Abstract
Background
Akkermansia muciniphila (AM) is a gram-negative, mucin-degrading bacteria inhabiting the gastrointestinal
tract associated with host phenotypes and disease states.
Objective
Explore characteristics of overweight and obese female early-stage (0 to II) breast
cancer patients with low AM relative abundance (LAM) vs high (HAM) enrolled in a presurgical
weight-loss trial.
Design
Secondary analysis of pooled participants in a randomized controlled trial (NCT02224807).
Participants/setting
During the period from 2014 to 2017, 32 female patients with breast cancer were randomized
to weight-loss or attention-control arms from time of diagnosis-to-lumpectomy (mean=30±9
days).
Intervention
All were instructed to correct nutrient deficiencies via food sources and on upper-body
exercises. The weight-loss group received additional guidance to promote 0.5 to 1
kg/wk weight-loss via energy restriction and aerobic exercise.
Main outcome measures
At baseline and follow-up, sera, fecal samples, two-24 hour dietary recalls and dual
x-ray absorptiometry were obtained. Bacterial DNA was isolated from feces and polymerase
chain reaction (16S) amplified. Inflammatory cytokines were measured in sera.
Statistical analyses performed
Differences between LAM and HAM participants were analyzed using t tests and nonparametric tests. Spearman correlations explored relationships between
continuous variables.
Results
Participants were aged 61±9 years with body mass index 34.8±6. Mean AM relative abundance
was 0.02% (0.007% to 0.06%) and 1.59% (0.59% to 13.57%) for LAM and HAM participants,
respectively. At baseline, women with HAM vs LAM had lower fat mass (38.9±11.2 kg
vs 46.4±9.0 kg; P=0.044). Alpha diversity (ie, species richness) was higher in women with HAM (360.8±84.8
vs 282.4±69.6; P=0.008) at baseline, but attenuated after weight-loss (P=0.058). At baseline, interleukin-6 level was associated with species richness (ρ=–0.471,
P=0.008) and fat mass (ρ=0.529, P=0.002), but not AM. Change in total dietary fiber was positively associated with
AM in LAM (ρ=0.626, P=0.002), but not HAM (ρ=0.436, P=0.180) participants.
Conclusions
Among women with early-stage breast cancer, body composition is associated with AM,
microbiota diversity, and interleukin-6 level. AM may mediate the effects of dietary
fiber in improving microbiota composition.
Keywords
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Biography
A. D. Frugé is an assistant professor, Department of Nutrition, Dietetics, and Hospitality Management, Auburn University, Auburn, AL.
Biography
W. Van der Pol is a bioinformatician II, Department of Computational Biology and Bioinformatics, University of Alabama at Birmingham, Birmingham.
Biography
C. D. Morrow is a professor, Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham.
Biography
L. Q. Rogers is a professor, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham.
Biography
Y. Tsuruta is a project coordinator, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham.
Biography
W. Demark-Wahnefried is a professor and Webb Endowed Chair, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham.
Article info
Publication history
Published online: November 09, 2018
Accepted:
August 28,
2018
Received:
February 28,
2018
Footnotes
STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.
FUNDING/SUPPORT This study was supported by the National Cancer Institute R21 (CA178359), P30 (CA013148), and R25 (CA047888). The following support the Microbiome Resource at the University of Alabama at Birmingham: School of Medicine, Comprehensive Cancer Center (P30AR050948), Center for AIDS Research (5P30AI027767), Center for Clinical Translational Science (UL1TR000165, UL1TR001417), and Heflin Center for Genomic Sciences.
ClinicalTrials.gov ID: NCT02224807.
AUTHOR CONTRIBUTIONS W. Demark-Wahnefried and L. Q. Rogers designed the trial and methods and obtained grant funding and W. Demark-Wahnefried provided trial oversight. C. D. Morrow and W. Van der Pol provided microbiome and bioinformatics analysis/expertise. Y. Tsuruta and A. D. Frugé processed data and biospecimens. A. D. Frugé and W. Van der Pol designed and performed this secondary analysis and A. D. Frugé composed the initial draft of the manuscript. All authors reviewed and commented on subsequent drafts of the manuscript.
Identification
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