Bacillus mojavensis postbiotics: transcriptomic and anticancer effects in colon cancer cells

Probiotics have been shown to exert antiproliferative effects on colon cancer cells. While these effects are often attributed to microbiome regulation, they may also result from bioactive metabolites produced by probiotic bacteria. In the present study, we investigated the impact of a cell-free extract, hereafter referred to as a postbiotic, derived from Bacillus mojavensis, a strain isolated from aguamiel (a traditional Mexican beverage). The antiproliferative activity was evaluated in SW480 human colon cancer cells using MTT and crystal violet assays, while antimigratory effects were assessed through a wound-healing assay. In addition, the ability of the postbiotic to counteract inflammatory proliferation was evaluated in SW480 cells treated with lipopolysaccharide (LPS). Biosafety was tested using peripheral blood mononuclear cells (PBMCs) from healthy donors. Results demonstrated that treatment with 25–50 µg/mL of B. mojavensis postbiotic reduced SW480 cell viability by 75.15% and 79.3%, respectively, and significantly inhibited cell migration after 24 h. Moreover, the postbiotic decreased LPS-induced proliferation without exerting any cytotoxic effect on PBMCs, underscoring its selectivity toward malignant cells. To elucidate the underlying mechanisms, transcriptomic profiling was performed, revealing extensive modulation of oncogenes and tumor suppressors, with enrichment of PI3K–Akt, MAPK, apoptosis, and cytokine receptor pathways. In conclusion, postbiotics from B. mojavensis isolated from aguamiel exhibit selective anticancer activity by inhibiting proliferation, migration, and inflammation-induced growth in colorectal cancer cells. Transcriptomic findings further support these effects. Bacillus mojavensis postbiotics selectively inhibit the proliferation and migration of SW480 colon cancer cells without compromising the viability of PBMCs. Postbiotics counteract LPS-induced inflammatory proliferation, supporting their anti-inflammatory and biosafety profile. Transcriptomic profiling revealed reprogramming of cancer-related pathways, including PI3K–Akt, MAPK, apoptosis, and exosome-mediated communication.