Gut microbiota perturbation is associated with acute sleep disturbance among rectal cancer patients

González-Mercado, Velda J.; Sarkar, Anujit; Penedo, Frank J.; Pérez-Santiago, Josué; McMillan, Susan C.; Marrero, Sara; Marrero-Falcón, Miguel A.; Munro, Cindy L.

doi:10.1111/jsr.12915

Cited by 11 publications

(8 citation statements)

References 14 publications

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“…Because of the small sample sizes, our results are exploratory in nature and should be interpreted with caution. Nonetheless, this proof-of-concept pilot study builds on prior evidence from our group that CRT-induced comorbidities/symptoms may be associated with gut-microbial dysbiosis (Gonzalez-Mercado et al, 2020; Gonzalez-Mercado et al, 2019). In the present study, we compared the severity of fatigue, sleep disturbance, and depression scores before and at the end of CRT between participants who developed co-occurring symptoms by the end of CRT ( n = 24) and those who developed no symptom ( n = 7).…”

Section: Discussionmentioning

confidence: 89%

“…A major gap in the prevention and management of CRT-associated co-occurring symptoms is that there are no known targets for effective interventions. Previous research suggests that gut microbial perturbation/dysbiosis, a disruption in the balance, diversity, and function of symbiotic intestinal microbial communities (Perez et al, 2020) may be an important correlate of the symptom experience among patients with pelvic cancer undergoing treatments, perhaps mediated by the gut–brain axis (Bajic et al, 2018; Gonzalez-Mercado et al, 2019, 2020; Jordan et al, 2018). We previously demonstrated that gut microbial dysbiosis in RC patients was characterized by significantly lower alpha (within-sample) diversity at the end of CRT compared to before treatment using both Shannon diversity (community diversity) and the observed operational taxonomic units (OTUs [community richness]) for the RC sample as a whole ( p < 0.05; Gonzalez-Mercado et al, 2020).…”

mentioning

confidence: 99%

“…We previously demonstrated that gut microbial dysbiosis in RC patients was characterized by significantly lower alpha (within-sample) diversity at the end of CRT compared to before treatment using both Shannon diversity (community diversity) and the observed operational taxonomic units (OTUs [community richness]) for the RC sample as a whole ( p < 0.05; Gonzalez-Mercado et al, 2020). In addition, Shannon diversity was associated with fatigue or sleep-disturbance scores (Gonzalez-Mercado et al, 2019, 2020). However, it is not yet known if there is a relationship between gut microbiome perturbation and co-occurrence of symptoms during CRT for RC.…”

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confidence: 99%

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Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study

González-Mercado

Henderson

Sarkar

et al. 2020

Biological Research For Nursing

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Purpose: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms. Methods: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24–28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R’s vegan package software. Results: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors. Conclusion: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.

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Section: Discussionmentioning

confidence: 89%

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confidence: 99%

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confidence: 99%

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Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study

González-Mercado

Henderson

Sarkar

et al. 2020

Biological Research For Nursing

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“…Recent evidence by our group (González-Mercado et al 2019;González-Mercado, Pérez-Santiago, et al, 2020) and others (Wang et al, 2015) suggests that gut microbial dysbiosis may play an important role in the pathogenesis of common symptoms including depressive symptoms, sleep disturbance, and fatigue. In this study, we observed no significant differences in microbial alpha diversity between rectal cancer patients with high as compared to low co-occurring symptoms before CRT.…”

Section: Low Bacterial Diversity Indices Do Not Associate With Co-occurring Symptomsmentioning

confidence: 97%

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

González-Mercado¹,

Lim

Yu³

et al. 2021

Biological Research For Nursing

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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.

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“…Changes in gut microbiota composition induced by factors such as cancer or its treatment have been suggested to be associated or potentially causal of dysbiosis (a disruption in the balance, diversity, and function of symbiotic intestinal microbial communities) [ 2 , 13 ] in depression and other comorbidities/symptoms [ 2 , 11 , 14 – 16 ]. We recently reported reduced alpha diversity (Shannon Diversity and Observed Operational Taxonomic Units (OTUs)) in rectal cancer patients in the middle and at the end of CRT compared to before CRT, suggesting that CRT is associated with alterations in gut microbiota composition [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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

González-Mercado

Lim

Saligan

et al. 2021

Depression Research and Treatment

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Background. The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. Methods. 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. Results. Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman’s rho = 0.42 to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman’s rho = − 0.43 to − 0.31 ) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. Conclusions. Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.

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Gut microbiota perturbation is associated with acute sleep disturbance among rectal cancer patients

Cited by 11 publications

References 14 publications

Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study

Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study

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

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

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