AUTHOR=Hou Xiaoying , Zhang Pei , Du Hongzhi , Chu Weihua , Sun Ruiqi , Qin Siyuan , Tian Yuan , Zhang Zunjian , Xu Fengguo 

TITLE=Akkermansia Muciniphila Potentiates the Antitumor Efficacy of FOLFOX in Colon Cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.725583

DOI=10.3389/fphar.2021.725583

ISSN=1663-9812

ABSTRACT=<p>FOLFOX (oxaliplatin, fluorouracil and calcium folinate) is the first-line chemotherapy regimen for colon cancer therapy in the clinic. It provides superior efficacy than oxaliplatin alone, but the underlying mechanism remains unclear. In the present study, pharmacomicrobiomics integrated with metabolomics was conducted to uncover the role of the gut microbiome behind this. First, <italic>in vivo</italic> study demonstrated that FOLFOX exhibited better efficacy than oxaliplatin alone in colon cancer animal models. Second, 16S rDNA gene sequencing analysis showed that the abundance of <italic>Akkermansia muciniphila</italic> (<italic>A. muciniphila</italic>) remarkably increased in the FOLFOX treated individuals and positively correlated with the therapeutic effect. Third, further exploration confirmed <italic>A. muciniphila</italic> colonization significantly enhanced the anti-cancer efficacy of FOLFOX. Last, metabolomics analysis suggested dipeptides containing branched-chain amino acid (BCAA) might be responsible for gut bacteria mediated FOLFOX efficacy. In conclusion, our study revealed the key role of <italic>A. muciniphila</italic> in mediating FOLFOX efficacy, and manipulating <italic>A. muciniphila</italic> might serve as a novel strategy for colon cancer therapy.</p>