How Do Gut Bacteria Affect Cancer Treatment?

Researchers found that, in patients with malignant melanoma (an aggressive skin cancer), treatment outcomes with Opdivo and immunotherapies such as Keytruda were associated with the gut microbiota. Previous studies had also reported an association between response to immunotherapy and gut microbiota, but their results were inconsistent.

NOTE: The microbiome refers to all the genetic information (genomes) of microorganisms in a particular environment. Microbiota is the community of microorganisms. The human gastrointestinal tract contains approximately 100 trillion microorganisms, most of them bacteria, viruses, fungi and protozoa.

Nature Medicine published a new study on February 28, 2022, in which researchers performed a meta-analysis of microbial sequencing data from a new study group (the Pittsburg cohort) and 4 previously published cohorts of melanoma patients who had received immunotherapy.

Predicting Treatment Response With the Pretreatment Fecal Microbiome

In the Pittsburg cohort of 94 patients, researchers collected stool samples from a total of 63 patients before immunotherapy began or within 4 months of starting it (Pittsburgh early sample cohort, P-ESC). The team also collected samples from 31 patients 4 months after treatment began (Pittsburg late sample cohort, P-LSC).

Patients receiving immunotherapy in the P-ESC group had a different fecal (stool) microbiome from patients who had not undergone treatment. The study ultimately showed that pretreatment microbiota composition had a much stronger association with progression-free survival, the most important indicator of a drug's ability to control advanced cancer. In contrast, no association was observed between the fecal microbiome and progression-free survival in the late sample cohort (P-LSC).

By analyzing the Pittsburg cohort together with previously published cohort studies, researchers identified bacteria associated with disease progression and nonprogression.

Results

Bacteria belonging to the Bacteroides genus and Probacteria phylum were associated with disease progression, while bacteria in the Actinobacteria phylum and the Lachnospiraceae/Ruminococcaceae family of Firmicutes were associated with nonprogression.

A microbiota rich in Lachnospiraceae spp. is associated with a favorable immunotherapy response, whereas a microbiota rich in Streptococcaceae spp. is associated with an unfavorable response and various immune-related side effects.

Patients with high levels of Streptococcus spp. had significantly shorter progression-free survival than those with low levels.

In conclusion, these findings shed light on the complex relationship between the gut microbiota and response to cancer immunotherapy, providing a roadmap for future studies and other cancers.