Search Results (106)

Currently, due to the complexity of obtaining samples, specific features of laboratory processing and analysis of the results, there is a lack of data on the microbial signature of the small intestine in healthy and diseased states of the upper gastrointestinal tract. Objective: To investigate the characteristics of the small intestinal microbiome in acute pancreatitis of varying severity and to identify correlations with clinical factors. Methods: This study included 30 patients with acute pancreatitis of varying severity treated between 1 January 2019 and 31 December 2021. The composition of the microbiota was analyzed by metagenomic sequencing of the 16S rRNA gene from jejunal samples. Results: The mortality rate in the study group was 23.3%. The small intestinal microbiome was dominated by Streptococcus (median relative abundance 19.2%, interquartile range 6.4–35.1%), Veillonella (3.4%; 0.6–7%), Granulicatella (2.7%; 0.6–5%), Fusobacterium (2.2%; 0.3–5.9%), Prevotella (1.5%; 0.3–8%), Haemophilus (0.9%; 0.2–10%), Gemella (0.8%; 0.2–4.3%), and Lactobacillus (0.2%; 0.1–0.9%). More severe disease was associated with decreased abundance of Neisseria mucosa, Parvimonas micra, and Megasphaera micronuciformis. In contrast, the relative abundance of the genera Streptococcus (species S. rubneri/parasanguinis/australis), Actinomyces, and several genera within the family Enterobacteriaceae was higher in these patients. Conclusions: The state of the microbiota has important prognostic value and correlates with the duration from the onset of the pain syndrome to the time of receiving qualified care in the hospital. Full article

Short-chain fatty acids (SCFAs) are metabolites derived from the fermentation of dietary fibre by gut bacteria. SCFAs function as essential regulators of host-microbiome interactions by participating in numerous physiological and pathological processes within the gastrointestinal (GI) tract. In recent years, the depletion of SCFAs has been increasingly linked to the pathogenesis of GI diseases. In this review, we summarize the current understanding of the therapeutic mechanisms of SCFAs in GI diseases, including inflammatory bowel disease, irritable bowel syndrome, metabolic dysfunction-associated steatotic liver disease, and acute pancreatitis. We next highlight potential therapeutic approaches that increase the endogenous production of SCFAs, including prebiotics, probiotics, and fecal microbiota transplantation. We conclude that, although SCFAs are promising therapeutic agents, further research is necessary due to variability in treatment efficacy, inconsistent clinical outcomes, and a limited understanding of SCFAs’ mechanisms of action. Full article

Celiac disease (CD) is a chronic and immune-mediated disorder triggered by the ingestion of gluten in some genetically predisposed individuals. CD can be associated with extra-gastrointestinal manifestations and diseases affecting several organs. In this review, the aim is to analyze and discuss the pancreatic alterations and/or comorbidities that could arise in the context of pediatric CD. Exocrine pancreatic insufficiency (EPI) can be observed in a variable fraction (up to 30%) of children diagnosed with CD at the diagnosis; indeed, it usually resolves after the implementation of a gluten-free diet (GFD). The main pathophysiological mechanisms of EPI could be represented by the impaired pattern of gastrointestinal hormones in CD patients. Conversely, pancreatitis seems to be a very rare comorbidity in CD children, since very few cases have been described in children. Therefore, there is no evidence that pancreatitis (including autoimmune forms) represents a relevant comorbidity in pediatric CD. Type 1 diabetes mellitus (T1DM) is a well-known and frequent comorbidity in CD children. The main determinant of this epidemiological association is the common HLA-related predisposing background, even if other (non-HLA-related) genetic and environmental factors (viruses, gut microbiome, and others) are likely to be also implicated in the development of both these autoimmune diseases. T1DM children with concomitant CD may experience specific challenges in the adherence to GFD, which has no negative impact on the glycemic and, in general, metabolic control of diabetes, if it is properly implemented and followed up. Full article

Pancreatic cancer (PC), with pancreatic ductal adenocarcinoma (PDAC) comprising about 90% of all cases, is one of the most aggressive and lethal solid tumors. PDAC remains one of the most significant challenges of oncology to this day due to its inadequate response to conventional treatment, gradual rise in incidence since 2004, and poor five-year survival rates. As cancer cells are the primary adversary in this uneven fight, they remain the primary research target. Nevertheless, increasing attention is being paid to the tumor microenvironment (TME). The most crucial TME constellation components are immune cells, especially macrophages, stellate cells and lymphocytes, fibroblasts, bacterial and fungal microflora, and neuronal cells. Depending on the particular phenotype of these cells, the composition of the microenvironment, and the cell ratio, patients can experience different disease outcomes and varying vulnerability to treatment approaches. This study aims to present the current knowledge and review the most up-to-date scientific findings regarding the microenvironment of PC. It contains detailed information on the structure and cellular composition of the stroma, including its impact on disease development, metastasis, and response to treatment, as well as the therapeutic opportunities that arise from targeting this tissue. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor early detection rates owing to the limited sensitivity and specificity of the current biomarker CA19-9. Gut microbiota dysbiosis plays a key role in PDAC pathogenesis. This study aimed to evaluate the noninvasive approach we developed, combining metagenome-derived microbial signatures with CA19-9, to improve PDAC detection. Methods: This study included 50 treatment-naïve patients with PDAC and their matched controls. Fecal samples were analyzed using shotgun metagenomic sequencing. Machine learning algorithms were used to develop and validate a diagnostic panel integrating microbial signatures and CA19-9 levels. Subgroup analyses were used to confirm the robustness of the microbial markers. Results: The combined models at both species and genus levels effectively distinguished patients with PDAC from healthy individuals, and their strong diagnostic efficacy and accuracy were demonstrated through rigorous validation. Conclusions: In conclusion, the combination of gut microbiome profiling and CA19-9 improves PDAC detection accuracy compared to the use of CA19-9 alone, showing promise for early and noninvasive diagnosis. Full article

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation. Full article

Pancreatic cancer is a major cause of cancer-associated mortality globally, characterized by a poor prognosis and limited therapeutic response. The current approach for treating pancreatic cancer involves locoregional control with surgical resection and systemic therapy in the form of cytotoxic chemotherapy. However, despite standard-of-care treatment, the outcomes remain dismal. Emerging evidence suggests that the gut microbiota plays a significant role in pancreatic carcinogenesis through dysbiosis, chronic inflammation and immune modulation. Dysbiosis-driven alterations in the gut microbiota composition can disrupt intestinal homeostasis, promote systemic inflammation and create a tumor-permissive microenvironment in the pancreas. Moreover, the gut microbiota modulates the efficacy of systemic therapies, including chemotherapy and immunotherapy, by impacting drug metabolism and shaping the tumor immune landscape. This review is mainly focused on exploring the intricate interplay between the gut microbiota and pancreatic cancer, and also highlighting its dual role in carcinogenesis and the therapeutic response. Full article

Background: Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the destruction of pancreatic β-cells, leading to absolute insulin deficiency. Despite advancements in insulin therapy and glucose monitoring, achieving optimal glycemic control remains a challenge. Emerging technologies and novel therapeutic strategies are transforming the landscape of T1D management, offering new opportunities for improved outcomes. Methods: This review synthesizes recent advancements in T1D treatment, focusing on innovations in continuous glucose monitoring (CGM), automated insulin delivery systems, smart insulin formulations, telemedicine, and artificial intelligence (AI). Additionally, we explore biomedical approaches such as stem cell therapy, gene editing, immunotherapy, gut microbiota modulation, nanomedicine-based interventions, and trace element-based therapies. Results: Advances in digital health, including CGM integration with hybrid closed-loop insulin pumps and AI-driven predictive analytics, have significantly improved real-time glucose management. AI and telemedicine have enhanced personalized diabetes care and patient engagement. Furthermore, regenerative medicine strategies, including β-cell replacement, CRISPR-based gene editing, and immunomodulatory therapies, hold potential for disease modification. Probiotics and microbiome-targeted therapies have demonstrated promising effects in maintaining metabolic homeostasis, while nanomedicine-based trace elements provide additional strategies to regulate insulin sensitivity and oxidative stress. Conclusions: The future of T1D management is shifting toward precision medicine and integrated technological solutions. While these advancements present promising therapeutic avenues, challenges such as long-term efficacy, safety, accessibility, and clinical validation must be addressed. A multidisciplinary approach, combining biomedical research, artificial intelligence, and nanotechnology, will be essential to translate these innovations into clinical practice, ultimately improving the quality of life for individuals with T1D. Full article

Cystic fibrosis (CF) patients experience higher risks of colorectal cancer but the pathogenesis is unclear. In the general population, polyketide synthase-positive (pks⁺) E. coli is implicated in intestinal carcinogenesis via the production of colibactin; however, the relevance in CF is unknown. In this study, we investigate pks⁺E. coli prevalence in CF and potential associations between pks⁺E. coli, gastrointestinal inflammation, and microbiome dynamics with fecal calprotectin and 16SrRNA gene taxonomic data. Cross-sectional analysis demonstrated no difference in pks⁺E. coli carriage between CF patients and healthy controls, 21/55 (38%) vs. 26/55 (47%), p = 0.32. Pks⁺E. coli was not associated with significant differences in mean (SD) calprotectin concentration (124 (154) vs. 158 (268) mg/kg; p = 0.60), microbial richness (159 (76.5) vs. 147 (70.4); p = 0.50) or Shannon diversity index (2.78 (0.77) vs. 2.65 (0.74); p = 0.50) in CF. Additionally, there was no association with exocrine pancreatic status (p = 0.2) or overall antibiotic use (p = 0.6). Longitudinally, CF subjects demonstrated intra-individual variation in pks⁺E. coli presence but no significant difference in overall prevalence. Future investigation into the effects of repeat exposure on risk profile and analysis of older CF cohorts is necessary to identify if associations with colorectal cancer exist. Full article

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, primarily due to its immunosuppressive tumor microenvironment (TME), which contributes to treatment resistance. Recent research shows that the microbiome, including microbial communities in the oral cavity, gut, bile duct, and intratumoral environments, plays a key role in PDAC development, with microbial imbalances (dysbiosis) promoting inflammation, cancer progression, therapy resistance, and treatment side effects. Microbial metabolites can also affect immune cells, especially natural killer (NK) cells, which are vital for tumor surveillance, therapy response and treatment-related side effects. Dysbiosis can affect NK cell function, leading to resistance and side effects. We propose that a combined biomarker approach, integrating microbiome composition and NK cell profiles, can help predict treatment resistance and side effects, enabling more personalized therapies. This review examines how dysbiosis contributes to NK cell dysfunction in PDAC and discusses strategies (e.g., antibiotics, probiotics, vaccines) to modulate the microbiome and enhance NK cell function. Targeting dysbiosis could modulate NK cell activity, improve the effectiveness of PDAC treatments, and reduce side effects. However, further research is needed to develop unified NK cell–microbiome interaction-based biomarkers for more precise and effective patient outcomes. Full article

The pancreas, previously considered a sterile organ, has recently been shown to harbor its own microbiota that may influence tumor biology and patient outcomes. Despite increasing interest in the impact of the microbiome on cancer, the relationship between pancreatic tissue and oral microbiomes in pancreatic ductal adenocarcinoma (PDAC) remains limited. In this study, the oral and pancreas tissue microbiomes of patients with PDAC were compared to patients with other periampullary cancers (DC/AC) and a healthy control group using 16S rRNA gene sequence analysis. The results showed a significant reduction in microbial diversity in the saliva of cancer patients compared to healthy controls, while the PDAC patients exhibited a distinct microbial profile in their pancreatic tissues, consisting predominantly of Firmicutes, Proteobacteria, and Actinobacter, after filtering the microbiome of the indoor environment. Notably, the presence of oral bacteria such as Anoxybacillus, Clostridium, and Bacillus in pancreatic tissues suggests potential translocation from the oral cavity. This study emphasizes the importance of understanding the role of body fluid and tissue microbiota in pancreatic cancer, proposing that oral dysbiosis may contribute to disease progression. Moreover, the results suggest that the microbiome of the indoor environment in which samples are collected and analyzed is also important in microbiota analysis studies. Full article

(1) Background: The modified Whipple procedure, or pylorus-preserving pancreaticoduodenectomy, is a complex surgical intervention used to treat pancreatic head tumors. While preserving digestive function, it is associated with significant perioperative risks. This study explores the clinical, immunological, and microbiome-related factors influencing postoperative complications, focusing on the interplay between patient comorbidities, systemic inflammation, and gut dysbiosis. (2) Methods: A retrospective analysis was conducted on 123 patients undergoing the modified Whipple procedure for pancreatic head tumors. Patients were categorized into two groups based on the occurrence of significant postoperative complications (Group A: with complications; Group B: without complications). Data on demographics, comorbidities, inflammatory markers (CRP, IL-6, procalcitonin), and gut microbiome composition were collected. Microbial diversity was evaluated using the Shannon Index, and logistic regression was performed to identify independent predictors of complications. (3) Results: Patients in Group A had a significantly higher prevalence of diabetes mellitus (43.1% vs. 20.8%; p = 0.02) and cardiovascular disease (35.3% vs. 13.9%; p = 0.01). Elevated inflammatory markers (CRP ≥ 40 mg/L, IL-6 ≥ 30 pg/mL, procalcitonin ≥ 0.5 ng/mL) were strongly associated with higher complication rates. Microbiome analysis indicated dysbiosis in Group A, with reduced Lactobacillus and Bifidobacterium levels, increased Enterobacteriaceae abundance, and a lower Shannon Index (<2). Patients exhibiting both dysbiosis and elevated inflammation had the highest complication rate (60%). Multivariate analysis identified diabetes, elevated IL-6, and dysbiosis as independent predictors of adverse outcomes. (4) Conclusions: Postoperative complications after the modified Whipple procedure are influenced by systemic inflammation and gut dysbiosis. A systematic preoperative assessment of microbiome health and inflammatory markers enables accurate risk stratification and personalized interventions, potentially reducing the incidence of complications and improving overall surgical outcomes. Full article

The gut microbiome plays an important role in the carcinogenesis of luminal gastrointestinal malignancies and response to antineoplastic therapy. Preclinical studies have suggested a role of intratumoral gammaproteobacteria in mediating response to gemcitabine-based chemotherapy in pancreatic ductal adenocarcinoma (PDAC). To our knowledge, this is the first study to evaluate the impact of the PDAC microbiome on chemotherapy response using samples from human pancreatic tumor resections. We performed 16S rRNA gene amplification and sequencing on both formalin-fixed paraffin-embedded (FFPE) and fresh frozen human PDAC resection samples. We analyzed frozen samples from 26 patients with resected PDAC and examined tumor and tumor-adjacent normal tissue. These patients represented nine long-term survivors (LTS) and nine short-term survivors (STS) after neoadjuvant gemcitabine therapy and eight control patients who did not receive any neoadjuvant therapy prior to resection. We also included FFPE samples from five patients, including tumor samples (3 samples per patient), tumor-adjacent normal tissue (2 per patient) and tumor-adjacent paraffin (1 per patient). Within frozen tissue, total DNA yields were high, but bacterial DNA was generally low, comparable to those seen in negative controls. In FFPE tissue, DNA yields were low and bacterial abundances were comparable in paraffin, tumor and normal PDAC samples. Gammaproteobacteria concentrations did not correlate with outcomes in patients treated with neoadjuvant gemcitabine-based chemotherapy. Our study found low microbial biomass in pancreatic tumor tissue, with no detectable association between bacterial taxa and chemotherapy outcomes. These results suggest a limited role of the microbiome in gemcitabine-based chemotherapy response in PDAC. Preclinical studies have implicated the pancreatic tumor microbiome in driving response to therapy. Cytidine deaminase, an enzyme produced by gammaproteobacteria, can metabolize gemcitabine and has been hypothesized to inhibit pancreatic tumor response to chemotherapy. Several clinical trials have evaluated the role of the tumor microbiome in pancreatic cancer treatment. We evaluated the impact of the pancreatic tumor microbiome on chemotherapy response using samples from human pancreatic tumor resections. We found a low microbial load that is partially attributable to contaminants and that gammaproteobacteria levels did not correlate with outcomes in patients with pancreatic cancer treated with gemcitabine-based chemotherapy. Full article

The intratumoral microbiome plays a significant role in many cancers, such as lung, pancreatic, and colorectal cancer. Pancreatic cancer (PC) is one of the most lethal malignancies and is often diagnosed at advanced stages. Fusobacterium nucleatum (Fn), an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in several extra-oral human diseases and, lately, in pancreatic cancer progression and prognosis. It is now recognized as oncobacterium. Fn engages in pancreatic tumorigenesis and metastasis through multifaceted mechanisms, including immune response modulation, virulence factors, control of cell proliferation, intestinal metabolite interactions, DNA damage, and epithelial–mesenchymal transition. Additionally, compelling research suggests that Fn may exert detrimental effects on cancer treatment outcomes. This paper extends the perspective to pancreatic cancer associated with Fn. The central focus is to unravel the oncogenomic changes driven by Fn in colonization, initiation, and promotion of pancreatic cancer development. The presence of Fusobacterium species can be considered a prognostic marker of PC, and it is also correlated to chemoresistance. Furthermore, this review underscores the clinical research significance of Fn as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment. It is thought that given the role of Fn in tumor formation and metastasis processes via its FadA, FapA, Fap2, and RadD, new therapies for tumor treatment targeting Fn will be developed. Full article

Pancreatic cancer constitutes a significant cause of cancer-related fatalities, with a five-year survival rate of only 12%. The most prevalent form of this disease is pancreatic ductal adenocarcinoma (PDAC). Given that a single therapeutic intervention has proven inadequate for the treatment of PDAC, it is essential to identify distinct molecular signatures that could improve treatment efficacy and alleviate the economic burden on patients. Surgery is recognized as the most effective treatment option for PDAC; however, only a small percentage of patients are candidates for this procedure due to the advanced stage of the disease at the time of diagnosis. In this context, we propose to explore the biology of PDAC with a focus on microbiome, epigenetics, and genetics. Our objective is to examine the existing knowledge in these areas and to identify potential pathways for personalized medicine. This approach holds promise for advancing our understanding of PDAC development, progression, and resistance to standard therapy. Full article