Publications by authors named "Daniel Spakowicz"

Metabolic dietary patterns, including the Empirical Dietary Index for Hyperinsulinaemia (EDIH) and Empirical Dietary Inflammatory Pattern (EDIP), are known to impact multiple chronic diseases, but the role of the colonic microbiome in mediating such relationships is poorly understood. Among 1,610 adults with faecal 16S rRNA data in the TwinsUK cohort, we identified the microbiome profiles for EDIH and EDIP (from food frequency questionnaires) cross-sectionally using elastic net regression. We assessed the association of the dietary pattern-related microbiome profile scores with circulating biomarkers in multivariable-adjusted linear regression.

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Background: Although depression is a leading cause of disability worldwide, the pathophysiological mechanisms underlying this disorder-particularly those involving the gut microbiome-are poorly understood.

Method: To investigate, we conducted a community-based observational study to explore complex associations between changes in the gut microbiome, cytokine levels, and depression symptoms in 52 participants (M = 49.56, SD = 13.

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Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

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Background: Breast cancer, the most common cancer type among women, was recently found to contain a specific tumor microbiome, but its impact on host biology remains unclear. CD8 tumor-infiltrating lymphocytes (TILs) are pivotal effectors of anti-tumor immunity that influence cancer prognosis and response to therapy. This study aims to elucidate interactions between CD8 TILs and the breast tumor microbiome and metabolites, as well as how the breast tumor microbiome may affect the tumor metabolome.

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Article Synopsis
  • - Microbes are significantly present in cancer tissues and influence tumor development and treatment outcomes, yet their exact interactions with tumors are not well understood.
  • - The study introduces MICAH, a novel analysis tool that uses a graph transformer to explore the relationships between intratumoral microbes and cancer, integrating their metabolic and phylogenetic data for better understanding.
  • - MICAH has been successfully applied to bacterial and fungal data from various cancer types, demonstrating its effectiveness in narrowing down microbial candidates for further experimental validation, ultimately enhancing our comprehension of tumor-microbe dynamics.
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  • The ROAR-LCT clinical trial aimed to assess the feasibility of a supportive care intervention combining physical therapy and progressive muscle relaxation for older adults with advanced lung cancer.
  • The study recruited 22 participants aged 60 and older with specific types of lung cancer, evaluating them through various physical and mental health measures before and after the 12-session program.
  • Out of those who consented, 81.8% began the intervention, and 61.1% completed enough sessions to meet the feasibility criteria, indicating a promising approach to improve care for this population.
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Fecal microbiota transplants (FMTs) recently entered the cancer therapeutics field as a method to resensitize treatment-resistant melanoma patients to immune checkpoint inhibitors (ICIs). In this issue of Cell Host & Microbe, Kim and colleagues extend its utility to other solid tumors, including esophageal and hepatocellular carcinomas..

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Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e.

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Unlabelled: Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and its potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICI). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs.

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Background: Depression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood.

Methods: We examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program.

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Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration.

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Introduction: Older adults with chronic disease prioritize functional independence. We aimed to describe the feasibility of capturing functional disability and treatment toxicity among older adults with lung cancer using a longitudinal comprehensive geriatric assessment (CGA) and molecular biomarkers of aging.

Methods: This prospective study included adults ≥60 years with any newly diagnosed non-small-cell lung cancer.

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  • Tumor hypoxia makes it harder for radiation therapy to work effectively, which can lead to worse outcomes for cancer patients.
  • Researchers studied how low oxygen levels in tumors might affect the microbes living inside them in patients with colorectal cancer.
  • They found that certain microbes in hypoxic tumors can predict poor patient outcomes, suggesting that the relationship between low oxygen, microbes, and radiation impacts treatment success.
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  • Head and Neck Squamous Cell Carcinoma (HNSCC) is a complex group of tumors influenced by the tumor microenvironment (TME), which includes microorganisms and immune cells, affecting treatment response and survival rates.
  • Researchers analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) to link specific microbes and gene expression patterns to overall survival (OS), finding that the presence of the Alphapapillomavirus 9 virus was associated with better survival outcomes.
  • The study revealed that HPV-negative tumors had a higher presence of certain harmful microbes and macrophages linked to tumor progression, suggesting the TME's potential role in predicting patient outcomes and understanding resistance to therapies.
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Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor.

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  • The study analyzed the human microbiome from four body sites in 86 participants over six years to understand its relationship with health and disease.
  • It found that microbiome stability varies by body site, with stool and oral microbiomes being more stable than those from skin and nasal areas, primarily influenced by host interactions.
  • The research highlights that individual-specific bacterial taxa are more stable and that changes in microbiome dynamics, especially in insulin-resistant individuals, can indicate disruptions related to metabolic diseases.
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Unlabelled: To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment.

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Unlabelled: Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses.

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The most common subtype of renal cell carcinoma is clear cell renal cell carcinoma (ccRCC). While localized ccRCC can be cured with surgery, metastatic disease has a poor prognosis. Recently, immunotherapy has emerged as a promising approach for advanced ccRCC.

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Background: This study examined how gut microbiota diversity and richness relate to T cell aging among 96 healthy adults of all ages. It also explored whether these links differed throughout the lifespan.

Methods: Peripheral blood was obtained from 96 study participants (N = 96, aged 21-72) to assess mRNA markers of T cell aging (p16ink4a, p14ARF, B3gat1, Klrg1) and DNA methylation.

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The microbiome plays a vital function in maintaining human health and homeostasis. Each microbiota has unique characteristics, including those of the gastrointestinal and female reproductive tract. Dysbiosis, or alterations to the composition of the microbial communities, impacts the microbiota-host relationship and is linked to diseases, including cancer.

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Purpose: Frailty in older adult cancer survivors after cancer treatments is associated with various health outcomes. However, there is less agreement on how frailty affects symptoms and health-related quality of life (HRQOL). This systematic review and meta-analysis aimed to evaluate the current literature on frailty, symptoms, and HRQOL, as well as the associations of frailty with these factors in older adult cancer survivors with chemotherapy.

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Unlabelled: The microbiome affects cancer, from carcinogenesis to response to treatments. New evidence suggests that microbes are also present in many tumors, though the scope of how they affect tumor biology and clinical outcomes is in its early stages. A broad survey of tumor microbiome samples across several independent datasets is needed to identify robust correlations for follow-up testing.

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Article Synopsis
  • The study looked at how using antibiotics (ABX) and proton-pump inhibitors (PPI) affects the health of patients with endometrial cancer who got special chemotherapy.
  • They found that using PPIs made patients live less time without cancer getting worse and also affected their overall survival negatively.
  • The researchers believe they need to learn more about how these medicines interact with chemotherapy and the body's bacteria to help improve treatment for cancer patients.
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Patients with human papillomavirus-negative head and neck squamous cell carcinoma (HPV-negative HNSCC) have worse outcomes than HPV-positive HNSCC. In our study, we used a published dataset and investigated the microbes enriched in molecularly classified tumor groups. We showed that microbial signatures could distinguish Hypoxia/Immune phenotypes similar to the gene expression signatures.

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