Metagenomic analysis during capecitabine therapy reveals microbial chemoprotective mechanisms and predicts drug toxicity in colorectal cancer patients DOI Creative Commons
Lars E. Hillege, Kai Trepka, Janine Ziemons

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Purpose Unpredictable chemotherapy side effects are a major barrier to successful treatment. Cell culture and mouse experiments indicate that the gut microbiota is influenced by influences anti-cancer drugs. However, metagenomic data from patients paired careful effect monitoring remains limited. Herein, we focus on oral fluoropyrimidine capecitabine (CAP). We investigate CAP-microbiome interactions through sequencing of longitudinal stool sampling cohort advanced colorectal cancer (CRC) patients. Methods established prospective study including 56 with CRC treated CAP monotherapy across 4 centers in Netherlands. Stool samples clinical questionnaires were collected at baseline, during cycle 3, post-treatment. Metagenomic assess microbial community structure gene abundance was transposon mutagenesis, targeted deletion, media supplementation experiments. An independent US used for model validation. Results treatment significantly altered composition pathway abundance, enriching menaquinol (vitamin K2) biosynthesis genes. Transposon library screens, deletions, confirmed protects Escherichia coli drug toxicity. Microbial genes associated decreased peripheral sensory neuropathy. Machine learning models trained this predicted hand-foot syndrome dose reductions an cohort. Conclusion These results suggest treatment-associated increases vitamin serve chemoprotective role bacterial host cells, implications toxicities outside gastrointestinal tract. provide proof-of-concept use microbiome profiling machine predict cohorts. observations foundation future human intervention studies, more in-depth mechanistic dissection preclinical models, extension other treatments.

Language: Английский

Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 422 - 422

Published: Feb. 10, 2025

The intricate relationship between anticancer drugs and the gut microbiome influences cancer treatment outcomes. This review paper focuses on role of integrity in enhancing efficacy safety drug therapy, emphasizing pharmacokinetic interactions microbiota. It explores how disruptions to composition, or dysbiosis, can alter metabolism, immune responses, side effects. By examining mechanisms disruption caused by drugs, this highlights specific case studies like cyclophosphamide, 5-fluorouracil, irinotecan, their impact microbial diversity clinical also discusses microbiome-targeted strategies, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation (FMT), as promising interventions enhance treatment. Furthermore, potential profiling personalizing therapy integrating these into practice is explored. Finally, proposes future research directions, developing novel biomarkers a deeper comprehension drug-microbiome interactions, respond current gaps knowledge improve patient outcomes care.

Language: Английский

Citations

1
Advancements in Antibacterial Therapy: Feature Papers DOI Creative Commons
Giancarlo Angeles Flores,

Gaia Cusumano,

Roberto Venanzoni

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(3), P. 557 - 557

Published: March 1, 2025

Antimicrobial resistance (AMR) is a growing global health crisis that threatens the efficacy of antibiotics and modern medical interventions. The emergence multidrug-resistant (MDR) pathogens, exacerbated by misuse in healthcare agriculture, underscores urgent need for innovative solutions. (1) Background: AMR arises from complex interactions between human, animal, environmental health, further aggravated overuse inadequate regulation antibiotics. Conventional treatments are increasingly ineffective, necessitating alternative strategies. Emerging approaches, including bacteriophage therapy, antimicrobial peptides (AMPs), nanotechnology, microbial extracellular vesicles (EVs), CRISPR-based antimicrobials, provide novel mechanisms complement traditional combating resistant pathogens. (2) Methods: This review critically analyzes advanced antibacterial strategies conjunction with systemic reforms such as stewardship programs, One Health framework, surveillance tools. These methods can enhance detection, guide interventions, promote sustainable practices. Additionally, economic, logistical, regulatory challenges impeding their implementation evaluated. (3) Results: technologies, CRISPR exhibit promising potential targeting mechanisms. However, disparities resource distribution barriers hinder widespread adoption. Public–private partnerships agriculture practices critical to overcoming these obstacles. (4) Conclusions: A holistic integrated approach essential mitigating impact AMR. By aligning therapeutic policies, fostering interdisciplinary collaboration, ensuring equitable distribution, we develop response this 21st-century challenge.

Language: Английский

Citations

1
The gut microbiota during tamoxifen therapy in patients with breast cancer DOI Creative Commons
Lars E. Hillege, David Barnett, Janine Ziemons

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 6, 2025

Tamoxifen is essential in treating estrogen receptor-positive (ER+) breast cancer, primarily through its active metabolite, endoxifen. Emerging research suggests potential interactions between tamoxifen and gut microbiota. This study investigates the effects of on microbiota composition postmenopausal ER+ human epidermal growth factor receptor 2 negative (HER2−) cancer patients explores correlations endoxifen plasma levels. prospective observational included ER+/HER2− patients. Fecal blood samples were collected before during 6–12 weeks therapy. Gut was analyzed using 16S rRNA amplicon sequencing hypervariable V4 gene region, levels measured liquid chromatography-mass spectrometry. Changes microbial diversity assessed, with to A total 62 included. significantly increased richness (p = 0.019), although overall community structure remained consistent pre- during-treatment samples. Notable changes observed specific taxa, significant increases genera such as Blautia (padjusted 0.003) Streptococcus 0.010), decreases Prevotella_9 0.006). No identified after multiple comparisons. therapy patients, though remains stable. The absence that while affects microbiota, role metabolism requires further study. More comprehensive needed understand relationship tamoxifen, therapeutic outcomes.

Language: Английский

Citations

0
Preconception maternal gut dysbiosis affects enteric nervous system development and disease susceptibility in offspring via the GPR41–GDNF/RET/SOX10 signaling pathway DOI Creative Commons
Cunzheng Zhang, Yuzhu Chen,

Ruqiao Duan

et al.

iMeta, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how microbiota alterations during preconception period influence remains limited. In this study, we investigated and mechanisms maternal dysbiosis on development enteric nervous system (ENS) mice. We found that exposure to antibiotics led abnormal ENS offspring, increasing their susceptibility water avoidance stress at adult stage. Metagenomic, targeted metabolomic, transcriptomic analyses revealed antibiotic disrupted expression genes crucial for embryonic by altering composition. Multi-omics analysis combined with Limosilactobacillus reuteri propionate gestational supplementation demonstrated metabolites may via GPR41-GDNF/RET/SOX10 signaling pathway. Our findings highlight critical importance maintaining a healthy before conception support normal offspring.

Language: Английский

Citations

0
Balancing act: counteracting adverse drug effects on the microbiome DOI Creative Commons
Jacobo de la Cuesta‐Zuluaga, Patrick Müller, Lisa Maier

et al.

Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

The human gut microbiome, a community of microbes that plays crucial role in our wellbeing, is highly adaptable but also vulnerable to drug treatments. This vulnerability can have serious consequences for the host, example, increasing susceptibility infections, immune, metabolic, and cognitive disorders. However, microbiome's adaptability provides opportunities prevent, protect, or even reverse drug-induced damage. Recently, several innovative approaches emerged aimed at minimizing collateral damage drugs on microbiome. Here, we outline these approaches, discuss their applicability different treatment scenarios, highlight current challenges, suggest avenues may lead an effective protection

Language: Английский

Citations

1
Empirically establishing drug exposure records directly from untargeted metabolomics data DOI Creative Commons
Haoqi Zhao, Kine Eide Kvitne, Corinna Brungs

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Despite extensive efforts, extracting information on medication exposure from clinical records remains challenging. To complement this approach, we developed the tandem mass spectrometry (MS/MS) based GNPS Drug Library. This resource integrates MS/MS data for drugs and their metabolites/analogs with controlled vocabularies sources, pharmacologic classes, therapeutic indications, mechanisms of action. It enables direct analysis drug metabolism untargeted metabolomics independent records. Our library facilitates stratification individuals in studies empirically detected medications, exemplified by drug-dependent microbiota-derived

Language: Английский

Citations

0
Metagenomic analysis during capecitabine therapy reveals microbial chemoprotective mechanisms and predicts drug toxicity in colorectal cancer patients DOI Creative Commons
Lars E. Hillege, Kai Trepka, Janine Ziemons

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Purpose Unpredictable chemotherapy side effects are a major barrier to successful treatment. Cell culture and mouse experiments indicate that the gut microbiota is influenced by influences anti-cancer drugs. However, metagenomic data from patients paired careful effect monitoring remains limited. Herein, we focus on oral fluoropyrimidine capecitabine (CAP). We investigate CAP-microbiome interactions through sequencing of longitudinal stool sampling cohort advanced colorectal cancer (CRC) patients. Methods established prospective study including 56 with CRC treated CAP monotherapy across 4 centers in Netherlands. Stool samples clinical questionnaires were collected at baseline, during cycle 3, post-treatment. Metagenomic assess microbial community structure gene abundance was transposon mutagenesis, targeted deletion, media supplementation experiments. An independent US used for model validation. Results treatment significantly altered composition pathway abundance, enriching menaquinol (vitamin K2) biosynthesis genes. Transposon library screens, deletions, confirmed protects Escherichia coli drug toxicity. Microbial genes associated decreased peripheral sensory neuropathy. Machine learning models trained this predicted hand-foot syndrome dose reductions an cohort. Conclusion These results suggest treatment-associated increases vitamin serve chemoprotective role bacterial host cells, implications toxicities outside gastrointestinal tract. provide proof-of-concept use microbiome profiling machine predict cohorts. observations foundation future human intervention studies, more in-depth mechanistic dissection preclinical models, extension other treatments.

Language: Английский

Citations

0