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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. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic and inflammatory skin disorder characterized by impaired barrier function and imbalanced immunity. Recent advances have revealed that dysbiosis of skin microbiota plays important roles in the pathogenesis and development of AD. Meanwhile, endogenous and external factors contribute to the dysbiosis of skin microbiota in AD. Additionally, various treatments, including topical treatments, phototherapy, and systemic biologics, have demonstrated positive impacts on the clinical outcomes, alongside with the modulations of cutaneous microbiota in AD patients. Importantly, therapeutics or products regulating skin microbiota homeostasis have demonstrated potential for AD treatment in early clinical studies. In this review, we underline changes of the skin microbiota correlated with AD. Meanwhile, we provide an overview of the skin microbiota regarding its roles in the pathogenesis and development of AD. Finally, we summarize therapeutic strategies restoring the skin microbial homeostasis in AD management. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) has experienced a steady increase in global incidence and prevalence recently. Current research into UC pathogenesis focuses on the complex interplay of genetic and environmental factors with the immune system and gut microbiome, leading to disruption of the intestinal barrier. Normally, the microbiome, intestinal epithelium, and immune system interact to maintain intestinal homeostasis. However, when this equilibrium is disturbed, a harmful cycle of dysbiosis, immune dysregulation, and inflammation emerges, resulting in intestinal barrier dysfunction and UC progression. Among various risk factors, diet significantly influences epithelial barrier integrity and architectural stability through both direct and indirect mechanisms, shaping the entire UC continuum from pre-clinical prevention to active phase treatment and remission maintenance. This review provides insights into the impact of dietary content and eating behaviors on UC, focusing on specific food, food groups, nutrients, and intermittent fasting, while providing a detailed explanation of why the gut microbiota may mediate the sustained effects of diet across all stages of UC. Additionally, it addresses the limitations of current studies, explores underexamined areas in UC dietary research and proposes potential directions for future research and expansion. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Introduction: The gut microbiota plays a pivotal role in influencing host health, through the production of metabolites and other key signalling molecules. While the impact of specific metabolites or taxa on host cells is well-documented, the broader impact of a disrupted microbiota on immune homeostasis is less understood, which is particularly important in the context of the increasing overuse of antibiotics. Methods: Female C57BL/6 mice were gavaged twice daily for four weeks with Vancomycin, Polymyxin B, or PBS (control). Caecal microbiota composition was assessed via 16S rRNA sequencing and caecal metabolites were quantified with NMR spectroscopy. Immune profiles of spleen and mesenteric lymph nodes (MLNs) were assessed by flow cytometry, and splenocytes assessed for ex vivo cytokine production. A generalised additive model approach was used to examine the relationship between global antibiotic consumption and IBD incidence. Results: Antibiotics significantly altered gut microbiota composition, reducing alpha-diversity. Acetate and butyrate were significantly reduced in antibiotic groups, while propionate and succinate increased in Vancomycin and PmB-treated mice, respectively. The MLNs and spleen showed changes only to DC numbers. Splenocytes from antibiotic-treated mice stimulated ex vivo exhibited increased production of TNF. Epidemiological analysis revealed a positive correlation between global antibiotic consumption and IBD incidence. Discussion: Our findings demonstrate that antibiotic-mediated dysbiosis results in significantly altered short-chain fatty acid levels but immune homeostasis in spleen and MLNs at steady state is mostly preserved. Non-specific activation of splenocytes ex vivo, however, revealed mice with perturbed microbiota had significantly elevated production of TNF. Thus, this highlights antibiotic-mediated disruption of the gut microbiota may program the host towards dysregulated immune responses, predisposing to the development of TNF-associated autoimmune or chronic inflammatory disease. [ABSTRACT FROM AUTHOR]

Objective: The global incidence and burden of Major Depressive Disorder (MDD) are increasing annually, with current antidepressant treatments proving ineffective for 30-40% of patients. Biomolecular mechanisms within the microbiota-gut-brain axis (MGBA) may significantly contribute to MDD, potentially paving the way for novel treatment approaches. However, integrating the MGBA with the psychological and environmental aspects of MDD remains challenging. This manuscript aims to: 1) investigate the underlying biomolecular mechanisms of MDD using a modeling approach, and 2) integrate this knowledge into a comprehensive 'spiraling risk factor model' to develop a biopsychosocial translational research framework for the prevention and treatment of MDD. Methods: For the first aim, a systematic review (PROSPERO registration) was conducted using PubMed, Embase, and Scopus to query literature published between 2016–2020, with select additional sources. A narrative review was performed for the second aim. Results: In addition to genetics and neurobiology, research consistently indicates that hyperactivation of the HPA axis and a pro-inflammatory state are interrelated components of the MGBA and likely underlying mechanisms of MDD. Dysregulation of the MGBA, along with imbalances in mental and physical conditions, lifestyle factors, and pre-existing treatments, can trigger a downward spiral of stress and anxiety, potentially leading to MDD. Conclusions: MDD is not solely a brain disorder but a heterogeneous condition involving biomolecular, psychological, and environmental risk factors. Future interdisciplinary research can utilize the integrated biopsychosocial insights from this manuscript to develop more effective lifestyle-focused multimodal treatment interventions, enhance diagnosis, and stimulate early-stage prevention of MDD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42020215412. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis (OA) is the most prevalent form of arthritis and affects over 528 million people worldwide. Degenerative joint disease involves cartilage degradation, subchondral bone remodeling, and synovial inflammation, leading to chronic pain, stiffness, and impaired joint function. Initially regarded as a "wear and tear" condition associated with aging and mechanical stress, OA is now recognized as a multifaceted disease influenced by systemic factors such as metabolic syndrome, obesity, and chronic low-grade inflammation. Recent studies have focused on the gut-joint axis to investigate how the gut microbiome modulates inflammation and pain in OA. Materials and Methods: A systematic review was conducted following the PRISMA guidelines and was registered with PROSPERO (CRD42024556265). This review included studies involving adults with symptomatic OA and analyzed the relationship between the gut microbiome and OA-related pain. Randomized and non-randomized clinical trials, case reports, editorials, and pilot studies were excluded. Searches were performed in PubMed, Cochrane Library, and Web of Science without publication date restrictions, and filtered for "observational studies". The study selection and data extraction were performed by two independent researchers, and the risk of bias was assessed using appropriate tools. Results: Five observational studies were included in the systematic review, and three were included in the meta-analysis. Two studies reported an association between different tryptophan metabolites and pain levels in patients with OA. Two other studies demonstrated a correlation between lipopolysaccharide levels and pain in OA. A fifth study confirmed the relationship between Streptococcus relative abundance of Streptococcus spp. and knee pain. These results were not supported by a meta-analysis, which found no significant association between the presence of pain in OA and the presence of bacilli of the genus Streptococcus or plasma markers of the tryptophan pathway. Conclusions: Current evidence indicates a potential link between gut microbiome dysbiosis and OA-related pain. However, methodological limitations preclude definitive conclusions. Further research using advanced techniques and larger cohorts is needed to validate and extend these findings and elucidate the underlying mechanisms. Targeted manipulation of the gut microbiome may be a valuable strategy for pain management in OA patients. [ABSTRACT FROM AUTHOR]

The microbiome of the human intestine is a regulator of health that modulates immune response and plays an important role in metabolism. The diversity, and abundance of microbiota communities in the gut have been shown to change in cirrhosis and its complications. We aimed to review the current knowledge regarding microbiota alterations in cirrhosis, its potential differences according to etiology, and its role in the development of cirrhosis complications. A systematic search of the online bibliographic database up to July 2024 was performed. Randomized controlled trials and observational and cohort studies that included a total or at least a cohort of cirrhotic adult patients were enlisted for data extraction and analysis. A total of 73 publications were included for data extraction. Alpha diversity was found to decrease in cirrhotic patients in 30/38 (78%) of the studies, while beta diversity in 20/22 (90%) presented significant differences between healthy and cirrhotic groups. Proteobacteria significantly increased in 20/27 (74%) studies, followed by Actinobacteria and Fusobacteria, while 22/25 (88%) studies found either a reduction in cirrhotic patients or increased abundance in healthy controls for Firmicutes and Bacteroidetes. The most abundant genera in hepatic encephalopathy groups were pathobionts such as Enterococcus and Streptococcus, followed by Vellionella and Escherichia. Heterogeneity was found among studies regarding Alpha diversity in hepatocellular carcinoma (HCC) as it was decreased in three studies, indifferent in five, and increased in three studies in comparison to cirrhotic non-HCC patients. The dysbiosis of the gut microbiota is associated with cirrhosis and the development of complications such as hepatic encephalopathy and hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the paranasal sinuses with a yet unknown etiology. As studies continue to elucidate the disease's heterogeneity inflammatory profile and presentation, there is a growing interest in the influence of the nasal microbiome on disease pathogenesis and chronicity. The sinus microbiota appear dominated by the Staphylococcus and Corynebacterium genera; known upper airway pathogens, such as Haemophilus influenza, are present in the upper airways of healthy individuals, though at relatively lower abundances than in CRS patients. Viral culprits may induce an unhindered local immune response that contributes to the recurrence and chronicity of inverted papillomas—benign mucosal lesions with the propensity for local destruction and malignant transformation that can be found in patients with a history of nasal infection. The persistence of inverted papillomas warrants investigation into their pathogenesis and how they may contribute to a nasal landscape promoting the chronicity of CRS. Further investigation is needed to uncover the interplay between resident microbiota and viral, fungal, and immunological influence. Discerning between 'healthy' and 'diseased' sinonasal microbiomes and 'keystone' species could shed light on CRS etiology and provide the opportunity for CRS treatment tailored to an individual's microbiome. This review aims to explore the interrelation of microbial residents in the pathogenesis and chronicity of the diseased sinonasal environment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder that profoundly impacts cognitive function and the nervous system. Emerging evidence highlights the pivotal roles of iron homeostasis dysregulation and microbial inflammatory factors in the oral and gut microbiome as potential contributors to the pathogenesis of AD. Iron homeostasis disruption can result in excessive intracellular iron accumulation, promoting the generation of reactive oxygen species (ROS) and oxidative damage. Additionally, inflammatory agents produced by pathogenic bacteria may enter the body via two primary pathways: directly through the gut or indirectly via the oral cavity, entering the bloodstream and reaching the brain. This infiltration disrupts cellular homeostasis, induces neuroinflammation, and exacerbates AD-related pathology. Addressing these mechanisms through personalized treatment strategies that target the underlying causes of AD could play a critical role in preventing its onset and progression. [ABSTRACT FROM AUTHOR]

Background/Objectives: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. Methods: Blood samples were collected from sixty-eight female FM patients (49.9 ± 12.35 years). Pain intensity was assessed by FIQ-R. The serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17, IFN-γ, as well as those of vitamin D (25(OH)D3) and the kynurenine/tryptophan ratio (Kyn/Trp) were determined by ELISA and HPLC, respectively. The plasma levels of the SCFAs acetate, butyrate, and propionate were detected by GC-MS. Results: A mean FIQ-R score indicated that the patients could be classified as having moderate FM. The mean levels of all cytokines, but IL-6 and IL-1β, were higher than the normal reference values. The highest concentrations of cytokines were observed in patients showing the highest FIQ-R scores and the lowest 25(OH)D3 levels. Deficient levels of acetate were found paralleled by an increase in Kyn/Trp. The highest acetate concentrations were detected in patients with the lowest FIQ-R scores and 25(OH)D3 levels. Significantly negative correlations were found between 25(OH)D3 concentrations and FIQ-R scores (p = 0.007) as well as IL-17 levels (p = 0.002) and between acetate and TNF-α (p = 0.040) as well as FIQ-R scores (p = 0.028), while significantly positive correlations were observed between Kyn/Trp and IL-17 (p = 0.027) as well as IFN-γ (p = 0.003). Conclusions: Our preliminary data suggest that the vitamin D status along with altered gut microbiota metabolism plays a major role in FM-related inflammatory pain. Replication of these findings in a larger cohort is required to provide additional insights. [ABSTRACT FROM AUTHOR]

Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapyinduced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a devastating pathological state causing motor, sensory, and autonomic dysfunction. To date, SCI remains without viable treatment for its patients. After the injury, molecular events centered at the lesion epicenter create a non-permissive environment for cell survival and regeneration. This newly hostile setting is characterized by necrosis, inflammation, demyelination, axotomy, apoptosis, and gliosis, among other events that limit locomotor recovery. This review provides an overview of the pathophysiology of SCI, highlighting the potential role of the gut microbiota in modulating the inflammatory response and influencing neurological recovery following trauma to the spinal cord. Emphasis on the bidirectional communication between the gut and central nervous system, known as the gut-brain axis is given. After trauma, the gut-brain/spinal cord axis promotes the production of pro-inflammatory metabolites that provide a non-permissive environment for cell survival and locomotor recovery. Therefore, any possible pharmacological treatment, including antibiotics and painkillers, must consider their effects on microbiome dysbiosis to promote cell survival, regeneration, and behavioral improvement. Overall, this review provides valuable insights into the pathophysiology of SCI and the evolving understanding of the role of the gut microbiota in SCI, with implications for future research and clinical practice. [ABSTRACT FROM AUTHOR]