8-week RCT (n = 114). For scalp disorders, oral Lacticaseibacillus paracasei ST11 reduced dandruff by 70% vs. 23% (placebo); Lactiplantibacillus plantarum TCI999 increased hair root diameter (n = 50, 12 weeks); a Lacticaseibacillus rhamnosus plus Bifidobacterium longum mixture improved alopecia areata by 56% vs. 30% (n = 26, 24 weeks). Conclusions: Biotic dermo-cosmetics can modulate the cutaneous microbiome and attenuate inflammation in acne and scalp disorders, with strongest evidence for multi-strain/synbiotic formulations. Formulation stability, strain specificity, regulatory heterogeneity, and lack of standardized microbiological endpoints remain key challenges; larger standardized RCTs with active comparators are needed. Full article

In this study, we evaluated the effects of a commercial blend of organic acids (formic acid and propionic acid) added to drinking water on the microbiota of broilers experimentally challenged with Salmonella enterica serovar Minnesota. A total of 108 broilers were randomly assigned to three groups, each with 36 birds: the Treatment group (treated with organic acids + challenge), a Positive Control group (challenge only), and a Negative Control group (no challenge). At seven days of age, broilers in the Treatment group received the organic acid blend through their drinking water (0.2 mL/L/drinking water). At nine days of age, broilers from the challenged groups were inoculated via feed with S. Minnesota (Treatment group—mean: 1.45 × 10⁴ CFU/g; Positive Control group—mean: 3.47 × 10⁴ CFU/g). Swab samples were collected for Salmonella enumeration and cecal content for bacterial community profiling using 16S-rDNA gene sequencing. Our results demonstrated that supplementation with organic acids positively modulated the cecal microbiota of broilers under S. Minnesota challenge. Broilers receiving the organic acid blend showed improvements in microbial community composition, including an increased abundance of bacterial genera associated with butyrate production, which are recognized for their beneficial effects on intestinal health. Overall, our findings suggest that the blend of organic acids may serve as a nutritional strategy for supporting intestinal health and microbiota stability in broilers challenged with S. Minnesota. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

Background: Dysbiosis, mucosal inflammation and increased intestinal permeability have been implicated in the pathophysiology of irritable bowel syndrome (IBS). Objective: To evaluate the effectiveness of a sequential butyrate–probiotic administration in reducing symptoms and improving stool consistency in patients with diarrhea-predominant (IBS-D) or mixed-type IBS (IBS-M). Methods: Two hundred adult patients were allocated to intervention (n = 105) or control (n = 95). The intervention group received ColonLife formulation (Εuro-Pharma S.r.l., Torino—Italy), consisting of two distinct capsules: the first containing butyric acid and grapefruit seed extract, and the second containing microencapsulated probiotic strains together with fructooligosaccharides (FOSs). Symptom severity, quality of life and stool consistency (Bristol Stool Scale) were assessed at baseline and three follow-up visits. Results: Baseline characteristics were comparable between groups (p > 0.05). Diarrhea severity decreased significantly in the intervention group (3.78 ± 1.01 to 3.31 ± 1.21; Δ − 0.47) compared with minimal change in controls (3.71 ± 1.05 to 3.62 ± 1.14; Δ − 0.08; p = 0.015). Stool consistency improved more in the intervention group (−1.18 ± 1.46 vs. −0.64 ± 1.41; p = 0.028), with normal stools increasing from 1.0% to 65.7% versus 4.2% to 36.8% in controls (p < 0.001). The degree of change in pain scores was similar between the two groups (p > 0.05). The degree of reduction in bloating scores was also similar between groups (p > 0.05). Quality of life improved in both groups (intervention: +0.68 ± 1.43; control: +0.71 ± 1.64; both p < 0.01), with no significant difference between groups (p > 0.05). Conclusions: Sequential butyrate–probiotic administration significantly improves diarrhea, stool consistency and gastrointestinal symptoms in IBS-D and IBS-M, supporting its role as a microbiota-targeted treatment. Full article

Background: Dental caries is a highly prevalent, biofilm-mediated disease characterized by microbial dysbiosis, excessive acid production, and progressive enamel demineralization. Although traditionally managed through restorative treatment, increasing attention has shifted toward preventive strategies focused on modulation of the oral microbiota and maintenance of ecological balance within the oral cavity. Methods: This narrative review summarizes current evidence regarding the ecological and mechanistic basis of dental caries and microbiota-centered prevention strategies. Literature published between January 2000 and March 2026 was retrieved from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar using keywords related to dental caries, oral microbiota, cariogenic bacteria, biofilms, probiotics, prebiotics, salivary diagnostics, metabolomics, quorum sensing, and artificial intelligence. Results: Current evidence demonstrates that dental caries is driven by ecological shifts favoring acidogenic and aciduric microorganisms within cariogenic biofilms. Emerging preventive approaches include dietary modification, oral hygiene optimization, probiotics, prebiotics, synbiotics, and functional dietary agents aimed at restoring microbial homeostasis and inhibiting cariogenic biofilm maturation. In addition, advances in salivary microbiome profiling, metabolomics, artificial intelligence-assisted predictive modeling, and smart responsive materials have shown promising potential for improving early diagnosis, risk assessment, and personalized prevention strategies. Conclusions: Microbiota-based approaches represent a promising paradigm shift in dental caries prevention by emphasizing ecological modulation rather than pathogen eradication alone. Continued interdisciplinary research integrating microbial ecology, diagnostics, biomaterials, and digital technologies may facilitate the development of personalized and preventive oral healthcare strategies. Full article

Background: Recurrent implantation failure (RIF) remains one of the most challenging conditions in reproductive medicine. Although increasing evidence implicates chronic endometritis (CE) and alterations of the endometrial microbiota in impaired implantation, the potential contribution of gastrointestinal dysfunction and intestinal dysbiosis remains poorly characterized. We hypothesized that, in a subgroup of women with pure RIF, reproductive failure may be associated with a broader mucosal phenotype involving both intestinal and endometrial compartments. Objective: To characterize the coexistence of gastrointestinal disorders, intestinal dysbiosis, CE, and endometrial microbial alterations in women diagnosed with pure RIF, and to descriptively report reproductive outcomes observed during subsequent multidisciplinary clinical management. Methods: This retrospective, single-centre, observational, hypothesis-generating study included women who met the strict ESHRE criteria for pure RIF, and were assessed at the “Federico II” IVF Centre, Naples, Italy. Patients underwent multidisciplinary assessment combining reproductive medicine, outpatient hysteroscopy, gastroenterological evaluation according to Rome IV criteria, conventional microbiological investigation and paired intestinal and endometrial microbiome characterization by 16S rRNA sequencing. Following clinical assessment, individualized gastroenterological management was undertaken according to routine practice. Reproductive outcomes were descriptively recorded during follow-up. Results: 19 women were analysed, all of whom met the Rome IV guidelines, and showed hysteroscopic and histologic signs of CE. Gut dysbiosis was identified in 94.7% (18/19) of patients, whereas endometrial microbial alterations were observed in 78.9% (15/19). In 84.2% (16/19) of the cohort, microbial profiles characterized by an abundance of Enterobacteriaceae in the intestinal and/or endometrial compartments were detected. Conventional microbiological positivity was present in less than half of patients, highlighting the distinction between microbiological infection and ecological microbial imbalance. During the follow-up period following completion of the personalized multidisciplinary treatment program, which included the administration of a well-characterized probiotic strain, Escherichia coli Nissle 1917, 11 women (57.9%) achieved a clinical pregnancy. Dysbiosis of the intestine was reported in 94.7% (18 out of 19) of participants, whereas endometrial microbiota disturbances were present in 78.9% (15 out of 19) of subjects. The Enterobacteriaceae-enriched microbiota profiles affecting the intestine and/or endometrium were seen in 84.2% (16 out of 19) of subjects. Out of 19 patients, 11 (57.9%) conceived during the follow-up period after gut-targeted treatment comprising Escherichia coli Nissle 1917. Conclusions: Women who meet strict criteria for pure RIF may represent a clinically identifiable subgroup characterized by the coexistence of gastrointestinal disorders, intestinal dysbiosis, CE, and endometrial microbial alterations. Rather than demonstrating therapeutic efficacy, the present study provides a translational and hypothesis-generating framework supporting the need for prospective validation of this integrated biological phenotype in women with pure RIF before evaluating personalized multidisciplinary management. Prospective controlled studies are warranted to evaluate whether gut-directed interventions may influence reproductive outcomes in this population. Full article