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Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

ABSTRACT: Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients. N=179 patients with colorectal cancer (stages I-IV) were included in the study. Pre-surgery stool samples were used to perform 16S rRNA gene sequencing (Illumina). Physical activity (MET hrs/wk) during the year before diagnosis was assessed by questionnaire and participants were classified as being active vs. inactive based on guidelines. BMI at baseline was abstracted from medical records. Patients were classified into four combinations of physical activity levels/BMI. Lower gut microbial diversity was observed among 'inactive' vs. 'active' patients (Shannon: P=0.01, Simpson: P=0.03), 'obese' vs. 'normal weight' patients (Shannon, Simpson, and Observed species: P=0.02, respectively), and 'overweight/obese/inactive' vs. 'normal weight/active' patients (Shannon: P=0.02, Observed species: P=0.04). Results differed by sex and tumor site. Two phyla and 12 genera (Actinobacteria and Fusobacteria, Adlercreutzia, Anaerococcus, Clostridium, Eubacterium, Mogibacteriaceae, Olsenella, Peptinophilus, Pyramidobacter, RFN20, Ruminococcus, Succinivibrio, Succiniclasticum) were differentially abundant across physical activity and BMI groups. This is the first evidence for associations of physical activity with gut microbiome diversity and abundances, directly among colorectal cancer patients. Our results indicate that physical activity may offset gut microbiome dysbiosis due to obesity. Alterations in gut microbiota may contribute mechanistically to the energy balance-colorectal cancer link and impact clinical outcomes.

SUBMITTER: Himbert C

PROVIDER: S-EPMC9641409 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

Himbert Caroline C Stephens W Zac WZ Gigic Biljana B Hardikar Sheetal S Holowatyj Andreana N AN Lin Tengda T Ose Jennifer J Swanson Eric E Ashworth Anjelica A Warby Christy A CA Peoples Anita R AR Nix David D Jedrzkiewicz Jolanta J Bronner Mary M Pickron Bartley B Scaife Courtney C Cohan Jessica N JN Schrotz-King Petra P Habermann Nina N Boehm Juergen J Hullar Meredith M Figueiredo Jane C JC Toriola Adetunji T AT Siegel Erin M EM Li Christopher I CI Ulrich Alexis B AB Shibata David D Boucher Kenneth K Huang Lyen C LC Schneider Martin M Round June L JL Ulrich Cornelia M CM

American journal of cancer research 20221015 10

Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients. N=179 patients with colorectal cancer (stages I-IV) were included in the study. Pre ...[more]

PMID: 36381318

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Project description:BackgroundThis study aimed to evaluate associations between physical activities, gut microbiome and survival outcomes among Chinese metastatic colorectal cancer (mCRC) patients.MethodsWe conducted a secondary analysis nested in a randomized controlled clinical trial (RCT) of a traditional Chinese herbal medicine for mCRC patients (ChiCTR2000029599). After one-month intervention, we followed up patients every six months for survival outcomes and the last follow-up was in August 2022 (median follow-up time 28.6 months). We assessed patients' physical activity (PA) through short form of the International Physical Activity Questionnaire (IPAQ-SF) and collected patients' stool samples at baseline. Kaplan-Meier survival analyses and Cox regression models were used to evaluate the association between PA level and overall survival outcomes. 16S rRNA sequencing approaches were utilized for the gut microbiome analysis.ResultsAmong 40 mCRC patients enrolled in the original RCT, 15 patients were still alive at the time of the last follow-up. The mean IPAQ score was 2569.5 MET-min/week for all patients, indicating a moderate PA level. Specifically, there were 7 patients in high PA level group, 2 patients in low PA level group and the rest were in middle PA group. Gut microbiome community difference analysis showed that patients with high PA levels had a significantly higher alpha diversity than that of the middle PA group (131.53 vs. 98.12, p = 0.04), an increased abundance of Phascolarctobacterium and Ruminococcaceae and a decreased abundance of Megasphaera at the genus level. Cox regression model showed that after controlling for the original tumor site and TCM treatment, high PA level was independently associated with a lower risk of death (relative risk 0.13, p = 0.014).ConclusionsHigh PA level could be associated with survival benefits among Chinese mCRC patient through its potential role on modulating gut microbiome. Our results could be referred to patients' education and future clinical study design.

Project description:BackgroundOverweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status.MethodA total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5-23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora.ResultThere was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated.ConclusionsThe richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this.

Dataset Information

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

Publications

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

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