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. Overall design: RNA-Seq was performed on PBMC samples from 30 FAP patients before a low-inflammatory diet (LID) and after three and six months after the dietary intervention.

长期膳食脂肪摄入可通过代谢炎症（metaflammation）影响癌症发生发展——代谢炎症是指由脂质代谢失调驱动的慢性低度炎症状态。携带遗传性APC基因突变、结直肠癌（colorectal cancer, CRC）发病风险达100%的家族性腺瘤性息肉病（Familial Adenomatous Polyposis, FAP）患者，目前主要依靠预防性结肠切除术及针对前列腺素-环氧合酶（prostaglandin-COX）等关键通路的抗炎治疗实现化学预防。
新兴的代谢相关免疫重编程（metabolic-associated immune reprogramming）概念促使我们探究：旨在减轻代谢炎症的营养干预是否能够恢复有效的免疫应答。
为此，我们纳入28名遵循低炎症饮食（low-inflammatory diet, LID）6个月的FAP患者开展研究。通过多组学分析——包括全身及局部水平的多参数免疫表征、转录组学、脂质组学及蛋白质组学——研究发现，低炎症饮食可重塑促炎相关脂质组分并调节免疫细胞功能。这一结果得到了多项验证：外周血单个核细胞（peripheral blood mononuclear cell, PBMC）转录程序中的炎症及髓系应答水平降低，离体Toll样受体（Toll-like receptor, TLR）激动剂刺激后的细胞因子分泌量减少。在肠道中，低炎症饮食可缩小息肉体积，并诱导与固有免疫记忆恢复相关的转录组改变。此外，低炎症饮食可降低血脂异常巨噬细胞的丰度——这是结直肠癌的不良预后因子。上述免疫代谢改变与患者生活质量的改善呈显著相关。
综上，本研究结果表明，低炎症饮食是一种极具前景的免疫调节策略，能够重塑局部免疫状态、减少结直肠息肉积聚并促进抗肿瘤免疫应答，为高危人群的结直肠癌预防提供了可行的膳食干预路径。
总体实验设计：对30名FAP患者在接受低炎症饮食前、饮食干预后3个月及6个月的外周血单个核细胞样本进行RNA测序分析。