RNA-Seq of PBMC of FAP patient before and after a low-inflammatory diet

Long-term dietary fat intake influences cancer development through metaflammation, a state of chronic low-grade inflammation driven by dysregulated lipid metabolism. Patients with Familial Adenomatous Polyposis (FAP), who carry hereditary APC gene mutations and have a 100% risk of developing colorectal cancer (CRC), currently rely on prophylactic colectomy and anti-inflammatory therapies targeting key pathways such as prostaglandin-COX for chemoprevention. The emerging concept of metabolic-associated immune reprogramming prompted us to investigate whether a nutritional intervention aimed at reducing metaflammation could restore an effective immune response. To address this, we studied 28 FAP patients who followed a low-inflammatory diet (LID) for six months. Multiomics analyses, including multiparametric immune profiling, transcriptomics, lipidomics, and proteomics at both systemic and local levels, revealed that LID reshaped proinflammatory-associated lipid species and modulated immune cell function. This was confirmed by a reduction in inflammatory and myeloid responses in PBMC transcriptional programs and decreased cytokine secretion following ex vivo TLR agonist stimulation. In the intestine, LID reduced polyp size and induced transcriptional changes associated with the restoration of innate immune memory. Additionally, LID decreased the abundance of dyslipidemic macrophages, a negative prognostic factor in CRC. These immunometabolic changes correlated with improved patient quality of life. Overall, these findings highlight LID as a promising immune-modulating strategy capable of reshaping local immunity, reducing FC accrual, and promoting antitumor immune responses, positioning dietary interventions as a viable approach for CRC prevention in high-risk individuals.