The gut microbiota from the general population during the first year of life

Abstract

The human gut microbiota consists of a complex community of microorganisms with bacteria as the major resident. Their role in the gut can be viewed as an extension of our genes and is often compared to a human organ. The gut bacterial community follows us from birth and throughout our lives and has an implied role in maintaining our health. Therefore, understanding factors that drive the early colonization is of great importance. As most studies are based on selected cohorts, there is still a lack of knowledge for the general population. The aim of this thesis was to fill the knowledge gaps related to the establishment of the gut bacteria, and the temporal changes during infancy in a general population. To address this aim, we analyzed biological samples from a subset of the 2400 motherchild pairs from the PreventADALL study. In total, we analyzed longitudinally collected biological samples from 244 mother-child pairs. Fecal samples were collected from mothers at 18 weeks of gestation, and their infants longitudinally (first fecal sample, at 3 months, 6 months, and 12 months of age), in addition to skin swabs of infants taken immediately after birth from 144 infants. These samples were analyzed for different marker genes (16S rDNA and RpoB), metagenome sequencing on subsets of infant samples (whole and reduced), in addition to metaproteomics and metabolomics on infant sample subsets. From our observations, the presence of Bacteroides in meconium, and on the infant skin was dependent on birth mode. Vaginal born infants had Bacteroides as a prominent member of the early gut community. Of the detected Bacteroides, two maternal dominant strains were prevalent in the infant samples and persisted as a gut bacterial member to at least 3 months of age. We identified a potentially globally distributed B. caccae strain, and a potential local strain of B. vulgatus. Moreover, based on the bacterial genomic content from the samples, diet seem to play a role in shaping the early gut microbiota. The gut bacterial community’s potential ability for nutrient utilization was skewed towards simple sugars, oligosaccharides, and mucins during early infancy, while this switched towards dietary components with the increasing infant age. The shift from breastmilk feeding to a diet consisting of solid foods was observed to increase the abundance of Clostridium and decline the Bifidobacterium. The combination of the diet- and bacterial shift was observed to have an effect on the fecal short-chain fatty acid propionate, and butyrate. We observed two gut community states during the transition from an infant- to an adult-like gut microbiota, represented by high and low fecal butyrate. Within this cohort, we observed that E. rectale and F. prausnitzii are potential key bacterial members for the increased butyrate production, while infants with low fecal butyrate associated with R. gnavus.

Tarmmikrobiotaen hos mennesker er sammensatt av et komplekst samfunn av mikroorganismer, hvor bakterier utgjør majoriteten. Rollen deres i tarmen kan bli sett på som en ekstensjon av våre gener, og blir ofte sammenliknet med et menneskelig organ. Sammensetningen av bakterier i tarmen følger oss fra fødselen og gjennom hele livet, og har blitt implisert i å spille en viktig rolle for å opprettholde vår helse. Derfor er det viktig å forstå faktorer som driver den tidlige koloniseringen. De fleste studier er basert på selekterte kohorter, og det er derfor mangel på kunnskap for den generelle populasjonen. Målet for denne oppgaven var å undersøke etableringen av tarmbakterier, og følge denne utviklingen over tid i en generell populasjon. For å nå dette målet analyserte vi biologiske prøver på en delmengde av de 2400 mor-barn parene fra PreventADALL studien. Totalt analyserte vi biologiske prøver samlet kontinuerlig fra 244 mor-barn par. Avføringsprøver ble samlet fra mødre 18 uker inn i svangerskapet, og deres barn (den første avføringsprøven, ved 3 måneder, 6 måneder, og 12 måneder), i tillegg til svaberprøver tatt fra den nyfødtes hud rett etter fødsel av 144 spedbarn. Disse prøvene ble analysert for markørgener (16S rDNA og RpoB), metagenomsekvensering på en mindre del av barna (hel- og redusert), i tillegg til metaproteomikk og metabolomikk på noen utvalgte barn.