Source: [openalex](https://doi.org/10.1017/erm.2026.10053)
Authors: Nayeralsadat Fatemi, Ali Mohammad Alizadeh, Zahra Sadeghloo, Amir Sadeghi
Venue: Expert Reviews in Molecular Medicine · 2026-05-26
AI relevance (4/5): Directly addresses autophagy mechanisms in cancer context; ncRNA-autophagy crosstalk is mechanistically relevant, though probiotic link is less established.
This review article examines how probiotics — beneficial live bacteria consumed through food or supplements — may influence colorectal cancer (CRC) by regulating two interconnected molecular systems: non-coding RNAs (ncRNAs) and autophagy. Autophagy is the cell's internal 'recycling' process, which can either suppress or promote cancer depending on context. Non-coding RNAs are RNA molecules that don't produce proteins but instead act as master regulators of gene expression. The authors synthesize evidence suggesting that probiotic-derived metabolites, particularly short-chain fatty acids like butyrate, can modulate ncRNA activity (including microRNAs and long non-coding RNAs), which in turn reprograms autophagic flux in colorectal epithelial and tumor cells. This three-way crosstalk creates potential therapeutic leverage points for precision oncology — meaning treatments tailored to a patient's specific molecular tumor profile. The review positions this mechanistic framework as a rationale for developing probiotic-based adjunct strategies alongside conventional CRC therapies. The key clinical implication is that gut microbiome modulation may be a tractable, low-toxicity approach to sensitizing CRC tumors to existing treatments by fine-tuning autophagic and epigenetic programs.
This is a narrative or systematic review article (exact methodology — whether systematic or scoping — is not definitively specified in the available metadata). The study aggregates published molecular biology, preclinical, and early clinical literature on three intersecting domains: probiotic mechanisms of action in the gut, ncRNA regulatory networks in CRC, and autophagy pathway biology. No primary patient cohort, animal experiment, or clinical trial was conducted as part of this work. As a synthesis article published in Expert Reviews in Molecular Medicine (2026), it draws on existing in vitro, in vivo, and where available translational human studies to construct an integrative mechanistic framework.
As a review rather than an original experimental study, this article cannot establish causality between probiotic administration, ncRNA changes, and autophagy modulation in human CRC patients — the proposed mechanistic crosstalk remains largely inferred from separate lines of preclinical evidence that have not been tested together in a unified model. The probiotic-ncRNA-autophagy axis has not been validated in prospective clinical trials, meaning the precision medicine applications described are speculative frameworks rather than evidence-based protocols. The review likely cannot fully account for inter-individual variation in microbiome composition, tumor mutational burden, and baseline autophagic tone, all of which would substantially affect therapeutic outcomes. The critical next experiment would be a controlled preclinical study in CRC organoids or mouse models combining specific probiotic strains with ncRNA profiling and autophagic flux measurement to establish dose-response relationships and directionality of effect.
This review extends [§92], which examines autophagy inhibition (via hydroxychloroquine) as a strategy to overcome treatment resistance in metastatic BRAF-mutant CRC, by providing a complementary mechanistic lens — namely that upstream ncRNA and microbiome signals govern autophagic flux and could be targeted non-pharmacologically. It parallels [§91], a Phase 3 trial of eRapa (rapamycin formulation) in familial adenomatous polyposis, insofar as both works are concerned with mTOR-autophagy pathway modulation in colorectal neoplasia, though the current review proposes probiotic rather than pharmacological mTOR intervention. The butyrate-mediated epigenetic mechanism discussed here also extends [§39], which addresses metformin-phytochemical combinations in metabolic liver disease via overlapping AMPK/mTOR/autophagy signaling, suggesting convergent metabolite-driven pathway modulation across gastrointestinal disease contexts. Additionally, this article parallels [§38] on mammalian lysophagy mechanisms, as both works grapple with context-specific regulation of selective autophagy subtypes relevant to cancer and cellular homeostasis.
