AUTHOR=Yu Tingting , Ji Ling , Lou Liqin , Ye Shiqing , Fang Xiaoting , Li Chen , Jiang Feizhao , Gao Hongchang , Lou Yongliang , Li Xiang 

TITLE=Fusobacterium nucleatum Affects Cell Apoptosis by Regulating Intestinal Flora and Metabolites to Promote the Development of Colorectal Cancer

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.841157

DOI=10.3389/fmicb.2022.841157

ISSN=1664-302X

ABSTRACT=<sec><title>Background/Aims</title><p>Intestinal flora, especially <italic>Fusobacterium nucleatum (Fn)</italic>, can affect the development of colorectal cancer (CRC). In this study, we examined the composition of intestinal flora and their metabolites in the tissues, serum and feces of CRC patients.</p></sec><sec><title>Materials and Methods</title><p>CRC tissues, adjacent normal colonic tissues, fecal and serum samples were collected from CRC patients who received surgical treatment between January 2018 and January 2020. Fecal and serum samples were collected from healthy individuals for comparison. In addition, fecal samples were collected from BALB/c female mice. SW480, a human CRC cell line, was utilized for <italic>in vitro</italic> studies. The experiments involved <sup>1</sup>H-NMR-based metabolomics analysis, targeted and untargeted mass spectrometry analysis, and intestinal flora 16S rDNA V4 region sequencing.</p></sec><sec><title>Results</title><p>The abundance of <italic>Bacteroides</italic> and propionic acid concentration were decreased and that of <italic>Lactobacillus</italic> and lactic acid concentration were increased in CRC tissues. In addition, the abundances of <italic>Ruminococcus</italic>, <italic>Prevotella</italic>, and <italic>Sutterell</italic> were decreased in CRC patients. The levels of leucine and isoleucine were decreased in the serum and tumor tissues of CRC patients. Aspartate, glutamate and glutathione levels were elevated in the tissues of CRC patients only. The serum glutamine, tyrosine, valine, alanine, and histidine levels were decreased significantly. Lactic acid inhibited and propionic acid promoted apoptosis among SW480 CRC cells.</p></sec><sec><title>Conclusion</title><p><italic>Fn</italic> affected the apoptosis of CRC cells and promoted the progression of CRC by affecting the distribution of intestinal flora, which altered the concentrations of metabolites such as lactic acid, propionic acid. Intestinal flora could regulate amino acid metabolism.</p></sec>