Diet and age are important determinants of the human gut microbiota, which are essential for metabolic regulation, immune homeostasis and healthy ageing. In the current study, we examined the association of vegetarian and nonvegetarian dietary patterns with gut microbiome diversity, composition and function in an Eastern Indian population. Using 16S rRNA V3–V4 sequencing, we profiled gut microbial communities in 18 healthy subjects divided into three age groups (20–35, 40–60 and ≥ 70 years). Young adult nonvegetarians appear to have more microbial richness than vegetarians; however, vegetarians have higher microbial evenness, with a substantial age-dependent change in both stability and variability. Pareto analysis revealed that vegetarians carried a lower abundance of harmful bacterial taxa but had a higher abundance of beneficial bacteria. Predicted functional profiling suggested that vegetarian gut microbiomes were predominantly enriched in biosynthesis and energy metabolism pathways associated with fibre fermentation and short-chain fatty acid production. By contrast, nonvegetarian gut microbiomes were enriched for pathways related to the degradation of amino acids, lipids and xenobiotics. Interestingly, older vegetarians had a core gut microbiome with less functional dispersion but no changes in richness, indicating increased stability as they aged. Overall, gut microbial community structure did not differ significantly by diet or age (PERMANOVA), although profiles were broadly similar among the dietary patterns; some subtle differences regarding certain taxa were observed: Bacteroides, Phocaeicola, Comamonas, Hungatella and Faecalimonas were different in vegetarians, whereas Segatella, Leyella, Dialister, Alloprevotella and Dorea were abundant in nonvegetarians. These results suggest that long-term dietary patterns of a particular type are associated with subtle shifts in specific microbial taxa, which may be relevant to metabolic homeostasis and healthy ageing without significantly altering community structure.
The gut microbiome is an important regulator of nutrition and immunity in fish, but it is highly sensitive to common aquaculture stressors (such as temperature shocks and air exposure during handling and transport) and influenced by host genetic factors, including immune function and mucus production. Triploid fish are commonly produced in aquaculture as they are sterile and have potentially higher growth rates. However, compared with their diploid counterparts, triploids have differences in morphology and susceptibility to stress, which could be related to the composition and diversity of the gut microbiome. Here, we exposed diploid and triploid rainbow trout (Oncorhynchus mykiss) to an early life stressor (cold shock) and assessed its effects on the composition and diversity of the gut microbiome five months later, through 16S rRNA sequencing. We found substantial differences in baseline microbiome diversity and composition between diploid and triploid fish, as well as in the microbiota's response to stress. Triploidy was associated with significantly reduced microbial richness and phylogenetic diversity, potential reduction in lactic acid producing bacteria, increased abundance of facultative pathogenic taxa from the family Enterobacteriaceae and elevated mortality. Early life acute stress caused shifts in microbiome communities in later life, promoting an increase in the relative abundance of Enterobacteriaceae and a reduction of potential probiotic taxa, which are more evident in triploids. Our results indicate that early life stress has long term consequences for the gut microbiome composition of rainbow trout, with disproportionately greater effects in triploids compared with diploids.
Background Branched‐chain amino acids (BCAAs) are established biomarkers of insulin resistance. However, their relationship with gut microbiota composition, dietary patterns, and systemic inflammation in African populations with Type 2 diabetes mellitus (T2DM) remains unexplored. This study investigated the association between plasma BCAAs, gut dysbiosis, dietary practices, and proinflammatory cytokines in T2DM patients in Sokoto, Nigeria. Methods This cross‐sectional study enrolled 126 participants: 63 T2DM patients and 63 age‐ and sex‐matched healthy controls. We quantified gut Bacteroidetes and Firmicutes using qPCR and defined dysbiosis as a bacterial load above the 75th percentile of controls—a structured questionnaire captured dietary patterns, including meal‐specific food choices. Plasma BCAAs, tumor necrosis factor alpha (TNF‐ α ), and interleukin‐6 (IL‐6) were measured by ELISA. We compared biomarker levels across groups (eubiosis, dysbiosis, controls) using the Kruskal–Wallis test with Dunn′s post hoc correction and assessed correlations using Spearman′s rank correlation. Results Plasma BCAAs were significantly elevated in T2DM patients with dysbiosis (median 100 μ mol/L, IQR 11.69–14.57) compared with eubiotic T2DM patients (88.1 μ mol/L, IQR 9.29–13.84) and controls (70.6 μ mol/L, IQR 7.46–10.64) ( H = 41.77, p < 0.001, η 2 H = 0.323). Dietary analysis of participants who consumed rice/swallow as breakfast shows the highest dysbiosis prevalence (83.3%, A O R = 0.31, 95 % C I : 0.21–0.91, p = 0.038). Notably, all participants who consumed oats at dinner or lunch presented with 100% dysbiosis prevalence. Vegetable/fruit consumption at lunch showed 82.8% dysbiosis prevalence ( χ 2 = 44.594, p < 0.001). Oral hypoglycemic agent (OHA) use demonstrated a strong association with dysbiosis ( χ 2 = 107.471, p < 0.001), with 82.4% of OHA users exhibiting dysbiosis ( A O R = 2.41, 95 % C I : 1.92–3.81). Among dysbiotic patients, the Firmicutes/Bacteroidetes (F/B) ratio correlated negatively with BCAAs ( r = –0.452, p = 0.008). BCAAs correlated positively with TNF‐ α ( r = 0.489, p = 0.001) and IL‐6 ( r = 0.401, p = 0.003) in the dysbiosis group. Hyperglycemic patients had significantly higher BCAAs than normoglycemic participants ( p < 0.001). Conclusion Plasma BCAAs are elevated in Nigerian T2DM patients with gut dysbiosis and correlate positively with systemic inflammation. The negative correlation between the F/B ratio and BCAAs challenges the simple paradigm that higher Firmicutes abundance uniformly drives BCAA elevation, suggesting that specific microbial taxa or functional pathways may be more relevant. Dietary patterns, particularly oat consumption, show strong associations with dysbiosis, warranting careful interpretation and further investigation. These findings support the gut–BCAA–inflammation axis in the pathophysiology of T2DM.
Current research on nutritional science focuses on the development of holistic, functionally active food matrices fortified with bioactive compounds to address chronic diseases. This review evaluates the scopes of Vigna umbellata (rice bean), an underutilized, climate-resilient legume as a reservoir of bioactive compounds and next-generation probiotics. V. umbellata is rich in resistant starch and nondigestible oligosaccharides, capable to function as a sustainable, nondairy carrier for symbiotic delivery. This research centers on the seed endophytes and their versatile mechanism of tolerance; which confer resistance against an array of hostile environments. Furthermore, the “biological refinery” of fermentation is discussed, facilitated by a simultaneous subtractive and additive process that not only removes antinutritional factors like phytic acid, but also enriches the food matrix. This paper also integrates metagenomic characterization with genome mapping that provides a framework for the valorization of V. umbellata in the global functional food landscape.
The microbiota–gut–brain axis (MGBA) is a dynamic bidirectional communication network that integrates microbial, neural, endocrine, and immune signals to regulate host physiology and behavior. This review synthesizes current evidence on the molecular mechanisms by which gut microbiota modulate brain function through endocrine signaling (hypothalamic–pituitary–adrenal axis and sex hormones), neurotransmitter synthesis (serotonin, dopamine, GABA), microbial metabolites (short-chain fatty acids, indoles, secondary bile acids), and neural pathways involving the enteric and autonomic nervous systems. It also highlights the role of cytokines and immune responses in maintaining intestinal and neurological homeostasis. Emerging findings underscore the ability of specific bacterial taxa and metabolites to influence neurodevelopment, behavior, and disease pathogenesis, including mood disorders, neurodegeneration, and autism spectrum disorders. However, the physiological relevance of many microbe-derived signals in humans remains poorly defined. Much of the current mechanistic evidence supporting these interactions derives from animal models, underscoring the need for carefully designed human studies to establish physiological relevance and translational validity. Clarifying dose thresholds, tissue-specific receptor responses, and bidirectional feedback loops is essential for advancing therapeutic applications. This review supports an integrative systems biology approach to understanding the MGBA, emphasizing the need for translational studies to validate preclinical findings in human physiological contexts.
The gut microbiome in Sauropsida—reptiles and wild birds—is vastly understudied. This lack of data and understanding creates an inefficiency in studies and conservation efforts. We address this through a collection of data from 64 published research papers. In this review, we provide a collection of data displaying microbiome variance within Sauropsida, specifically looking at the effects of variables such as captivity status, sex, age, health, and exposure to pollutants. We provide data on commonly used diversity metrics and the geographic bias to universities. The most common dominant microbes across taxa are Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, with variation across the orders. Our results revealed areas that were insufficient in the Sauropsida, displaying a lack of research in biomarkers, Crocodilia, sexes, ages, and results of polluted habitats. The lack of research on these variables serves as a launching point for further research to build further understanding in conservation efforts.
Gastrointestinal mucositis (GI‐M) is a dose‐limiting complication of chemotherapy initiated by direct cytotoxic injury to the intestinal epithelium. It is then perpetuated by aberrant immune responses driven by the host and their microbiota. GI‐M presentation is heterogeneous, hypothesized to be influenced by patient factors including genomic variability, comorbidities, and, more recently, unique gut microbiota signatures. We aimed to identify microbial attributes that differ between patients that developed GI‐M compared with those that did not and use this information to identify/characterize novel microbial biotherapeutics. Archived stool samples collected from N = 12 patients undergoing standard‐dose chemotherapy were used. GI‐M was defined using the CTCAE. Microbial composition was assessed by 16S rRNA gene sequencing and the most differentially abundant taxon, Blautia luti, was identified for in vitro characterization. Blautia luti supernatants (BLSPNs) were isolated and investigated in vitro. Of the 12 patients recruited, four were included in the “high toxicity” group. B. luti levels strongly correlated with toxicity outcomes ( r = 0.744). Chemotherapy‐induced cell death in colonic epithelial cells was attenuated when treated prophylactically, concurrently, and therapeutically with BLSPN ( p = 0.0087, p = 0.0022, and p = 0.0166, respectively). Notably, 20% BLSPN enhanced Roseburia intestinalis ( p = 0.0015) and F. prausnitzii ( p = 0.0007) growth, but prevented Escherichia coli outgrowth ( p = 0.0002) under oxidative conditions. In conclusion, B. luti strongly correlates with GI‐M risk and demonstrates in vitro behaviors that address defined drivers of GI‐M etiology.
The criticality of the first 1000 days of life in setting the stage for the colonization and development of infant gut microbiota cannot be negotiated. Multiple interactions going on within this period contribute to the composition and diversity of microbes found in this ecosystem, making it essential for shaping long‐term health in an individual. Factors such as maternal physiology, delivery mode, nutritional practices, and environmental exposure influence the presence, nature, and diversity of the microbiome found within the gut. Increasing evidence connects early interruption of the gut community to immunological, metabolic, and neurodevelopmental disorders, making the understanding of this dynamic ecosystem necessary. This narrative review is based on literature published between 2020 and 2025, retrieved from databases including PubMed, Web of Science, and Scopus. It synthesised cohort studies and trials, tracing microbiome changes across antenatal, peripartum, and postnatal periods to reveal an integrated developmental continuum. Our consolidated analysis uncovers the Bifidobacterium ‐SCFA‐sIgA axis as the characteristic hallmark of healthy microbial succession. Fiber consumption in maternal diets, breast milk microbiome priming, and Bifidobacterium and Lactobacillus seeding during vaginal delivery all enhance beneficial colonization and diversity, whereas cesarean section, formula feeding, and antibiotic exposure disrupt diversity, lowering Bifidobacterium by about 2%–30% and increasing Clostridium abundance. Vaginal seeding, multistrain probiotics, and prebiotic‐enriched formulas offer measurable restoration of eubiosis and immune tolerance improvement. We underscore the importance of standardized multiomics approaches and balanced global representation in microbiome research. Our synthesis collectively stressed early microbial stewardship as a practical means for preventing chronic disease and advancing public health by optimizing maternal nutrition, delivery care, and infant feeding practices.
Background and Aims Interactions between host noncoding RNAs (ncRNAs) and the tumor‐associated microbiome represent an emerging regulatory axis in cancer biology. Despite individual advances, a unified mechanistic framework integrating ncRNA biology, microbial oncology, and epitranscriptomic regulation remains absent. This review synthesizes current evidence, critically appraises methodological limitations, and identifies priority research directions for this interdisciplinary field. Key Findings MicroRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) engage in bidirectional crosstalk with oncogenic microorganisms—including Helicobacter pylori , Fusobacterium nucleatum , Epstein–Barr virus (EBV), human papillomavirus (HPV), and hepatitis B virus (HBV)—through virulence factor signaling, viral‐encoded ncRNAs, and metabolite‐mediated epigenetic mechanisms. Conversely, host ncRNAs modulate the intratumoral microbial ecosystem by regulating innate immunity, epithelial barrier integrity, and extracellular vesicle (EV)–mediated communication. N6‐methyladenosine (m6A) modifications—installed by METTL3–METTL14 writers, removed by FTO/ALKBH5 erasers, and interpreted by YTHDF/IGF2BP readers—regulate ncRNA biogenesis and stability, constituting an additional regulatory stratum that intersects both ncRNA and microbiome‐dependent oncogenic pathways. Conclusions An integrated hypothesis is proposed in which ncRNAs, the intratumoral microbiome, and epitranscriptomic m6A regulation may form a functionally interdependent oncogenic network. Although direct evidence for all three axes operating simultaneously in the same tumor model remains limited, this framework has potential implications for biomarker discovery and combination therapeutic strategies and identifies priority directions for mechanistic and clinical validation research.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, amyloid-beta accumulation, and neuronal dysfunction. Emerging evidence suggests that the microbiota–gut–brain axis may play an important role in AD pathogenesis through interactions involving immune regulation, microbial metabolites, intestinal permeability, and neuroinflammatory pathways. Alterations in gut microbial composition have been associated with increased systemic inflammation, blood–brain barrier dysfunction, oxidative stress, and amyloid-related pathology in both experimental and clinical studies. This narrative review summarizes current evidence regarding the relationship between gut microbiota dysbiosis and AD, with particular emphasis on mechanistic pathways, microbiota-derived metabolites, neuroinflammation, and microbiota-targeted therapeutic strategies. Experimental studies have demonstrated that probiotics, prebiotics, synbiotics, dietary interventions, and fecal microbiota transplantation may influence neuroinflammatory and cognitive outcomes through modulation of the gut microbiota. However, available human evidence remains limited and heterogeneous due to variations in study design, microbiome analysis methods, patient populations, and therapeutic protocols. Although growing evidence supports a potential association between gut microbiota dysbiosis and AD progression, definitive causal relationships remain incompletely understood. Further large-scale longitudinal studies and standardized clinical trials are required to clarify the diagnostic and therapeutic potential of microbiota-based interventions in AD management.
Periodontopathogenic bacteria have been increasingly implicated in the prognosis of colorectal cancer. Among these microorganisms, Fusobacterium nucleatum has been frequently detected in tumor tissues and associated with unfavorable clinical outcomes. However, observational evidence remains heterogeneous, and quantitative synthesis focusing specifically on survival outcomes is still limited. This systematic review and meta-analysis of observational cohort studies is aimed at evaluating the association between periodontopathogenic bacteria and survival outcomes in patients with colorectal cancer. Searches were performed in PubMed, Embase, Scopus, and Web of Science, covering the last 10 years. Only human cohort studies reporting adjusted estimates for survival-related outcomes were included. Data extraction and risk-of-bias assessment were independently performed by two reviewers, and meta-analyses were conducted using random-effects models. Five cohort studies met the eligibility criteria, four of which were included in the quantitative synthesis. The meta-analysis demonstrated a significant association between the presence of periodontopathogenic bacteria and poorer survival outcomes in colorectal cancer, with a pooled hazard ratio of 1.84 (95% CI: 1.38–2.46) and low observed statistical heterogeneity. This association was consistently observed for F. nucleatum. These findings suggest that periodontopathogenic bacteria, particularly F. nucleatum, may play an important role in colorectal cancer prognosis and could serve as potential prognostic biomarkers and emerging therapeutic targets.
The coevolution of the human brain and microbiome has emerged as a pivotal area of research, highlighting the interactions that have shaped human development. Human accelerated regions (HARs), which are genomic sequences that evolved rapidly in humans, play an important role in brain development, influencing cognitive functions and susceptibility to neurological disorders. We report a descriptive enrichment of gut microbiota–associated host genetic factors within HARs based on the intersection of curated microbiome-host associations with HAR genomic intervals. We also curate microbe–metabolite–host gene links and perform pathway- and network-based analyses to nominate candidate signaling routes through which microbiome-associated metabolites could influence host neurodevelopmental programs. Maternal microbial status during pregnancy has been implicated in shaping fetal developmental environments, primarily through effects on maternal immune tone and circulating microbial or microbe-modulated metabolites. Evidence for direct effects on fetal neurodevelopment is strongest in animal models, whereas human evidence remains largely associative and confounded. In this review and integrative computational synthesis, we identify HAR-overlapping host genetic factors linked to gut microbial taxa and nominate candidate metabolite-pathway relationships (including JAK-STAT, prolactin, and retinoid-related pathways) that may plausibly interface with neurodevelopmental processes; these results are hypothesis-generating and motivate mechanistic follow-up research. The manuscript also explores how evolutionary theories, including the expensive tissue hypothesis and hologenome theory, contextualize these host–microbe interactions. These findings have important potential implications for developing therapeutic strategies aimed at mitigating neurodevelopmental disorders and enhancing brain health through microbiome modulation.
Infectious diseases continue to pose a significant challenge to global health, particularly with the emergence of multidrug-resistant pathogens. Understanding host–pathogen interactions (HPIs) is fundamental to uncovering mechanisms of infection, immunity, and adaptation. This narrative review provides a panoramic view of molecular and systems-level insights into host defense and pathogen virulence, emphasizing Caenorhabditis elegans as a versatile in vivo model. Studies from our laboratory and others highlight how conserved immune modules, including p38 MAPK, JNK-MAPK, TGF-β, and insulin/IGF-1 signaling, mediate survival, stress adaptation, and longevity during bacterial infection. Transcriptomic, proteomic, and metabolomic investigations reveal infection-induced remodeling of proteostasis, energy metabolism, and post-translational regulations. Recent metabolomics and transgenerational studies demonstrate how pathogens influence neural, reproductive, and metabolic networks to generate heritable adaptive traits. Integrating findings across multiple systems, such as C. elegans, Drosophila, Zebrafish, and mammalian organoid systems, establishes a translational continuum linking innate and adaptive immunity. Emerging frameworks such as the Host–Pathogen Interaction Phenotype Ontology (HPIPO) and AI-driven multiomic modeling enable predictive mapping of infection outcomes. Collectively, these advances transform infection biology from descriptive observation to a data-driven, systems immunology discipline, offering new avenues for precision antimicrobial or anti-infective development, vaccine design, and therapeutic interventions.
Probiotics are emerging as promising alternative therapies with diverse health applications, particularly in enhancing immunity and combating infectious diseases. This scoping review synthesizes evidence on the immunomodulatory and antimicrobial effects of well-characterized strains, particularly species of Bifidobacterium and Lactobacillus. Probiotics contribute to gut health by strengthening intestinal barrier integrity, modulating immune responses, and producing antitoxins. They also demonstrate antiviral, antibacterial, and antifungal activity across experimental and clinical studies, with documented benefits in acute infectious diarrhea, respiratory tract infections, urinary tract infections, and selected fungal and bacterial diseases. Probiotics can be categorized into wild-type and recombinant strains. While conventional wild-type probiotics offer health benefits, they are limited by strain-dependent efficacy, variable stress tolerance, and uncertain dosing requirements. In contrast, recombinant probiotics engineered through genetic modification are designed to improve stability, antimicrobial peptide production, toxin neutralization, colonization resistance, and vaccine-delivery potential. Despite these advantages, the clinical use of recombinant probiotics necessitates careful consideration of safety concerns. These include immune dysregulation, mutagenesis, adverse metabolic effects, horizontal gene transfer, and excessive immune activation. Overall, substantial gaps remain regarding optimal dosing, timing of administration, long-term safety, and comparative effectiveness across strains. Future research should integrate mechanistic studies with well-designed clinical trials to define when and how probiotics—whether conventional or recombinant—can be safely incorporated into infectious disease management.
Anthocyanins are bioactive flavonoids with recognized capacity to modulate gut microbiota composition, microbial metabolism, and host physiological signaling. However, their nutraceutical and therapeutic applications are constrained by poor physicochemical stability, limited bioavailability, and rapid gastrointestinal degradation. Nanotechnology-based delivery systems have emerged as promising strategies to enhance anthocyanin protection, regulate release kinetics, and improve targeted colonic delivery. This review critically examined anthocyanin-loaded nanocarriers, including polymeric, lipid-based, protein-based, polysaccharide-based, and hybrid systems, with particular emphasis on their mechanistic interactions with the gut microbiota. Key pathways discussed include microbiota-responsive release, microbial biotransformation, short-chain fatty acid production, intestinal barrier modulation, and immune signaling. Current evidence from in vitro and animal studies suggests that nanoencapsulation improves anthocyanin stability, microbial accessibility, and colonic retention; however, robust human clinical validation remains limited. Major translational barriers include incomplete mechanistic understanding, lack of standardized dose–response frameworks, insufficient long-term safety assessment, regulatory uncertainty, and industrial scalability challenges. Future progress will require standardized methodologies, multiomics integration, physiologically relevant translational models, rigorous clinical investigation, and harmonized regulatory frameworks to advance anthocyanin-loaded nanocarriers toward evidence-based microbiota-targeted nutraceutical and precision nutrition applications.
Neuroinflammatory disorders, such as Alzheimer’s disease (AD) and multiple sclerosis (MS), are increasingly recognized as systemic inflammatory syndromes rather than isolated brain pathologies. A central regulator of this systemic response is the microbiota–gut–brain axis (MGBA), where dysbiosis-induced disruption accelerates neuroinflammation and compromises blood-brain barrier (BBB) integrity. Plant-derived compounds (PDCs) offer a promising multitarget approach for these complex disorders; however, their clinical translation is frequently hindered by poor bioavailability and chemical complexity. This review evaluates how computational methods facilitate the discovery of PDCs that modulate the MGBA. Network pharmacology maps the interactions between these compounds and multiple molecular targets involved in inflammation and gut homeostasis. Furthermore, molecular docking and molecular dynamics simulations characterize the binding affinity and structural stability of these interactions. In silico ADMET models are additionally employed to predict pharmacokinetic profiles, safety, and BBB permeability. Together, these approaches provide a robust, time-efficient strategy to identify natural therapies, including bioactive microbial metabolites that bypass traditional bioavailability constraints. Future integration of artificial intelligence (AI) and multiomics holds the potential to further decode the synergistic interactions between PDCs and the gut microbiome, paving the way for personalized neuroprotective strategies.
The complications that arise from pregnancy such as preterm birth (PTB), preeclampsia, and neonatal sepsis continue to pose significant threats to maternal and neonatal health worldwide. Early detection and treatment are crucial in reducing the morbidity and mortality of these complications. The human microbiome, particularly during the perinatal period, has also been seen as a critical regulator of immune and metabolic health, influencing both maternal and infant outcomes. This narrative review responds to the application of microbiome signatures as predictors for maternal and neonatal health biomarkers. We summarize new evidence linking dysbiosis of both maternal gut and vaginal microbiomes with PTB, preeclampsia, and gestational diabetes mellitus (GDM). We further discussed how the neonatal microbiome affects immune development and is association to sepsis risk. This review also briefly addresses the crossroads of multiomics data to enhance precision medicine, the shortcomings in designing adequately powered clinical trials, and the standardization and regulatory hurdles confronting the microbiome field. As much as the potential of microbiome signatures for predictive diagnostics in maternal and neonatal health is high, there are daunting challenges to overcome. They include the dynamic nature of the neonatal microbiome, the nature of multiomics data complexity, and invoking standardized methodologies and robust clinical trials. Nevertheless, the incorporation of microbiome-based biomarkers into medicine has the potential to move toward more personalized, noninvasive, and effective management of maternal and neonatal health.
Purpose The microbiome is increasingly recognised as a contributor to pancreatic ductal adenocarcinoma (PDAC) pathogenesis, presenting opportunities for biomarker discovery and therapeutic intervention. Characterising microbial signatures associated with PDAC could improve early detection to improve survival outcomes. Experimental Design While previous studies on the PDAC microbiome have focused primarily on faecal samples, this study employed 16S rRNA gene amplicon sequencing to profile the bacteriome across 226 biospecimens ( n = 111 PDAC, n = 115 control) collected from the mouth, stomach, duodenum, bile and pancreas. We assessed alpha and beta diversity, taxonomic composition, relative abundance and prevalence of bacterial communities across these upper gastrointestinal tract sites. Results Microbial diversity was significantly higher in the PDAC cohort, particularly in the stomach, duodenum and bile, with the latter showing unexpectedly high richness. While five dominant phyla (Pseudomonadota, Bacillota, Actinomycetota, Bacteroidota and Fusobacteriota) were shared between cohorts, the PDAC cohort harboured a greater number of unique low‐abundance taxa and displayed distinct site‐specific microbial profiles compared with control samples. Notable microbial shifts included enrichment of Pseudomonas , Acinetobacter , Geobacillus and Corynebacterium , genera previously implicated in inflammation, immune modulation and tumour persistence. Microbial clustering was strongly influenced by anatomical site and moderately by ethnicity, suggesting complex host–microbiome interactions in PDAC. Conclusions This study demonstrates distinct, site‐specific microbial variation in PDAC and supports an association for the microbiome in PDAC development and progression, warranting further mechanistic investigation.
Chronic liver diseases (CLDs) are a heterogeneous group of disorders that involve progressive damage to the liver cells, leading to inflammation, metabolic disorders, and fibrosis. There is increasing evidence that abnormal iron metabolism is an important contributing factor in CLDs that intersects with immune, metabolic, and microbial pathways. At the core of systemic iron metabolism is the hepcidin–ferroportin pathway, whereby hepatic hepcidin regulates iron export and distribution. Hepcidin signaling is abnormal in CLDs with varying etiology-specific patterns of iron overload or functional iron sequestration. In parallel with these advances in iron metabolism is the gut–liver axis in microbiota-driven iron metabolism and hepatic inflammation. Gut microbiota imbalance affects iron absorption in the gut, inflammatory pathways, and hepatic hepcidin signaling through microbial metabolites, immune activation through endotoxin, and bile acid pathways. Another key player in CLDs is the iron-dependent form of programmed cell death called ferroptosis through lipid peroxidation pathways. Ferroptosis is an important pathway in CLDs that links abnormal iron metabolism with hepatocyte damage, immune activation, and fibrosis progression. Ferroptosis pathways are cell-type specific; although they cause damage to hepatocytes, they may also prevent fibrosis through the killing of activated hepatic stellate cells. In this review article, we will explore the current evidence on the interaction between abnormal iron metabolism through the hepcidin–ferroportin pathway, gut microbiota imbalance, and the new player in CLDs, the ferroptosis pathway. Although many of these pathways are still in the preclinical or early clinical stages of intervention, an understanding of the iron–microbiota–ferroptosis triad provides an important platform for understanding CLDs through the identification of new targets for intervention.
