Microbiota In Preterm Infants Research Articles

Linking preterm infant gut microbiota to nasograstric enteral feeding tubes: exploring potential interactions and microbial strain transmission

IntroductionPreterm birth is a growing problem worldwide. Staying at a neonatal intensive care unit (NICU) after birth is critical for the survival of preterm infants whose feeding often requires the use of nasogastric enteral feeding tubes (NEFT). These can be colonized by hospital-associated pathobionts that can access the gut of the preterm infants through this route. Since the gut microbiota is the most impactful factor on maturation of the immune system, any disturbance in this may condition their health. Therefore, the aim of this study is to assess the impact of NEFT-associated microbial communities on the establishment of the gut microbiota in preterm infants.Material and methodsA metataxonomic analysis of fecal and NEFT-related samples obtained during the first 2 weeks of life of preterm infants was performed. The potential sharing of strains isolated from the same set of samples of bacterial species involved in NICU's outbreaks, was assessed by Random Amplification of Polymorphic DNA (RAPD) genotyping.ResultsIn the samples taken 48 h after birth (NEFT-1 and Me/F1), Staphylococcus spp. was the most abundant genera (62% and 14%, respectively) and it was latter displaced to 5.5% and 0.45%, respectively by Enterobacteriaceae. Significant differences in beta diversity were detected in NEFT and fecal samples taken at day 17 after birth (NEFT-3 and F3) (p = 0.003 and p = 0.024, respectively). Significant positive correlations were found between the most relevant genera detected in NEFT-3 and F3. 28% of the patients shared at least one RAPD-PCR profile in fecal and NEFT samples and 11% of the total profiles were found at least once simultaneously in NEFT and fecal samples from the same patient.ConclusionThe results indicate a parallel bacterial colonization of the gut of preterm neonates and the NEFTs used for feeding, potentially involving strain sharing between these niches. Moreover, the same bacterial RAPD profiles were found in neonates hospitalized in different boxes, suggesting a microbial transference within the NICU environment. This study may assist clinical staff in implementing best practices to mitigate the spread of pathogens that could threaten the health of preterm infants.

Dynamic impact of delivery modes on gut microbiota in preterm infants hospitalized during the initial 4 weeks of life

Preterm infants face a high risk of various complications, and their gut microbiota plays a pivotal role in health. Delivery modes have been reported to affect the development of gut microbiota in term infants, but its impact on preterm infants remains unclear. Here, we collected fecal samples from 30 preterm infants at five-time points within the first four weeks of life. Employing 16 S rRNA sequencing, principal coordinates analysis, the analysis of similarities, and the Wilcoxon rank-sum test, we examined the top dominant phyla and genera, the temporal changes in specific taxa abundance, and their relationship with delivery modes, such as Escherichia-Shigella and Enterococcus based on vaginal delivery and Pluralibacter related to cesarean section. Moreover, we identified particular bacteria, such as Taonella, Patulibacter, and others, whose proportions fluctuated among preterm infants born via different delivery modes at varying time points, as well as the microbiota types and functions. These results indicated the influence of delivery mode on the composition and function of the preterm infant gut microbiota. Importantly, these effects are time-dependent during the early stages of life. These insights shed light on the pivotal role of delivery mode in shaping the gut microbiota of preterm infants and have significant clinical implications for their care and management.

SOME POTENTIAL REQUIREMENTS FOR THE FORMATION OF THE GUT MICROBIOTA IN PRETERM INFANTS: PART 1

Abnormal microbial colonization of the gut from birth in newborns aff ects growth, development, and health, leading to short- and long-term adverse eff ects. The microbiota of preterm infants diff ers from that of term ones. This is because preterm infants and their mothers have more complicated prenatal and postnatal health conditions and anatomically- functional immaturity of organs and systems depending on gestational age. Maternal conditions, antibiotics, type of feeding, and use of probiotics can signifi cantly aff ect the gut microbiota of preterm infants in the early neonatal period; however, these eff ects decrease with age. Although some factors and processes are diffi cult to intervene or avoid, understanding the potential factors and determinants will help to develop timely strategies to promote a healthy gut microbiota in preterm infants. This review discusses potential determinants of gut microbial colonization in preterm infants,the underlying mechanisms, and recommendations for addressing adverse eff ects.

Characteristics of intestinal microbiota in preterm infants and the effects of probiotic supplementation on the microbiota.

In this study, we investigated the characteristics of the intestinal microbiota of preterm infants, and then analyzed the effects of probiotics supplementation on intestinal microbiota in preterm infants. This study enrolled 64 infants born between 26 and 32 weeks gestational age (GA) and 22 full-term infants. 34 premature infants received oral probiotic supplementation for 28 days. Stool samples were obtained on the first day (D1) and the 28th day (D28) after birth for each infant. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System, specifically targeting the V3-V4 hyper-variable regions of the 16S rDNA gene. The sequencing results were then used to compare and analyze the composition and diversity index of the intestinal microbiota. There was no significant difference in meconium bacterial colonization rate between premature and full-term infants after birth (p > 0.05). At D1, the relative abundance of Bifidobacterium, Bacteroides, and Lactobacillus in the stool of preterm infants was lower than that of full-term infants, and the relative abundance of Acinetobacter was higher than that of full-term infants. The Shannon index and Chao1 index of intestinal microbiota in preterm infants are lower than those in full-term infants (p < 0.05). Supplementation of probiotics can increase the relative abundance of Enterococcus and Enterobacter, and reduce the relative abundance of Escherichia and Clostridium in premature infants. The Chao1 index of intestinal microbiota decreased in preterm infants after probiotic supplementation (p < 0.05). The characteristics of intestinal microbiota in preterm infants differ from those in full-term infants. Probiotic supplementation can reduce the relative abundance of potential pathogenic bacteria and increase the abundance of beneficial microbiota in premature infants.

Gut microbiota of preterm infants in the neonatal intensive care unit: a study from a tertiary care center in northern India.

Disruptions of the gut microbiota of preterm infants admitted to the neonatal intensive care unit (NICU) during the first 2 weeks of life are of critical importance. These infants are prone to various complications, including necrotizing enterocolitis (NEC) and sepsis. Studying the gut microbiota will improve outcomes in preterm infants. In the present study, we examined the gut microbiota of preterm infants admitted to the NICU in the first month of life. Neonates admitted to the NICU were recruited, and stool samples were collected weekly from the seventh day of the infant's life until the 30th day of life. DNA was extracted using a DNeasy Powersoil DNA isolation kit. 16S rRNA gene sequencing targeting the V3-V4 region was performed using the MiSeq platform. Sequenced reads were processed on DADA2 pipeline to obtain an amplicon sequence variant (ASV) table. All bioinformatic and statistical analyses were performed using different packages in the R statistical framework. Fourteen preterm infants were recruited, and 48 samples were collected. Alpha diversity metrics, observed ASV count, and Shannon index were found to have no differences in any clinical variables. Permutational multivariate analysis of variance (PERMANOVA) showed discrimination of neonates by gestational age and administration of probiotics. Differential abundance analysis showed a decreased abundance of Bifidobacterium Breve in extremely preterm infants (gestational age <28 weeks) compared to moderate preterm infants (gestational age 29-32 weeks). Supplementation with probiotics decreased Acinetobacter and increased Bifidobacterium in the gut of preterm neonates regardless of gestational age. Gestational age and probiotic supplementation alter the gut microbiota of preterm infants admitted to the NICU.

The effect of in-hospital breast milk intake on the gut microbiota of preterm infants

The aim of this study was to explore the effect of in-hospital breast milk intake on the development of early gut microbiota in preterm infants in two dimensions: longitudinal over time and cross-sectional between groups. Researchers collected preterm infants' general data baseline characteristics, recorded their daily breast milk intake, probiotics, and antibiotics use, and collected their stool specimens at 1st week, 2ndweek, 3rd week and 4th week after birth. The researchers analyzed the effect of breast milk on gut microbiota of preterm infants by bioinformatics methods of intra-group longitudinal variation of gut microbiota structure and diversity in preterm infants and cross-sectional differences between >70% in-hospital breast milk intake (BM) group and ≤70% (PF) group. A total of 60 preterm infants were included in this study, and a total of 213 stool specimens were retained. BM had statistically different Shannon and Simpson indices between the first and fourth week after admission (P<0.05), both of them showed a lower diversity in the later week than in the previous week. The Shannon index and Simpson index of BM from week 3 onwards were statistically different from PF (P<0.05), and the Shannon index and Simpson index of BM were lower than those of PF. Significantly statistical differences (P<0.05) were found in the beta diversity of gut microbiota in preterm infants as time progressed, and both showed a lower beta diversity in the later week than in the preceding week. The dominant taxa of PF in the first postnatal week were Bifidobacterium animalis, etc., the dominant taxa of BM in the third postnatal week were Clostridium_sensu_stricto _1, etc. CONCLUSIONS: The development and evolution of gut microbiota in preterm infants' in-hospital period was a continuous, non-random process, and similar trends in species composition and changes in gut microbes emerged in preterm infants with different ratio of breast milk intake. In the NICU setting, alpha diversity was lower in preterm infants in the >70% breast milk intake group than in the ≤70% group when compared between groups at the same time, which may be related to delayed maturation of gut microbes and represents a more developmental gut time window.

The impact of neonatal intensive care unit antibiotics on gut bacterial microbiota of preterm infants: a systematic review

Preterm infants encounter an unnatural beginning to life, with housing in neonatal intensive care units (NICUs) where they are exposed to antibiotics. Although the effectiveness of antibiotics in infection control is well established, the short- and long-term unintended effects on the microbiota of preterm infants receiving antibiotic treatment are yet to be quantified. Our aim was to investigate the unintended consequences of NICU antibiotics on preterm infants’ gut microbiota. We searched three electronic databases—Embase, PubMed, and Scopus—for records from 2010 to October 2022. Eligibility criteria included intervention and observational studies that collected stool samples and analyzed microbiota data on the effect of antibiotics on the gut microbiota of preterm infants using 16S rRNA sequencing. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the quality of the studies was judged using the Cochrane Collaboration Tool for assessing risk of bias (RoB2) for clinical trials, while non-randomized studies were assessed using the Newcastle–Ottawa Scale (NOS). The initial searches yielded 7,605 papers, of which 21 were included in the review. The selected studies examined 3,669 stool samples that were collected longitudinally from 878 preterm infants in seven different countries. Preterm infants exposed to antibiotics had a reduced bacterial diversity, an increased relative abundance of pathogenic bacteria such as Enterobacteriaceae, and a decrease or absence of symbiotic bacteria such as Bifidobacterium spp., which have been shown to assist in immunity development. Antibiotic discontinuation restored diversity, with variances linked to the antibiotic spectrum and treatment duration in some but not all cases. Breastfeeding confounded the association between antibiotic use and dysbiosis. Intriguingly, the reduction of γ-aminobutyric acid (GABA), a crucial neurotransmitter for early brain development, was linked to the depletion of Veillonella spp. Despite the apparent benefits of using antibiotics on preterm infants, we conclude that they should be used only when absolutely necessary and for a short period of time. Mothers’ milk is recommended to hasten the restoration of disrupted microbiota.

Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A.

Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. Surprisingly, we also observed intradonor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the antibacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the antibacterial BrmIgA reactivity displays interindividual heterogeneity but intraindividual stability. These findings have important implications for how breast milk shapes the development of the preterm infant microbiota and protects against necrotizing enterocolitis.

Alterations in the intestinal microbiota of preterm infants with neurodevelopmental impairments: a prospective cohort study

To investigate the difference in intestinal microbiota between preterm infants with neurodevelopmental impairment (NDI) and those without NDI. In this prospective cohort study, the preterm infants who were admitted to the neonatal intensive care unit of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from September 1, 2019 to September 30, 2021 were enrolled as subjects. According to the assessment results of Gesell Developmental Scale at the corrected gestational age of 1.5-2 years, they were divided into two groups: normal (n=115) and NDI (n=100). Fecal samples were collected one day before discharge, one day before introducing solid food, and at the corrected gestational age of 1 year. High-throughput sequencing was used to compare the composition of intestinal microbiota between groups. Compared with the normal group, the NDI group had a significantly higher Shannon diversity index at the corrected gestational age of 1 year (P<0.05). The principal coordinate analysis showed a significant difference in the composition of intestinal microbiota between the two groups one day before introducing solid food and at the corrected gestational age of 1 year (P<0.05). Compared with the normal group, the NDI group had a significantly higher abundance of Bifidobacterium in the intestine at all three time points, a significantly higher abundance of Enterococcus one day before introducing solid food and at the corrected gestational age of 1 year, and a significantly lower abundance of Akkermansia one day before introducing solid food (P<0.05). There are significant differences in the composition of intestinal microbiota between preterm infants with NDI and those without NDI. This study enriches the data on the characteristics of intestinal microbiota in preterm infants with NDI and provides reference for the microbiota therapy and intervention for NDI in preterm infants.

Пробіотики, кишкова мікробіота та захворювання, пов’язані з незрілістю травного каналу, у значно недоношених немовлят

Interruption of the formation of gut microbiota in preterm infants increases the probability of necrotizing enterocolitis (NEC) and late-onset neonatal sepsis (LOS). The use of probiotics can reduce the corresponding risk. Purpose - to evaluate the clinical effectiveness of enteral administration of Lactobacillus reuteri DSM 17938 in reducing the incidence of NEC, LOS, and overall mortality in infants with gestational age (GA) ≤32 weeks, as well as the effect of the probiotic on the formation of the gut microbiota. Materials and methods. 100 newborns with GA ≤32 weeks and birth weight ≤1500 g were enrolled in the open randomized study. 50 infants in the probiotic group until reaching postmenstrual age (PMA) of 36 weeks received Lactobacillus reuteri DSM 17938 at a dose of 108 CFU/day with enteral feeding (EF), and 50 infants in the comparison group received standard treatment. The primary effectiveness criteria were the incidence of NEC, LOS, and overall mortality. As the secondary criteria, the duration of the period to reach the full EF, the number of episodes of feeding intolerance, duration of antibacterial therapy, weight at PMA of 36 weeks, and length of hospital stay were used. Results. The administration of Lactobacillus reuteri DSM 17938 at a dose of 108 CFU/day neither reduced the incidence of NEC and LOS nor overall mortality. This intervention, however, significantly reduced the length of hospital stay in infants with GA ≥28 weeks (56.0 (46.0-71.0) days vs 65.0 (60.0-87.9) days; р=0.03), and was associated with the earlier achievement of full enteral volume (23.0 (16.0-37.0) days vs 30.0 (18.0-37.0) days; р=0.26) and fewer episodes of feeding intolerance in infants with GA &lt;28 weeks (1.0 (1.0-3.0) vs 3.0 (3.0-4.0); р=0.19). No effect of the probiotic therapy on the gut colonization by Lactobacillus spp. and Bifidobacterium spp. was observed. Conclusions. Enteral administration of Lactobacillus reuteri DSM 17938 improves tolerance to EF and reduces the period to achieve full EF and the total length of hospital stay in preterm infants. The effect of this probiotic on the incidence of NEC and LOS, as well as the postnatal formation of the gut microbiota, requires further study. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Microbiota from Preterm Infants Who Develop Necrotizing Enterocolitis Drives the Neurodevelopment Impairment in a Humanized Mouse Model.

Necrotizing enterocolitis (NEC) is the leading basis for gastrointestinal morbidity and poses a significant risk for neurodevelopmental impairment (NDI) in preterm infants. Aberrant bacterial colonization preceding NEC contributes to the pathogenesis of NEC, and we have demonstrated that immature microbiota in preterm infants negatively impacts neurodevelopment and neurological outcomes. In this study, we tested the hypothesis that microbial communities before the onset of NEC drive NDI. Using our humanized gnotobiotic model in which human infant microbial samples were gavaged to pregnant germ-free C57BL/6J dams, we compared the effects of the microbiota from preterm infants who went on to develop NEC (MNEC) to the microbiota from healthy term infants (MTERM) on brain development and neurological outcomes in offspring mice. Immunohistochemical studies demonstrated that MNEC mice had significantly decreased occludin and ZO-1 expression compared to MTERM mice and increased ileal inflammation marked by the increased nuclear phospho-p65 of NFκB expression, revealing that microbial communities from patients who developed NEC had a negative effect on ileal barrier development and homeostasis. In open field and elevated plus maze tests, MNEC mice had worse mobility and were more anxious than MTERM mice. In cued fear conditioning tests, MNEC mice had worse contextual memory than MTERM mice. MRI revealed that MNEC mice had decreased myelination in major white and grey matter structures and lower fractional anisotropy values in white matter areas, demonstrating delayed brain maturation and organization. MNEC also altered the metabolic profiles, especially carnitine, phosphocholine, and bile acid analogs in the brain. Our data demonstrated numerous significant differences in gut maturity, brain metabolic profiles, brain maturation and organization, and behaviors between MTERM and MNEC mice. Our study suggests that the microbiome before the onset of NEC has negative impacts on brain development and neurological outcomes and can be a prospective target to improve long-term developmental outcomes.

The role of Klebsiella populations in preterm infants.

The preterm infant microbiota is dominated by Enterobacteriaceae (Escherichia, Klebsiella or Enterobacter spp.), Enterococcus and Staphylococcus spp. Recent work has demonstrated the development of this microbiota is predictable and driven by simple microbe-microbe interactions. Because of their systemic immaturity, including an underdeveloped immune system, preterm infants are susceptible to a range of infections. Numerous retrospective studies have examined the association of the preterm gut microbiota with diseases such as necrotizing enterocolitis (NEC), early-onset sepsis and late-onset sepsis. To date, no single bacterium has been associated with infection in these infants, but a Klebsiella/Enterococcus-dominated faecal microbiota is associated with an increased risk of developing NEC. Staphylococci aid and enterococci inhibit establishment/maintenance of gastrointestinal Klebsiella populations in preterm infants, though the mechanisms underlying these interactions are poorly understood. Klebsiella spp. recovered from healthy and sick preterm infants display similar antimicrobial resistance and virulence profiles, giving no clues as to why some infants develop potentially life-threatening diseases while others do not. The identification of cytotoxin-producing Klebsiella oxytoca sensu lato in the gut microbiota of some preterm infants has led to the suggestion that these bacteria may contribute to NEC in a subset of neonates. This mini review highlights current knowledge on Klebsiella spp. contributing to the preterm gut microbiota and provides insights into areas of research that warrant further attention.

Variable preterm oral microbiome stabilizes and reflects a full-term infant profile within three months.

Preterm infants suffer higher morbidity and mortality rates compared to full-term infants, but little is known about how changes to oral and respiratory tract microbiota may impact disease development. Here, very preterm neonates (n = 50) were selected to study oral and respiratory microbiota development during the first few months post-birth, where 26 individuals were diagnosed with BPD and/or sepsis. These infants were compared to 14 healthy full-term infants and 16 adults. Microbiota diversity, composition, and species abundances were calculated from 16S ribosomal RNA gene sequences in buccal swabs and tracheal aspirates at two time points (within a week and 1-3 months post-birth). Collection time point was the biggest factor to significantly influence the preterm oral microbial diversity and composition. In addition, BPD and sepsis were linked to distinct preterm oral microbiota diversity and composition, and opportunistic pathogens previously associated with these diseases were identified in the initial sample for both healthy preterm neonates and those with the disease. Compared to the full-term infant and adult dataset, preterm infant diversity and composition was initially significantly different, but resembled full-term infant diversity and composition over time. Overall, consequences of microbiota development need further examination in preterm infant infections and later development. Non-gut microbiota research on preterm infants is limited. At one week post-birth, preterm infants harbor distinct oral microbiota that are not shared with full-term children or adults, eventually becoming similar to full-term infants at 36 weeks postmenstrual age. DNA from potential opportunistic pathogens was observed in the mouth and lungs of preterm infants within a week of birth, and microbes associated with BPD were identified in the lungs. Oral microbiota in preterm infants over the first 2-3 months is unique and may be connected to short- and long-term health outcomes in these children.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Alteration of the gut microbiota after surgery in preterm infants with necrotizing enterocolitis.

To investigate the dynamic changes in the intestinal microbiota in preterm infants with necrotizing enterocolitis (NEC) before and after treatment via a prospective case-control study. Preterm infants with NEC and preterm infants with similar age and weight (control group) were enrolled in this study. They were divided into NEC_Onset (diagnosis time), NEC_Refeed (refeed time), NEC_FullEn (full enteral nutrition time), Control_Onset, and Control_FullEn groups according to the time of the fecal material collected. Except for basic clinical information, fecal specimens of the infants were obtained as well at indicated times for 16S rRNA gene sequencing. All infants were followed up after discharge from the NICU, and the growth data of the corrected age of 12 months were acquired from the electronic outpatient system and telephonic interviews. A total of 13 infants with NEC and 15 control infants were enrolled. A gut microbiota analysis showed that the Shannon and Simpson indices were lower in the NEC_FullEn group than in the Control_FullEn group (p < .05). Methylobacterium, Clostridium_butyricum, and Acidobacteria were more abundant in infants with NEC during diagnosis. Methylobacterium and Acidobacteria were remained plentiful in the NEC group until the end of treatment. These bacteria species were significantly positively correlated with CRP and negatively correlated with platelet count. The rate of delayed growth was higher in the NEC group than in the control group (25% vs. 7.1%) at 12 months of corrected age, but there was no significant difference. In addition, the pathways of synthesis and degradation of ketone bodies were more active in the NEC subgroups, including both the NEC_Onset group and the NEC_FullEn group. The pathway of sphingolipid metabolism was more active in the Control_FullEn group. Even after reaching the full enteral nutrition period, alpha diversity in infants with NEC who underwent surgery was lower than that in the control group infants. It may take more time to reestablish the normal gut flora of NEC infants after surgery. The pathways of the synthesis and degradation of ketone bodies and sphingolipid metabolism might be related to the pathogenesis of NEC and physical development after the occurrence of NEC.

Bifidobacterium: Host-Microbiome Interaction and Mechanism of Action in Preventing Common Gut-Microbiota-Associated Complications in Preterm Infants: A Narrative Review.

The development and health of infants are intertwined with the protective and regulatory functions of different microorganisms in the gut known as the gut microbiota. Preterm infants born with an imbalanced gut microbiota are at substantial risk of several diseases including inflammatory intestinal diseases, necrotizing enterocolitis, late-onset sepsis, neurodevelopmental disorders, and allergies which can potentially persist throughout adulthood. In this review, we have evaluated the role of Bifidobacterium as commonly used probiotics in the development of gut microbiota and prevention of common diseases in preterm infants which is not fully understood yet. The application of Bifidobacterium as a therapeutical approach in the re-programming of the gut microbiota in preterm infants, the mechanisms of host-microbiome interaction, and the mechanism of action of this bacterium have also been investigated, aiming to provide new insights and opportunities in microbiome-targeted interventions in personalized medicine.

Dysbiosis in Gut Microbiota in Children Born Preterm Who Developed Autism Spectrum Disorder: A Pilot Study.

The gut microbiota was reported to differ between children with autism spectrum disorder (ASD) and typically developing (TD) children, and dysbiosis of the gut microbiota in preterm infants is common. Here, we explored the characteristics of gut microbiota in children born preterm with ASD. We performed 16S rRNA gene sequencing using stool samples from ASD children born preterm and TD children born preterm. Alpha diversity was significantly greater in the ASD group. A comparison of beta diversity showed different clusters. Linear discriminant analysis effect size analysis revealed significantly more Firmicutes in the ASD group compared with the TD group. In conclusion, the gut microbiota in children born preterm differs between children with ASD and TD.

Dynamic Changes of the Gut Microbiota in Preterm Infants With Different Gestational Age

The gut microbiota plays a key role in the pathogenesis of diseases affecting preterm infants and gestational age is one of the important factors which affect the gut microbiota of infants. To determine the characteristics of the gut microbiota in preterm infants of different gestational ages from birth to 1 year after birth, we collected 622 fecal samples from neonates of different gestational ages at different time points after birth. According to the gestational ages, the samples were divided into four groups, extremely preterm, very preterm, moderate to late preterm, and term group. Meconium and fecal samples at day 14, 28, 120, and 365 after birth were collected. 16S rRNA sequencing was performed and the composition and structure of the gut microbiota in preterm infants of different gestational age was compared with that of term infants. In our study, alpha diversity of meconium in extremely preterm group was higher than very preterm group, moderate to late preterm group and term group and alpha diversity of meconium in preterm group was decreased with increasing of gestational age. At day 14 to day 120 after birth, alpha diversity of term and moderate to late preterm group were significantly higher than other two preterm groups. However, moderate to late preterm group owned the highest alpha diversity which was higher than term group at day 365 after birth. Besides, the results shown the duration of opportunistic pathogen such as Klebsiella and Enterococcus which dominant colonization was different in different gestational age groups. As well as the probiotics, such as Bifidobacterium, which abundance enriched at different time point in different gestational age groups. We profiled the features of dynamic changes of gut microbiome from different gestational ages infants. The results of our research provide new insights for individualized interventions of specific microbes of preterm infants with different gestational ages at different time points after birth.

First 1000 Days and Beyond After Birth: Gut Microbiota and Necrotizing Enterocolitis in Preterm Infants.

Preterm birth remains a major maternal and infant health issue worldwide particularly with an increase in the global preterm birth rate, which requires more interventions to manage the consequences of preterm birth. In addition to traditional complications, recent studies have shown that the succession of gut microbiota of preterm infants is disordered due to the systemic physiological immaturity, which confers negative influences on the growth, development, and health of infants. In the present study, we briefly discussed the prevalence of preterm birth worldwide and then highlighted the signatures of gut microbiota in preterm infants within the first 1000 days of life after the birth categorized into birth, infancy, and childhood. Afterward, we focused on the potential association of clinical phenotypes typically associated with preterm birth (i.e., necrotizing enterocolitis) with gut microbiota, and the potential directions for future studies in this field are finally discussed.

Minimal Effects of Medium-Chain Triglyceride Supplementation on the Intestinal Microbiome Composition of Premature Infants: A Single-Center Pilot Study.

Compared to term infants, the microbiota of preterm infants is less diverse and often enriched for potential pathogens (e.g., members of the family Enterobacteriaceae). Additionally, antibiotics are frequently given to preterm infants, further destabilizing the microbiota and increasing the risk of fungal infections. In a previous communication, our group showed that supplementation of the premature infant diet with medium-chain triglyceride (MCT) oil reduced the fungal burden of Candida spp. in the gastrointestinal tract. The objective of this study was to determine whether MCT supplementation impacts the bacterial component of the microbiome. Pre-term infants (n = 17) receiving enteral feedings of either infant formula (n = 12) or human milk (n = 5) were randomized to MCT supplementation (n = 9) or no supplementation (n = 8). Fecal samples were taken at randomization and prior to MCT supplementation (Week 0), on days 5–7 (Week 1) and day 21 (Week 3). After DNA extraction from samples, the QIIME2 pipeline was utilized to measure community diversity and composition (genera and phyla). Our findings show that MCT supplementation did not significantly alter microbiota diversity or composition in the gastrointestinal tract. Importantly, there were no significant changes in the family Enterobacteriaceae, suggesting that MCT supplementation did not enrich for potential pathogens. MCT holds promise as a therapeutic intervention for reducing fungal colonization without significant impact on the bacterial composition of the host gastrointestinal tract.