Neonatal Gut Microbiota Research Articles

Intrauterine antibiotic exposure affected neonatal gut bacteria and infant growth speed

Although abundant evidence has suggested that early-life antibiotic exposure was associated with adipogenesis later in life, limited data were available on the effect of intrauterine antibiotic exposure on infant growth and growth speed. Additionally, few studies have investigated the role of the neonatal gut microbiota in the above association. In this study, we examined the association between intrauterine cumulative antibiotic exposure and infant growth and explored the potential role of the neonatal gut microbiota in the association. 295 mother-child pairs from the Shanghai Maternal-Child Pairs Cohort (MCPC) study were included, and meconium samples and infant growth measurements were assessed. Z-scores of length-for-age, weight-for-age (weight-for-age), and body mass index (BMI)-for-age (BMI-for-age) were calculated. Eighteen common antibiotics were measured in meconium. Multivariable linear regression models were applied to test the interrelationships between antibiotic exposure, diversity indicators, and the relative abundance of selected bacterial taxa from phylum to genus levels from least absolute shrinkage and selection operator (LASSO) and infant growth indicators. The detection rates of the 18 antibiotics, except for chlortetracycline, penicillin, and chloramphenicol, were below 10 %. Penicillin was found to be positively associated with infant growth at birth and with growth speed from 2 to 6 months. The Pielou and Simpson indexes were negatively associated with meconium penicillin. Nominally significant associations between penicillin and the relative abundances of several bacterial taxa from the phyla Proteobacteria, Bacteroidetes, and Firmicutes were found. The Pielou and Simpson indexes were also found to be negatively associated with infant growth. Among taxa selected from LASSO regression, the relative abundances of the phyla Actinobacteria and Firmicutes and order Bifidobacteriales were found to be significantly associated with weight and BMI growth speeds from 2 to 6 months. In conclusion, intrauterine antibiotic exposure can affect infant growth. The neonatal gut microbiota might play a role in the abovementioned association.

Spontaneous preterm delivery is reflected in both early neonatal and maternal gut microbiota

BackgroundAberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization.MethodsFecal samples were collected from 55 preterm neonates (<35 gestational weeks), 51 mothers, and 25 full-term neonates during the first 3–4 postpartum days. Gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing.ResultsPreterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after spontaneous delivery than iatrogenic delivery and not dependent on delivery mode.ConclusionsThe initial preterm gut microbiota is distinct from term microbiota. Spontaneous preterm birth is reflected in the early neonatal and maternal gut microbiota. Transmission of gut microbes from mother to neonate is determined by spontaneous preterm delivery, but not by mode of birth.ImpactThe initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode.Our study provides new evidence regarding the early gut colonization patterns in preterm infants.Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention.

Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: anopen-labelsingle-centerrandomizedparallel controlled study.

Antibiotics, a common strategy used for neonatal infection, show consistent effect on the gut microbiota of neonates. Supplementation with probiotics has become increasingly popular in mitigating the loss of the gut microbiota. However, no clear consensus recommending the use of probiotics in the infection of neonates currently exists. This study examined the effects of probiotics on the gut microbiota of infectious neonates when used concurrently with or during the recovery period following antibiotic therapy. Fifty-five full-term neonates diagnosed with neonatal infections were divided into the following groups: NI (no intervention, antibiotic therapy only), PCA (probiotics used concurrently with antibiotics), and PAA (probiotics used after antibiotics). The NI group received antibiotic treatment (piperacillin-tazobactam) for 1week and the PCA group received antibiotic treatment together with probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) for 1week. The PAA group received antibiotic treatment for 1week followed by probiotics for 1week. Fecal samples were collected at four time nodes: newborn, 1week, 2weeks, and 42days after birth. The composition of the gut microbiota was determined by the high-throughput sequencing of 16S rRNA amplicons. Antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of Bifidobacterium and Lactobacillus. The use of probiotics did not restore the overall diversity of the gut microbiota. However, using probiotics simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium. These results suggest that the early use of probiotics may have a potential ability to remodel the gut microbiota during recovery from antibiotic treatment. However, further study is required to fully understand the long-term effects including the clinical benefits.

New Insights Into Microbiota Modulation-Based Nutritional Interventions for Neurodevelopmental Outcomes in Preterm Infants.

Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.

Gestational diabetes mellitus is associated with the neonatal gut microbiota and metabolome

BackgroundGestational diabetes mellitus (GDM) is a metabolic disease that occurs in pregnant women and increases the risk for the development of diabetes. The relationship between GDM and meconium microbiota and metabolome remains incompletely understood.MethodsFour hundred eighteen mothers (147 women with GDM and 271 normal pregnant women) and their neonates from the GDM Mother and Child Study were included in this study. Meconium microbiota were profiled by 16S rRNA gene sequencing. Meconium and maternal serum metabolome were examined by UPLC-QE.ResultsMicrobial communities in meconium were significantly altered in neonates from the GDM mothers. A reduction in alpha diversity was observed in neonates of GDM mothers. At the phylum level, the abundance of Firmicutes and Proteobacteria changed significantly in neonates of GDM mothers. Metabolomic analysis of meconium showed that metabolic pathways including taurine and hypotaurine metabolism, pyrimidine metabolism, beta-alanine metabolism, and bile acid biosynthesis were altered in GDM subjects. Several changed metabolites varying by the similar trend across the maternal serum and neonatal meconium were observed.ConclusionAltogether, these findings suggest that GDM could alter the serum metabolome and is associated with the neonatal meconium microbiota and metabolome, highlighting the importance of maternal factors on early-life metabolism.

Deviations in the gut microbiota of neonates affected by maternal group B Streptococcus colonization

BackgroundGroup B Streptococcus (GBS) infection is the leading cause of septicemia, meningitis, and pneumonia in neonates. Aberrant gut colonization in early life may predispose children to various diseases in adulthood. However, the associations between gut microbial changes and GBS colonization is still unclear.ResultsThe composition and diversity of meconium microbiota in GBS group were similar to that of healthy controls. However, we identified several specific taxa that were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p < 0.05, LDA > 2.0). Particularly, the relative abundance of Lactobacillus paracasei was significantly reduced, indicating a role in GBS colonization.ConclusionsOur study presented a series of bacterial species colonized by GBS, thus providing novel evidence in support of initial intestinal microbiota dysbiosis in the neonates with mother’s GBS colonization.

Milk-derived osteopontin shapes the development of the intestinal microbiota

Abstract Breast-feeding is important for the growth and development of infants, delivering nutritional support as well as a wealth of immunological factors that provide protection while the infant immune system matures. Formula-fed infants have an increased risk of negative health outcomes, including obesity, autoimmunity, and infections, and display dysbiosis of the intestinal microbiota compared to breast-fed infants. Of the many components of milk, bioactive proteins provide a potential mechanism by which breast milk can impact the infant microbiota. One protein of interest is osteopontin (OPN), a highly glycosylated phosphoprotein involved in a range of physiological processes including bone mineralization, inflammation, wound healing, and homeostasis of lymphoid cells in the intestinal epithelium. Osteopontin constitutes about 2% of the protein component of milk; however, the impacts of milk-derived osteopontin on the development of the infant microbiota are not yet well understood. We propose that milk-derived osteopontin plays a critical role in the development of the neonatal gut microbiota, and that lack of osteopontin intake during the post-natal period leads to gut dysbiosis.

Early life administration of milk fat globule membrane promoted SCFA-producing bacteria colonization, intestinal barriers and growth performance of neonatal piglets.

Milk fat globule membrane (MFGM) possesses various nutritional and biological benefits for mammals, whereas its effects on neonatal gut microbiota and barrier integrity remained unclear. This study investigated the effects of MFGM administration on microbial compositions and intestinal barrier functions of neonatal piglets. Sixteen newborn piglets were randomly allocated into a CON group or MFGM group, orally administered with saline or MFGM solution (1 g/kg body weight) respectively during the first postnatal week, and all piglets were breastfed during the whole neonatal period. The present study found that the MFGM oral administration during the first postnatal week increased the plasma immunoglobulin (Ig) G level, body weight and average daily gain of piglets (P < 0.05) on 21 d. Additionally, MFGM administration enriched fecal SCFA-producing bacteria (Ruminococaceae_UCG-002, Ruminococaceae_UCG-010, Ruminococaceae_UCG-004, Ruminococaceae_UCG-014 and [Ruminococcus]_gauvrearuii_group), SCFA concentrations (acetate, propionate and butyrate; P < 0.05) and their receptor (G-protein coupled receptor 41, GPR41). Furthermore, MFGM administration promoted intestinal villus morphology (P < 0.05) and barrier functions by upregulating genes of tight junctions (E-cadherin, claudin-1, occludin and zonula occludin 1 [ZO-1]), mucins (mucin-13 and mucin-20) and interleukin (IL)-22 (P < 0.05). Positive correlation was found between the beneficial microbes and SCFA levels pairwise with the intestinal barrier genes (P < 0.05). In conclusion, orally administrating MFGM during the first postnatal week stimulated SCFA-producing bacteria colonization and SCFA generation, enhanced intestinal barrier functions and consequently improved growth performance of neonatal piglets on 21 d. Our findings will provide new insights about MFGM intervention for microbial colonization and intestinal development of neonates during their early life.

Role of cesarean section in the development of neonatal gut microbiota: A systematic review.

BackgroundThe delivery mode is one of the factors affecting the type of colonization of the human gut. Gut colonization affects all stages of the human life cycle, and the type of gut microbiome can contribute to immune system function, the development of some diseases, and brain development; and it has a significant impact on a newborn’s growth and development.MethodsTerms defined as MeSH keywords were searched by the databases, and web search engines such as PubMed, ClinicalTrials.gov, Embase, Scopus, ProQuest, Web of Science, and Google Scholar were searched between 2010 and 2020. The quality of each study was assessed according to the Newcastle–Ottawa scale, and seven eligible and high-quality studies were analyzed.FindingThe abundances of Bacteroides and Bifidobacterium during the first 3 months of life; Lactobacillus and Bacteroides during the second 3 months of life; Bacteroides and Bifidobacterium during the second 6 months of life; and Bacteroides, Enterobacter, and Streptococcus after the first year of life were higher in vaginal delivery-born infants. While infants born by cesarean section (CS) had higher abundances of Clostridium and Lactobacillus during the first 3 months of life, Enterococcus and Clostridium during the second 3 months of life, and Lactobacillus and Staphylococcus after the first year of life.DiscussionDelivery mode can affect the type of the human intestinal microbiota. The CS-born babies had lower colonization rates of Bifidobacterium and Bacteroides, but they had higher colonization rates of Clostridium, Lactobacillus, Enterobacter, Enterococcus, and Staphylococcus. Given the effect of microbiota colonization on neonatal health, it is therefore recommended to conduct further studies in order to investigate the effect of the colonization on the delivery mode and on baby’s growth and development.Application to practiceThe aim of this study was to investigate the role of CS in the development of the neonatal gut microbiota.

Early initiation of breastfeeding and gut microbiota of neonates: A literature review

PurposeThe purpose of this systematic review is to examine a study of early initiation of breastfeeding for the development of neonatal intestinal microbiota. MethodThe method used was an online database that has been published. Keywords used include breast milk composition; compare breastfed and formula-fed (breastmilk and formula milk); gut microbiota in infants; early initiation. ResultsBased on the review of 12 selected articles, it was found that breast milk contains various prebiotics that can be transmitted to infants through breastfeeding. The dominant prebiotics is Lactobacillus spp., Bifidobacterium spp., and Staphylococcus spp. which has different amounts depending on the type of breast milk provided. ConclusionBreastfeeding has many benefits, especially for the baby's immunity and digestion. Giving early initiation of breastfeeding means giving breastfeeding early in life so that it greatly affects the development of good bacterial colonies in infants.

Identification of New Potential Biotherapeutics from Human Gut Microbiota-Derived Bacteria.

The role of the gut microbiota in health and disease is well recognized and the microbiota dysbiosis observed in many chronic diseases became a new therapeutic target. The challenge is to get a better insight into the functionality of commensal bacteria and to use this knowledge to select live biotherapeutics as new preventive or therapeutic products. In this study, we set up a screening approach to evaluate the functional capacities of a set of 21 strains isolated from the gut microbiota of neonates and adults. For this purpose, we selected key biological processes involved in the microbiome-host symbiosis and known to impact the host physiology i.e., the production of short-chain fatty acids and the ability to strengthen an epithelial barrier (Caco-2), to induce the release of the anti-inflammatory IL-10 cytokine after co-culture with human immune cells (PBMC) or to increase GLP-1 production from STC-1 endocrine cell line. This strategy highlighted fifteen strains exhibiting beneficial activities among which seven strains combined several of them. Interestingly, this work revealed for the first time a high prevalence of potential health-promoting functions among intestinal commensal strains and identified several appealing novel candidates for the management of chronic diseases, notably obesity and inflammatory bowel diseases.

Strain inheritance and neonatal gut microbiota development: A meta-analysis

As many inflammatory and metabolic disorders have been associated with structural deficits of the human gut microbiota, the principles and mechanisms that govern its initialization and development are of considerable scientific interest and clinical relevance. However, our current understanding of the developing gut microbiota dynamics remains incomplete. We carried out a large-scale, comprehensive meta-analysis of over 1900 available metagenomic shotgun samples from neonates, infants, adolescents, and their families, using our recently introduced SameStr program for strain-level microbiota profiling and the detection of microbial strain transfer and persistence. We found robust associations between fecal microbiota composition and age, as well as delivery mode, which was measurable for up to two years of life. C-section was associated with increased relative abundances of non-gut species and delayed transition from a predominantly oxygen-tolerant to intolerant microbial community. Unsupervised networks based on shared strain profiles generated family-specific clusters connecting infants, their siblings, parents and grandparents and, in one case, suggested strain transfer between neonates from the same hospital ward, but could also be used to identify potentially mislabeled metagenome samples. Vaginally delivered newborns shared more strains with their mothers than C-section infants, but strain sharing was reduced if mothers underwent antibiotic treatment. Shared strains persisted in infants throughout the first year of life and belonged to the same bacterial species as strains that were shared between adults and their parents. Irrespective of delivery type, older children shared strains with their mothers and fathers and, into adulthood, could be accurately distinguished from unrelated sample pairs. Prominent fecal commensal bacteria were both among frequently transferred (e.g. Bacteroides and Sutterella) and newly acquired taxa (e.g. Blautia, Faecalibacterium, and Ruminococcus). Our meta-analysis presents a more detailed and comprehensive picture of the highly dynamic neonatal and infant fecal microbiota development than previous studies and presents evidence for taxonomic and functional compositional differences early in life between infants born naturally or by C-section, which persist well into adolescence.

When a Neonate Is Born, So Is a Microbiota.

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one’s life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the “sterile womb”. Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject.

Maternal Gestational &lt;i&gt;Bifidobacterium bifidum&lt;/i&gt; TMC3115 Treatment Shapes Construction of Offspring Gut Microbiota and Development of Immune System and Induces Immune Tolerance to Food Allergens

Background: Our previous studies has proved that Bifidobacterium bifidum TMC3115 (TMC3115) treatment during infancy could protect neonates from adulthood allergy. However, whether it could still protect offspring from allergic diseases when treatment during maternal pregnancy and the underlying mechanisms remain unclear. Methods: Pregnant BALB/c mice were gavaged with TMC3115 until delivery. Offspring were reared until weaning (postnatal day 21, PND21) and then sensitized with ovalbumin (OVA) until PND49. Vaginal, gut, and breast milk microbiota were sequenced. Immunoglobulin and cytokines, splenic and colonic gene expressions, and fecal short chain fatty acids (SCFAs) were measured. Findings: After maternal TMC3115 treatment, the microbiota of maternal breast milk from newborn offspring and gut microbiota of neonates and at weaning were changed the most, and levels of serum and breast milk immunoglobulin and of splenic cytokines as well as mRNA expression of colonic intestinal development indicators were all significantly altered in offspring in different stages. Synchronous changes in the specific microbiota were found in the maternal gut, vagina, and breast milk and in the offspring gut microbiota, such as Proteobacteria. After sensitization with OVA, there was no significant change in levels of serum IgE or OVA-specific IgE/IgG1 in the offspring in TMC3115 group; however, IgM, expression of colonic Ki67, Muc2, and tight junction proteins and production of fecal SCFAs were significantly increased as were the relative abundances of Lactobacillus and Lachnospiraceae NK4A136 group. Interpretation: Our results suggested that the day of birth and weaning were the important “window of opportunity” for neonatal gut microbiota construction and that maternal treatment with TMC3115 could play a profound modulatory effect on the development of the immune system in offspring at different stages. Maternal TMC3115 treatment may induce immune tolerance to allergens in OVA-stimulated offspring and enhance intestinal tissue development and barrier function and primary immune response to allergens through modulating gut microbiota and SCFA production. Funding Information: This work was supported by the National Natural Science Foundation of China (Grant number: 81372982). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The animal experiment facility and animals used for the present study were officially approved by the Experimental Animal Management Committee of Sichuan Government. Experimental protocols were approved by the West China School of Public Health Medical Ethics Committee of Sichuan University (Approved number: SYXK2018-011).

Development of gut microbiota and bifidobacterial communities of neonates in the first 6 weeks and their inheritance from mother

ABSTRACT Microbiota especially Bifidobacterium play an important role in adjusting and maintaining homeostatic balance within the infant intestine. The aim of this study was to elucidate the relationship between maternal and infant gut microbiota and identify the Bifidobacterium species that may transfer from mother to infant over the first 42 days of the infant’s life. Nineteen mother-infant-pair fecal samples were collected and the diversity and composition of the total bacterial and Bifidobacterium communities were analyzed via 16S rDNA and bifidobacterial groEL gene high throughput sequencing. The results revealed that the relative abundance of Bifidobacterium was significantly higher in the infant gut while Parabacteroides, Blautia, Coprococcus, Lachnospira and Faecalibacterium were at lower relative abundance in 7-day and 42-day infant fecal samples compared to the maternal samples. The maternal gut has more B. pseudocatenulatum. In the infant group, B. breve and B. dentium relative abundance increased while B. animalis subsp. lactis decreased from days 7 to 42. Additionally, B. longum subsp. longum isolated from FGZ16 and FGZ35 may have transferred from mother to infant and colonized the infant gut. The results of the current study provide insight toward the infant gut microbiota composition and structure during the first 42 days and may help guide Bifidobacterium supplementation strategies in mothers and infants.

Early life environmental exposures have a minor impact on the gut ecosystem following a natural birth

ABSTRACT A growing body of evidence suggests that the environment is an important source of colonizing bacteria for the gastrointestinal tract of C-section delivered infants, who undergo multiple birth-related interventions; however, the extent to which environmental microbes impact vaginally delivered infants remains unclear. Here we investigated the impact of rural and urban environmental exposures on microbial establishment and immunity in vaginally delivered mice. We simulated rural and urban home environments by adding soil types to cages from breeding to weaning. Our aims were to determine the impact of rural and urban soil exposures on the gut microbiome in young mice and to understand whether these changes persisted into adulthood. Host immune cytokines and microbial short-chain fatty acids were quantified to understand the impact on immunity. We found that early-life soil exposure had a minor effect on the richness of the neonatal gut microbiota contributing 5% and 9% variation in the bacterial community structure between mice during early-life and adulthood, respectively. Exposure to urban soil increased Clostridiaceae and propionic acid which persisted into adulthood. While soil exposure had a limited effect on the gut taxa, systemic cytokine and chemokine profiles were altered in adulthood. The findings presented here show that unlike in C-section deliveries previously reported, environmental exposures following a natural birth have a limited impact on the gut microbial taxa but potentially play an important role in immune-mediated disease susceptibility later in life.

Bacteremia Due to Kosakonia cowanii in a Preterm Neonate

Abstract Objective Low-birthweight infants admitted to neonatal intensive care units are at high risk of hospital-acquired infections by opportunistic pathogens. The gut microbiota of preterm neonates lacks commensal bacteria providing a barrier against pathogens. We report a case of bacteremia due to Kosakonia cowanii in a preterm neonate. Case Report A female baby of 680 g was delivered through a cesarean-section at 28 weeks of gestation due to intrauterine growth retardation and fetal rhythm abnormalities. On day 27, two blood cultures grew gram-negative bacilli in a context of functional ileus. No reliable identification could be obtained using matrix assisted laser desorption ionization-time of flight, biochemical reactions with the VITEK 2 GN ID card, or 16S rDNA sequencing. K. cowanii was finally identified by gyrB sequencing. The source of infection may have been either the central venous catheter or translocation from the gut microbiota. Evolution was favorable after 14 days of cefepime (combined with amikacin for 5 days) and central venous catheter removal. Conclusion K. cowanii is a member of the Enterobacteriaceae family that was recently reclassified from the Enterobacter genus. Human infections due to K. cowanii are scarce and have mainly been associated with traumatic inoculation from plants or transient gut colonization. K. cowanii may be an underestimated opportunistic pathogen in susceptible populations such as preterm neonates.

Breastfeeding restored the gut microbiota in caesarean section infants and lowered the infection risk in early life

BackgroundThe initialization of the neonatal gut microbiota (GM) is affected by diverse factors and is associated with infant development and health outcomes.MethodsIn this study, we collected 207 faecal samples from 41 infants at 6 time points (1, 3, and 7 days and 1, 3, and 6 months after birth). The infants were assigned to four groups according to delivery mode (caesarean section (CS) or vaginal delivery (VD)) and feeding pattern (breastfeeding or formula milk).ResultsThe meconium bacterial diversity was slightly higher in CS than in VD. Three GM patterns were identified, including Escherichia/Shigella-Streptococcus-dominated, Bifidobacterium-Escherichia/Shigella-dominated and Bifidobacterium-dominated patterns, and they gradually changed over time. In CS infants, Bifidobacterium was less abundant, and the delay in GM establishment could be partially restored by breastfeeding. The frequency of respiratory tract infection and diarrhoea consequently decreased.ConclusionThis study fills some gaps in the understanding of the restoration of the GM in CS towards that in VD.

Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function

BackgroundEarly microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences.MethodsGut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response.ResultsMicrobiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles.ConclusionsMode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.Trial registrationNCT03552939.5sgR3F5xhntXpgP8tH2u1iVideo

Effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates: a prospective randomized controlled trial

OBJECTIVE To study the effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates. METHODS The neonates with hyperbilirubinemia who were hospitalized from January to December 2018 were enrolled and randomly divided into an observation group (n=61) and a control group (n=63). The neonates in the observation group were treated with phototherapy combined with Saccharomyces boulardii, and those in the control group were treated with phototherapy combined with placebo. Treatment outcomes were compared between the two groups. Fecal samples were collected 72 hours after treatment and 16s rRNA high-throughput sequencing was used to compare the features of gut microbiota between the two groups. RESULTS There was no significant difference in the total serum bilirubin level between the two groups before treatment (P>0.05). At 24, 48, and 72 hours after treatment, the observation group had a significantly lower level of total serum bilirubin than the control group (P<0.05). Compared with the control group, the observation group had a significantly lower proportion of neonates requiring phototherapy again [20% (12/61) vs 75% (47/63), P<0.05]. Compared with the control group, the observation group had a significantly higher abundance of Bacteroides (P<0.05) and a significantly lower abundance of Escherichia coli and Staphylococcus in the intestine at 72 hours after treatment (P<0.05). CONCLUSIONS In neonates with hyperbilirubinemia, phototherapy combined with Saccharomyces boulardii can effectively reduce bilirubin level and prevent the recurrence of jaundice. Saccharomyces boulardii can favour the treatment outcome by regulating the gut microbiota of neonates.