Frontiers in microbiology · 2026
Butyrate-associated antiproliferative and antitumor effects of Eubacterium limosum KGMB01548 in colorectal cancer.
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Yu Seung Yeob, Bak Jeong Eun, Oh Byeong Seob, Ryu Seoung Woo, Park Hyebin, Yu Dong Jin, Lee Jiyoung, Kim Ji-Sun, Lee Ju Huck
Аннотация
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.
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.