The key finding
A scoping review published in 2026 examined 19 studies—18 preclinical and one human trial—investigating whether probiotics, prebiotics, and synbiotics affect two important cellular markers in colorectal cancer: p53 and Ki-67. p53 is a protein that triggers cell death in damaged cells, while Ki-67 indicates how rapidly cells are dividing. Most preclinical studies suggested that these biotic supplements may modulate tumor-related pathways, often by activating p53 or suppressing Ki-67, though the direction and magnitude of effects varied considerably depending on which bacterial strain was used and the experimental model. The single human trial was far too limited to draw clinical conclusions.
What the study looked like
This was a scoping review following PRISMA-ScR guidelines, meaning researchers systematically searched five major databases (PubMed, SciELo, BVS/Lilacs, Embase, and Web of Science) without restricting publication year or language. They mapped all available evidence on how prebiotics (non-digestible fibers that feed beneficial gut bacteria), probiotics (live beneficial bacteria), and synbiotics (combinations of both) influence p53 and Ki-67 expression in colorectal cancer. Of the 19 included studies, ten assessed p53, seven evaluated Ki-67, and two examined both markers. Eighteen studies were conducted in laboratory animals or cell cultures, while only one was a randomized clinical trial in humans. The interventions varied widely in bacterial strain composition, dosage, duration of exposure, and methods used to measure biomarkers.
Why researchers think this happened
The gut microbiota—trillions of bacteria living in our intestines—is increasingly recognized as influential in colorectal cancer development. Changes in the composition of these microbial communities are linked to both tumor initiation and progression. The researchers hypothesize that biotic supplements work by restoring a healthier microbial balance, which in turn modulates cellular pathways controlling tumor cell proliferation and programmed cell death (apoptosis). Specifically, certain probiotic strains may produce metabolites or signaling molecules that activate p53, a tumor suppressor protein that halts cell division and triggers apoptosis in damaged cells. Conversely, reduced Ki-67 expression suggests fewer cells are actively dividing, potentially slowing tumor growth. However, the paper emphasizes that effects are highly strain-specific—different bacterial species and even different strains within a species produced different results across various laboratory models.
How to read this carefully
This review highlights several important limitations. First, nearly all evidence comes from preclinical studies—experiments in mice, rats, or cell cultures—which do not necessarily translate to human biology. The single human trial was insufficient to establish clinical relevance. Second, there was enormous heterogeneity: studies used different probiotic strains, varying doses, different exposure durations, and inconsistent methods for measuring p53 and Ki-67. This makes it nearly impossible to compare results or identify which interventions might be most promising. Third, the review found no consistent directionality—some studies showed beneficial modulation of these markers, others showed mixed or neutral effects. Importantly, association between marker changes and actual cancer outcomes (survival, tumor size, recurrence) remains unclear. Readers should not interpret these findings as evidence that probiotics prevent or treat colorectal cancer.
What this means for everyday life
While this review suggests that gut bacteria and their metabolic products may influence cellular processes relevant to colorectal cancer, the evidence is far too preliminary to guide supplement choices. The findings underscore that not all probiotics are the same—strain identity matters enormously—and what works in a mouse model may not work in humans. Given the complexity and individual variation in our gut microbiomes, taking random probiotic supplements is unlikely to replicate laboratory results. For those interested in gut health and cancer prevention, it may be worth focusing on dietary patterns known to support beneficial gut bacteria—such as eating diverse plant fibers, fermented foods, and whole grains—rather than relying on specific supplements. Anyone concerned about colorectal cancer risk should prioritize established prevention strategies: regular screening, maintaining a healthy weight, limiting red and processed meat, exercising regularly, and avoiding smoking and excessive alcohol.