一项增加结肠和外周血 SCFA 的随机饮食干预措施可调节健康人群的血液 B 细胞和 T 细胞区室。

A randomized dietary intervention to increase colonic and peripheral blood SCFAs modulates the blood B- and T-cell compartments in healthy humans.

机构信息

Department of Gastroenterology and Department of Immunology and Pathology, Central Clinical School, Monash University and Alfred Hospital, Melbourne, Australia; Department of Immunology and Pathology, Central Clinical School, Monash University and Alfred Hospital, Melbourne, Australia; Department of Microbial Diseases, UCL Eastman Dental Institute, University College London, London, United Kingdom.

Department of Gastroenterology and Department of Immunology and Pathology, Central Clinical School, Monash University and Alfred Hospital, Melbourne, Australia.

出版信息

Am J Clin Nutr. 2022 Nov;116(5):1354-1367. doi: 10.1093/ajcn/nqac246. Epub 2023 Feb 10.

DOI:10.1093/ajcn/nqac246

PMID:36084000

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9630882/

Abstract

BACKGROUND

SCFAs have immune-modulating effects in animal models of disease. However, there is limited evidence that this may occur in humans.

OBJECTIVES

This study aimed to determine the effects of increased exposure to SCFAs via dietary manipulation on colonic fermentation and adaptive immune cells.

METHODS

Twenty healthy young adults (18-45 y of age) underwent a blinded randomized crossover dietary intervention, consuming a high-SCFA diet and a matched low-SCFA diet for 21-d with a 21-d washout in between. SCFAs were provided through resistant starch, inulin, and apple cider vinegar. Blood and 3-d total fecal output were collected at baseline and at the end of each diet. GC was used to measure fecal and plasma SCFA. Flow cytometry was used for peripheral blood immunophenotyping.

RESULTS

According to a paired samples Wilcoxon test, the high-SCFA diet was associated with significantly higher fecal SCFA concentrations [median (IQR); 86.6 (59.0) compared with 75.4 (56.2) µmol/g, P = 0.02] and lower fecal ammonia concentrations [26.2 (14.7) compared with 33.4 (18.5) µmol/g, P = 0.04] than the low-SCFA diet. Plasma propionate [9.87 (12.3) compared with 4.72 (7.6) µmol/L, P = 0.049] and butyrate [2.85 (1.35) compared with 2.02 (1.29) µmol/L, P = 0.03] were significantly higher after the high-SCFA diet than after the low-SCFA diet. Blood total B cells [184 (112) compared with 199 (143) cells/µL, P = 0.04], naive B cells [83 (66) compared with 95 (89) cells/µL, P = 0.02], Th1 cells [22 (19) compared with 29 (16) cells/µL, P = 0.03], and mucosal-associated invariant T cells [62 (83) compared with 69 (114) cells/µL, P = 0.02] were significantly lower after the high-SCFA diet than the low-SCFA diet.

CONCLUSIONS

Increasing colonic and peripheral blood SCFA has discrete effects on circulating immune cells in healthy humans following 3-wk intervention. Further studies (e.g., in patients with inflammatory disease) are necessary to determine whether 1) these changes have immunomodulatory effects, 2) they are therapeutically beneficial, and 3) prolonged intake might be required. This trial is registered at the Australian New Zealand Clinical Trials Registry as ACTRN12618001054202.

摘要

背景

短链脂肪酸（SCFAs）在疾病动物模型中具有免疫调节作用。然而，仅有有限的证据表明这种作用可能发生在人类中。

目的

本研究旨在确定通过饮食干预增加 SCFA 暴露对结肠发酵和适应性免疫细胞的影响。

方法

20 名健康的年轻成年人（18-45 岁）接受了一项盲法随机交叉饮食干预，分别摄入高 SCFA 饮食和匹配的低 SCFA 饮食 21 天，中间有 21 天的洗脱期。通过抗性淀粉、菊粉和苹果醋提供 SCFA。在基线和每个饮食结束时采集血液和 3 天的总粪便。气相色谱法（GC）用于测量粪便和血浆 SCFA。流式细胞术用于外周血免疫表型分析。

结果

根据配对样本 Wilcoxon 检验，高 SCFA 饮食与粪便 SCFA 浓度显著升高[中位数（IQR）；86.6（59.0）比 75.4（56.2）µmol/g，P=0.02]和粪便氨浓度降低[26.2（14.7）比 33.4（18.5）µmol/g，P=0.04]有关，而低 SCFA 饮食则没有。血浆丙酸[9.87（12.3）比 4.72（7.6）µmol/L，P=0.049]和丁酸[2.85（1.35）比 2.02（1.29）µmol/L，P=0.03]在高 SCFA 饮食后明显高于低 SCFA 饮食后。血液总 B 细胞[184（112）比 199（143）细胞/µL，P=0.04]、幼稚 B 细胞[83（66）比 95（89）细胞/µL，P=0.02]、Th1 细胞[22（19）比 29（16）细胞/µL，P=0.03]和黏膜相关不变 T 细胞[62（83）比 69（114）细胞/µL，P=0.02]在高 SCFA 饮食后明显低于低 SCFA 饮食后。

结论

在健康人群中，3 周干预后，增加结肠和外周血 SCFA 对循环免疫细胞有明显影响。还需要进一步的研究（例如，在炎症性疾病患者中）来确定 1）这些变化是否具有免疫调节作用，2）它们是否具有治疗益处，以及 3）是否需要长期摄入。该试验在澳大利亚和新西兰临床试验注册处注册，编号为 ACTRN12618001054202。