Unfavourable intrauterine environment contributes to abnormal gut microbiome and metabolome in twins

Abstract

ObjectiveFetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes.DesignWe profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up.ResultsAdverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances of Enterococcus and Acinetobacter and downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants.ConclusionDysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.

The interplay of gut microbiota between donors and recipients determines the efficacy of fecal microbiota transplantation

“…Stool samples were collected from patients and donors in sterilized Eppendorf tubes and stored at −80°C. 59 These samples were used to extract microbial DNA for sequencing. The V4–V5 region of the bacterial 16S rRNA gene was amplified using Phusion High-Fidelity PCR Master Mix with HF buffer (New England Biolabs, England) and then sequenced on the Illumina MiSeq platform (Illumina, Inc.) using standard Illumina sequencing protocols.…”

Changes in the Gut Microbiome and Pathologies in Pregnancy

“…A study of 150 pairs of twins using 16S ribosomal RNA and metagenomic sequencing showed a correlation between increased bacterial diversity early in life and intrauterine FGR in twins. A reduction in Enterococcus and Acinetobacter numbers was observed in twin-born FGR infants and there was a lowering in the level of methionine and cysteine in stool samples taken after birth and after 2–3 years of follow-up [ 66 ]. It is also suspected that the level of cysteine in the stool may be correlated with the future physical development of the child [ 66 ].…”

“…A reduction in Enterococcus and Acinetobacter numbers was observed in twin-born FGR infants and there was a lowering in the level of methionine and cysteine in stool samples taken after birth and after 2–3 years of follow-up [ 66 ]. It is also suspected that the level of cysteine in the stool may be correlated with the future physical development of the child [ 66 ]. Oscillospira and Coprococcus participate in the synthesis of butyrate, which is an energy source for the epithelial cells of the small intestine, regulating glucose metabolism and reducing inflammation in the organism [ 67 ].…”

“…Oscillospira and Coprococcus participate in the synthesis of butyrate, which is an energy source for the epithelial cells of the small intestine, regulating glucose metabolism and reducing inflammation in the organism [ 67 ]. The study by Yang’s team showed an increased number of the above-mentioned butyrate markers in twins with FGR, which may compensate for intrauterine malnutrition [ 66 ]. By sequencing the 16S rDNA amplicon collected from pregnant women with FGR and the control group, stool samples showed significant differences in the growth of Bacteroides, Faecalibacterium and Lachnospira in patients with FGR [ 68 ].…”

Impacts of Delivery Mode and Maternal Factors on Neonatal Oral Microbiota

“…However, the properties of the microbiota of humans were largely a black box ( Cho and Blaser, 2012 ). And human symbiotic microbiota had a vital effect on the early and long-term neonatal physiological consequences ( Al-Shehri et al, 2016 ; Fujimura et al, 2016 ; Yang et al, 2022 ). For instance, the dysbiosis of the neonatal gut microbiome encouraged immune cell dysfunction related to childhood atopy ( Fujimura et al, 2016 ).…”