Search Results (222)

Background: The dynamic advancement of pediatric hemato-oncology and intensified therapeutic protocols have significantly increased survival rates while simultaneously highlighting the challenge of long-term treatment complications. Within the cohort of adolescent and young adult (AYA) survivors, delayed neurocognitive deficits, often manifesting as the chemobrain phenotype, and psychosocial disorders constitute a particularly substantial burden. Contemporary neurogastroenterological evidence indicates a fundamental role of persistent dysbiosis and gut–brain axis dysfunction in the pathogenesis of these alterations. This review aims to critically synthesize translational evidence elucidating the impact of iatrogenic gut microbiota damage and modifiable dietary patterns on the development of long-term neurocognitive sequelae in survivors of early childhood cancer. Methods: A systematized narrative review was conducted in accordance with the SANRA guidelines by integrating data from in vivo models and observational studies. A comprehensive literature search across the PubMed, Embase, Cochrane Central, Scopus, and Web of Science databases up to June 2026 was performed utilizing the Population, Exposure, and Outcomes (PEO) framework. Results: Oncological therapies, including myeloablative conditioning and broad-spectrum antibiotic therapy, induce a microbial scar phenomenon characterized by the depletion of commensal Firmicutes in favor of resistant pathobionts. The subsequent decline in the synthesis of neuroprotective short-chain fatty acids (SCFAs) alongside the pathological activation of the kynurenine pathway disrupts central nervous system homeostasis. Translocation of lipopolysaccharides (LPSs) across the compromised intestinal barrier generates systemic inflammation recognized as inflammaging, which, in turn, stimulates neurotoxic microglial hyperreactivity. This pathophysiological cascade is accelerated by a pro-inflammatory Western diet, whereas anti-inflammatory interventions such as the MIND diet and postbiotics demonstrate measurable restorative potential. Conclusions: The pathophysiology of delayed neurotoxicity is largely a consequence of systemic neuroinflammation driven by intestinal dysbiosis. Implementing individualized dietary and microbiome-targeted strategies into survivorship care protocols constitutes a crucial direction for clinical prophylaxis. Validating their clinical efficacy in the AYA population necessitates prospective randomized controlled trials integrated with shotgun metagenomic sequencing. Full article

Parturient paresis remains a major economic challenge in global ruminant production, causing acute periparturient hypocalcemia and predisposing high-yielding animals to a cluster of secondary pathologies. Traditional narratives often treat regulatory pathways in isolation, whereas this review synthesizes multi-organ endocrine networks to address the kinetic dyssynchrony between mammary calcium drain and homeostatic recruitment velocity. Beyond the classical parathyroid hormone–vitamin D axis, we integrate the mammary–gut–bone axis into a unified endocrine model, highlighting the critical role of the serotonin–parathyroid hormone-related protein rheostat for skeletal mineral mobilization and the fibroblast growth factor 23–Klotho axis in prepartum phosphorus-induced feedback suppression. We evaluate the molecular mechanisms underlying target-organ receptor resistance, driven by vitamin D receptor downregulation and epigenetic aging, which precipitate homeostatic feedback failure. Regarding clinical management, this synthesis contrasts reactive parenteral interventions with proactive nutritional priming strategies, such as negative dietary cation–anion difference acidification, zeolite-based gastrointestinal binders, and exogenous vitamin D or 5-hydroxytryptophan supplementation. Additionally, the role of microbiota-derived short-chain fatty acids in gut-bone communication and the potential of genomic selection to breed livestock with heritable metabolic resilience are explored. Ultimately, this comprehensive framework emphasizes a paradigm shift from emergency treatment to precision nutritional and genetic prophylaxis to mitigate PP across diverse ruminant species. Full article

The gut microbiota is a metabolically active ecosystem that influences host physiology through bioactive metabolites and interactions with host signaling pathways. Recent research has established a bidirectional gut–muscle axis in which microbial metabolites and muscle-derived factors (myokines) regulate muscle protein synthesis, degradation, regeneration, fiber-type specification, and overall muscle performance. Studies using germ-free, antibiotic-treated, probiotic-supplemented, and fecal microbiota transplantation models demonstrate that the gut microbiota is a critical determinant of skeletal muscle mass and function. Key mediators include short-chain fatty acids, bile acids, aromatic amino acid metabolites, microbial-associated molecular patterns, and methylamine metabolites. This review summarizes current mechanistic knowledge of gut–muscle communication and its relevance to livestock production. In monogastric livestock, particularly pigs and poultry, microbiota transplantation experiments and targeted probiotic interventions provide causal evidence that gut microbial communities influence muscle growth, muscle fiber composition, intramuscular fat deposition, carcass traits, and meat quality, including tenderness, marbling, water-holding capacity, and flavor. Several studies have also identified specific microbial taxa and metabolites capable of transferring desirable production phenotypes. In contrast, evidence in ruminants remains largely associative and originates mainly from multi-omics and dietary intervention studies. Future research should validate causal mechanisms, identify robust microbial biomarkers, and develop species-specific microbiome-based strategies for precision livestock production. Full article

Despite the traditional application of Sophora moorcroftiana (Benth.) Baker seeds for liver disorders, the capacity of its 70% ethanol extract (SMS) to alleviate metabolic dysfunction-associated steatotic liver disease (MASLD) and the underlying gut–liver axis mechanisms remain unclear. In this study, a high-fat diet (HFD)-induced MASLD mouse model was established to investigate the protective effects of SMS and its regulatory role in the interplay among gut microbiota, short-chain fatty acids (SCFAs), and inflammation. Serum, intestinal, and hepatic samples were collected to evaluate inflammatory responses, intestinal barrier integrity, and hepatic lipid metabolism. Gut microbiota composition and SCFA profiles were analyzed using 16S rRNA sequencing and metabolomics. In LPS-stimulated Caco-2 cells, SMS reduced inflammatory cytokines and TLR4/MyD88/NF-κB-associated signaling. The results demonstrated that SMS markedly alleviated hepatic steatosis by reducing triglyceride synthesis and hepatocellular lipid accumulation. In addition, SMS promoted the proliferation of beneficial bacteria, including Bifidobacterium and Akkermansia, and increased the production of SCFAs, particularly butyrate. SMS also restored intestinal barrier integrity through upregulation of Occludin and Claudin-1, thereby reducing circulating lipopolysaccharide (LPS) levels. Furthermore, SMS attenuated inflammation by inhibiting activation of the TLR4/NF-κB signaling pathway. Collectively, these findings demonstrate that SMS alleviates MASLD through coordinated modulation of gut microbiota composition, SCFA metabolism, intestinal barrier function, and inflammatory responses, highlighting its potential as a therapeutic strategy targeting the gut–liver axis. Full article

Background: Gut microbiota plays a key role in the aging process, with age-related microbial shifts contributing to chronic inflammation, metabolic dysfunction, frailty, and cognitive decline. Despite growing interest, an integrated synthesis of how diet and lifestyle modifications influence gut microbiota remains limited. This overview of reviews summarizes the current evidence on how dietary and lifestyle interventions shape microbial composition and affect aging outcomes. Methods: Following the PRISMA guidelines, we searched PubMed and Scopus for English-language reviews (January 2023–October 2025) including human adults aged ≥ 18 years, evaluating dietary or lifestyle interventions, and reporting gut microbiota with healthy-aging outcomes. Quality of the reviews was appraised using the SANRA tool. Results: Mediterranean and plant-based diets, calorie restriction, and microbiota-targeted approaches such as probiotics, prebiotics, symbiotics, and fecal microbiota transplantation were associated with increases in short-chain fatty acid-producing bacteria, including Faecalibacterium, Bifidobacterium, Lactobacillus, and Akkermansia muciniphila, while reducing pro-inflammatory taxa. These changes were linked to improved metabolic and immune function, reduced inflammaging, lower frailty, and greater physical resilience. Cognitive benefits included decreased neuroinflammation and a lower risk of Alzheimer’s and Parkinson’s diseases. Conclusions: Maintaining microbial balance through targeted dietary strategies may support healthier, more resilient aging, offering practical insights for public health and clinical nutrition planning. Full article

Feed efficiency classification based on residual feed intake (RFI) and residual intake and gain (RIG) is widely used to identify biologically efficient animals, yet it remains unclear whether this classification reflects consistent differences in digestive, fermentative, and metabolic processes. This study evaluated the effects of RFI and RIG classification on nutrient intake, apparent digestibility, ruminal fermentation, nitrogen metabolism, microbial protein synthesis, and gaseous emissions in confined lambs. Thirty-eight weaned Texel ewe lambs underwent a 60-day performance test using an automated feed intake system and were classified as high-efficiency, neutral, or low-efficiency based on both indices. Animals were individually housed in respirometric chambers where emissions of methane, carbon dioxide, nitrous oxide, and ammonia were assessed by cavity ring-down spectroscopy; apparent digestibility was determined from total collections of feed, orts, faeces, and urine; microbial protein synthesis was estimated from urinary purine derivatives; and ruminal short-chain fatty acid profiles were determined by gas chromatography. Feed efficiency classification did not significantly affect body weight, nutrient intake, apparent digestibility, ruminal fermentation parameters, nitrogen balance, microbial protein synthesis, or greenhouse gas emissions. Principal component analysis revealed two major biological gradients related to nutrient intake and utilisation (42.9%) and ruminal fermentation and gaseous emissions (23.3%), together explaining 66.2% of total variance, but showing no clear separation among efficiency groups. These findings indicate that the digestive, fermentative, and nitrogen metabolism variables evaluated in this study did not account for the observed variation in feed efficiency. Because the regression underlying RIG explained little additional variation (R² = 0.01), these conclusions primarily reflect feed efficiency as classified by RFI, suggesting that other physiological mechanisms may play a more important role in determining feed efficiency in confined Texel ewe lambs. Full article

Aquaculture is central to global food security, but intensification of production has increased disease risk and environmental pressure. The gut microbiome of aquatic organisms is now recognized as a key mediator of host physiology, nutrition, immunity, and pathogen resistance, making it a promising alternative to antimicrobial-based disease control. This review summarizes current knowledge on the composition, assembly, and functional roles of the gut microbiome in fish and crustaceans of aquacultural importance. Major bacterial phyla include Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, Actinobacteria, and Verrucomicrobia. Community structure is shaped by environment, diet, host age, genetics, stress, and stochastic processes, with differences between marine and freshwater systems. The microbiome contributes to immune defense through short-chain fatty acid production, Toll-like receptor signaling, cytokine regulation, mucosal immunoglobulin responses, antimicrobial peptide and bacteriocin production, and competitive exclusion of pathogens. It also supports productivity by improving nutrient assimilation, vitamin and enzyme synthesis, and feed conversion. Probiotics, prebiotics, and synbiotics are discussed as strategies for targeted microbiome modulation, although unstable colonization and the lack of standardized protocols remain major challenges. Overall, targeted microbiome manipulation offers a promising route toward sustainable, antimicrobial-reduced aquaculture. Full article

Short-chain fatty acids (SCFAs), acetate, propionate, and butyrate, are typically produced in a 3:1:1 ratio, respectively, via microbial fermentation of non-digestible carbohydrates, and to a lesser degree, from undigested protein. The effects of individual SCFAs on adipocyte function have been described; however, the effects of SCFAs in combination on adipocyte function remain unknown. Mature 3T3-L1 adipocytes were treated with a 1 mM total dose of acetate, propionate, and butyrate combined in a 3:1:1 ratio, respectively, for 24 h ± lipopolysaccharide (LPS, 10 ng/mL) under both normoxic and hypoxic (via the addition of 100 µM cobalt chloride) environmental conditions. In both normoxic and hypoxic LPS-stimulated conditions, SCFAs increased the secretion of adiponectin and reduced the secretion of resistin, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1/C-C motif chemokine ligand (CCL)2, and RANTES/CCL5, in addition to reducing intracellular protein levels of activated (i.e., the ratio of phosphorylated-to-total) nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) p65 and signal transducer and activator of transcription 3 (STAT3) (p < 0.05). Additionally, SCFA treatment reduced leptin secretion only in LPS-stimulated normoxic environmental conditions compared to control (p < 0.05). In normoxic conditions, SCFA + LPS increased mRNA expression of genes involved in fat storage), fatty acid recycling, and lipolysis, whereas in hypoxic conditions, SCFA + LPS decreased mRNA expression of genes involved in fat storage and triglyceride synthesis (p < 0.05), indicating different effects of SCFAs on adipocyte metabolic function depending on hypoxia status. Collectively, combined SCFAs in a 3:1:1 ratio beneficially modify the adipocyte adipokine secretory profile under both normoxic and hypoxic environmental conditions. Full article

Metabolic Syndrome (MetS) is a complex and multifactorial condition characterized by insulin resistance, visceral obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which contribute to increased cardiovascular risk. Central to its pathophysiology is metainflammation, a persistent inflammatory state closely linked to oxidative stress and mitochondrial dysfunction. This review aims to provide an integrated and updated overview of the interplay between metainflammation, oxidative stress, mitochondrial dysfunction, and organokine signaling in the development and progression of MetS and its cardiovascular complications. Current evidence indicates that mitochondrial dysfunction plays a pivotal role by promoting excessive production of reactive oxygen species (ROS), impairing ATP synthesis, and disrupting redox balance, thereby exacerbating insulin resistance and endothelial dysfunction. In parallel, dysregulated secretion of organokines—including adipokines, myokines, hepatokines, cardiokines, osteokines, and renokines—alters interorgan communication and amplifies pro-inflammatory and atherogenic pathways. Additionally, gut microbiota contributes to metabolic homeostasis through the production of short-chain fatty acids, whereas dysbiosis is associated with worsening metabolic parameters. Collectively, these interconnected mechanisms establish a self-perpetuating cycle that drives metabolic dysfunction and cardiovascular disease progression. This review highlights the central role of the metainflammation–mitochondrial dysfunction axis and emphasizes the importance of organokine-mediated crosstalk as a key regulator of systemic metabolism. Targeting these pathways may represent a promising strategy for the prevention and management of MetS and its associated complications. Full article

Background/Objectives: Major depressive disorder (MDD) has been increasingly associated with alterations of the gut microbiome through the microbiota–gut–brain axis. However, published findings remain highly heterogeneous, limiting identification of reproducible microbial signatures associated with depression. This systematic review aimed to evaluate reproducible taxonomic and functional gut microbiome alterations in patients with MDD compared with healthy controls. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science Core Collection, and the Cochrane Library for studies published between January 2016 and December 2025. Observational human studies evaluating gut microbiome composition in adults with clinically diagnosed MDD and healthy control groups were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Due to substantial methodological heterogeneity, findings were synthesized using structured qualitative narrative analysis. Results: Sixteen observational studies were included in the qualitative synthesis. Findings related to alpha diversity were inconsistent across studies, whereas beta diversity alterations demonstrated greater reproducibility across independent cohorts. The most recurrent microbiome pattern involved depletion of short-chain fatty acid (SCFA)-producing bacteria, particularly Faecalibacterium and Roseburia, together with recurrent alterations affecting members of the Ruminococcaceae, Lachnospiraceae, and Clostridia groups. Functional microbiome alterations demonstrated greater consistency than higher-level taxonomic findings and included reduced butyrate synthesis pathways, dysregulated amino acid and tryptophan metabolism, increased lipopolysaccharide biosynthesis, and enrichment of pro-inflammatory microbial signatures. Antidepressant-naïve cohorts generally demonstrated more homogeneous dysbiosis patterns than mixed-treated populations. Conclusions: Current evidence suggests that functional gut microbiome dysregulation may represent a more reproducible biological feature of MDD than isolated taxonomic alterations alone. However, substantial heterogeneity in study design, participant characteristics, sequencing methodologies, and analytical approaches continues to limit clinical translation. Large-scale longitudinal multi-omics studies using standardized methodologies are required to clarify the role of the gut microbiome in depressive disorders and to evaluate the potential utility of microbiome-based biomarkers and interventions in mental health and public health practice. Full article

Depression and anxiety are increasingly understood to involve systemic biological processes, where chronic stress, immune dysregulation, and vascular dysfunction converge on brain-relevant symptoms. Fermented foods are widely studied as psychobiotic candidates, yet results remain inconsistent because products vary in chemistry, viability, sodium, and biogenic amines, and trials often rely on broad symptom outcomes without exposure verification. A major gap is the lack of a reusable, mechanism-first framework that links what a product delivers to barrier, endothelial, and neurovascular target engagement. As a narrative and conceptual review rather than a systematic review, the article integrates mechanistic evidence into a conceptual framework rather than undertaking quantitative evidence synthesis. It addresses that gap by treating fermented vegetables, dairy, soy, and selected Brazilian cassava ferments and artisanal cheeses as metabolite-engineering platforms mapped onto a tri-barrier remodeling axis from gut epithelium to endothelium and platelets to the blood–brain barrier. We synthesize dosing-resolved metabolite modules, including short-chain fatty acids, tryptophan-derived indoles, bile acids, neuroactive small molecules, and peptide and exopolysaccharide fingerprints, and align them with interpretable readouts for permeability, endotoxemia proxies, endothelial activation, immunothrombosis, and epigenetic aging pace. Here we highlight how this modular framework converts heterogeneous food studies into testable exposure hypotheses, guides comparator design and phenotype stratification, and clarifies why null results can be informative. To maintain a focused scope, the review uses selected fermented-food families as representative test platforms rather than attempting a complete survey of global fermented foods. The emphasis is therefore placed on mechanisms, exposure verification, and trial-design principles that can be transferred to other products. Full article

Neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD) are regarded as systemic illnesses, mainly characterized by long-term neuroinflammation, metabolic dysregulation and barrier dysfunction. All these factors interact through the gut–immune–brain axis. The Mediterranean diet, rich in plant-based foods, olive oil, and fish, has been consistently associated with slower cognitive decline and reduced risk of neurodegeneration in observational studies and some clinical trials. This review provides a systems-level synthesis that distinguishes itself from previous narratives by integrating disease-specific mechanistic frameworks with multi-omics-guided precision nutrition strategies. We summarize recent evidence showing that this dietary pattern can remodel gut microbiota composition and enhance the production of bioactive metabolites such as short-chain fatty acids (SCFAs). These metabolites are associated with improved intestinal barrier integrity, reduced systemic inflammation, and potential modulation of brain functions. Within the central nervous system, diet-related metabolites have been linked to reduced neuroinflammation via modulation of microglial and astrocytic states. They have been linked to protection of mitochondrial function, maintenance of proteostasis, and preservation of blood–brain barrier (BBB) integrity. In AD and PD patients, adherence to this diet is associated with favorable changes in pathological hallmarks, including amyloid-beta (Aβ), tau, and α-synuclein accumulation. Nowadays, multi-omics tools, including single-cell transcriptomics, spatial transcriptomics and microbiome analysis, are widely used in this field, which helps researchers explore these complicated effects more deeply. Importantly, individual responses to the diet vary considerably due to differences in genetic background, gut microbial composition, and metabolic phenotypes, which underscore the need to move from generalized dietary guidelines toward personalized precision nutrition. The Mediterranean diet is not only a dietary pattern but also an effective way to modulate neuro-immune and metabolic networks. However, current evidence remains largely observational, and we critically discuss the need for more randomized controlled trials (RCTs) and standardized multi-omics data analysis frameworks. To sum up, the Mediterranean diet plays a neuroprotective role via the gut–immune–brain axis, and multi-omics techniques promote the development of precision nutrition. More trials and improved multi-omics systems are required to apply these research results in clinical practice. Full article

Postbiotics are defined as preparations of inanimate microorganisms and/or their components that confer a health benefit on the host. Although interest in postbiotics has increased substantially, their translational use in functional foods remains insufficiently characterized with respect to preparation identity, production methodology, food-matrix compatibility, mechanistic specificity, and regulatory positioning. This PRISMA-guided structured review aims to synthesize current evidence on postbiotics in functional food and nutraceutical contexts, with particular emphasis on preparation-based characterization, gut–brain axis-related mechanisms and clinical findings, food matrix applicability, and regulatory and health-claim considerations. Unlike broader postbiotic reviews that mainly address definitions, general health effects, or technological stability, this review integrates preparation identity, production process, gut–brain axis-related evidence, food matrix compatibility, and regulatory/health-claim translation within a single functional food framework. A structured literature search was conducted in Scopus and Web of Science Core Collection and was completed on 16 February 2026. The search strategy included three conceptual blocks: postbiotic and inactivation-based preparation terms, functional food/nutraceutical and food matrix terms, and gut–brain axis-related clinical and mechanistic terms. Cosmetic, topical, veterinary, animal feed, and aquaculture-focused publications were excluded. The export files contained 131 records from Scopus and 136 from the Web of Science Core Collection, yielding 267 records after applying document-type and language filters. After manually removing duplicates, 237 unique records were screened. Following title/abstract screening, 176 records were excluded as outside the scope of the review, and 61 publications were retained for full-text assessment and final thematic synthesis. The review was reported according to applicable PRISMA 2020 items. The evidence was organized into three thematic domains: gut–brain axis-related clinical findings, mechanistic evidence, and food matrix/product development applications. Heat-inactivated preparations, including Lactobacillus gasseri CP2305 and Lactiplantibacillus plantarum SNK12, have shown preliminary effects on stress-related symptoms, sleep quality, and selected neuroendocrine or inflammatory biomarkers in human studies. Mechanistic pathways include gut barrier integrity, immunomodulation, short-chain fatty acid signaling, tryptophan–kynurenine–serotonin metabolism, vagal communication, and regulation of the hypothalamic–pituitary–adrenal axis. Food matrix studies support the potential application of postbiotics in fermented dairy products, cereal-based systems, plant-based matrices, powders, concentrates, and bioactive packaging; however, matrix-dependent effects on bioavailability, sensory quality, and biological activity remain incompletely defined. Postbiotics provide a stable translational platform for functional-food development, but their scientific and commercial use requires clear characterization of the microbial source, production process, inactivation method, retained active fractions, dose metric, delivery matrix, and clinically meaningful endpoint. Future studies should avoid broad category-level claims and prioritize preparation- and matrix-defined human evidence with standardized safety reporting. Full article

Introduction: Breast milk is the best food for a growing infant during the first 6 months of life. The presence of trans fatty acids (TFAs) in breast milk can interfere with the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), increasing the risk of developing, among other issues, asthma or atopic dermatitis. TFAs are not synthesised de novo in the human body. Their content in breast milk may be a good marker of short-term dietary intake of these compounds by breastfeeding mothers. However, the literature shows differences in the assessment of the relationship between dietary TFAs intake and TFAs content in breast milk. Furthermore, the decrease in the TFAs content in food observed recently seems to make it impossible to use Craig-Schmidt’s formula to estimate the TFAs content in the diet or in breast milk. The aim of this study was to confirm the possibility of using TFAs content in breast milk as a marker of their short-term intake within the breastfeeding mother’s diet, together with an attempt at preliminary quantitative determination of the relationship between these parameters. Materials: The study material was collected from a single breastfeeding mother and included 10 breast milk samples and 10 samples of daily food rations reconstructed based on the 24 h food consumption survey. Methods: The content of fatty acids, including TFAs, was determined by gas chromatography–mass spectrometry (GC-MS). Results: The TFAs content in the whole-day mother’s diet and in 100 mL of breast milk ranged from 0.11 to 0.54 g/day and from 0.02 to 0.07 g, respectively. A strong statistically significant (p < 0.05) positive correlation between these parameters was found. Equations for an exploratory linear relationship between the TFAs content in a breastfeeding mother’s diet and the concentration of these fatty acids in breast milk have been developed. Due to the small number of samples, these data should be interpreted very cautiously and validated in a larger cohort. Conclusions: This single-participant pilot study suggests that TFAs content in breast milk may be a marker of the dietary intake of these compounds from the previous day. It seems that the dietary habits of breastfeeding mothers of twins are a significant factor influencing the composition of breast milk and, consequently, the nutritional quality of breastfed infants. Full article

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 85% of patients receiving neurotoxic regimens, often leading to dose reduction and impaired quality of life, yet effective preventive or therapeutic options remain scarce. Emerging evidence implicates chemotherapy-induced gut microbiota dysbiosis in CIPN pathogenesis via a gut–nerve axis. Concurrently, rectal ozone insufflation (ROI) has been shown to modulate the gut microbiota and reduce inflammation in preclinical models. This article critically examines the evidence on the role of gut dysbiosis in CIPN, evaluates the microbiota-modulating capacity of rectal ozone therapy (OT), and assesses the biological plausibility of ozone as a microbiota-targeting intervention for CIPN, while explicitly distinguishing between established evidence and hypothetical mechanisms. Evidence synthesis: Neurotoxic agents induce dysbiosis marked by reduced microbial diversity, loss of short-chain fatty acid-producing bacteria, and expansion of pro-inflammatory taxa. Preclinical models demonstrate a causal role for specific microbial communities in CIPN, with microbiota depletion or fecal transplantation modulating neuropathic phenotypes. In human cohorts, dysbiosis severity correlates with CIPN symptoms. Preclinical studies show that ROI restores microbial balance, enhances short-chain fatty acid levels, and strengthens intestinal barrier function via Nrf2/HO-1 and SIRT1 pathways. Preliminary retrospective data from small case series (n = 7 and n = 15) report sustained symptom improvement in CIPN patients receiving OT. However, no human study has directly linked ozone-induced microbiota changes to clinical outcomes, and the clinical evidence for OT in CIPN remains limited to uncontrolled observations. Conclusions: Convergent preclinical evidence supports a biological rationale for investigating ROI as a microbiota-targeting intervention in CIPN. However, this rationale remains largely hypothetical in the clinical setting. High-quality randomized controlled trials with longitudinal microbiome profiling are urgently needed to establish mechanistic causality and to determine whether the promising preclinical findings translate into clinically meaningful benefits. Until such evidence is available, the framework presented here should be regarded as hypothesis-generating rather than as a basis for clinical practice. Full article