| Summary: | Gut microbiota dysbiosis with increased pathogenic bacteria and decreased beneficial bacteria is associated with colorectal cancer (CRC) development. This study examined the effect of a newly developed probiotic formula in modulating CRC-related bacteria. We developed a probiotic formula containing three bifidobacteria (<i>B. adolescentis</i>, <i>B. longum</i>, and <i>B. bifidum</i>) based on the identification of bacterial species that showed significant correlations with CRC-related bacteria including <i>Fusobacterium nucleatum</i> (<i>Fn</i>), <i>Lachnoclostridium sp. m3</i>, <i>Clostridium hathewayi</i> (<i>Ch</i>), and <i>Bacteroides clarus</i> (<i>Bc</i>). We co-cultured <i>Fn</i> with each bifidobacterium or the combined formula and examined the growth of <i>Fn</i> by qPCR. The three individual bifidobacteria significantly inhibited the growth of <i>Fn</i> compared to the control treatment (24~65% inhibition; all <i>p</i> < 0.001). The combination of the three bifidobacteria showed a greater inhibitory effect on <i>Fn</i> growth (70% inhibition) than the individual bifidobacteria (all <i>p</i> < 0.05). We further examined the effect of the probiotic formula in a pilot study of 72 subjects (40 on probiotics; 32 with no intervention) for 4 weeks and followed them up for 12 weeks. The relative fecal abundances of the bifidobacteria in the formula and the CRC-related markers (<i>Fn</i>, <i>m3</i>, <i>Ch</i>, and <i>Bc</i>) were quantitated by qPCR before and after the intervention, and the combined CRC risk score (4Bac; <i>Fn, m3</i>, <i>Ch</i>, and <i>Bc</i>) was evaluated. Subjects with probiotics intervention showed significantly increased abundances of the bifidobacteria from week 2 to week 5 compared to baseline (<i>p</i> < 0.05), and the abundances dropped to baseline levels after the cessation of the intervention. There were significant decreases in the levels of CRC-related markers (<i>Fn</i> and <i>m3</i>) and the CRC risk score (4Bac) from week 2 to week 12 compared to baseline levels (<i>p</i> < 0.05) in the intervention group but not in the control group. A novel probiotic formula containing <i>B. adolescentis</i>, <i>B. longum</i>, and <i>B. bifidum</i> was effective in inhibiting the growth of <i>F. nucleatum</i> in vitro and improving the gut microbial environment against CRC development.
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