Infant Microbiome Research Articles

Development of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort.

The first few years of life is a key period for the development of the gut microbiome. However, our current understanding of this topic is largely biased toward Western populations. In this study, we characterized the development and determinants of the gut microbiome in a prospective cohort of 112 term Chinese children by sequencing 713 stool samples collected at nine time points from birth to 3 years of age using 16S rRNA gene sequencing. We revealed alterations in the composition and alpha and beta diversities of the gut microbiota across the first 3 years of life. We identified mode of delivery, feeding mode, and intrapartum antibiotics as the major determinants of the early-life gut microbiome, the effects of all of which persisted up to 12 months. Importantly, by conducting a nested case-control study, we showed that alterations in the infant gut microbiota precede the development of eczema. Interestingly, we identified a depletion of Bacteroides and an enrichment of Clostridium sensu stricto 1 in the gut microbiome of infants with eczema at 1 year old. The same patterns were also observed in C-section-born infants within the same time frames, suggesting a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema. Our study has revealed important associations between the gut microbiome and eczema in infancy and has established the basis for potential prevention/treatment of eczema via modulation of the gut microbiota. IMPORTANCE Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera Clostridium sensu stricto 1 and Finegoldia in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of Bacteroides from 1 to 6 months of age and an enrichment of Clostridium sensu stricto 1 at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.

Sociodemographic Factors and Intestinal Microbiome Development in Preterm, Very Low Birth Weight Infants.

Preterm very low birth weight (VLBW) infants are at risk for intestinal morbidities and dysbiotic development of the intestinal microbiome. Despite the influence of sociodemographic factors on premature infant health outcomes, whether they shape the intestinal microbiome early in life is not clear. The objective was to explore the associations between race, sex, and socioeconomic status and the intestinal microbiome of VLBW infants during the first 4 weeks of life. This was a secondary analysis of data from an ongoing randomized trial of 79 infants ≤30 weeks' gestation and ≤1,500 g. Stool samples were collected at week 1 through week 4, frozen to -80°C and analyzed by 16S rRNA sequencing of the V4 region using Illumina MiSeq. Reads were analyzed to measure α and β diversity as well as relative abundance of bacteria in the intestinal microbiome. Of the 79 infants, 63 had at least one sample available. Twenty-three (37%) of infants were African American, 30 (48%) were male, and 44 (71%) had Medicaid insurance. There were no statistically significant (<0.05) differences in α diversity or β diversity, and the differential abundance analysis suggests limited patterns of distinction in the intestinal microbiome between non-African American and African American infants, male and female infants, and infants with maternal private or Medicaid insurance. Our results suggest race, sex, and socioeconomic status shape colonization of specific microorganisms to a limited extent. Future studies should confirm these findings and determine clinical relevance through further study of differentially abundant microorganisms and additional factors contributing to colonization patterns. · Diversity of the gut microbiome was similar between infants of varying race, sex, and socioeconomic status.. · We observed sociodemographic-linked differences in colonization of individual taxa.. · Further study is required to confirm these results and the clinical relevance of these findings..

Interactions with alloparents are associated with the diversity of infant skin and fecal bacterial communities in Chicago, United States.

Social interactions shape the infant microbiome by providing opportunities for caregivers to spread bacteria through physical contact. With most research focused on the impact of maternal-infant contact on the infant gut microbiome, it is unclear how alloparents (i.e., caregivers other than the parents) influence the bacterial communities of infant body sites that are frequently contacted during bouts of caregiving, including the skin. To begin to understand how allocare may influence the diversity of the infant microbiome, detailed questionnaire data on infant-alloparent relationships and specific allocare behaviors were coupled with skin and fecal microbiome samples (four body sites) from 48 infants living in Chicago, United States. Data from 16S rRNA gene amplicon sequencing indicated that infant skin and fecal bacterial diversity showed strong associations (positive and negative) to having female adult alloparents. Alloparental feeding and co-sleeping displayed stronger associations to infant bacterial diversity compared to playing or holding. The associations with allocare behaviors differed in magnitude and direction across infant body sites. Bacterial relative abundances varied by infant-alloparent relationship and breastfeeding status. This study provides some of the first evidence of an association between allocare and infant skin and fecal bacterial diversity. The results suggest that infants' exposure to bacteria from the social environment may vary based on infant-alloparent relationships and allocare behaviors. Since the microbiome influences immune system development, variation in allocare that impacts the diversity of infant bacterial communities may be an underexplored dimension of the social determinants of health in early life.

Longitudinal dynamics of the gut microbiome and metabolome in peanut allergy development

Rising rates of peanut allergy (PA) motivate investigations of its development to inform prevention and therapy. Microbiota and the metabolites they produce shape food allergy risk. We sought to gain insight into gut microbiome and metabolome dynamics in the development of PA. We performed a longitudinal, integrative study of the gut microbiome and metabolome of infants with allergy risk factors but no PA from a multicenter cohort followed through mid-childhood. We performed 16S rRNA sequencing, short chain fatty acid measurements, and global metabolome profiling of fecal samples at infancy and at mid-childhood. In this longitudinal, multicenter sample (n= 122), 28.7% of infants developed PA by mid-childhood (mean age 9 years). Lower infant gut microbiome diversity was associated with PA development (P= .014). Temporal changes in the relative abundance of specific microbiota and gut metabolite levels significantly differed in children who developed PA. PA-bound children had different abundance trajectories of Clostridium sensu stricto 1 sp (false discovery rate (FDR)= 0.015) and Bifidobacterium sp (FDR= 0.033), with butyrate (FDR= 0.045) and isovalerate (FDR= 0.036) decreasing over time. Metabolites associated with PA development clustered within the histidine metabolism pathway. Positive correlations between microbiota, butyrate, and isovalerate and negative correlations with histamine marked the PA-free network. The temporal dynamics of the gut microbiome and metabolome in early childhood are distinct for children who develop PA. These findings inform our thinking on the mechanisms underlying and strategies for potentially preventing PA.

Influence of infant microbiome on health and development.

The microbiome is a complex ecosystem comprising microbes, their genomes, and the surrounding environment. The microbiome plays a critical role in early human development, including maturation of the host immune system and gastrointestinal tract. Multiple factors, including diet, anti-biotic use, and other environmental exposures, influence the establishment of the microbiome during infancy. Numerous studies have identified associations between the microbiome and neonatal diseases, including necrotizing enterocolitis, sepsis, and malnutrition. Furthermore, there is compelling evidence that perturbation of the microbiome in early life can have lasting developmental effects that increase an individual's risk for immune and metabolic diseases in later life. Supplementation of the microbiome with probiotics reduces the risk of necrotizing enterocolitis and sepsis in at-risk infants. This review focuses on the structure and function of the infant microbiome, the environmental and clinical factors that influence its assembly, and its impact on infant health and development.

The association between gut microbiome and growth in infants with cystic fibrosis

BackgroundIn cystic fibrosis (CF), pathophysiologic changes in the gastrointestinal tract lead to malnutrition and altered gut microbiome. Microbiome alterations have been linked to linear growth, gut inflammation and respiratory manifestations. Elucidating these gut microbiome alterations may provide insight into future nutritional management in CF. MethodsInfants were followed for 12-months at four sites in the United States (US-CF) and Australia (AUS-CF). 16S rRNA gene sequencing was performed on longitudinal stool samples. Associations between microbial abundance and age, antibiotic prophylaxis, malnutrition, and breast feeding were evaluated using generalized linear mixed models. Taxonomic and predictive functional features were compared between groups. ResultsInfants with CF (N = 78) were enrolled as part of a larger study. AUS-CF infants had higher mean weight-for-age z-scores than US-CF infants (p = 0.02). A subset of participants (CF N = 40, non-CF disease controls N = 10) provided stool samples for microbiome analysis. AUS-CF infants had lower stool alpha diversity compared to US-CF infants (p < 0.001). AUS-CF infants had higher relative abundance of stool Proteobacteria compared to US-CF infants which was associated with antibiotic prophylaxis (p < 0.001). Malnutrition (weight-for-age <10th percentile) was associated with depleted Lactococcus (p < 0.001). Antibiotic prophylaxis (p = 0.002) and malnutrition (p = 0.012) were linked with predicted decreased activity of metabolic pathways responsible for short chain fatty acid processing. ConclusionsIn infants with CF, gut microbiome composition and diversity differed between the two continents. Gut microbial diversity was not linked to growth. The relationship between malnutrition and antibiotic prophylaxis with reduced SCFA fermentation could have implications for gut health and function and warrants additional investigation.

Low-dose perinatal supplementation with Enterococcus faecalis increases concentrations of short-chain fatty acids in the offspring but does not protect against allergic asthma.

Childhood allergic asthma is associated with a dysbiotic gut microbiome in early life, and maternal perinatal treatment with probiotics is a potential way alter the infant microbiome, which may improve asthma outcomes. This study used a mouse model to examine the effect of maternal supplementation with the probiotic Enterococcus faecalis on faecal short-chain fatty acid (SCFA) concentrations and asthma risk in the offspring. Pregnant/lactating mice were treated daily, from gestation day 6 to postnatal day 21, with an oral suspension of 106, 107 or 108 colony-forming units of a live preparation of the probiotic E. faecalis (Symbioflor®1). At weaning, offspring were subjected to an ovalbumin-induced experimental asthma protocol. Faeces were collected from the mothers and offspring at several different time points to determine SCFA concentrations. It was found that maternal supplementation with E. faecalis did not alter litter size, sex ratio or offspring weight, and was associated with an increase in SCFAs in offspring faeces at weaning and after allergy induction. However, allergic offspring from E. faecalis supplemented mothers showed no difference in asthma severity when compared with allergic offspring from control mothers. In conclusion, although maternal perinatal supplementation with low-dose E. faecalis was associated with increased faecal SCFAs in the offspring, it did not protect against offspring asthma. This is may be because SCFA concentrations were not increased to an immunoprotective level. We recommend that future studies concentrate on probiotic supplementation in high-risk cases, for instance, to repair gut dysbiosis resulting from antibiotic use in pregnant mothers or their infants.

Postmortem Nasopharyngeal Microbiome Analysis of Zambian Infants With and Without Respiratory Syncytial Virus Disease: A Nested Case Control Study.

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and lower respiratory tract infections in children in their first year of life, disproportionately affecting infants in developing countries. Previous studies have found that the nasopharyngeal (NP) microbiome of infants with RSV infection has specific characteristics that correlate with disease severity, including lower biodiversity, perturbations of the microbiota and differences in relative abundance. These studies have focused on infants seen in clinical or hospital settings, predominantly in developed countries. We conducted a nested case control study within a random sample of 50 deceased RSV+ infants with age at death ranging from 4 days to 6 months and 50 matched deceased RSV- infants who were all previously enrolled in the Zambia Pertussis and RSV Infant Mortality Estimation (ZPRIME) study. All infants died within the community or within 48 hours of facility admittance. As part of the ZPRIME study procedures, all decedents underwent one-time, postmortem NP sampling. The current analysis explored the differences between the NP microbiome profiles of RSV+ and RSV- decedents using the 16S ribosomal DNA sequencing. We found that Moraxella was more abundant in the NP microbiome of RSV+ decedents than in the RSV- decedents. Additionally, Gemella and Staphylococcus were less abundant in RSV+ decedents than in the RSV- decedents. These results support previously reported findings of the association between the NP microbiome and RSV and suggest that changes in the abundance of these microbes are likely specific to RSV and may correlate with mortality associated with the disease.

Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial

The microbiomes of cesarean-born infants differ from vaginally delivered infants and are associated with increased disease risks. Vaginal microbiota transfer (VMT) to newborns may reverse C-section-related microbiome disturbances. Here, we evaluated the effect of VMT by exposing newborns to maternal vaginal fluids and assessing neurodevelopment, as well as the fecal microbiota and metabolome. Sixty-eight cesarean-delivered infants were randomly assigned a VMT or saline gauze intervention immediately after delivery in a triple-blind manner (ChiCTR2000031326). Adverse events were not significantly different between the two groups. Infant neurodevelopment, as measured by the Ages and Stages Questionnaire (ASQ-3) score at 6months, was significantly higher with VMT than saline. VMT significantly accelerated gut microbiota maturation and regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolisms, within 42days after birth. Overall, VMT is likely safe and may partially normalize neurodevelopment and the fecal microbiome in cesarean-delivered infants.

Compositional Variations between Adult and Infant Skin Microbiome: An Update.

Human skin and its commensal microbiome form the first layer of protection to the outside world. A dynamic microbial ecosystem of bacteria, fungi and viruses, with the potential to respond to external insult, the skin microbiome has been shown to evolve over the life course with an alteration in taxonomic composition responding to altered microenvironmental conditions on human skin. This work sought to investigate the taxonomic, diversity and functional differences between infant and adult leg skin microbiomes. A 16S rRNA gene-based metataxonomic analysis revealed significant differences between the infant and adult skin groups, highlighting differential microbiome profiles at both the genus and species level. Diversity analysis reveals differences in the overall community structure and associated differential predicted functional profiles between the infant and adult skin microbiome suggest differing metabolic processes are present between the groups. These data add to the available information on the dynamic nature of skin microbiome during the life course and highlight the predicted differential microbial metabolic process that exists on infant and adult skin, which may have an impact on the future design and use of cosmetic products that are produced to work in consort with the skin microbiome.

Antibiotic therapy and necrotizing enterocolitis

Antibiotic therapy remains a cornerstone of treatment of both medical and surgical presentations of necrotizing enterocolitis (NEC). However, guidelines regarding the administration of antibiotics for the treatment of NEC are lacking and practices vary amongst clinicians. Although the pathogenesis of NEC is unknown, there is consensus that the infant gastrointestinal microbiome contributes to the disease. The presumed connection between dysbiosis and NEC has prompted some to study whether early prophylactic enteral antibiotics can prevent NEC. Yet others have taken an opposing approach, studying whether perinatal antibiotic exposure increases the risk of NEC by inducing a state of dysbiosis. This narrative review summarizes what is known about antibiotics and their association with the infant microbiome and NEC, current antibiotic prescribing practices for infants with medical and surgical NEC, as well as potential strategies to further optimize the use of antibiotics in this population of infants.

The impact of the microbes on puppies and kittens microbiota: a review

Recently it was discovered that canine and feline neonates are not born in a sterile environment as was stated previously. The acquisition, colonization, and maintenance of early life microbiota is a rapidly developing area of research. In humans it has been seen that the infant microbiome plays an essential role in human health and its composition is determined by maternal–offspring exchanges of microbiota. Even though this topic is becoming more and more important in dogs and cats, the exact role of the neonatal microbiome is not yet known. In this review, the current knowledge about the neonatal microbiome in puppies and kittens is summarized.

Impact of exposure to per- and polyfluoroalkyl substances on fecal microbiota composition in mother-infant dyads

There is growing evidence suggesting that chemical exposure alters gut microbiota composition. However, not much is known about the impact of per- and polyfluoroalkyl substances (PFAS) on the gut microbial community. Here, in a mother-infant study, we set out to identify the gut bacterial species that associate with chemical exposure before (maternal) and after (maternal, infant) birth. Paired serum and stool samples were collected from mother-infant dyads (n = 30) in a longitudinal setting. PFAS were quantified in maternal serum to examine their associations with the microbial compositions (determined by shotgun metagenomic sequencing) in mothers and infants. High maternal exposure to PFAS was consistently associated with increased abundance of Methanobrevibacter smithii in maternal stool. Among individual PFAS compounds, PFOS and PFHpS showed the strongest association with M. smithii. However, maternal total PFAS exposure associated only weakly with the infant microbiome. Our findings suggest that PFAS exposure affects the composition of the adult gut microbiome.

Ability of Bifidobacterium breve 702258 to transfer from mother to infant: the MicrobeMom randomized controlled trial

The composition of the infant microbiome can have a variety of short- and long-term implications for health. It is unclear if maternal probiotic supplementation in pregnancy can affect the infant gut microbiome. This study aimed to investigate if maternal supplementation of a formulation of Bifidobacterium breve 702258 from early pregnancy until 3 months postpartum could transfer to the infant gut. This was a double-blinded, placebo-controlled, randomized controlled trial of B breve 702258 (minimum 1 × 109 colony-forming units) or placebo taken orally from 16 weeks' gestation until 3 months postpartum in healthy pregnant women. The primary outcome was presence of the supplemented strain in infant stool up to 3 months of life, detected by at least 2 of 3 methods: strain-specific polymerase chain reaction, shotgun metagenomic sequencing, or genome sequencing of cultured B breve. A total of 120 individual infants' stool samples were required for 80% power to detect a difference in strain transfer between groups. Rates of detection were compared using the Fisher exact test. A total of 160 pregnant women with average age of 33.6 (3.9) years and mean body mass index of 24.3 (22.5-26.5) kg/m2, of whom 43% were nulliparous (n=58), were recruited from September 2016 to July 2019. Neonatal stool samples were obtained from 135 infants (65 in intervention and 70 in control group). The presence of the supplemented strain was detected through at least 2 methods (polymerase chain reaction and culture) in 2 infants in the intervention group (n=2/65; 3.1%) and none in the control group (n=0; 0%; P=.230). Direct mother-to-infant strain transfer of B breve 702258 occurred, albeit infrequently. This study highlights the potential for maternal supplementation to introduce microbial strains into the infant microbiome.

Parental factors that impact the ecology of human mammary development, milk secretion, and milk composition—a report from “Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)” Working Group 1

The goal of Working Group 1 in the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to outline factors influencing biological processes governing human milk secretion and to evaluate our current knowledge of these processes. Many factors regulate mammary gland development in utero, during puberty, in pregnancy, through secretory activation, and at weaning. These factors include breast anatomy, breast vasculature, diet, and the lactating parent’s hormonal milieu including estrogen, progesterone, placental lactogen, cortisol, prolactin, and growth hormone. We examine the effects of time of day and postpartum interval on milk secretion, along with the role and mechanisms of lactating parent-infant interactions on milk secretion and bonding, with particular attention to the actions of oxytocin on the mammary gland and the pleasure systems in the brain. We then consider the potential effects of clinical conditions including infection, pre-eclampsia, preterm birth, cardiovascular health, inflammatory states, mastitis, and particularly, gestational diabetes and obesity. Although we know a great deal about the transporter systems by which zinc and calcium pass from the blood stream into milk, the interactions and cellular localization of transporters that carry substrates such as glucose, amino acids, copper, and the many other trace metals present in human milk across plasma and intracellular membranes require more research. We pose the question of how cultured mammary alveolar cells and animal models can help answer lingering questions about the mechanisms and regulation of human milk secretion. We raise questions about the role of the lactating parent and the infant microbiome and the immune system during breast development, secretion of immune molecules into milk, and protection of the breast from pathogens. Finally, we consider the effect of medications, recreational and illicit drugs, pesticides, and endocrine-disrupting chemicals on milk secretion and composition, emphasizing that this area needs much more research attention.

Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population

The human microbiome seeding starts at birth, when pioneer microbes are acquired mainly from the mother. Mode of delivery, antibiotic prophylaxis, and feeding method have been studied as modulators of mother-to-infant microbiome transmission, but other key influencing factors like modern westernized lifestyles with high hygienization, high-calorie diets, and urban settings, compared with non-westernized lifestyles have not been investigated yet. In this study, we explored the mother-infant sharing of characterized and uncharacterized microbiome members via strain-resolved metagenomics in a cohort of Ethiopian mothers and infants, and we compared them with four other cohorts with different lifestyles. The westernized and non-westernized newborns' microbiomes composition overlapped during the first months of life more than later in life, likely reflecting similar initial breast-milk-based diets. Ethiopian and other non-westernized infants shared a smaller fraction of the microbiome with their mothers than did most westernized populations, despite showing a higher microbiome diversity, and uncharacterized species represented a substantial fraction of those shared in the Ethiopian cohort. Moreover, we identified uncharacterized species belonging to the Selenomonadaceae and Prevotellaceae families specifically present and shared only in the Ethiopian cohort, and we showed that a locally produced fermented food, injera, can contribute to the higher diversity observed in the Ethiopian infants' gut with bacteria that are not part of the human microbiome but are acquired through fermented food consumption. Taken together, these findings highlight the fact that lifestyle can impact the gut microbiome composition not only through differences in diet, drug consumption, and environmental factors but also through its effect on mother-infant strain-sharing patterns.

Epidemiological and microbiome associations of Clostridioides difficile carriage in infancy and early childhood

ABSTRACT There has been an increase in the prevalence of Clostridioides difficile (C. diff) causing significant economic impact on the health care system. Although toxigenic C. diff carriage is recognized in infancy, there is limited data regarding its longitudinal trends, associated epidemiolocal risk factors and intestinal microbiome characteristics. The objectives of our longitudinal cohort study were to investigate temporal changes in the prevalence of toxigenic C.diff colonization in children up to 2 years, associated epidemiological and intestinal microbiome characteristics. Pregnant mothers were enrolled prenatally, and serial stool samples were collected from their children for 2 years. 2608 serial stool samples were collected from 817 children. 411/817 (50%) were males, and 738/817 (90%) were born full term. Toxigenic C.diff was detected in 7/569 (1%) of meconium samples, 116/624 (19%) of 2 m (month), 221/606 (37%) of 6 m, 227/574 (40%) of 12 m and 18/235 (8%) of 24 m samples. Infants receiving any breast milk at 6 m were less likely to be carriers at 2 m, 6 m and 12 m than those not receiving it. (p = 0.002 at 2 m, p < 0.0001 at 6 m, p = 0.022 at 12 m). There were no robust differences in the underlying alpha or beta diversity between those with and without toxigenic C. diff carriage at any timepoint, although small differences in the relative abundance of certain taxa were found. In this largest longitudinal cohort study to date, a high prevalence of toxigenic C. diff carrier state was noted. Toxigenic C. diff carrier state in children is most likely a transient component of the dynamic infant microbiome.

MP70-11 DEFINING THE URINARY MICROBIOME OF THE HEALTHY INFANT BLADDER.

You have accessJournal of UrologyCME1 Apr 2023MP70-11 DEFINING THE URINARY MICROBIOME OF THE HEALTHY INFANT BLADDER. Viktor Flores, Seth Reasoner, Leslie Peard, Benjamin Abelson, Carmila Manuel, Gerald Van Horn, Abby Taylor, Cyrus Adams, Mark Adams, John Thomas, John Pope, John Brock, Grace Morales, Jonathan Schmitz, Douglass Clayton, and Maria Hadjifrangiskou Viktor FloresViktor Flores More articles by this author , Seth ReasonerSeth Reasoner More articles by this author , Leslie PeardLeslie Peard More articles by this author , Benjamin AbelsonBenjamin Abelson More articles by this author , Carmila ManuelCarmila Manuel More articles by this author , Gerald Van HornGerald Van Horn More articles by this author , Abby TaylorAbby Taylor More articles by this author , Cyrus AdamsCyrus Adams More articles by this author , Mark AdamsMark Adams More articles by this author , John ThomasJohn Thomas More articles by this author , John PopeJohn Pope More articles by this author , John BrockJohn Brock More articles by this author , Grace MoralesGrace Morales More articles by this author , Jonathan SchmitzJonathan Schmitz More articles by this author , Douglass ClaytonDouglass Clayton More articles by this author , and Maria HadjifrangiskouMaria Hadjifrangiskou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003338.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A decade ago, the ”healthy” bladder was presumed to be a sterile organ. The advent of expanded quantitative urine culture (EQUC) and incorporation of 16S rRNA sequencing in studying the urinary microbiome have now disproven this long-held dogma. To date, the pediatric urinary microbiome of healthy infants has not been characterized using EQUC and 16S rRNA. The aim of this study is to identify the cultivatable urobiome of male infants and characterize a representation of the core microbiome using 16S rRNA sequencing. METHODS: IRB approval was obtained to collect catheterized urine samples from healthy infants less than 12 months of age undergoing an elective circumcision. Exclusion criteria included prior history of UTI, genitourinary anomaly, or urethral catheterization. Urine aliquots were plated in 5% Sheep’s Blood and Brucella agar plates and incubated anaerobically and aerobically for up to 5 days. Speciation of bacterial isolates were verified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Environmental control samples were collected from the operating room also analyzed. Urine samples were shipped to University of California at San Diego Microbiome Center for DNA extraction and sequencing. Following DNA extraction, the V4 hypervariable 16S rRNA region was amplified using standardized primers from the Earth Microbiome Project and reads were processed using R programming. RESULTS: Fifty patients were enrolled. Sixty-four percent of patients grew organisms using EQUC, ranging from 1 to 5 unique species. Infants born full term were more likely to grow an organism using EQUC (p=0.03), but there was no difference in microbiome diversity with 16S rRNA sequencing based on method of infant delivery, birth term status, or prior antibiotic exposure. Forty different cultivatable species were identified, with the highest representation in the Actinomycetaceae (18%), Enterobacteriaceae and Staphylococcaceae families (13%). The most common species was Actinotignum schaalii seen in 18% of infants. 16S sequencing demonstrated that the core microbiome of infants is composed of bacteria from the phyla Actinobacteria, Bacteroides, Firmicutes, and Proteobacteria. CONCLUSIONS: Using EQUC we identified uncommon bacterial isolates in 64% of healthy infant samples, with 40 distinct organisms. A core microbiome representation of the infant bladder was identified with 16S rRNA sequencing. Our results demonstrate that a urinary microbiome can be detected in healthy infants using culturing and sequencing methods. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1008 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Viktor Flores More articles by this author Seth Reasoner More articles by this author Leslie Peard More articles by this author Benjamin Abelson More articles by this author Carmila Manuel More articles by this author Gerald Van Horn More articles by this author Abby Taylor More articles by this author Cyrus Adams More articles by this author Mark Adams More articles by this author John Thomas More articles by this author John Pope More articles by this author John Brock More articles by this author Grace Morales More articles by this author Jonathan Schmitz More articles by this author Douglass Clayton More articles by this author Maria Hadjifrangiskou More articles by this author Expand All Advertisement PDF downloadLoading ...

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory Tcell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

The Nonbacterial Microbiome: Fungal and Viral Contributions to the Preterm Infant Gut in Health and Disease.

The intestinal microbiome is frequently implicated in necrotizing enterocolitis (NEC) pathogenesis. While no particular organism has been associated with NEC development, a general reduction in bacterial diversity and increase in pathobiont abundance has been noted preceding disease onset. However, nearly all evaluations of the preterm infant microbiome focus exclusively on the bacterial constituents, completely ignoring any fungi, protozoa, archaea, and viruses present. The abundance, diversity, and function of these nonbacterial microbes within the preterm intestinal ecosystem are largely unknown. Here, we review findings on the role of fungi and viruses, including bacteriophages, in preterm intestinal development and neonatal intestinal inflammation, with potential roles in NEC pathogenesis yet to be determined. In addition, we highlight the importance of host and environmental influences, interkingdom interactions, and the role of human milk in shaping fungal and viral abundance, diversity, and function within the preterm intestinal ecosystem.