TY - JOUR
T1 - Obesity modulates the gut microbiome in triple-negative breast cancer
AU - Hossain, Fokhrul
AU - Majumder, Samarpan
AU - David, Justin
AU - Bunnell, Bruce A.
AU - Miele, Lucio
N1 - Funding Information:
This research was supported in part by Louisiana Clinical and Translational Science Center (LACaTS) grant U54 GM104940 and the NIH P20 CA233374 grant from the National Cancer Institute (NCI).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10
Y1 - 2021/10
N2 - Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous sub-type of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflam-mation, and failure of cancer immunotherapy. However, the debate on what constitutes a “healthy” gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity–tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.
AB - Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous sub-type of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflam-mation, and failure of cancer immunotherapy. However, the debate on what constitutes a “healthy” gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity–tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.
KW - 16S rRNA sequencing
KW - Commensal microbiota
KW - Metagenomic analyses
KW - Triple-negative breast cancer (TNBC)
UR - http://www.scopus.com/inward/record.url?scp=85117217140&partnerID=8YFLogxK
U2 - 10.3390/nu13103656
DO - 10.3390/nu13103656
M3 - Article
C2 - 34684657
AN - SCOPUS:85117217140
SN - 2072-6643
VL - 13
JO - Nutrients
JF - Nutrients
IS - 10
M1 - 3656
ER -