Fecal short-chain fatty acids in young children and their mothers are not associated with progression to islet autoimmunity

<jats:p>&lt;p dir="ltr"&gt;Objective: Reduced microbial short-chain fatty-acids (SCFA) have been implicated in type-1-diabetes (T1D) risk. We investigated fecal SCFA concentrations in mother-infant dyads from pregnancy to the onset of islet autoimmunity (IA) to test whether decreased fecal SCFA concentrations increase islet autoimmunity (IA) risk.&lt;/p&gt;&lt;p dir="ltr"&gt;Research design and methods&lt;/p&gt;&lt;p dir="ltr"&gt;Children with a first-degree relative with T1D and their mothers were followed in the Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort study. A nested case-control design included n=54 infant-cases that developed  1 persistent islet autoantibodies/clinical T1D and n=161 age- and sex-matched controls without IA. Stool (n=1120 samples) from each pregnancy trimester in mothers (median n=2 samples) and from birth in infants (median n=6 samples) up until IA onset were used to quantify SCFAs by LC/MS. Weighted-conditional logistic-regression and linear mixed-effect models investigated associations between SCFAs and IA-onset.&lt;/p&gt;&lt;p dir="ltr"&gt; Results&lt;/p&gt;&lt;p dir="ltr"&gt;Fecal SCFAs were not associated with IA-onset, and SCFA profiles through pregnancy and early-childhood were similar between cases and controls. Infant fecal SCFA concentrations increased until age 1 year. Introduction of solid foods significantly increased acetate (FDR=0.000028) and summed primary SCFA (FDR=0.00784) concentrations. Higher infant BMI z-scores correlated with higher fecal acetate (FDR=0.0767) and butyrate (FDR=0.0590). Mothers with T1D had lower acetate (FDR=0.0696), butyrate (FDR=0.0959) and propionate (FDR=0.0696) than mothers without T1D during pregnancy. Concentrations of these three SCFA were lower in infants of mothers with versus without T1D (FDR=0.0073, FDR=0.0603, 0.0479, respectively). &lt;/p&gt;&lt;p dir="ltr"&gt;Conclusion&lt;/p&gt;&lt;p dir="ltr"&gt;These data do not support that lower fecal SCFA concentrations across pregnancy and early-life are directly associated with IA development. &lt;/p&gt;&lt;p&gt;&lt;br&gt;&lt;/p&gt;</jats:p>