RT Journal Article SR Electronic T1 Lactobacillus gallinarum modulates the gut microbiota and produces anti-cancer metabolites to protect against colorectal tumourigenesis JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 2011 OP 2021 DO 10.1136/gutjnl-2020-323951 VO 71 IS 10 A1 Sugimura, Naoki A1 Li, Qing A1 Chu, Eagle Siu Hong A1 Lau, Harry Cheuk Hay A1 Fong, Winnie A1 Liu, Weixin A1 Liang, Cong A1 Nakatsu, Geicho A1 Su, Anthony Chin Yang A1 Coker, Olabisi Oluwabukola A1 Wu, William Ka Kei A1 Chan, Francis Ka Leung A1 Yu, Jun YR 2022 UL http://gut.bmj.com/content/71/10/2011.abstract AB Objective Using faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.Design The tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.Results L. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size <3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum-treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo.Conclusion L. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.All data relevant to the study are included in the article or uploaded as supplementary information.