Nationwide cohort study reveals low bifidobacteria and distinct microbiota composition and function in Swedish newborns

In a nationwide study (PREVENT) addressing the longitudinal development of 253 infants in Sweden (744 stool samples), we used deep metagenomic sequencing to determine the bacterial composition. We focused on the 200 fecal samples collected during the first 6 months of life from 146 infants who were predominantly breast-fed. Unsupervised analysis of these infants’ microbial gut composition revealed three distinct foundational community types: CT1 infants had high Bifidobacterium spp. levels, CT2 infants had only B. breve at low abundances but high Bacteroidota, and CT3 infants had virtually no Bifidobacterium spp. but elevated levels of pathobionts. Surprisingly, we observed a clear bimodal distribution of Bifidobacterium spp., the canonical taxa associated with early-life colonization. Sixty samples from predominantly (58%) vaginally-born infants did not contain any detectable gut Bifidobacterium genomes (<0.001%; confirmed by 16S rRNA amplicon sequencing and qPCR analysis). The remaining 140 samples showed high relative Bifidobacterium abundance (median 70%), notably including B. breve, B. longum subsp. longum and B. longum subsp. infantis. Infants lacking Bifidobacterium spp. showed crying after feeding and contained an unusual gut microbiota composition, dominated by known pathobionts such as Clostridium neonatale or Klebsiella michiganensis. The metagenome-based predicted functional capacity of the gut of infants lacking Bifidobacterium spp. showed an increased levels of potentially undesired genes involved in mucus degradation, sporulation processes, and flagella production, while the Bifidobacterium-colonized infants were enriched in starch degradation, glutamate transport, and aromatic amino acid production. Notably, we found that a pathway for the production of lactate derivatives of tryptophan and other aromatic amino acids with anti-inflammatory activity was more abundant in the latter group. Our results indicate that infants lacking Bifidobacterium spp. contain unusual gut microbiota architecture and functions that are associated with health issues. This pattern is more prevalent in PREVENT than observed in many other studies, underscoring the importance of early testing, while long-term follow-up and potential nutritional advice should be addressed in future studies.Clinical Trials NCT06285630.