Investigating prenatal and perinatal factors on meconium microbiota: a systematic review and cohort study.

BACKGROUND: The first-pass meconium has been suggested as a proxy for the fetal gut microbiota because it is formed in utero. This systematic review and cohort study investigated how pre- and perinatal factors influence the composition of the meconium microbiota. METHODS: We performed the systematic review using Covidence by searching PubMed, Scopus, and Web of Science databases with the search terms "meconium microbiome" and "meconium microbiota". In the cohort study, we performed 16 S rRNA gene sequencing on 393 meconium samples and analyzed the sequencing data using QIIME2. RESULTS: Our systematic review identified 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition in relation to subsequent health of infants but gave only limited comparative evidence regarding factors related to the composition of the meconium microbiota. The cohort study pointed to a low-biomass microbiota consisting of the phyla Firmicutes, Proteobacteria and Actinobacteriota and the genera Staphylococcus, Escherichia-Shigella and Lactobacillus, and indicated that immediate perinatal factors affected the composition of the meconium microbiota more than did prenatal factors. CONCLUSIONS: This finding supports the idea that the meconium microbiota mostly starts developing during delivery. IMPACT: It is unclear when the first-pass meconium microbiota develops, and what are the sources of the colonization. In this systematic review, we found 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition relative to subsequent health of infants, but there was no consensus on the factors affecting the meconium microbiota development. In this cohort study, immediate perinatal factors markedly affected the meconium microbiota development while prenatal factors had little effect on it. As the meconium microbiota composition was influenced by immediate perinatal factors, the present study supports the idea that the initial gut microbiota develops mainly during delivery.

Development of gut mycobiome in infants and young children: a prospective cohort study.

BACKGROUND: The composition of the gut fungal microbiome, mycobiome, is likely associated with human health. Yet, the development of gut mycobiome is poorly understood in infants and children. Here we investigate how perinatal events influence the development of gut mycobiome. METHODS: In this prospective cohort study of 140 infants, we used ITS gene sequencing of fecal samples from birth to the age of 18 months. We compared gut mycobiome composition according to delivery mode and exposure to intrapartum antibiotics during vaginal delivery. RESULTS: At birth, gut mycobiome were dominated by the genus Candida, at 6-month stool samples by Malassezia and Cystofilobasidium, and the 18-month stool samples by Trichosporon and unidentified fungi. Perinatal factors altered mycobiome. At 18 months, gut mycobiome of infants born vaginally consisted mostly of Trichosporon (32%) and unidentified fungi (31%), while those born via Cesarean section delivery samples had mycobiome dominated by Saccharomyces (50%). At the age of 18 months, those exposed to intrapartum antibiotics had mycobiome dominated by Trichosporon (66%) not seen in those unexposed to antibiotics. CONCLUSIONS: Delivery mode and exposure to intrapartum antibiotic prophylaxis were markedly associated with gut mycobiome composition from birth to 18 months of age. IMPACT: The composition of the gut mycobiome is likely associated with human health. Yet, the development of gut mycobiome is poorly understood in infants and children. In this prospective cohort study, delivery mode and exposure to intrapartum antibiotic prophylaxis were markedly associated with gut mycobiome composition from birth to 18 months of age. The impact of intrapartum antibiotic prophylaxis on fungal microbiome in vaginally born infants, previously shown to influence gut bacteriome composition, may be explained by the interaction between bacteria and fungi. Gut mycobiome composition likely deserves further investigation in relation to gut microbiome and health in children.

Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants.

BACKGROUND: Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods. METHODS: We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics. RESULTS: We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant. CONCLUSIONS: Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods. IMPACT: We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants. This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods. This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.

Gut Mycobiome in Atopic Dermatitis and in Overweight Young Children: A Prospective Cohort Study in Finland.

Gut bacterial alterations have been previously linked to several non-communicable diseases in adults, while the association of mycobiome is not well understood in these diseases, especially in infants and children. Few studies have been conducted on the association between gut mycobiome and non-communicable diseases in children. We investigated gut mycobiome composition using 194 faecal samples collected at birth, 6 months after birth, and 18 months after birth in relation to atopic dermatitis (AD) and overweight diagnoses at the age of 18 or 36 months. The mycobiome exhibited distinct patterns, with Truncatella prevalent in the meconium samples of both overweight and non-overweight groups. Saccharomyces took precedence in overweight cases at 6 and 18 months, while Malassezia dominated non-overweight samples at 6 months. Saccharomyces emerged as a consistent high-abundance taxon across groups that had dermatitis and were overweight. We found a weak association between gut mycobiome and AD at birth and overweight at 18 months when using machine learning (ML) analyses. In ML, unidentified fungi, Alternaria, Rhodotorula, and Saccharomyces, were important for classifying AD, while Saccharomyces, Thelebolus, and Dothideomycetes were important for classifying overweight. Gut mycobiome might be associated with the development of AD and overweight in children.

Gut microbiome-derived bacterial extracellular vesicles in patients with solid tumours.

INTRODUCTION: Gut microbiome-derived nanoparticles, known as bacterial extracellular vesicles (bEVs), have garnered interest as promising tools for studying the link between the gut microbiome and human health. The diverse composition of bEVs, including their proteins, mRNAs, metabolites, and lipids, makes them useful for investigating diseases such as cancer. However, conventional approaches for studying gut microbiome composition alone may not be accurate in deciphering host-gut microbiome communication. In clinical microbiome research, there is a gap in the knowledge on the role of bEVs in solid tumor patients. OBJECTIVES: Analyzing the functionality of bEVs using (meta)genomics and proteomics could highlight the unique aspects of host-gut microbiome interactions in solid tumor patients. Therefore, we performed a comparative analysis of the proteome and microbiota composition of gut microbiome-derived bEVs isolated from patients with solid tumors and healthy controls. METHODS: After isolating bEVs from the feces of solid tumor patients and healthy controls, we performed spectrometry analysis of their proteomes and next-generation sequencing (NGS) of the 16S gene. We also investigated the gut microbiomes of feces from patients and controls using 16S sequencing and used machine learning to classify the samples into patients and controls based on their bEVs and fecal microbiomes. RESULTS: Solid tumor patients showed decreased microbiota richness and diversity in both the bEVs and feces. However, the bEV proteomes were more diverse in patients than in the controls and were enriched with proteins associated with the metabolism of amino acids and carbohydrates, nucleotide binding, and oxidoreductase activity. Metadata classification of samples was more accurate using fecal bEVs (100%) compared with fecal samples (93%). CONCLUSION: Our findings suggest that bEVs are unique functional entities. There is a need to explore bEVs together with conventional gut microbiome analysis in functional cancer research to decipher the potential of bEVs as cancer diagnostic or therapeutic biomarkers.

Delivery Mode and Perinatal Antibiotics Influence the Infant Gut Bacteriome and Mycobiome: A Network Analysis.

Both exposure to antibiotics at birth and delivery via Caesarean section influence the gut bacteriome's development in infants. Using 16S rRNA and internal transcribed spacer sequencing on the Ion Torrent platform, we employed network analysis to investigate the bacterial and fungal interkingdom relationships in the gut microbiome from birth to age 18 months in a prospective cohort study of 140 infants. The gut microbiome at ages six and 18 months revealed distinctive microbial interactions, including both positive and negative associations between bacterial and fungal genera in the gut ecosystem. Perinatal factors, delivery mode and intrapartum antibiotic exposure affected the associations between bacterial and fungal species. In infants exposed and unexposed to perinatal antibiotics, the gut microbiome formed distinct networks for the bacteriome and mycobiome. The fungi Saccharomyces, Trichosporon, Pezoloma, Cystofilobasidium, Rigidoporus and Fomitopsis were strongly associated with exposure to antibiotics at birth. Hyaloscypha, Trichosporon, Fomitopsis and Vishniacozyma were strongly associated with the control group that was not exposed to antibiotics. Five distinct networks were formed according to delivery mode. The present study confirms that bacteria and fungi clearly interact in the infant gut ecosystem. Furthermore, perinatal factors appear to influence the relationships between bacteria and fungi in the developing gut microbiome.

Bacterial extracellular vesicles - brain invaders? A systematic review.

Introduction: Knowledge on the human gut microbiota in health and disease continues to rapidly expand. In recent years, changes in the gut microbiota composition have been reported as a part of the pathology in numerous neurodegenerative diseases. Bacterial extracellular vesicles (EVs) have been suggested as a novel mechanism for the crosstalk between the brain and gut microbiota, physiologically connecting the observed changes in the brain to gut microbiota dysbiosis. Methods: Publications reporting findings on bacterial EVs passage through the blood-brain barrier were identified in PubMed and Scopus databases. Results: The literature search yielded 138 non-duplicate publications, from which 113 records were excluded in title and abstract screening step. From 25 publications subjected to full-text screening, 8 were excluded. The resulting 17 publications were considered for the review. Discussion: Bacterial EVs have been described with capability to cross the blood-brain barrier, but the mechanisms behind the crossing remain largely unknown. Importantly, very little data exists in this context on EVs secreted by the human gut microbiota. This systematic review summarizes the present evidence of bacterial EVs crossing the blood-brain barrier and highlights the importance of future research on gut microbiota-derived EVs in the context of gut-brain communication across the blood-brain barrier.

Maternal microbiota communicates with the fetus through microbiota-derived extracellular vesicles.

BACKGROUND: Reports regarding the presence of bacteria in the fetal environment remain limited and controversial. Recently, extracellular vesicles secreted by the human gut microbiota have emerged as a novel mechanism for host-microbiota interaction. We aimed to investigate the presence of bacterial extracellular vesicles in the fetal environment during healthy pregnancies and determine whether extracellular vesicles derived from the gut microbiota can cross biological barriers to reach the fetus. RESULTS: Bacterial extracellular vesicles were detectable in the amniotic fluid of healthy pregnant women, exhibiting similarities to extracellular vesicles found in the maternal gut microbiota. In pregnant mice, extracellular vesicles derived from human maternal gut microbiota were found to reach the intra-amniotic space. CONCLUSIONS: Our findings reveal maternal microbiota-derived extracellular vesicles as an interaction mechanism between the maternal microbiota and fetus, potentially playing a pivotal role in priming the prenatal immune system for gut colonization after birth. Video Abstract.

Impact of Streptococcus salivarius K12 on Nasopharyngeal and Saliva Microbiome: A Randomized Controlled Trial.

BACKGROUND: Probiotic lactobacilli have been ineffective in preventing acute otitis media. In contrast to lactobacilli, alpha-hemolytic streptococci belong to the core microbiome of nasopharynx. METHODS: We investigated the effects of Streptococcus salivarius K12 probiotic on the saliva and nasopharyngeal microbiome in 121 children attending daycare. Children were randomly allocated to receive oral K12 product for 1 month or no treatment. We obtained saliva and nasopharyngeal samples at study entry, at 1 and 2 months. The next-generation sequencing of the bacterial 16S gene was performed. RESULTS: After the intervention, the diversity of saliva or nasopharyngeal microbiome did not differ between groups. The proportion of children with any otopathogen did not differ between the groups. At 1 month, the abundance of otopathogens in nasopharynx was lower in K12 group compared with that in control children (34% vs. 55%, P = 0.037). When we compared each otopathogen separately, Moraxella was the only group lower in the treatment group. We could not verify the reduction of Moraxella when an alternative Human Oral Microbiome Database taxonomy database was used. In children receiving K12 product, the mean abundance of S. salivarius was greater in saliva after the intervention (0.9% vs. 2.0%, P = 0.009). CONCLUSIONS: The use of S. salivarius K12 probiotic appeared to be safe because it did not disrupt the normal microbiome in young children. Even though a short-term colonization of S. salivarius was observed in the saliva, the impact of S. salivarius K12 probiotic on the otopathogens in nasopharyngeal microbiome remained uncertain.

Presence of distinctive microbiome in the first-pass meconium of newborn infants.

We critically evaluated the fetal microbiome concept in 44 neonates with placenta, amniotic fluid, and first-pass meconium samples. Placental histology showed no signs of inflammation. Meconium samples were more often bacterial culture positive after vaginal delivery. In next-generation sequencing of the bacterial 16S gene, before and after removal of extracellular and PCR contaminant DNA, the median number of reads was low in placenta (48) and amniotic fluid (46) and high in meconium samples (14,556 C-section, 24,860 vaginal). In electron microscopy, meconium samples showed extracellular vesicles. Utilizing the analysis of composition of microbiomes (ANCOM) against water, meconium samples had a higher relative abundance of Firmicutes, Lactobacillus, Streptococcus, and Escherichia-Shigella. Our results did not support the existence of the placenta and amniotic fluid microbiota in healthy pregnancies. The first-pass meconium samples, formed in utero, appeared to harbor a microbiome that may be explained by perinatal colonization or intrauterine colonization via bacterial extracellular vesicles.