Dysbiosis in the Gut Microbiome of Pembrolizumab-Treated Non-Small Lung Cancer Patients Compared to Healthy Controls Characterized Through Opportunistic Sampling.
Haris Charalambous, Cameron Brown, Paris Vogazianos, Kyriaki Katsaounou, Elpiniki Nikolaou, Ioannis Stylianou, Elisavet Papageorgiou, Dimitris Vraxnos, Aristos Aristodimou, Jianxiang Chi, Paul Costeas, Christos Shammas, Yiorgos Apidianakis, Athos Antoniades
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Abstract
Background: The gut microbiome influences the host immune system, cancer development and progression, as well as the response to immunotherapy during cancer treatment. Here, we analyse the composition of the gut bacteriome in metastatic Non-Small Cell Lung Cancer (NSCLC) patients receiving Pembrolizumab immunotherapy within a prospective maintenance trial through opportunistic sampling during treatment.
Methods: The gut microbiome profiles of NSCLC patients were obtained from stool samples collected during Pembrolizumab treatment and analysed with 16S rRNA metagenomics sequencing. Patient profiles were compared to a group of healthy individuals of matching ethnic group, age, sex, BMI and comorbidities.
Results: A significant decrease in the treated patients was observed in two prominent bacterial families of the phylum Firmicutes, Lachnospiraceae and Ruminoccocaceae, which comprised 31.6% and 21.8% of the bacteriome in the healthy group but only 10.9% and 14.2% in the treated patient group, respectively. Species within the Lachnospiraceae and Ruminococcaceae families are known to break down undigested carbohydrates generating short chain fatty acids (SCFA), such as butyrate, acetate and propionate as their major fermentation end-products, which have been implicated in modifying host immune responses. In addition, a significant increase of the Bacteroidacaeae family (Bacteroidetes phylum) was observed from 10.7% in the healthy group to 23.3% in the treated patient group. Moreover, and in agreement with previous studies, a decrease in the Firmicutes to Bacteroidetes ratio in the metastatic NSCLC Pembrolizumab-treated patients was observed.
Conclusion: The observed differences indicate dysbiosis and a compromised intestinal health status in the metastatic NSCLC Pembrolizumab-treated patients. This data could inform future studies of immunotherapy treatment responses and modulation of the gut microbiome to minimise dysbiosis prior or concurrent to treatment.
期刊介绍：
Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society.
The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
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