Metagenome association study of the gut microbiome revealed biomarkers linked to chemotherapy outcomes in locally advanced and advanced lung cancer

Abstract

Background: The gut microbiome is important in the development and immunotherapy efficacy of lung cancer. However, the relationship between the intestinal flora and chemotherapy outcomes remains unclear and was investigated in this study. Methods: We analyzed baseline stool samples from patients with locally advanced and advanced lung cancer before chemotherapy treatment, through metagenomics of the gut microbiota. The composition, diversity, function, and metabolic pathway analysis were compared among patients with different clinical outcomes. Results: From 64 patients, 33 responded to treatment (responders) and 31 did not (nonresponders). Streptococcus mutans and Enterococcus casseliflavus were enriched in responders (P < 0.05), while 11 bacteria including Leuconostoc lactis and Eubacterium siraeum were enriched in nonresponders (P < 0.05) by variance analysis. Responders were associated with significantly higher Acidobacteria and Granulicella, while Streptococcus oligofermentans, Megasphaera micronuciformis, and Eubacterium siraeum were more abundant in nonresponders by Lefse analysis. Streptococcus mutans and Enterococcus casseliflavus were further identified as bacterial markers relevant to responders using unsupervised clustering, and Leuconostoc lactis and Eubacterium siraeum were related to nonresponders. The L-glutamate degradation VIII pathway was enriched in responders (P = 0.014), and the C4 photosynthetic carbon assimilation cycle, reductive TCA cycle I, and hexitol fermentation to lactate, formate, ethanol, and acetate were enriched in nonresponders (P < 0.05). Additionally, significant associations of bacterial species with clinical phenotypes were observed by Spearman correlation analysis. Conclusions: The specific gut microbiome of patients with lung cancer might be connected to the clinical outcomes of chemotherapy.

Gut Microbiota as Potential Biomarker and/or Therapeutic Target to Improve the Management of Cancer: Focus on Colibactin-Producing Escherichia coli in Colorectal Cancer

“…Numerous preclinical studies have demonstrated the involvement of the gut microbiome in the efficacy of a range of chemotherapies such as cyclophosphamide [ 81 ], oxaliplatin [ 74 , 82 ] or gemcitabine [ 83 ] in CRC and other cancer types. More recently, a metagenome association study in lung cancer patients showed that Streptococcus mutans and Enterococcus casseliflavus were linked to better chemotherapy outcomes [ 84 ]. Clinical evidence-based research on the role of potential gut microbial biomarkers for predicting patient’s response to chemotherapy is scarce.…”

Veillonellaceae family members uniquely alter the cervical metabolic microenvironment in a human three-dimensional epithelial model

“…In addition, V. montpellierensis, another Veillonella species, has been isolated from patients suffering from endocarditis 26 and acute otitis media infections 27 . Similar to V. atypica, M. micronuciformis has also been isolated from the oral and gut microbiomes and is implicated in gastric cancer and response to chemotherapy [28][29][30] .…”

Emerging Evidence of the Gut Microbiome in Chemotherapy: A Clinical Review

“…The seventeen selected studies included a total of 742 patients with a range of 8 – 126 participants in each of the studies. Cancers studied included CRC (n=5) ( 26 , 29 , 38 , 39 ), AML (n=3) ( 28 , 30 , 31 ), BCa (n=2) ( 24 , 36 ), Non-Hodgkin’s lymphoma (n=2) ( 32 , 33 ), lung cancer (n=1) ( 23 ), ovarian cancer (n=1) ( 27 ), liver cancer (n=1) ( 25 ), and various other types of cancers (n=3) ( 24 , 34 , 35 ). Six studies were conducted in China ( 23 , 26 , 27 , 29 , 38 , 39 ), three in the USA ( 28 , 30 , 31 ), two in France ( 32 , 33 ), two in Japan ( 25 , 36 ), and one each in Austria ( 35 ), Australia ( 34 ) and Israel ( 24 ).…”