Effect of Radium-223 on the Gut Microbiota of Prostate Cancer Patients: A Pilot Case Series Study

Abstract

Radium-223 (Ra-223) is a targeted nuclear medicine therapy for castration-resistant prostate cancer with bone metastases. Its major route of elimination is the intestine. There is overwhelming evidence that the gut microbiota is altered by ionizing radiation (IR) from radiotherapy treatments. Nevertheless, it is known that extrapolation of outcomes from radiotherapy to nuclear medicine is not straightforward. The purpose of this study was to prospectively determine the effect of Ra-223 on selected important bacteria from the gut microbiota. Stool samples from three prostate cancer patients and two healthy individuals were obtained, processed, and analysed. We specifically measured the relative change of the abundance of important bacteria, determined by the 2−ΔΔC method. We found that Ra-223 influenced the gut microbiota composition. The most relevant changes were increases of Proteobacteria and Atopobacter; and decreases of Bacteroidetes, Prevotella, Lactobacillus, Bifidobacterium, Clostridium coccoides, and Bacteroides fragilis. Additionally, our experiment confirms that the composition of gut microbiota from prostate cancer patients is altered. No significant correlation was found between each subject’s gut microbiome profile and their clinical indices. Despite its limited sample, the results of this pilot study suggest that ionizing radiation from Ra-223 alters the gut microbiota composition and that the gut microbiota of prostate cancer patients has an increase of the bacteria with known prejudicial effects and a decrease of the ones with favorable effects.

Bones and guts – Why the microbiome matters

“…Indeed, increased abundance of Proteobacteria has been previously identified as a potential indicator of inflammation and disease [51] . In contrast, Lactobacillus, Clostridium leptum, and Clostridium coccoides were decreased in PCa patients [48] . Lactobacillus has been shown to have anti-cancer effects in colorectal cancer, and both Clostridium species contribute to SCFA production [52] , [53] , [54] .…”

“…Moreover, Lactobacillus animalis supplementation in patients with osteonecrosis of the femoral head has been found to have protective effects on the bone microenvironment, inducing angiogenesis and bone growth [55] . After receiving Ra-223, levels of Bacteroidetes, Prevotella, Lactobacillus, Bidifidobacterium, Clostridium coccoides, and Bacteroides fragilis were all decreased [48] . Taken together, this data suggests that bone metastatic PCa patients have altered gut microbial signatures, and these signatures are further altered by Ra-223 treatment.…”

“…Ra-223 is the only treatment targeting PCa bone metastasis that significantly improves overall survival, but unfortunately only by a few months (mean = 3 months) [47] . Interestingly, the phyla relative abundances of Proteobacteria and Actinobacteria were elevated in PCa patients with bone metastasis compared with controls before receiving Ra-223 treatment [48] . Increased Actinobacteria abundance has been found to be a risk factor for both breast and lung cancers [49] .…”

Exploring the Involvement of Gut Microbiota in Cancer Therapy-Induced Cardiotoxicity

“…Radiotherapy results in dysregulation of the gut microbiota, which negatively affects the diversity and richness of gut bacterial diversity, potentially causing an enrichment of harmful microbiota ( Proteobacteria and Fusobacteria ) and a decrease in beneficial microbiota ( Faecalibacterium and Bifidobacterium ) [ 47 , 48 ]. El Alam et al discovered a significant alteration in the gut microbiome composition during pelvic chemotherapy and radiotherapy (CRT), with increases in Proteobacteria and decreases in Clostridiales , whereas after CRT, the gut microbiome composition changed, with increases in Bacteroides species [ 49 ].…”

Association between gut microbiota and benign prostatic hyperplasia: a two-sample mendelian randomization study

“…The relationship between GM dysbiosis and several diseases has been established; some examples include periodontal disease, cancer, obesity, diabetes, and chronic fatigue syndrome ( Ditto et al., 2021 ). However, a growing number of studies have shown that differences between healthy and bio-imbalanced microbiota may be associated with prostate diseases, such as chronic prostatitis, BPH, prostate cancer, and other prostate diseases ( Fernandes et al., 2022 ). Tsai et al.…”