Characteristics of gut microbiota of term small gestational age infants within 1 week and their relationship with neurodevelopment at 6 months

Abstract

IntroductionSmall for gestational age (SGA) infants are at a higher risk of neurodevelopmental delay than infants appropriate for gestational age (AGA). Previous studies have confirmed that gut microbiota in early life influences subsequent neurodevelopment. However, few studies have reported corresponding data in SGA populations.ObjectiveWe aimed to evaluate the characteristics of the gut microbiota of term SGA infants and the associations between the gut microbiota in SGA infants and neurodevelopmental outcomes at 6 months of age.MethodsFecal samples were collected on days 1, 3, 5, and 7 from term SGA and AGA infants born between June 2020 and June 2021 at the Peking University First Hospital. 16S ribosomal deoxyribonucleic acid amplicon sequencing was used to analyze the fecal microbiota. We followed up for 6 months and used the Ages and Stages Questionnaires-3 (ASQ-3) to evaluate the neurodevelopmental outcomes among SGA infants.ResultsA total of 162 neonates were enrolled, with 41 SGA infants (25.3%) in the study group and 121 AGA infants (74.7%) in the control group. The gut microbial diversity in the SGA group was lower than that in the AGA group on days 1, 3, 5, and 7. Non-metric multidimensional scaling and analysis of similarities showed significant differences between the two groups. The SGA group had increased relative abundances of Ralstonia (3, 5, and 7 days) and Clostridium (3 and 7 days). The dominant microorganisms of the SGA group were Ralstonia on day 1, Escherichia_Shigella on days 3 and 7, and Clostridia on day 5. We found that the gut microbial diversity of SGA infants with poor communication scores was higher than that of SGA infants with good communication scores on day 3. Fine motor scores were negatively correlated with the relative abundance of Bacteroides_fragilis on day 1. A negative correlation was observed between gross motor scores and relative abundance of Clostridium_saccharobutylicum on day 7. Bacteroidota, Bacteroidia, Bacteroides, and Bacteroides_fragilis were the dominant microorganisms in the good communication score group on day 7. Communication scores were positively correlated with the relative abundance of Bacteroidota, Bacteroides, and Bacteroides_fragilis on day 7.ConclusionThe gut microbial diversity of term SGA infants was significantly lower in the first week of life than that of term AGA infants. Certain pathogenic and conditional pathogenic bacteria, such as Escherichia_Shigella, Ralstonia and Clostridium increased or formed the dominant microbiota in SGA infants. Alpha diversity, Bacteroidota, Bacteroides, Bacteroides_fragilis, and Clostridium_saccharobutylicum found in SGA infants may be associated with neurodevelopmental outcomes at 6 months of age, indicating possible therapeutic targets for clinical intervention.

Intestinal flora and linear growth in children

“…In SGA newborns, certain pathogenic and conditional pathogenic bacteria, such as Shigella , Ralstonia , and Clostridium , increased or became the dominant microbiota. Bacteroides fragilis and Clostridium saccharobutylicum were detected in SGA newborns and may be linked to neurodevelopmental outcomes at 6 months ( 44 ).…”

“…Lactobacillus and Bifidobacterium have been shown to promote fetal growth, but pathogenic bacteria such as Shigella , Ralstonia , and Clostridium have been found to inhibit baby growth ( 29 , 39 ). Furthermore, particular early-life microbes such as Bacteroides fragilis and Clostridium saccharobutylicum are important for offspring brain development, which can affect baby health and long-term health ( 44 ). As a result, sensible treatments to change maternal or offspring microbiome from pregnancy to early childhood have significant implications for offspring health.…”

“…The microbiome of newborns born via cesarean section is mostly derived from the mother's skin and the hospital environment ( 85 ). The most important factors influencing prenatal growth and development are prenatal weight gain ( 28 – 30 ), premature birth ( 31 , 38 , 39 ), and being small for gestational age ( 41 , 44 ). According to research, these elements are linked to the creation and features of newborn gut flora.…”

“…Table 4 illustrates the clinical studies on intestinal microbiota and child growth in this review based on the cities/countries where the research was conducted, as well as the research methodology used, characteristics of the included populations, and main conclusions. Currently, the countries and regions undertaking study on this topic are primarily centered in Europe ( 28 – 30 , 37 , 38 , 45 , 47 , 54 , 57 ), the United States ( 33 , 43 , 46 , 48 , 51 , 56 ), and China ( 39 , 44 , 53 , 62 , 76 ), with Africans, Bangladeshis, Europeans, and Chinese being the primary research subjects recruited. The primary areas of study are premature birth, intrauterine growth retardation, environmental sanitation, malnutrition, and so on.…”

The Molecular Gut-Brain Axis in Early Brain Development

“…The infant acquires a new microbial family due to changes in the gut microbiota and brain developmental stages. Recent study found that a lower gut microbial diversity was associated with a higher risk of neurodevelopmental delay for the small for gestational age (SGA) infants compared with the appropriate for gestational age (AGA) infants [ 56 ].…”