Food Frontiers· 2026Q1
Retinoik Asit Takviyesi, Bağırsak İltihabına Bağlı Depresyonu SPI1 İnhibisyonu Yoluyla Hafifletir
Supplementing With the Vitamin A Metabolite Retinoic Acid Can Alleviate Negative Affective States Caused by SPI1‐Induced Immune and Metabolic Dysfunctions Following Intestinal Barrier Impairment
- 0atıf
- Q1SCImago
- 2026yıl
Kısa özet
Retinoik asit (ATR) takviyesi, hematopoietik kök hücrelerde miyeloid eğilimi düzelterek ve retinoik asit metabolizmasını geri yükleyerek, ülseratif kolit (UC) modelinde SPI1'i inhibe ederek depresyon semptomlarını hafifletir.
Yapay zekâ ile başlık ve abstract'tan üretildi; tam metin okunmaz.
Ana noktalar
- SPI1, ülseratif kolit (UC) modelinde hematopoietik kök hücrelerde miyeloid eğilimi indükleyerek depresif fenotiplere neden olur.
- SPI1'in inhibisyonu bu miyeloid eğilimi düzeltir ve depresyon semptomlarını hafifletir.
- SPI1, retinoik asit metabolizmasıyla nedensel bir ilişkiye sahiptir ve inhibisyonu ilgili gen ifadesini normalleştirir.
- Eksojen all-trans retinoik asit (ATR) uygulaması miyeloid eğilimi düzeltir ve UC kaynaklı depresyonu tedavi eder.
Yapay zekâ ile başlık ve abstract'tan üretildi; tam metin okunmaz.
Özet (abstract)
ABSTRACT Ulcerative colitis (UC) and depression (DP) are significant comorbidities in epidemiological research. However, the mechanisms underlying UC‐induced DP remain poorly understood. Myeloid differentiation and retinoic acid metabolic dysregulation are implicated in both conditions, yet their interconnection in the context of comorbidity is unclear. This study investigates the role of SPI1 in mediating UC‐induced DP through the modulation of retinoic acid metabolism and hematopoietic stem cell myeloid bias, exploring the immune‐metabolic‐gut axis. This study employed multi‐technique approach to determine whether SPI1 exacerbates UC‐induced DP by influencing retinoic acid metabolism and myeloid bias. Methods included genome‐wide and proteome‐wide Mendelian randomization (MR), in vivo imaging, qRT‐PCR, metabolomics, transcriptomics, flow cytometry, behavioral tests, immunofluorescence, immunohistochemistry, in silico knockout and overexpression analyses, various machine‐learning models, molecular docking, and molecular dynamics simulations to comprehensively evaluate our hypothesis. Our findings indicate that myeloid bias in hematopoietic stem cells occurs during UC‐induced DP and is regulated by SPI1. Inhibiting SPI1 reshapes this myeloid bias and alleviates depressive phenotypes. Furthermore, SPI1 shows a significant causal relationship with retinol‐binding protein 2 (RBP2), a key player in retinoic acid metabolism. SPI1 inhibition restored Cyp26a1 levels and normalized the transcription of RBP2 and other retinoic acid metabolism‐related genes, thereby rescuing metabolic homeostasis. Exogenous administration of all‐trans retinoic acid (ATR) also corrected myeloid bias and exerted therapeutic effects against UC‐induced DP. These findings highlight the pivotal role of SPI1 in UC‐induced DP and suggest the potential of exogenous ATR supplementation as preventive or therapeutic strategy for patients with this comorbidity.
Yazarların özeti; kaynağından alınmıştır. Food Frontiers, 2026 · DOI ↗
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Alan: Biyolojik Psikiyatri
Biological PsychiatryNeuroscience