Dataset Information

Impact of Pelvic Radiation Therapy for Prostate Cancer on Global Metabolic Profiles and Microbiota-Driven Gastrointestinal Late Side Effects: A Longitudinal Observational Study.

ABSTRACT:

Purpose

Radiation therapy to the prostate and pelvic lymph nodes (PLNRT) is part of the curative treatment of high-risk prostate cancer. Yet, the broader influence of radiation therapy on patient physiology is poorly understood. We conducted comprehensive global metabolomic profiling of urine, plasma, and stools sampled from patients undergoing PLNRT for high-risk prostate cancer.

Methods and materials

Samples were taken from 32 patients at 6 timepoints: baseline, 2 to 3 and 4 to 5 weeks of PLNRT; and 3, 6, and 12 months after PLNRT. We characterized the global metabolome of urine and plasma using ¹H nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography-mass spectrometry, and of stools with nuclear magnetic resonance. Linear mixed-effects modeling was used to investigate metabolic changes between timepoints for each biofluid and assay and determine metabolites of interest.

Results

Metabolites in urine, plasma and stools changed significantly after PLNRT initiation. Metabolic profiles did not return to baseline up to 1 year post-PLNRT in any biofluid. Molecules associated with cardiovascular risk were increased in plasma. Pre-PLNRT fecal butyrate levels directly associated with increasing gastrointestinal side effects, as did a sharper fall in those levels during and up to 1 year postradiation therapy, mirroring our previous results with metataxonomics.

Conclusions

We showed for the first time that an overall metabolic effect is observed in patients undergoing PLNRT up to 1 year posttreatment. These metabolic changes may effect on long-term morbidity after treatment, which warrants further investigation.

SUBMITTER: Ferreira MR

PROVIDER: S-EPMC8609156 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionSow mortality in the U.S. swine industry has increased in recent years, for which pelvic organ prolapse (POP) is a major contributor, accounting for 21% of all sow mortality. Dysbiosis of microbial communities has been associated with disease and reproductive dysfunction in several species, and previous studies have shown changes in vaginal microbiota in sows with increased risk for POP during late gestation. However, there is insufficient knowledge surrounding the potential relationship between fecal microbiota and POP in sows. Therefore, the study objective was to identify differences in sow fecal microbiota and determine if fecal and vaginal microbial communities are correlated in relation to POP risk.MethodsSows were evaluated for POP risk using an established perineal scoring system, with a perineal score (PS) of 1 (PS1) presuming little to no risk of POP to a PS of 3 (PS3) presuming high risk of POP. In the current study, 2,864 sows were scored during gestation week 15, and 1.0%, 2.7%, and 23.4% of PS1, PS2, and PS3 sows, respectively, subsequently experienced POP. Fecal swabs (n = 215) were collected between gestation days 108-115, DNA was extracted, and 16S rRNA gene amplicon sequencing libraries were analyzed using mothur, phyloseq and SAS in reference to PS and POP outcome. Additionally, co-occurrence networks were constructed using CoNet to compare fecal and vaginal microbiota from the same cohort of sows and identify correlations between different taxa.ResultsDifferences in fecal community composition (PERMANOVA; P < 0.05), structure (alpha diversity measurements; P < 0.05), and 13 individual operational taxonomic units (OTUs) were revealed between PS1 and PS3 assigned sows. No differences in fecal microbiota were detected as a result of POP outcome. However, the abundances of several taxa were correlated across sample collection sites, suggesting the fecal and vaginal microbial communities may be related to one another.DiscussionCollectively, fewer differences in the fecal microbiota exist in sows with differing risk for POP compared to the vaginal microbiota, suggesting the vaginal microbiome may be more relevant in relation to POP outcome, although correlations between fecal and vaginal communities may provide insight for strategies to combat POP.