Division of Rheumatology, Allergy, and Clinical Immunology, School of Medicine, University of California, Davis, California, USA.
Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Liver Int. 2024 Oct;44(10):2834-2846. doi: 10.1111/liv.16060. Epub 2024 Aug 5.
There is increased interest in utilizing dietary interventions to alter the progression of autoimmune diseases. These efforts are driven by associations of gut microbiota/metabolites with levels of short-chain fatty acids (SCFAs). Propionate is a key SCFA that is commonly used as a food preservative and is endogenously generated by bacterial fermentation of non-digestible carbohydrates in the gut. A thesis has suggested that a diet rich in propionate and other SCFAs can successfully modulate autoimmunity. Herein, we investigated the effect of long-term administration of propionylated high-amylose resistant starches (HAMSP) on the course of murine primary biliary cholangitis.
Groups of female ARE-Del mice were fed an HAMSP diet either before or after disease onset. A detailed immunobiological analysis was performed involving autoantibodies and rigorous T-cell phenotyping, including enumeration of T-cell subsets in the spleen, liver, intestinal intraepithelial lymphocytes and lamina propria by flow cytometry. Histopathological scores were used to assess the frequency and severity of liver inflammation and damage to hepatocytes and bile ducts.
Our results demonstrate that a long-term propionate-yielding diet re-populated the T-cell pool with decreased naïve and central memory T-cell subsets and an increase in the effector memory T cells in mice. Similarly, long-term HAMSP intake reduced CD4CD8 double-positive T cells in intraepithelial lymphocytes and the intestinal lamina propria. Critically, HAMSP consumption led to moderate-to-severe hepatocellular steatosis in ARE-Del mice, independent of the stage of autoimmune cholangitis.
Our data suggest that administration of HAMSP induces both regulatory and effector T cells. Furthermore, HAMSP administration resulted in hepatocellular steatosis. Given the interest in dietary modulation of autoimmunity and because propionate is widely used as a food preservative, these data have significant implications. This study also provides new insights into the immunological and pathological effects of chronic propionate exposure.
人们越来越关注利用饮食干预来改变自身免疫性疾病的进程。这些努力的动力来自于肠道微生物群/代谢物与短链脂肪酸 (SCFA) 水平的关联。丙酸盐是一种关键的 SCFA，通常用作食品防腐剂，并且是肠道中细菌发酵不可消化碳水化合物产生的内源性物质。有研究表明，富含丙酸盐和其他 SCFA 的饮食可以成功调节自身免疫。在此，我们研究了长期给予丙酰化高直链淀粉抗性淀粉 (HAMSP) 对小鼠原发性胆汁性胆管炎病程的影响。
雌性 ARE-Del 小鼠的实验组在疾病发作前或发作后给予 HAMSP 饮食。通过详细的免疫生物学分析，包括自身抗体和严格的 T 细胞表型分析，包括使用流式细胞术计数脾脏、肝脏、肠道上皮内淋巴细胞和固有层中的 T 细胞亚群，来评估 T 细胞亚群。使用组织病理学评分评估肝脏炎症和肝细胞及胆管损伤的频率和严重程度。
我们的结果表明，长期产生丙酸盐的饮食会使 T 细胞库重新填充，幼稚和中央记忆 T 细胞亚群减少，效应记忆 T 细胞增加。同样，长期摄入 HAMSP 可减少上皮内淋巴细胞和肠道固有层中的 CD4CD8 双阳性 T 细胞。重要的是，HAMSP 摄入导致 ARE-Del 小鼠发生中等至重度肝细胞脂肪变性，与自身免疫性胆管炎的阶段无关。
我们的数据表明，HAMSP 的给予会诱导调节性和效应性 T 细胞。此外，HAMSP 给予导致肝细胞脂肪变性。鉴于对饮食调节自身免疫的兴趣，并且因为丙酸盐广泛用作食品防腐剂，这些数据具有重要意义。本研究还为慢性丙酸盐暴露的免疫和病理影响提供了新的见解。
