King’s College London (KCL) led the study, which identifies the gut bacteria (Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila) and their possible roles in a better immune response.
“This study shows the chances of survival based on healthy microbes nearly doubled between subgroups,” explains Tim Spector, study team member and Professor of Genetic Epidemiology at KCL.
“The ultimate goal is to identify which specific features of the microbiome are directly influencing the clinical benefits of immunotherapy to exploit these features in new personalised approaches to support cancer immunotherapy.
“But in the meantime, this study highlights the potential impact of good diet and gut health on chances of survival in patients undergoing immunotherapy.”
Largest patient cohorts
The study bought together the largest cohort of patients (165) with melanoma and samples of their gut microbiome from five clinical centres in the UK, the Netherland and Spain.
Researchers from CIBIO Department of the University of Trento, the European Institute of Oncology in Italy, University of Groningen in the Netherlands as well as KCL began sequencing the gut microbiome of these gut samples using a number of metagenomic techniques.
The study also included datasets from 147 metagenomic samples gathered from previously published studies.
Machine learning analysis also confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) to the treatment for melanoma.
The team found that the gut microbiome has a relevant, but cohort-dependent, association with the response to the treatment. However, no single species could be regarded as a fully consistent biomarker across studies.
An additional finding was that the microbiome itself is strongly influenced by factors including patient constitution, use of proton pump inhibitors and diet that should be considered in future longitudinal studies.
“Overall, the role of the human gut microbiome in immune checkpoint inhibitor (ICI) treatment response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders,” the study concludes.
“Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course.”
Co-author of the study Professor Nicola Segata from the University of Trento says: “Our study shows that studying the microbiome is important to improve and personalise immunotherapy treatments for melanoma.
“However, it also suggests that because of the person-to-person variability of the gut microbiome, even larger studies must be carried out to understand the specific gut microbial features that are more likely to lead to a positive response to immunotherapy.”
Unique gut microbiome
In discussing the findings, the team points to the gut microbiome as unique in each individual, even when considering identical twins. A large part of this uniqueness is encoded at the level of single strains.
The team adds that links between the gut microbiome and ICI response can also be partially cancer specific and influenced by many factors that are inherently difficult to account for.
“Even within the same cancer (sub)type, it is unlikely that the same microbiome features can reflect the uniqueness of the genetic and immune characteristics of each tumour, meaning that expectations on the existence of a universal, very accurate and highly reproducible link between the human microbiome and ICI response should be lowered,” the study highlights.
“Continued efforts should thus be put into performing metagenomic investigations at substantially larger scales with improved representation of distinct populations while controlling for clinical covariates and ensuring that samples are collected and processed in the same manner and using the same techniques.”
Source: Nat Med
Published online: doi.org/10.1038/s41591-022-01695-5
“Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma.”
Authors: Lee, K.A., Thomas, A.M., Bolte, L.A. et al.