Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types

Abstract

The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed "settler types", based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/ or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked. PLOS ONE | https://doi.org/10.1371/journal.pone.0228133 February 5, 2020 1 / 15 OPEN ACCESS Citation: Eck A, Rutten NBMM, Singendonk MMJ, Rijkers GT, Savelkoul PHM, Meijssen CB, et al. (2020) Neonatal microbiota development and the effect of early life antibiotics are determined by two distinct settler types. PLoS ONE 15(2): e0228133.

The Relationship between the Infant Gut Microbiota and Allergy. The Role of Bifidobacterium breve and Prebiotic Oligosaccharides in the Activation of Anti-Allergic Mechanisms in Early Life

“…In the long term, antibiotic therapy in infants and young children may have a significant impact on the process of microbiota development and on microbial programming of anti-allergic mechanisms later in life [29,30]. Table 1 presents a summary of studies showing the effect of antibiotic exposure in perinatal and early post-natal periods on the composition of intestinal microbiota [26,[31][32][33][34][35][36][37][38]. Studies in children from the age of 0 to 3 years showed that the microbiota of antibiotic-treated children was less diverse, with a lower abundance of the phylum Actinobacteria (with the genus Bifidobacterium), the genus Lactobacillus, Bacteroides, and had fewer stable bacterial communities in comparison with that in untreated children [38].…”

Transient neonatal antibiotic exposure increases susceptibility to late-onset sepsis driven by microbiota-dependent suppression of type 3 innate lymphoid cells

“…Establishment of the microbiome during the neonatal period depends on multiple factors, including mode of delivery, breast versus formula feeding, gestational age, infant hospitalization, maternal diet and antibiotic use by the infant 14 , 15 . While antibiotics are beneficial for treating human bacterial infections, even short regimens can impact human gut microbial populations 16 – 18 and prolonged broad-spectrum antibiotic therapy can significantly alter the normal balance of beneficial bacteria 19 .…”

“…short regimens can impact human gut microbial populations [16][17][18] and prolonged broad-spectrum antibiotic therapy can significantly alter the normal balance of beneficial bacteria 19 .…”

Neonatal intestinal dysbiosis

“…Exposure to intrapartum antibiotics for prevention of Group B streptococcal sepsis and/or due to cesarean section is extremely common and impacts the neonatal intestinal microbiota [ 47 , 48 ]. In addition to antibiotics [ 49 ], other medications commonly administered to mothers and/or infants that alter the intestinal microbiota include acid blocking agents [ 50 , 51 ], selective serotonin reuptake inhibitors, metformin and laxatives [ 52 , 53 ]. Recent demonstrations of altered infant microbiota with exposure to environmental toxins [ 54 , 55 ], maternal smoking [ 56 ], and proximity to furry animals [ 42 , 57 ] underscore the many factors affecting this community.…”

“…In very preterm infants, the primary determinants of the composition of the intestinal microbiota are the post-menstrual age and age in weeks [ 34 , 35 ], however, multiple other factors are also influential including antenatal corticosteroids, mode of delivery, antibiotic exposure, feeding type, feeding tube dwell time and biofilms, gender, and stress [ 58 – 61 ]. Table 1 presents several examples of alterations in the infant fecal microbiota related to perinatal exposures [ 43 , 47 – 49 , 56 , 57 , 60 , 62 – 67 ].…”