Short-chain fatty acids (SCFA) in infants' plasma and corresponding mother's milk and plasma in relation to subsequent sensitisation and atopic disease

Abstract

Background: Short-chain fatty acids (SCFAs) in intestinal contents may influence immune function, while less is known about SCFAs in blood plasma. The aims were to investigate the relation between infants' and maternal plasma SCFAs, as well as SCFAs in mother's milk, and relate SCFA concentrations in infant plasma to subsequent sensitisation and atopic disease.

Methods: Infant plasma (N = 148) and corresponding mother's milk and plasma were collected four months postpartum. Nine SCFA (formic, acetic, propionic, isobutyric, butyric, succinic, valeric, isovaleric, and caproic acid) were analysed by UPLC-MS. At 12 months of age, atopic disease was diagnosed by a pediatric allergologist, and sensitisation was measured by skin prick test. All families participated in the Swedish birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment).

Findings: Infants with sensitisation, atopic eczema, or food allergy had significantly lower concentrations of five, three, and two SCFAs, respectively, in plasma at four months. Logistic regressions models showed significant negative associations between formic, succinic, and caproic acid and sensitisation [OR_adj (95% CI) per SD: 0.41 (0.19-0.91); 0.19 (0.05-0.75); 0.25 (0.09-0.66)], and between acetic acid and atopic eczema [0.42 (0.18-0.95)], after adjusting for maternal allergy. Infants' and maternal plasma SCFA concentrations correlated strongly, while milk SCFA concentrations were unrelated to both. Butyric and caproic acid concentrations were enriched around 100-fold, and iso-butyric and valeric acid around 3-5-fold in mother's milk, while other SCFAs were less prevalent in milk than in plasma.

Interpretation: Butyric and caproic acid might be actively transported into breast milk to meet the needs of the infant, although mechanistic studies are needed to confirm this. The negative associations between certain SCFAs on sensitisation and atopic disease adds to prior evidence regarding their immunoregulatory potential.

Funding: Swedish Research Council (Nr. 2013-3145, 2019-0137 and 2023-02217 to A-S.S.), Swedish Research Council for Health, Working Life and Welfare FORTE, Nr 2018-00485 to A.W.), The Swedish Asthma and Allergy Association's Research Fund (2020-0020 to A.S.).

Keywords: Atopic eczema; Breast milk; Food allergy; Infant/maternal plasma; Sensitisation; Short-chain fatty acids.

Fig. 1

Median concentrations (μmol/L) of short-chain fatty acid (SCFA) concentrations in infant plasma (white bars, N = 148), maternal plasma (striped bars, N = 142), and breast milk (black bars, N = 128). Error bars, 95% CI.

Fig. 2

Correlations between maternal plasma and breast milk and infant plasma concentrations of individual SCFAs (Spearman’s rank correlation). Red color denotes a positive correlation; blue color denotes a negative correlation. Number of samples: breast milk vs. maternal plasma, N = 125; breast milk vs. infant plasma, N = 128; maternal plasma vs. infant plasma, N = 142. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001. Rho and p-values are specified in Supplemental Table S2.

Fig. 3

Spearman correlations between dietary intake and SCFAs in maternal plasma and breast milk. Food intake was assessed to reflect maternal intake between 3 and 4 months postpartum. Significant correlations are denoted with asterisks as p < 0.001 = ∗∗∗, p < 0.01 = ∗∗, and p < 0.05 = ∗. The red color indicates a positive correlation. The blue color denotes a negative correlation.

Fig. 4

Distribution of atopic conditions of the infants who were included in the statistical calculations.

Fig. 5

Difference in SCFA concentrations in plasma at four months of age in those who were sensitised at 12 months of age (N = 11) compared to infants who were non-allergic and non-sensitised at 12 months of age (N = 109). Allergic sensitisation was defined as a positive skin prick test (>3 mm) to at least one allergen. The following SCFA concentrations did not differ significantly between the groups and are therefore not displayed: acetic acid, propionic acid, butyric acid, and isovaleric acid. Differences in SCFA concentrations were measured with Mann–Whitney U-test.

Fig. 6

Difference in SCFA concentrations in infant plasma between infants with food allergies (N = 14, upper part) or atopic eczema (N = 19, lower part) and non-allergic, non-sensitised infants (N = 109). The following SCFA concentrations did not differ significantly between the groups and are therefore not displayed: formic acid, propionic acid, butyric acid, isovaleric acid, and caproic acid. Differences in SCFA concentrations were measured with Mann–Whitney U-test.