In the current microbiome research, we recognise that there is a long journey from identifying a single strain to understanding the altered community, then nailing down the general questions of altered microbiome to the specific role of individual player as a game changer. A recent publication in Gut has shown us one of these journeys to achieve a groundbreaking goal. Su et al 1 have identified a probiotic species Lactococcus lactis reduced in patients with colorectal cancer (CRC) using three independent cohorts. They successfully isolated a new L. lactis strain, HkyuLL 10, from healthy human stools, and verified this strain by whole genome sequencing. HkyuLL 10 treatment is able to suppress tumorigenesis in experimental colon cancer models (Apc min/+ mice and carcinogen-induced azoxymethane (AOM)-dextran sodium sulfate (DSS) mice) by enriching endogenous probiotic species to alleviate microbial dysbiosis. Of note, the protective function of HkyuLL 10 is through α-mannosidase. α-mannosidase made by HkyuLL 10 has demonstrated its beneficial role in suppressing human CRC cells, patient-derived organoids, and CRC in xenograft mice. Interestingly, HkyuLL 10 is able to suppress CRC tumorigenesis in germ-free mice, suggesting that HkyuLL 10 alone is sufficient to confer protective effect in microbiota-depleted mice. Thus, this study has demonstrated that a new strain HkyuLL 10 exhibits protective …