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

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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.

Original languageEnglish
Pages (from-to)1354-1367
Number of pages14
JournalThe American Journal of Clinical Nutrition
Issue number5
Publication statusPublished - Nov 2022


  • adaptive immunity
  • B cells
  • colonic fermentation
  • dietary fiber
  • resistant starch
  • short-chain fatty acids
  • T cells

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