Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential

Abstract

The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. We link these enriched functions to individual-specific strains, which are transmitted from mothers to neonates in case of VD. The stimulation of primary human immune cells with LPS isolated from early stool samples of VD neonates results in higher levels of tumour necrosis factor (TNF-α) and interleukin 18 (IL-18). Accordingly, the observed levels of TNF-α and IL-18 in neonatal blood plasma are higher after VD. Taken together, our results support that CSD disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming.

The urgent need for microbiology literacy in society

“…Microbes can impact on our lives in so many ways and are thus relevant to many personal decisions we take, such as whether to give birth by caesarean (aseptic) or natural delivery (colonization of the newborn by maternal microbes; Wampach et al, 2018), breast-feed [delivery to the baby of protective antibodies against pathogens, human milk oligosaccharides favouring bifidobacteria thought to orchestrate healthy development of immune systems (Gomez de Agüero et al, 2016;Moossavi et al, 2018), maternal microbes present in breast milk, etc. (Milani et al, 2017)], frequently use powerful disinfectants to clean the home (reduce exposure of infants to microbiome diversification and its health benefits: Finlay and Arrieta, 2016;Gilbert and Yee, 2016;Bach, 2018;Sharma and Gilbert, 2018; or indeed hospitals: see Caselli, 2017), be vaccinated or treated for an infection (Lane et al, 2018), use phosphorus-containing household cleaning products (Richards et al, 2015; can contribute to eutrophication and harmful algal blooms in local waters), use germicidal soaps (can cause dysbiosis of skin microbiota; Gilbert and Yee, 2016), acquire a companion dog (facilitates microbiota exchanges, Trinh et al, 2018; increases phosphorus inputs into the watershed, Hobbie et al, 2017) or what food to eat (e.g., beef, which has a substantial methane footprint; beef and dairy products whose consumption is correlated with cancers, zur Hausen et al, 2017; other meats and vegetables: provenance, shelf-life, associations with known risk factors, etc.)…”

Breast milk-derived human milk oligosaccharides promote Bifidobacterium interactions within a single ecosystem

“…The early-life developmental window represents a critical time for microbe-host interactions as this is when foundations for future health and well-being are established. Colonisation of pioneer microbes shortly after birth represents a key first step in this mutualistic relationship; shaping the developing microbial community, and in turn impacting numerous host physiological processes [1][2][3][4][5]. Although the microbiota of adults is complex in nature, the gastrointestinal (GI) tract of full-term healthy infants is relatively simplistic, dominated by the genus Bifidobacterium that can persist into early childhood [3,6].…”

The association between caesarean section delivery and later life obesity in 21-24 year olds in an Urban South African birth cohort

“…It has been suggested that infants born via VD are exposed mainly to microorganisms in the birth canal or vaginal environment, and that those delivered by CS are exposed to micro flora on their mother’s skin [43–45]. The abundance of Coprococcus and Ruminococcus of the family Lachnospiraceae was also reported by Tun et al (2018) in infants delivered through CS – signifying dysbiosis in early life [44].…”