Gut microbiota responses to complementary food sources differ by milk feeding type

Early-life nutrition shapes host-microbe interactions with lasting consequences for health. While dietary patterns are known to influence the infant gut microbiome, the impact of solid food source (homemade, commercial, or mixed) has not been examined. Our aims were to determine how solid food source at 6 months relates to infant gut microbiome diversity and composition at 1 year, and whether relationships differ by milk feeding type..

We conducted a secondary analysis within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Solid food source was assessed at 6 months, and stool samples at 1 year were profiled using 16S rRNA sequencing. Generalized linear models were used to assess alpha-diversity; permutational multivariate analysis of variance (PERMANOVA) was used to evaluate beta-diversity based on OTU-level Bray-Curtis dissimilarities; and Microbiome Multivariate Association with Linear Models 2 (MaAsLin2), using centered log-ratio normalization, was used to examine taxa-level associations, adjusting for relevant perinatal and dietary covariates. Effect modification by milk feeding type (human milk, formula, combination, or weaned) at 6 months and 1 year was examined. Benjamini-Hochberg correction was applied (p < 0.05; q < 0.25).

A total of 368 infants were included. At 6 months, most were mixed-fed (n = 154; 41.8 %), followed by homemade-fed (n = 143; 38.9 %) and commercially-fed (n = 71; 19.3 %). Solid food source explained only 0.53 % of gut microbiota variability. Differences were most pronounced in formula-fed infants: at 6 months, those given homemade or mixed foods showed higher abundances of Firmicutes, Turicibacteraceae, and Turicibacter compared with commercially fed infants. Within this group, mixed feeding was further linked to higher Eubacteriaceae and Lachnospiraceae (all q < 0.25). At 1 year, formula-fed infants who received homemade foods had higher microbial diversity (p = 0.028) but lower Shannon diversity (p = 0.041) than those receiving commercial foods, suggesting shifts in both community richness and evenness. No significant differences in gut microbiome diversity and composition were observed in the overall cohort or among infants receiving human milk or fully weaned (q > 0.25).

Solid food source is a previously under-investigated driver of infant microbiome variability, with effects contingent on milk feeding. Human milk may buffer against dietary choices, whereas formula-fed infants show heightened sensitivity to complementary food source, informing precision nutrition in early life.