Gut microbial signature in lung cancer patients highlights specific taxa as predictors for durable clinical benefit

We aimed to determine microbial signature linked with lung cancer (LC) diagnosis and to define taxa linked with durable clinical benefit (DCB) of advanced LC patients. Stool samples for microbial 16S amplicon sequencing and clinical data were collected from 75 LC patients (50 of which were treated with checkpoint inhibitors) and 31 matched healthy volunteers. We compared LC to healthy controls and patients with DCB to those without. LC patients had lower alpha-diversity and higher between-subject diversity. Random Forests model to differentiate LC cases from controls ROC-AUC was 0.74. Clostridiales, Lachnospiraceae, and Faecalibacterium prausnitzii taxa abundance was decreased in LC compared to controls. High Akkermansia muciniphila correlated with DCB (HR 4.26, 95% CI 1.98-9.16), not only for the immunotherapy-treated patients. In addition, high Alistipes onderdonkii (HR 3.08, 95% CI 1.34-7.06) and high Ruminococcus (HR 7.76, 95% CI 3.23-18.65) correlated with DCB.Our results support the importance of gut microbiome in LC. We have validated the apparent predictive value of Akkermansia muciniphila, and highlighted Alistipes onderdonkii and Ruminococcus taxa correlation with DCB. Upon additional validations those can be used as biomarkers or as targets for future therapeutic interventions.

Automated summary

This study aimed to identify a microbial signature associated with lung cancer (LC) diagnosis and to define specific taxa linked with durable clinical benefit (DCB) in advanced LC patients. Stool samples and clinical data were collected from 75 LC patients, including 50 who received checkpoint inhibitors, and 31 healthy volunteers. Comparisons were made between LC patients and healthy controls, as well as between patients with and without DCB. The findings suggest that LC patients have lower diversity and higher variation in their gut microbiome compared to controls. Specific taxa, such as Clostridiales, Lachnospiraceae, and Faecalibacterium prausnitzii, were found to be decreased in LC patients compared to controls. Additionally, high abundance of Akkermansia muciniphila was associated with DCB, suggesting its potential as a biomarker. High abundance of Alistipes onderdonkii and Ruminococcus were also correlated with DCB. These findings highlight the importance of the gut microbiome in LC and suggest potential biomarkers or therapeutic targets for future interventions.