Butyrate-associated antiproliferative and antitumor effects of Eubacterium limosum KGMB01548 in colorectal cancer
- 1Korean Collection for Type Cultures, Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology
- 2University of Science and Technology (UST)
- 3Department of Biomedical Science, Sunchon National University
Abstract
Introduction: Recent work has shown that Eubacterium limosum suppresses colorectal cancer (CRC), but the contribution and cellular actions of its short-chain fatty acids remain incompletely defined.
Methods: We characterized E. limosum KGMB01548, a human gut isolate, and examined the antitumor activity of its cell-free culture supernatant (ElCFS).
Results: ElCFS preferentially inhibited the proliferation of human HCT116 and murine CT26 CRC cells while having little effect on non-malignant CCD 841 CoN colonic cells. The activity persisted after heat and enzymatic treatments, and pH-dependent liquid–liquid extraction indicated that a small organic acid was a major bioactive component. High-performance liquid chromatography detected 13.77 mM butyrate and 23.33 mM acetate in ElCFS. At approximately the concentration delivered by 10% ElCFS, sodium butyrate (NaB; 1.3 mM) produced comparable antiproliferative activity, whereas sodium acetate did not, supporting butyrate as a major candidate contributor to ElCFS activity. ElCFS and approximately concentration-matched NaB increased histone H3 acetylation, consistent with histone deacetylase inhibition, and induced apoptosis, as evidenced by PARP and caspase-3 cleavage and p53 phosphorylation. Their antiproliferative effects were markedly attenuated under glucose-depleted conditions. In a CT26 syngeneic tumor model, peritumoral administration of ElCFS reduced tumor growth, indicating that secreted E. limosum metabolites retained local antitumor activity outside the intestinal route. Oral pre-administration of live E. limosum also reduced subsequent tumor burden. Furthermore, 16S rRNA gene profiling suggested modest changes in several putative short-chain-fatty-acid-producing taxa and in PICRUSt2-predicted butyrate-biosynthesis potential, without a major change in alpha diversity.
Discussion: Together, these findings link E. limosum KGMB01548 to butyrate-associated histone acetylation, apoptosis, glucose-sensitive antiproliferative activity, and tumor suppression, supporting further investigation of this gut commensal and its secreted metabolites as microbiome-derived approaches for CRC control.
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BibTeX
@article{yu2026butyrateassociated,
title = {{Butyrate-associated antiproliferative and antitumor effects of Eubacterium limosum KGMB01548 in colorectal cancer}},
author = {Seung Yeob Yu and Jeong Eun Bak and Byeong Seob Oh and Seoung Woo Ryu and Hyebin Park and Dong Jin Yu and Jiyoung Lee and Ji-Sun Kim and Ju Huck Lee},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1973432},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1973432/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Butyrate-associated antiproliferative and antitumor effects of Eubacterium limosum KGMB01548 in colorectal cancer
AU - Seung Yeob Yu
AU - Jeong Eun Bak
AU - Byeong Seob Oh
AU - Seoung Woo Ryu
AU - Hyebin Park
AU - Dong Jin Yu
AU - Jiyoung Lee
AU - Ji-Sun Kim
AU - Ju Huck Lee
PY - 2026
DA - 2026/10/06
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1973432
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1973432/full
AB - Introduction: Recent work has shown that Eubacterium limosum suppresses colorectal cancer (CRC), but the contribution and cellular actions of its short-chain fatty acids remain incompletely defined. Methods: We characterized E. limosum KGMB01548, a human gut isolate, and examined the antitumor activity of its cell-free culture supernatant (ElCFS). Results: ElCFS preferentially inhibited the proliferation of human HCT116 and murine CT26 CRC cells while having little effect on non-malignant CCD 841 CoN colonic cells. The activity persisted after heat and enzymatic treatments, and pH-dependent liquid–liquid extraction indicated that a small organic acid was a major bioactive component. High-performance liquid chromatography detected 13.77 mM butyrate and 23.33 mM acetate in ElCFS. At approximately the concentration delivered by 10% ElCFS, sodium butyrate (NaB; 1.3 mM) produced comparable antiproliferative activity, whereas sodium acetate did not, supporting butyrate as a major candidate contributor to ElCFS activity. ElCFS and approximately concentration-matched NaB increased histone H3 acetylation, consistent with histone deacetylase inhibition, and induced apoptosis, as evidenced by PARP and caspase-3 cleavage and p53 phosphorylation. Their antiproliferative effects were markedly attenuated under glucose-depleted conditions. In a CT26 syngeneic tumor model, peritumoral administration of ElCFS reduced tumor growth, indicating that secreted E. limosum metabolites retained local antitumor activity outside the intestinal route. Oral pre-administration of live E. limosum also reduced subsequent tumor burden. Furthermore, 16S rRNA gene profiling suggested modest changes in several putative short-chain-fatty-acid-producing taxa and in PICRUSt2-predicted butyrate-biosynthesis potential, without a major change in alpha diversity. Discussion: Together, these findings link E. limosum KGMB01548 to butyrate-associated histone acetylation, apoptosis, glucose-sensitive antiproliferative activity, and tumor suppression, supporting further investigation of this gut commensal and its secreted metabolites as microbiome-derived approaches for CRC control.
SN - 1664-302X
ER -