Predictable modulation of cancer treatment outcomes by the gut microbiota

Abstract

The gut microbiota has the potential to influence the efficacy of cancer therapy. Here, we investigated the contribution of the intestinal microbiome on treatment outcomes in a heterogeneous cohort that included multiple cancer types to identify microbes with a global impact on immune response. Human gut metagenomic analysis revealed that responder patients had significantly higher microbial diversity and different microbiota compositions compared to non-responders. A machine-learning model was developed and validated in an independent cohort to predict treatment outcomes based on gut microbiota composition and functional repertoires of responders and non-responders. Specific species, Bacteroides ovatus and Bacteroides xylanisolvens, were positively correlated with treatment outcomes. Oral gavage of these responder bacteria significantly increased the efficacy of erlotinib and induced the expression of CXCL9 and IFN-γ in a murine lung cancer model. These data suggest a predictable impact of specific constituents of the microbiota on tumor growth and cancer treatment outcomes with implications for both prognosis and therapy.

A metagenome association study of gut microbiome revealed biomarkers for chemotherapy efficacy in locally advanced and advanced lung cancer

“…Data from a previous report has suggested that the treatment effects, including chemotherapy or a combination of chemotherapy with immunotherapy, in cancer patients are positively correlated with some speci c types of gut microbiota, such as Bacteroides ovatus and Bacteroides xylanisolvens [38]. However, the correlation between the e cacy of chemotherapy in lung cancer patients and certain speci c ora is still unclear.…”

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

“…In contrast, Clostridium symbiosum and Ruminococcus gnavus were enriched in NR. 54 A second study analyzing fecal composition prior to preoperative concurrent chemoradiations in 45 rectal cancer patients concluded that Duodenibacillus massiliensis was linked to complete responses. 55 Altogether, the emerging field of oncoimmunomicrobiology is progressively integrating the gut microbiota into the parameters that determine the cancer immune set-point governing the clinical efficacy of immuno-chemo-radio-therapy.…”

A Significant Question in Cancer Risk and Therapy: Are Antibiotics Positive or Negative Effectors? Current Answers and Possible Alternatives

“…It seems, therefore, possible that taking into consideration the status of their microbiome may improve the use of antimicrobial agents, as well as the treatment outcomes for cancer patients [156]. Protocols for microbiota modulation may provide tools to achieve predictive information on cancer treatment outcomes [157][158][159].…”