Influence of Singular First Foods on the Infant Gut Microbiome: A Randomized Controlled Trial

The gastrointestinal microbiome, integral to immune function, inflammation, and metabolism, becomes less malleable with age, making early dietary exposures, particularly first complementary foods (CFs), important in its development.

This study aimed to evaluate the effect of different first CFs on the infant gut microbiome in a pilot, randomized, controlled trial.

Vaginally delivered, exclusively human milk (HM) fed infants (n = 43) with no prior CF exposure were randomized to 1 of 4 groups (oatmeal cereal, beef, carrot, or prune) (NCT05492253). Infants were fed the randomized food (with HM) for 1 wk (phase 1), followed by oatmeal cereal for another week (phase 2). Daily stool samples were collected and sequenced (full-length V1-V9 16S rRNA gene amplicons).

In phase 1, oatmeal cereal increased observed amplicon sequence variants compared with beef (P = 0.024). Prune increased Bacteroides ovatus (P = 0.001) and Klebsiella pneumoniae (P = 0.011), whereas oatmeal cereal increased Enterococcus spp. (P = 0.030) relative to beef. In phase 2, oatmeal cereal following beef resulted in increased Shannon diversity (P = 0.0497) and following prune increased Faith's phylogenetic diversity (P = 0.015). Unweighted UniFrac distances differed when oatmeal cereal followed prune compared with continuing oatmeal cereal (P = 0.042). Veillonella infantium increased with continued oatmeal cereal consumption compared with beef (P = 0.002) or carrot (P = 0.002), followed by oatmeal cereal. After prune, oatmeal cereal increased Lactobacillus rhamnosus and Enterococcus faecalis, and decreased K. pneumoniae and Clostridium neonatale (all P < 0.05).

Beef as a CF is nutritionally desirable as it contains important minerals lacking in HM, yet resulted in a less diverse microbial profile. Because fruit and vegetables yielded comparable diversity to cereals, future research should investigate whether introducing meat alongside fruits and vegetables offers a balanced alternative to early reliance on cereals and further evaluate how first foods influence taxa abundance at the genus and species level and the resulting immune-related and metabolic pathways. This trial was registered in clincaltrials.gov as NCT05492253.