Abstract
BACKGROUND: Chemokine (C-C motif) ligand 17 (CCL17; also known as thymus
and activation-regulated chemokine or TARC) is a pro-allergic factor,
and high CCL17 levels in cord blood (CB) precede the allergic
predisposition later in life. Offspring of pregnant mice treated with
short-chain fatty acid (SCFA) have been shown to be protected against
allergic diseases. The maternal microbial metabolome during pregnancy
may affect foetal allergic immune responses. To examine this, the
associations between CB CCL17 and gut SCFA levels in pregnant Japanese
women were investigated here. METHODS: This study was conducted as part
of the Chiba Study of Mother and Child Health; 434 healthy pregnant
women were recruited. The CB CCL17 and maternal non-specific IgE levels
were measured using CB sera at birth and maternal sera at 32 weeks of
gestation. Stool samples were collected from pregnant women at 12 (n =
59) and 32 (n = 58) weeks of gestation and used for gut microbiota
analysis, based on barcoded 16S rRNA sequencing and metabolite levels.
RESULTS: The CB CCL17 levels correlated negatively with butyrate
concentrations at 12 weeks of gestation. In contrast, CB CCL17 levels
correlated positively with isobutyrate levels at 12 weeks of gestation,
and valerate and lactate concentrations at 32 weeks of gestation in
maternal faeces. CONCLUSION: The metabolites in maternal faeces may
alter the foetal immune responses. This study provides the first link
between maternal metabolites during pregnancy and the risk of allergic
diseases in human offspring, even before birth.