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However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat\u2010killed <jats:italic>Mycobacterial tuberculosis<\/jats:italic> and live <jats:italic>Mycobacterium bovis<\/jats:italic> (Bacillus Calmette\u2013Gu\u00e9rin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the <jats:italic>Reg3<\/jats:italic> family genes. Furthermore, interleukin\u201022 production by T helper cells contributed to the anti\u2010inflammatory activity of <jats:italic>Mycobacteria<\/jats:italic>. 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