Radiotherapy and the gut microbiome: facts and fiction

Abstract

An ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating “hot” versus “cold” tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple ‘-omic’ approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi “-omic” approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.

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

“…Yi et al [ 86 ] identified potential microbial biomarkers for predicting the response to nCCRT in locally advanced rectal cancer: butyrate-producing bacteria, including Roseburia , Dorea , and Anaerostipes were overrepresented in responders, whereas Coriobacteriaceae and Fusobacterium were markedly higher in non-responders. Although gut dysbiosis could be a relevant biomarker to predict radiotherapy-induced mucositis [ 87 , 88 ], the direct impact on the patients’ response to radiotherapy has not yet been investigated yet. Recently Guo et al described in mice that radiation survivors could be identified by specific bacterial and metabolite profiles (Lachnosspiraceae and Enterococcaceae increases and downstream metabolites such as propionate and tryptophan pathways) [ 89 ].…”

Acute Radiation Syndrome and the Microbiome: Impact and Review

“…Through this research, genus-and species-level identification and abundance across individuals and across their body regions (Table 1) have uncovered high inter-individual and intraindividual microbiota diversity that is impacted by co-evolutionary selection, age, diet, and geographic region (Mackie et al, 1999;Spor et al, 2011;Lozupone et al, 2012;Morgan and Huttenhower, 2012; or challenges (Bäckhed et al, 2005). Investigation of the virome, mycobiome, and archaea components of the microbiota broadly and particularly in response to radiation has been lacking (Rosenberg and Zilber-Rosenberg, 2013;Roy and Trinchieri, 2017;Liu et al, 2021). It is possible that broader insights into the impact of nonbacterial components of the GI microbiota might be obtained through non-targeted shotgun metagenomic sequencing techniques that would be capable of assessing radiation responses in the nonbacterial compartments of the GI microbiota (Campo et al, 2020;Kaźmierczak-Siedlecka et al, 2020;Turkington et al, 2021).…”

“…As noted above, most studies of the effect of radiation on the GI microbiome have been conducted in the context of cancer radiotherapy, and recent reviews summarize the literature in that context (Liu et al, 2021;Tonneau et al, 2021). Indeed, therapeutic abdominopelvic radiation exposure frequently results in intestinal dysfunction and dysbiosis, with acute radiation enteritis complications observed in 50% or more of abdominally irradiated cancer patients (Touchefeu et al, 2014).…”

A Perspective on the Role of Microbiome for Colorectal Cancer Treatment

“…As a novel approach to augment cancer therapy, they are thought to improve the diversity profile of the intestinal microbiota and reduce the extent of chronic inflammation and production of carcinogenic material in dysbiosis [ 2 , 95 , 96 ]. Prebiotics are non-digestible food constituents that selectively alter the growth of certain host-beneficial bacteria [ 97 ]. The combination of probiotics and prebiotics is called synbiotics.…”