Gill, Paul A; Muir, Jane G; Gibson, Peter R; van Zelm, Menno C; (2022) A Randomized Dietary Intervention to Increase Colonic and Peripheral Blood Short-Chain Fatty Acids Modulates the Blood B- and T-cell Compartments in Healthy Humans. The American Journal of Clinical Nutrition , Article nqac246. 10.1093/ajcn/nqac246. (In press).

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Abstract

BACKGROUND: Short-chain fatty acids (SCFA) 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 SCFA via dietary manipulation on colonic fermentation and adaptive immune cells. METHODS: Twenty healthy, young adults (18-45 years of age) underwent a blinded, randomized, cross-over dietary intervention, consuming a high-SCFA producing diet and matched low-SCFA diet for 21 days with 21-day wash-out in between. SCFA were provided through resistant starch, inulin and apple cider vinegar. Blood and 3-day total fecal output were collected at baseline and at the end of each diet. Gas chromatography was used to measure fecal and plasma SCFA. Flow cytometry was used for peripheral blood immuno-phenotyping. RESULTS: High-SCFA diet was associated with significantly (paired samples Wilcoxon test) higher median [IQR] fecal SCFA concentrations (86.6 [59.0] vs 75.4 [56.2] µmol/g, P = 0.02) and significantly lower median fecal ammonia concentrations (26.2 [14.7] vs 33.4 [18.5] µmol/g, P = 0.04) than the low-SCFA diet. Plasma propionate (9.87 [12.3] vs 4.72 [7.6] µmol/L, P = 0.049) and butyrate (2.85 [1.35] vs 2.02 [1.29] µmol/L, P = 0.03) were significantly higher after high-SCFA diet than after low-SCFA diet. Blood total B cells (184 [112] vs 199 [143] cells/µL, P = 0.04), naive B cells (83 [66] vs 95 [89] cells/µL, P = 0.02), Th1 cells (22 [19] vs 29 [16] cells/µL, P = 0.03) and mucosal-associated invariant T (MAIT) cells (62 [83] vs 69 [114] cells/µL, P = 0.02) were significantly lower after high-SCFA diet than low-SCFA diet. CONCLUSION: Increasing colonic and peripheral blood SCFA has discrete effects on circulating immune cells in healthy humans following 3-week intervention. Further studies, e.g., in patients with inflammatory disease, are necessary to determine if these changes have immunomodulatory effects, whether these are therapeutically beneficial, and whether prolonged intake might be required. Clinical trial registry: Australian New Zealand Clinical trials registry: ACTRN12618001054202. <https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375342&isReview=true>.

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