Search Results (19)

Increasing evidence suggests pancreatic cancer develops within a host–microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome–tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes. Full article

Chemotherapy- and/or radiotherapy-induced oral mucositis (CRIOM) is a common complication in patients with head and neck cancer, driven largely by excessive proinflammatory cytokine signalling and treatment-associated bacterial dysbiosis. This narrative review synthesizes current mechanistic evidence and summarizes emerging therapeutic strategies targeting these pathways. Research indicates that elevated levels of IL-1β, IL-6, TNF, iNOS, and nitric oxide amplify tissue injury and ulceration, while disruption of oral and gut microbial communities, characterized by loss of beneficial commensals and enrichment of pathogenic taxa, further exacerbates mucosal inflammation. Anti-inflammatory agents, including pentoxifylline, atorvastatin, trans-caryophyllene, azilsartan, recombinant human IL-11, and low-level laser therapy have been shown in preclinical models to reduce cytokine levels and promote mucosal healing. Similarly, microbiome-targeted approaches, such as oral microbiota transplantation and multi-strain probiotic formulations, have demonstrated potential in restoring microbial balance and attenuating CRIOM severity, with current evidence including both preclinical and clinical studies. Overall, current findings highlight cytokine toxicity and dysbiosis as synergistic drivers of CRIOM and support anti-inflammatory and microbiome-modulating strategies as promising adjunctive approaches; however, further well-designed clinical studies are required to validate their efficacy and guide clinical translation. Full article

Nickel is a pervasive heavy metal with the potential for multi-route exposure, raising significant concerns regarding systemic toxicity. Although Ni²⁺ has been implicated in nickel sulfate NiSO₄-induced neurotoxicity, its underlying mechanisms remain incompletely elucidated. The present study investigates the role of NiSO₄-induced ferroptosis as a potential contributor to neurotoxicity. C57BL/6 mice were administered NiSO₄ daily via oral gavage at doses of 50, 100, and 200 mg/kg over 28 days. Neurobehavioral assessments, histopathological examination, transmission electron microscopy, and molecular profiling were conducted to evaluate brain injury and ferroptotic activity. Gut microbiota composition and intestinal barrier integrity were systematically evaluated. In vitro, HT22 cells were subjected to NiSO₄ treatment, followed by integrative transcriptomic analysis complemented by pharmacological and genetic manipulation to delineate the contributions of ferroptosis and autophagy. The results demonstrated that NiSO₄ exposure inhibited body weight gain, elicited depression-like behaviors, and initiated ferroptosis, evidenced by ultrastructural mitochondrial damage and dysregulated expression of glutathione peroxidase 4/acyl-CoA synthetase long chain family member 4 (GPX4/ACSL4). Furthermore, NiSO₄ caused gut microbiota dysbiosis and compromised the intestinal barrier, which was correlated with the induction of ferroptosis in neuronal cells of the brain. In HT22 cells, NiSO₄ elicited dose-dependent cytotoxicity and lactate dehydrogenase (LDH) release. KEGG pathway enrichment analysis further revealed that NiSO₄ treatment significantly upregulated pathways associated with ferroptosis, autophagy, and lysosomal function. Moreover, both ferrostatin-1 and rapamycin attenuated NiSO₄-induced cytotoxicity and ferroptosis, indicating that autophagy serves a protective function against ferroptotic cell death. Additionally, overexpression of Transcription Factor EB (TFEB) attenuated NiSO₄-induced ferroptosis by downregulating ACSL4, and upregulating GPX4, implicating the autophagy–lysosome pathway in the protective regulation of this cell death process. In summary, our findings indicated that NiSO₄-induced neurotoxicity was strongly associated with gut microbiota dysbiosis and coincided with ferroptosis in the brain, while stimulation of the autophagy–lysosome pathway conferred neuroprotective effects via modulating TFEB-dependent anti-ferroptotic mechanisms. These findings offer novel insights for risk assessment and therapeutic strategies of nickel-related neurotoxicity. Full article

Background/Objectives: Eosinophilic esophagitis (EoE) and achalasia are two chronic esophageal disorders, characterized by inflammatory and neuromotor dysfunction, respectively, that share overlapping immune-inflammatory features. Emerging evidence suggests that dysbiosis of the oral and esophageal microbiota may represent a common determinant in their pathophysiology. This review aims to provide a comparative and integrated overview of microbial and immune alterations in EoE and Achalasia, with potential diagnostic and therapeutic implications. Methods: A bibliographic search was conducted on PubMed and Scopus including clinical studies, experimental research, and review articles published between 2015 and 2025. The keywords Eosinophilic Esophagitis, Achalasia, Microbiota, and Dysbiosis were used for article selection. Results: In EoE, several studies demonstrated increased bacterial diversity with predominance of Prevotella and reduction of Streptococcus, findings associated with greater inflammatory severity and epithelial barrier dysfunction. Conversely, Achalasia is characterized by reduced microbial diversity and a shift from Gram-positive commensals to Gram-negative taxa capable of activating pro-inflammatory pathways (TLR4-MYD88-NF-κB), leading to neuronal loss and impaired peristalsis. Conclusions: Both EoE and Achalasia share the hallmark of dysbiosis, although with distinct immune profiles (Th2 vs. Th17). The identification of specific microbial “signatures” suggests promising perspectives for non-invasive biomarkers and microbiota-targeted therapies, including probiotics and glycan-modulating strategies. Further prospective studies are needed to clarify causal mechanisms and validate microbiota manipulation as a complementary therapeutic approach in esophageal diseases. Full article

Soybean isoflavones (SIFs), a group of secondary metabolites, have antioxidant, anti-inflammatory, and hormone-like activities. Supplementation with SIFs in the diet was reported to promote lactation performance in ruminants. The present study was performed to further decipher the effect of various concentrations of SIFs on growth and slaughter performance, serum parameters, meat quality, and ruminal microbiota in fattening goats. After a two-week acclimation, a total of 27 5-month-old Guanzhong male goats (18.29 ± 0.44 kg) were randomly assigned to control (NC), 100 mg/d SIF (SIF1), or 200 mg/d SIF (SIF2) groups. The experimental period lasted 56 days. The weight of the large intestine was greater (p < 0.05) in the SIF1 and SIF2 groups compared with the NC group. Meat quality parameters indicated that SIF1 supplementation led to lower (p < 0.05) cooking loss and shear force (0.05 < p < 0.10). The 16S rRNA sequencing analysis demonstrated that SIF1 supplementation led to lower (p < 0.05) proportions of Papillibacter and Prevotellaceae_UCG-004 but greater (p < 0.05) CAG-352 abundance in the rumen; these responses might have contributed to the improvement in production performance. In conclusion, meat quality and ruminal microbiome could be manipulated in a positive way by oral supplementation with 100 mg/d of SIFs in fattening goats. Thus, this study provides new insights and practical evidence for the introduction of SIFs as a novel additive in goat husbandry. Full article

Immunotherapy represents an attractive avenue for cancer therapy due to its tumour specificity and relatively low frequency of adverse effects compared to other treatment modalities. Despite many advances being made in the field of cancer immunotherapy, very few immunotherapeutic treatments have been approved for difficult-to-treat solid tumours such as triple negative breast cancer (TNBC), glioblastoma multiforme (GBM), and advanced prostate cancer (PCa). The anatomical location of some of these cancers may also make them more difficult to treat. Many trials focus solely on immunotherapy and have failed to consider or manipulate, prior to the immunotherapeutic intervention, important factors such as the microbiota, which itself is directly linked to lifestyle factors, diet, stress, social support, exercise, sleep, and oral hygiene. This review summarises the most recent treatments for hard-to-treat cancers whilst factoring in the less conventional interventions which could tilt the balance of treatment in favour of success for these malignancies. Full article

Trillions of diverse microbes reside in the gut and are deeply interwoven with the human physiological process, from food digestion, immune system maturation, and fighting invading pathogens, to drug metabolism. Microbial drug metabolism has a profound impact on drug absorption, bioavailability, stability, efficacy, and toxicity. However, our knowledge of specific gut microbial strains, and their genes that encode enzymes involved in the metabolism, is limited. The microbiome encodes over 3 million unique genes contributing to a huge enzymatic capacity, vastly expanding the traditional drug metabolic reactions that occur in the liver, manipulating their pharmacological effect, and, ultimately, leading to variation in drug response. For example, the microbial deactivation of anticancer drugs such as gemcitabine can lead to resistance to chemotherapeutics or the crucial role of microbes in modulating the efficacy of the anticancer drug, cyclophosphamide. On the other hand, recent findings show that many drugs can shape the composition, function, and gene expression of the gut microbial community, making it harder to predict the outcome of drug-microbiota interactions. In this review, we discuss the recent understanding of the multidirectional interaction between the host, oral medications, and gut microbiota, using traditional and machine-learning approaches. We analyze gaps, challenges, and future promises of personalized medicine that consider gut microbes as a crucial player in drug metabolism. This consideration will enable the development of personalized therapeutic regimes with an improved outcome, ultimately leading to precision medicine. Full article

Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. A novel promising therapeutic target for AD is the microbiota. Numerous studies have highlighted the involvement of the skin and gut microbiota in the pathogenesis of AD. The resident microbiota at these two epithelial tissues can modulate skin barrier functions and host immune responses, thus regulating AD progression. For example, the pathogenic roles of Staphylococcus aureus in the skin are well-established, making this bacterium an attractive target for AD treatment. Targeting the gut microbiota is another therapeutic strategy for AD. Multiple oral supplements with prebiotics, probiotics, postbiotics, and synbiotics have demonstrated promising efficacy in both AD prevention and treatment. In this review, we summarize the association of microbiota dysbiosis in both the skin and gut with AD, and the current knowledge of the functions of commensal microbiota in AD pathogenesis. Furthermore, we discuss the existing therapies in manipulating both the skin and gut commensal microbiota to prevent or treat AD. We also propose potential novel therapies based on the cutting-edge progress in this area. Full article

In our previous research, Lactiplantibacillus plantarum-12 alleviated inflammation in dextran sodium sulfate (DSS)-induced mice by regulating intestinal microbiota and preventing colon shortening (p < 0.05). The purpose of the present study was to evaluate whether L. plantarum-12 could ameliorate the colon cancer symptoms of azoxymethane (AOM)/DSS-treated C57BL/6 mice. The results showed that L. plantarum-12 alleviated colonic shortening (from 7.43 ± 0.15 to 8.23 ± 0.25) and weight loss (from 25.92 ± 0.21 to 27.75 ± 0.88) in AOM/DSS-treated mice. L. plantarum-12 oral administration down-regulated pro-inflammatory factors TNF-α (from 350.41 ± 15.80 to 247.72 ± 21.91), IL-8 (from 322.19 ± 11.83 to 226.08 ± 22.06), and IL-1β (111.43 ± 8.14 to 56.90 ± 2.70) levels and up-regulated anti-inflammatory factor IL-10 (from 126.08 ± 24.92 to 275.89 ± 21.87) level of AOM/DSS-treated mice. L. plantarum-12 oral administration restored the intestinal microbiota dysbiosis of the AOM/DSS treated mice by up-regulating beneficial Muribaculaceae, Lactobacillaceae, and Bifidobacteriaceae levels and down-regulating pathogenic Proteobacteria, Desulfovibrionaceae, and Erysipelotrichaceae levels. As a result, the fecal metabolites of the AOM/DSS-treated mice were altered, including xanthosine, uridine, 3,4-methylenesebacic acid, 3-hydroxytetradecanedioic acid, 4-hydroxyhexanoylglycine, beta-leucine, and glycitein, by L. plantarum-12 oral administration. Furthermore, L. plantarum-12 oral administration significantly ameliorated the colon injury of the AOM/DSS-treated mice by enhancing colonic tight junction protein level and promoting tumor cells death via down-regulating PCNA (proliferating cell nuclear antigen) and up-regulating pro-apoptotic Bax. (p < 0.05). Taken together, L. plantarum-12 oral administration could ameliorate the colon cancer burden and inflammation of AOM-DSS-treated C57BL/6 mice through regulating the intestinal microbiota, manipulating fecal metabolites, enhancing colon barrier function, and inhibiting NF-κB signaling. These results suggest that L. plantarum-12 might be an excellent probiotic candidate for the prevention of colon cancer. Full article

Microbiota dysbiosis has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological changes affecting the gut-brain neural axis, mental health, and general well-being. However, current animal studies using oral gavage and gnotobiotic animals do not allow for non-invasive long-term access to gut microbiome. The purpose of the present study was to evaluate the feasibility of 3D-printed fistula implants through the body wall and into the cecum of rats to obtain long-term access to gut microbiome. Cecal fistulas were designed and 3D-printed using a high temperature resin (Formlabs; acrylic and methacrylic mixture). Nine male Sprague-Dawley rats underwent the fistula implantation. Food intake, body weight, and body fat were measured to determine the impact of fistula manipulation. Gut microbiome, vagal afferents in the hindbrain, and microglia activation were analyzed to determine if fistula implantation disrupted the gut-brain neural axis. We found that the procedure induced a transient decrease in microbial diversity in the gut that resolved within a few weeks. Fistula implantation had no impact on food intake, body weight, fat mass, or microglia activation. Our study shows that 3D-printed cecal fistula implantation is an effective procedure that allows long-term and minimally invasive access to gut microbiome. Full article

Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC. Full article

In healthy hosts, trillions of microbes colonise the gut and oral cavity in a well-balanced state, maintaining a mutually beneficial relationship. Loss of this balance, termed dysbiosis, is strongly implicated in the pathogenesis of colorectal cancer (CRC). However, the roles of microbiota and dysbiosis in CRC treatment remain poorly understood. Recent studies suggest that the gut microbiota has the ability to affect the host response to chemotherapeutic agents by enhancing drug efficacy, promoting chemoresistance and mediating chemotherapy-induced toxicity and side effects via a variety of mechanisms. Several other studies have also proposed manipulation of the microbiota to optimise CRC treatment. In this review, we summarise the current advancement of knowledge on how microbiota and CRC treatments interact with each other and how this interaction may shed some light on the development of personalised microbiota manipulations that improve CRC treatment outcomes. Full article

The human skin microbiota is essential for maintaining homeostasis and ensuring barrier functions. Over the years, the characterization of its composition and taxonomic diversity has reached outstanding goals, with more than 10 million bacterial genes collected and cataloged. Nevertheless, the study of the skin microbiota presents specific challenges that need to be addressed in study design. Benchmarking procedures and reproducible and robust analysis workflows for increasing comparability among studies are required. For various reasons and because of specific technical problems, these issues have been investigated in gut microbiota studies, but they have been largely overlooked for skin microbiota. After a short description of the skin microbiota, the review tackles methodological aspects and their pitfalls, covering NGS approaches and high throughput culture-based techniques. Recent insights into the “core” and “transient” types of skin microbiota and how the manipulation of these communities can prevent or combat skin diseases are also covered. Finally, this review includes an overview of the main dermatological diseases, the changes in the microbiota composition associated with them, and the recommended skin sampling procedures. The last section focuses on topical and oral probiotics to improve and maintain skin health, considering their possible applications for skin diseases. Full article

Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota—and also the bacteria present in the oral cavity—act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota—composition, intra- and inter-species relationships, metabolic functions—could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of “healthy” bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications—even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease. Full article

T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated through the administration of antibiotics and oral gavage of bacteria. Alterations in the gut microbiome were analysed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumour efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mice. Anti-tumour efficacy was restored following oral gavage of faecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, transferred bacterial species and host mouse strain were critical determinants of the anti-tumour efficacy of Tim-3 blockade. Bacterial gavage did not increase the alpha diversity of gut microbiota in antibiotic-treated mice but did alter the microbiome composition, which was associated with the restoration of the anti-tumour efficacy of Tim-3 blockade. Conclusively, our results indicate that gut microbiota modulation may improve the therapeutic efficacy of Tim-3 blockade during concomitant antibiotic treatment. The administered bacterial species and host factors should be considered in order to achieve therapeutically beneficial modulation of the microbiota. Full article