Co-Occurrence of Symptoms and Gut Microbiota Composition Before Neoadjuvant Chemotherapy and Radiation Therapy for Rectal Cancer: A Proof of Concept

Abstract

Purpose: To examine a) whether there are significant differences in gut microbial diversity and in the abundance of gut microbial taxa; and b) differences in predicted functional pathways of the gut microbiome between those participants with high co-occurring symptoms and those with low co-occurring symptoms, prior to neoadjuvant chemotherapy and radiation therapy (CRT) for rectal cancer. Methods: Rectal cancer patients (n = 41) provided stool samples for 16 S rRNA gene sequencing and symptom ratings for fatigue, sleep disturbance, and depressive symptoms prior to CRT. Descriptive statistics were computed for symptoms. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. Results: Participants with high co-occurring symptoms (n = 19) had significantly higher bacterial abundances of Ezakiella, Clostridium sensu stricto, Porphyromonas, Barnesiella, Coriobacteriales Incertae Sedis, Synergistiaceae, Echerichia-Shigella, and Turicibacter compared to those with low co-occurring symptoms before CRT (n = 22). Biosynthesis pathways for lipopolysaccharide, L-tryptophan, and colanic acid building blocks were enriched in participants with high co-occurring symptoms. Participants with low co-occurring symptoms showed enriched abundances of Enterococcus and Lachnospiraceae, as well as pathways for β-D-glucoronosides, hexuronide/hexuronate, and nicotinate degradation, methanogenesis, and L-lysine biosynthesis. Conclusion: A number of bacterial taxa and predicted functional pathways were differentially abundant in patients with high co-occurring symptoms compared to those with low co-occurring symptoms before CRT for rectal cancer. Detailed examination of bacterial taxa and pathways mediating co-occurring symptoms is warranted.

Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study

“…Participants showed significantly higher mean depressive symptom scores (12.4 ± 8.7) indicating higher severity of depression at the end than before CRT (9.4 ± 7.7, t (47) = −3.1, p < 0.003). Ten participants (25%) before CRT and fifteen participants (38%) at the end of CRT had depressive symptom scores that exceeded the cutoff score for depression of ≥15 [ 17 , 22 ].…”

“…Forty newly diagnosed rectal cancer patients programmed to receive CRT were included in this study. Eligibility criteria have been described in our previous publications including the following: (1) being at least 18 years of age; (2) no history of inflammatory conditions, infectious conditions, other cancers, sleep disorders, or comorbidities associated with sleep disturbance (e.g., sleep apnea); and (3) with no prior use of antidepressant medications, anti-insomnia medications, antibiotics, probiotics, prebiotics, steroids, or immune-suppressant agents one month before each assessment time-point [ 2 , 14 , 15 , 17 , 18 ]. Data collection was conducted from September 2017 to April 2019 at three ambulatory radiotherapy facilities in Tampa Bay, Florida, United States.…”

“…Information for each variable is summarized in Table 1 . Depression was assessed by the clinician-rated 17-item Hamilton Rating Scale for Depression (HAM-D 17 ) [ 19 ], using the conventional Structured Interview Guide for the HAM-D [ 17 , 20 ]. The forms were administered prior, and at the last week of CRT treatment.…”

“…In our study, the Cronbach alphas for the HAM-D 17 was 0.86 at before treatment and 0.84 at the end of CRT. A cutoff score of ≥15 has been used previously in cancer patients to screen for depression, with higher scores indicating more symptoms of depression [ 17 , 22 ].…”

“…Stool sample collection and 16S rRNA gene analysis procedures have been described previously by our group [ 2 , 17 ]. Statistical differences between depression scores were computed using a two-tailed t -test with a significance threshold of 0.05.…”