Probiotic-postbiotic crosstalk in the gut microbiome: emerging mechanisms in colorectal homeostasis and cancer prevention – a systematic review

Abstract

The gut microbiome is increasingly recognized as a critical determinant of gastrointestinal health and disease, and interactions between probiotic microorganisms and their bioactive metabolites, known as postbiotics, play a fundamental role in maintaining colorectal homeostasis. Recent evidence suggests that disruption of these interactions contributes to colorectal carcinogenesis, while restoration of microbial balance may provide novel preventive and therapeutic opportunities. This systematic review aimed to evaluate the role of probiotic-postbiotic interactions in colorectal homeostasis and their potential implications in colorectal cancer prevention through published literature from 2020 to 2025. A structured search of peer-reviewed literature was conducted using PubMed, Scopus, and Web of Science, and studies examining gut microbiota composition, probiotic supplementation, postbiotic metabolites, and colorectal disease outcomes were included. Data were systematically extracted and synthesized to evaluate associations between microbial diversity, functional metabolites, inflammatory pathways, and colorectal pathology. The reviewed literature consistently demonstrated that probiotic genera such as Lactobacillus and Bifidobacterium enhance the production of beneficial postbiotics, particularly short-chain fatty acids including butyrate, acetate, and propionate. These metabolites were associated with improved epithelial barrier function, suppression of inflammatory signaling pathways, modulation of host immunity, and inhibition of tumorigenic processes. A balanced gut microbiome was associated with a reduced incidence of colorectal adenomas and carcinomas, whereas dysbiosis was linked to chronic inflammation, epithelial dysfunction, and increased cancer risk. Overall, probiotic–postbiotic crosstalk represents a critical mechanistic pathway in colorectal homeostasis and cancer prevention, supporting the development of microbiome-targeted interventions aimed at reducing colorectal cancer burden, although further prospective clinical and mechanistic studies are warranted.