Natural probiotic present in gut shortly after birth

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Sep 10 2024

Newborn babies harbor pioneer bacteria in the gut shortly after birth with the potential to develop new personalized therapeutic probiotics

In a recent study in Nature Microbiology, researchers characterized the gut microbiome of 1,288 United Kingdom (UK) neonates using large-scale fecal metagenomics.

Background

Human gut microbiome colonization begins at birth and is affected by environmental and maternal factors. The United Kingdom Baby Biome Study (BBS) discovered that maternal transfer of primary gut colonizers is altered in cesarean sections and newborns with antibiotic exposure, exposing neonatal gut microbes to antibiotic-resistant organisms.

The study implies 'priority effects' in human intestinal microbiome assembly, in which the arrival sequence of initial colonizer species impacts microbiome assembly during primary biological succession. However, limited research concerning the priority effects among neonatal gut microbiomes exists due to scarce longitudinal, high-resolution human gut microbiome data.

About the study

In the present study, researchers investigated the effects of microbial priority on neonatal gut microbiota (NGM). They increased the first phase of their BBS study (BBS1) cohort by 688 neonates in the second phase (BBS2), almost doubling the sampling effort.

The study included healthy, full-term newborns. Parents collected their fecal samples at home in the first three weeks of life (day 4, week 1, and week 3) and later in infancy. Researchers obtained maternal fecal samples at the hospital around the time of delivery. When they collected stool samples, mothers filled out a brief form about their feeding habits and antibiotic exposure. Whole-genome sequencing evaluated the samples using the Genome Taxonomy Database (GTDB).

The researchers examined three BBS2 subgroups: 183 newborn-mother dyads (14% of study participants), 359 neonatal phase samples (28%), and 302 neonatal and infancy samples (23%). Partitioning around medoids (PAM) clustering on 1,904 BBS neonatal gut metagenomes identified the key colonizers driving gut microbial community structure throughout the newborn era. The Dirichlet multinomial mixture (DMM) approach validated the results.

Researchers used 1,249 high-quality isolates (N = 133) and metagenome-assembled genomes from the associated community state samples to identify functional differences among NGM community states. Multivariable fixed-effect logistic regressions determined the adjusted odds ratios (AOR), controlling for potential confounders. Sensitivity analysis showed characteristics linked with the NGM community state that changed between weeks one and three.

Researchers created mono-colonized gnotobiotic lines of wild-type C57BL/6N mice via oral gavage and daily exposure to 2′-fucosyllactose (2′-FL) in drinking water. They obtained murine fecal samples for colony count, and quantitative polymerase chain reaction (qPCR) determined the absolute bacterial load. The researchers infected the mice with opportunistic pathogens, E. faecalis or K. oxytoca.

Results

The team divided the NGM into three states. A particular microbe dominated each state. Host and clinical variables such as mother age, parity, and ethnicity regulated these states. Asian mothers were more likely than White mothers to develop BB (AOR, 2.1) but less likely to contain EF (AOR, 0.6). The community state with E. faecalis predominance exhibited stochastic microbiome assembly and persistently elevated pathogen burdens into infancy.

Contrastingly, Bifidobacterium-dominated community states, namely Bifidobacterium longum and B. breve, demonstrated stable microbiome assemblies with long-term microbial colonization resistance, likely resulting from functional adaptations in specific strains to breastmilk-rich neonatal diets. DMM and PAM methods yielded consistent results on community state allocations and core microbe compositions. The community states were present across all sampling periods among BBS participants. The findings indicate that B. breve, B. longum, and E. faecalis dominate early life in newborns.

B. longum and E. faecalis displayed more microbial diversity, whereas other moderately numerous species coexisted with the driving species. The development of an E. faecalis community state was independently associated with having a cesarean delivery and receiving intrapartum antibiotics during labor. Bifidobacterium breve was the only community state impacted by host characteristics but unaffected by clinical factors. B. breve genomes have the enzyme required to metabolize the most prevalent HMO component, 2′-FL, which is rare in BL (5.0%) and lacking in E. faecalis.

The study found that the newborn gut microbiota separated into three community states, each dominated by a particular microbial species. The team found Bifidobacterium breve, B. longum subs. longum, and E. faecalis as taxonomic drivers in each state.

Consistent with the human observation, Bifidobacterium breve exhibited priority effects with resistance to pathogen colonization in the mouse model, emphasizing the importance of Bifidobacteria species as primary gut colonizers in influencing microbiome organization and function during early life. Primary colonizer species succession influences the formation of the newborn gut microbiota, as do prenatal and perinatal variables.

The study proposes a logical species selection strategy for baby interventional studies and next-generation therapies.