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A narrative review from gut to lungs: non-small cell lung cancer and the gastrointestinal microbiome

Background and objective: The gut microbiome has emerged as an important gateway to improving therapeutic outcomes in lung cancer, especially for immunotherapy. Our objective is to review the impact of the bidirectional relationship between the gut microbiome, lung cancer, and the immune system, and to identify areas of future research.

Methods: We conducted a search on PubMed, EMBASE, and ClinicalTrials.gov using the search terms non-small cell lung cancer (NSCLC), gut microbiome, and microbiota until July 11, 2022. The authors screened resulting studies independently. Results were synthesized and presented descriptively.

Key content and findings: Sixty original published studies were identified from PubMed (n=24) and EMBASE (n=36), respectively. Twenty-five ongoing clinical studies were identified on ClinicalTrials.gov. Gut microbiota has been shown to influence tumorigenesis and modulate tumor immunity via local and neurohormonal mechanisms depending on the microbiome ecosystem that populates the gastrointestinal tract. Probiotics, antibiotics, and proton pump inhibitors (PPIs), amongst other medications, can impact gut microbiome health, leading either to improved or worsened therapeutic outcomes with immunotherapy. Most clinical studies assess the impact of the gut microbiome, but emerging data suggest microbiome composition in other host sites may be important.

Conclusions: A strong relationship exists between gut microbiome, oncogenesis, and anticancer immunity. Although the underlying mechanisms are poorly understood, immunotherapy outcomes seem to depend on host-related factors such as gut microbiome alpha diversity, relative abundance of microbial genera/taxa, and extrinsic factors such as prior or concurrent exposure to probiotics, antibiotics, and other microbiome-modifying drugs.

 

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Title: The Bidirectional Relationship Between the Gut Microbiome, Lung Cancer, and the Immune System: A Review and Future Research Directions

Abstract: The gut microbiome has recently gained attention for its potential role in improving therapeutic outcomes in lung cancer, particularly in the context of immunotherapy. This review aims to examine the impact of the bidirectional relationship between the gut microbiome, lung cancer, and the immune system, while identifying areas for future research. A comprehensive search was conducted on PubMed, EMBASE, and ClinicalTrials.gov using relevant search terms until July 11, 2022. Sixty original published studies and twenty-five ongoing clinical studies were included in the analysis. The findings demonstrate that the gut microbiota can influence tumorigenesis and modulate tumor immunity through local and neurohormonal mechanisms, depending on the composition of the gut microbiome. Medications such as probiotics, antibiotics, and proton pump inhibitors (PPIs) can affect gut microbiome health, leading to either improved or worsened therapeutic outcomes with immunotherapy. While most clinical studies have focused on the impact of the gut microbiome, emerging data suggest that microbiome composition in other host sites may also be important. In conclusion, a strong association exists between the gut microbiome, oncogenesis, and anticancer immunity. Although the underlying mechanisms are not yet fully understood, it appears that immunotherapy outcomes are influenced by host-related factors, such as gut microbiome alpha diversity and relative abundance of microbial genera/taxa, as well as extrinsic factors such as exposure to probiotics, antibiotics, and other microbiome-modifying drugs. Future research should further investigate these relationships and explore the potential of targeting the gut microbiome as a therapeutic strategy in lung cancer.

Keywords: gut microbiome, lung cancer, non-small cell lung cancer (NSCLC), microbiota, immunotherapy, tumorigenesis, tumor immunity, alpha diversity, microbial genera, probiotics, antibiotics, proton pump inhibitors (PPIs), therapeutic outcomes, future research.

Introduction: The gut microbiome has emerged as a promising avenue for improving therapeutic outcomes in lung cancer, especially in the context of immunotherapy. Accumulating evidence suggests that the gut microbiota, which colonizes the gastrointestinal tract, plays a vital role in tumorigenesis and the modulation of tumor immunity. Understanding the bidirectional relationship between the gut microbiome, lung cancer, and the immune system is crucial for advancing our knowledge and identifying potential strategies to optimize treatment approaches. This review aims to provide an overview of the current knowledge on this topic and highlight areas that require further investigation.

Methods: A comprehensive search was conducted on PubMed, EMBASE, and ClinicalTrials.gov using relevant search terms, including non-small cell lung cancer (NSCLC), gut microbiome, and microbiota, until July 11, 2022. The identified studies were independently screened by the authors, and the results were synthesized and presented descriptively.

Results: A total of sixty original published studies were identified from PubMed (n=24) and EMBASE (n=36). Additionally, twenty-five ongoing clinical studies were identified on ClinicalTrials.gov. The existing literature demonstrates that the gut microbiota can influence the process of tumorigenesis and modulate tumor immunity through local and neurohormonal mechanisms. The impact of the gut microbiome on therapeutic outcomes with immunotherapy is influenced by the specific composition of the microbiome ecosystem in the gastrointestinal tract. Notably, certain medications, including probiotics, antibiotics, and proton pump inhibitors (PPIs), can affect gut microbiome health and subsequently impact treatment responses. While most clinical studies have primarily focused on the gut microbiome, emerging evidence suggests that microbiome composition in other host sites may also be important.

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