Fig. 2: Integrated therapeutic framework targeting microbiome–host axes in CRC. | npj Biofilms and Microbiomes

Fig. 2: Integrated therapeutic framework targeting microbiome–host axes in CRC.

From: Gut microbiome–driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming

Fig. 2

This figure presents an integrative mechanistic and therapeutic model illustrating how modulation of the gut microbiome can reprogram neural, endocrine, immune, and metabolic pathways to counteract CRC progression. The neural pathway highlights microbiota–neuro–immune crosstalk where microbial disruption of epithelial junctions activates β-catenin, NF-κB, and STAT3 signaling, driving neuroinflammation and tumor-promoting innervation; therapeutic strategies include β-adrenergic blockade, SCFA-producing probiotics and postbiotics, vagal activation, and FMT restoring IL-10-producing commensals to reinforce epithelial integrity. The endocrine pathway emphasizes dysregulated GLP-1/PYY/5-HT signaling and bile acid metabolism, where interventions such as high-fiber and polyphenol-rich diets, FXR/TGR5 agonists, β-glucuronidase-inhibiting probiotics, metformin, and chrononutrition restore hormonal balance and barrier function. The immune pathway describes chronic inflammation, immune evasion, and MDSC recruitment driven by taxa like Fusobacterium nucleatum, ETBF, and pks⁺ E. coli; targeted depletion, immunostimulatory probiotics, FMT combined with checkpoint blockade, postbiotics, and anti-inflammatory nutrients (omega-3s, curcumin, resveratrol) reactivate cytotoxic immunity and suppress tumor-promoting inflammation. Finally, the metabolic pathway depicts mitochondrial inhibition, Warburg-like reprogramming, and oncometabolite accumulation through AhR activation and SASP induction; therapeutic strategies include prebiotics and engineered probiotics to enhance butyrate/propionate, colibactin synthesis inhibitors, modulation of microbial AhR ligands, antioxidants, and metabolic interventions to restore redox and immune–metabolic balance. Collectively, these interventions illustrate a systems-level therapeutic framework where microbiome-directed strategies reestablish epithelial, metabolic, immune, and neuroendocrine homeostasis, attenuating colorectal tumorigenesis.

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