P3.09-03 Alteration of Gut Microbiome in Lung Cancer Patients

AbstractCachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in cachexia by integrating shotgun metagenomics and plasma metabolomics of 31 lung cancer patients. The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, and vitamins were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in cachectic patients. The involvement of the gut microbiome in cachexia was further observed in a high-performance machine learning model using solely gut microbial features. Our study demonstrates the links between cachectic host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible therapeutic applications.

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The gut microbiome can be used to predict the gastrointestinal response and efficacy of lung cancer patients undergoing chemotherapy

Annals of Palliative Medicine ◽

10.21037/apm-20-2183 ◽

2020 ◽

Vol 9 (6) ◽

pp. 4211-4227

Author(s):

Min Zhang ◽

Huan Zhou ◽

Shanshan Xu ◽

Dan Liu ◽

Ye Cheng ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Gut Microbiome ◽

Lung Cancer Patients

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Distinct gut microbial communities and metabolic functions are associated with cachexia in lung cancer patients

10.21203/rs.3.rs-30539/v1 ◽

2020 ◽

Author(s):

Yueqiong Ni ◽

Zoltan Lohinai ◽

Yoshitaro Heshiki ◽

Balazs Dome ◽

Judit Moldvay ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Patients ◽

Clinical Setting ◽

Gut Microbiome ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Lung Cancer Patients ◽

Microbial Species ◽

Functional Pathways

Abstract Background Cachexia is associated with decreased survival in cancer patients and has a prevalence of up to 80%. The etiology of cachexia is poorly understood, and limited treatment options exist. Here, we investigated the role of the human gut microbiome in the clinical setting by integrating shotgun metagenomics and plasma metabolomics of 38 lung cancer patients, with known cachexia status. Results The cachexia group showed significant differences in the gut microbial composition, functional pathways of the metagenome, and the related plasma metabolites compared to non-cachectic patients. Branched-chain amino acids (BCAAs), methylhistamine, as well as vitamins, were significantly depleted in the plasma of cachexia patients, which was also reflected in the depletion of relevant gut microbiota functional pathways. The enrichment of plasma BCAAs and 3-oxocholic acid in non-cachectic patients were positively correlated with the gut microbial species Prevotella copri and Lactobacillus gasseri, respectively. Furthermore, the gut microbiota capacity for lipopolysaccharides biosynthesis was significantly enriched in the cancer cachectic patients. The involvement of gut microbiome in cachexia was further observed in a high-performance machine learning model that uses solely gut microbial taxonomic and pathway features to differentiate cachectic from non-cachectic cancer patients. Conclusions Our study demonstrates the links between host metabolism and specific gut microbial species and functions in a clinical setting, suggesting that the gut microbiota could have an influence on cachexia with possible future therapeutic applications.

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Impact of antibiotic (ATB) exposure prior to immune checkpoint inhibitor (ICI) treatment on overall survival (OS): A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.303 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 303-303

Author(s):

Lawson Eng ◽

Rinku Sutradhar ◽

Yue Niu ◽

Ning Liu ◽

Ying Liu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Gut Microbiome ◽

Therapeutic Option ◽

Population Level ◽

Population Based ◽

Dose Effect ◽

Lung Cancer Patients ◽

Exposure Windows ◽

The Impact

303 Background: ICIs are a common therapeutic option for many solid tumors. While prior studies have shown that ATB exposure may negatively impact ICI outcomes through gut microbiome changes, many were small studies with heterogeneity in ATB classes and exposure windows. Here, we performed a population level retrospective cohort study to evaluate the impact of ATB exposure prior to ICI on OS. Methods: We used administrative data to identify a cohort of cancer patients > 65 years of age receiving ICIs from June 2012 to October 2018 in Ontario, Canada and deterministically linked with databases to obtain socio-demographic and clinical co-variates and ATB prescription claims. Multivariable cox-proportional hazard models evaluated the impact of ATB exposure both within 1 year and 60 days prior to starting ICI on OS, adjusted for age, gender, body mass index, comorbidities, autoimmune history, hospitalization in the past year and treatment facility level at start of ICI therapy. Results: Among 2737 patients, median age 73; 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab; 53% were lung cancer, 34% melanoma. Median ATB treatment duration for patients receiving ATB within 1 year (59%) and 60 days (19%) prior to ICI were 14 days (SD = 32) and 9 days (SD = 13) respectively. Median OS estimate was 306 days. Any ATB exposure within 1 year prior to ICI was associated with worse OS (aHR = 1.12 95% CI [1.12-1.23] p = 0.03). A non significant dose effect was seen based on weeks of ATB exposure 1 year prior to ICI (aHR = 1.01 per week [1.00-1.02] p = 0.10). ATB class analysis identified fluoroquinolone exposure within 1 year (aHR = 1.26 [1.13-1.40] p < 0.001) and 60 days before ICI (aHR = 1.20 [0.99-1.45] p = 0.06) were associated with worse OS; with a dose effect based on total weeks of exposure over 1 year (aHR = 1.07 per week [1.03-1.11] p < 0.001) and 60 days (aHR = 1.12 per week [1.03-1.23] p = 0.01). Subgroup analysis showed similar results for patients receiving anti-PD1 ICIs, where patients exposed to fluoroquinolone both 1 year (aHR = 1.28 [1.15-1.44] p < 0.001) and 60 days (aHR = 1.19 [0.98-1.44] p = 0.08) before ICIs had poorer OS with dose effects observed based on weeks of fluoroquinolone exposure. Similarly, subgroup analyses based on disease site identified that lung cancer patients exposed to fluoroquinolones 1 year before starting ICIs (aHR = 1.22 [1.06-1.39] p = 0.005) and melanoma patients exposed to fluoroquinolones 60 days before starting ICIs (aHR = 1.66 [1.12-2.47] p = 0.01) had poorer OS. Conclusions: Exposure to ATBs and specifically fluoroquinolones prior to ICI therapy is associated with worse OS. Interventions aimed at altering the gut microbiome may be required to help improve outcomes for patients on ICIs with prior ATB exposure.

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Alteration of Gut Microbiome in Lung Cancer Patients

10.1101/640359 ◽

2019 ◽

Author(s):

Li Ming ◽

Yu Fang ◽

Chen Xiaohui ◽

Zhou Huan ◽

Wei Xiaoqing ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Gut Microbiome ◽

Treatment Strategies ◽

Cancer Development ◽

Healthy Individuals ◽

Lung Cancer Patients ◽

Microbial Dysbiosis ◽

Treatment Naïve ◽

Immunological Relationship

ABSTRACTLung cancer is the leading cause of cancer death. Better understanding of factors and pathways involved in lung cancer is needed to improve diagnose and treatment strategies. Recent studies have provided insights into the possible correlation between intestinal dysbiosis and cancer development. Although the immunological relationship between gut and lung had been suggested by many researches, however, to date, no study had investigated the characterization of gut microbiome in treatment naïve lung cancer patients, whether it is distinct from that of health individuals and contribute to the onset and development of lung cancer remain unclear. In this study, we investigated whether gut microbiome of lung cancer patients (LC, n=28) is altered compare with that of matched healthy individuals (HC, n=19) by high throughout sequencing of the V3-V4 regions of 16S rDNA in their fecal samples. We also identified microbiota signatures specific for different histological types of lung cancer, including SSC, ADC, and SCLC. The gut microbiome of lung cancer patients is characterized by decreased relative abundance of Prevotella, and increased bacteria groups such as Actinomyces, and Streptococcus, etc. We also detected a mild structural shift in gut microbiome between ADC and SCLC patients. Our results showed that the gut microbiome of lung cancer patients altered significantly compared with healthy individuals. However, the association between microbial dysbiosis and lung cancer is not clearly understood, future studies involving larger cohorts and metagenomics, or metabolomics, may elucidate the correlations between gut microbiota and lung cancer development.IMPORTANCEThis is the first report to show the alteration of gut microbiome in lung cancer patients. Our results showed that the gut microbiome of lung cancer patients altered significantly compared with healthy individuals.

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Alteration of Gut Microbiome in Lung Cancer Patients- A Pilot Study

10.21203/rs.3.rs-236933/v1 ◽

2021 ◽

Author(s):

Ming Li ◽

Fang Yu ◽

Xiaohui Chen ◽

Huan Zhou ◽

Yinhui Liu ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

16S Rdna ◽

Gut Microbiome ◽

Treatment Strategies ◽

Cancer Development ◽

Lung Cancer Patients ◽

Microbial Dysbiosis ◽

Rdna Sequencing ◽

Treatment Naïve

Abstract Lung cancer is the leading cause of cancer death. Better understanding of factors and pathways involved in lung cancer is needed to improve diagnose and treatment strategies. Recent studies have provided insights into the possible correlation between intestinal dysbiosis and cancer development. Although the immunological relationship between gut and lung had been suggested by many researches, however, to date, no study had investigated the characterization of gut microbiome in treatment naïve lung cancer patients, whether it is distinct from that of health individuals and contribute to the onset and development of lung cancer remain unclear. In this study, we investigated whether gut microbiome of lung cancer patients (LC, n=28) is altered compare with that of matched healthy individuals (HC, n=19) by high throughout sequencing of the V3-V4 regions of 16S rDNA in their fecal samples. We also identified microbiota signatures specific for different histological types of lung cancer, including squamous cell carcinoma (SCC), adenocarcinoma (ADC) and small cell lung cancer (SCLC). 16S rDNA sequencing results showed that the gut microbiome of lung cancer patients is characterized by decreased relative abundance of Prevotella, and increased bacteria groups such as Actinomyces, and Streptococcus, etc. We also detected an obvious structural shift in gut microbiome between ADC and SCLC patients. However, given the limited number of study cases, the association between microbial dysbiosis and lung cancer is not clearly understood, future studies involving larger cohorts and metagenomics, or metabolomics, may elucidate the correlations between gut microbiota and lung cancer development.

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