Western diets and chronic diseases

Nature Medicine, Год журнала: 2024, Номер 30(8), С. 2133 - 2147

Опубликована: Июль 31, 2024

Язык: Английский

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Gut microbiome and immune checkpoint inhibitor toxicity

European Journal of Cancer, Год журнала: 2025, Номер 216, С. 115221 - 115221

Опубликована: Янв. 5, 2025

Язык: Английский

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The gut microbiome and cancer response to immune checkpoint inhibitors

Journal of Clinical Investigation, Год журнала: 2025, Номер 135(3)

Опубликована: Фев. 2, 2025

Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy ICIs in fighting tumors outside gut. Certain strains commensal promote antitumor responses to variety preclinical mouse tumor models. Patients with who respond have different microbiome compared that don't Fecal microbiota transplants (FMTs) from into mice phenocopy patient responses: FMTs responders response ICIs, whereas nonresponders do not response. In patients, had complete can overcome resistance progress on treatment. However, variable. Though emerging studies indicate immunity absence this Review will focus demonstrate relationships between and ICIs. We explore investigating which models, associated receiving mechanisms by immunity, how microbiome-based therapies be translated clinic.

Язык: Английский

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The intestinal microbiome and metabolome discern disease severity in cytotoxic T-lymphocyte-associated protein 4 deficiency

Microbiome, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 11, 2025

Abstract Background Cytotoxic T-lymphocyte-associated protein 4 deficiency (CTLA4-D) is an inborn error of immunity (IEI) caused by heterozygous mutations, and characterized immune cell infiltration into the gut other organs, leading to intestinal disease, dysregulation autoimmunity. While regulatory T-cell dysfunction remains central CTLA4-D immunopathogenesis, mechanisms driving disease severity pathology are unknown but likely involve dysbiosis. We determined whether microbiome metabolome could distinguish individuals with severe identify biomarkers severity. Results The genera Veillonella Streptococcus emerged as that distinguished from healthy cohorts both National Institutes Health (NIH) Clinical Center, USA (NIH; CTLA-D, n = 32; controls, 16), a geographically distinct cohort Center for Chronic Immunodeficiency (CCI) Medical - University Freiburg, Germany (CCI; CTLA4-D, 25; 24). Since IEIs in general may be associated perturbations microbiota, control common variable immunodeficiency (CVID, 20) was included evaluate CTLA4-D-specific microbial signature. Despite IEI-associated changes, two bacterial retained their specificity CTLA4-D. further identified metabolomic signatures patients having vs. mild disease. Microbiome changes were stool profiles predicted metabolic pathways. These differences impacted presence gastrointestinal manifestations partially reversed treatment abatacept and/or sirolimus. Conclusions Loss diversity dysbiosis causing observed Albeit some these features shared CVID, highlight fact reflect underlying dysregulation. Identified candidate distinguishing based on should studied prospectively determine predictive value, investigated potential therapeutic ta.

Язык: Английский

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The relationship between the gut microbiota and thyroid disorders

Nature Reviews Endocrinology, Год журнала: 2024, Номер 20(9), С. 511 - 525

Опубликована: Июнь 21, 2024

Язык: Английский

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Improving UTI Diagnostics in Oncology: Reliability of Reflex Urine Culture in Immunosuppressed Neutropenic and Non-neutropenic Cancer Patients

Clinical Infectious Diseases, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Urinary tract infections are prone to overdiagnosis, and reflex urine culture protocols offer a valuable opportunity for diagnostic stewardship in this arena. However, there is no recommended standard testing approach. Cancer patients often excluded from protocols, especially if severely immunosuppressed or neutropenic. The aim of study was evaluate the performance characteristics screening studies, including dipstick urinalysis nitrite leukocyte esterase microscopy white blood cell count, detect significant pathogen growth. A retrospective 58,098 cultures with paired without performed at Memorial Sloan Kettering Center New York City, evaluating data January 1, 2018, December 31, 2020. considered negative only were undetected. had predictive value (NPV) 98% clinically bacteriuria voided urine, 95% catheterized urine. Notably, test screen maintained high NPV among neutropenia those antibiotic exposure before testing. Finally, presence pyuria ≥10 cells per power field on offered negligible incremental benefit samples urinalysis. Reflex contingent upon safe effective platform cancer neutropenia.

Язык: Английский

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Gut Microbiota–Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer

Cancer Management and Research, Год журнала: 2025, Номер Volume 17, С. 171 - 192

Опубликована: Янв. 1, 2025

Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade detection. Although have shown promising results, especially solid tumors, patient responses vary widely due multiple intrinsic and extrinsic factors within tumor microenvironment. Emerging evidence suggests gut microbiota plays pivotal role modulating at site may even influence outcomes patients receiving ICIs. This review explores complex interactions between microenvironment, examining how these could impact effectiveness of ICI therapy. Furthermore, we discuss dysbiosis, an imbalance composition, contribute resistance ICIs, highlight microbiota-targeted strategies potentially overcome this challenge. Additionally, studies investigating diagnostic potential profiles patients, considering microbial markers might aid early detection stratification By integrating insights from preclinical clinical studies, aim shed light on microbiome modulation adjunct tool, paving way for personalized approaches optimize outcomes.

Язык: Английский

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The gut microbiota improves the efficacy of immune-checkpoint inhibitor immunotherapy against tumors: From association to cause and effect

Cancer Letters, Год журнала: 2024, Номер 598, С. 217123 - 217123

Опубликована: Июль 20, 2024

Immune-checkpoint inhibitors (ICIs), including anti-PD-1/PD-L1 therapeutic antibodies, have markedly enhanced survival across numerous cancer types. However, the limited number of patients with durable benefits creates an urgent need to identify response biomarkers and develop novel strategies so as improve response. It is widely recognized that gut microbiome a key mediator in shaping immunity. Additionally, shows significant potential predicting enhancing efficacy ICI immunotherapy against cancer. Recent studies encompassing mechanistic analyses clinical trials microbiome-based therapy shown cause-and-effect relationship between modulation immunotherapeutic response, greatly contributing establishment will overcome resistance treatment. In this review, we outline current state research advances discuss future directions utilizing enhance tumors.

Язык: Английский

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Inflammation mediated by gut microbiome alterations promotes lung cancer development and an immunosuppressed tumor microenvironment

Cancer Immunology Research, Год журнала: 2024, Номер 12(12), С. 1736 - 1752

Опубликована: Сен. 13, 2024

Abstract Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed progressive changes in microbial diversity composition are closely coupled with tobacco-associated lung adenocarcinoma a human-relevant mouse model. Furthermore, we demonstrated loss of antimicrobial protein Lcn2 these mice exacerbates protumor inflammatory phenotypes while further reducing diversity. Yet, how alterations impinge on development remains poorly understood. In this study, investigated role using fecal microbiota transfer delineated pathway by which incurred fostered proliferation proinflammatory bacteria genus Alistipes, triggering inflammation. This inflammation propagated systemically, exerting immunosuppression within tumor microenvironment, augmenting growth through an IL6-dependent mechanism dampening response to immunotherapy. Corroborating our preclinical findings, found patients higher relative abundance Alistipes species diminished neoadjuvant These insights reveal microbiome-induced present new potential targets for interception

Язык: Английский

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Gut Microbiota, Deranged Immunity, and Hepatocellular Carcinoma

Biomedicines, Год журнала: 2024, Номер 12(8), С. 1797 - 1797

Опубликована: Авг. 7, 2024

Background: Liver cancer, particularly hepatocellular carcinoma (HCC), is a significant gastrointestinal disease with mortality rate as high nearly 80% within five years. The disease’s pathophysiology involves deranged immune responses and bile acid metabolism, the gut microbiota (GM) playing crucial role. Recent research highlights potential of GM in influencing HCC treatment outcomes, especially regarding checkpoint inhibitors (ICIs). However, few patients currently benefit from ICIs due to lack effective response biomarkers. Aims methods: This review aimed explore literature on issues, focusing response, dysbiosis. included studies PubMed, Medline, major gastroenterology hepatology meetings, using keywords like microbiota, system, liver inhibitors. Results: dysbiosis significantly impacts making it promising biomarker for ICI response. Modulating can enhance efficacy, although more needed confirm its direct therapeutic benefits HCC. Conclusions: integral cancer pathogenesis Its modulation offers avenues improving prognosis immunotherapy.

Язык: Английский

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