Infant Microbiota Research Articles

Problems of gut microbiota formation as a risk factor for the development of immunopathological diseases and opportunities for their prevention: A review

The formation of infant intestinal microbiota begins in the womb when there is a selective transport of certain bacteria from the intestine through the placenta and amniotic fluid which has been proved in experiments. The mode of delivery has a significant impact on the establishment of the intestinal biocenosis: babies born by caesarean section show a slower colonisation rate and a higher risk of developing food allergies later in life. Antibiotic therapy at an early age can permanently alter the composition of the intestinal microbiota and has a proven risk of developing a range of diseases, both immunopathological and metabolic. The type of feeding also has a significant impact. Exclusive breastfeeding from birth promotes the establishment of a bifidobacterial and bacteroide-dominated infant microbiota. Supplementation at birth and early transfer to complementary feeding contribute to microbiocenosis alteration and sensitisation to cow's milk protein. Probiotics due to their protective and immunomodulatory effects can improve the composition of the microbiota of breast milk and the baby's gut and their perinatal administration reduces the risk of food allergies and other diseases.

Effect of breast milk with or without bacteria on infant gut microbiota

BackgroundThe breast milk microbiome could be a source of infant intestinal microbiota. Several studies have found that some breast milk is extremely low in bacteria or is even sterile. There are limited studies on the effect of milk without bacteria on the infant gut microbiota. The purpose of this study was to investigate the gut microbiota of infants fed with bacterial milk or sterile milk. Meanwhile, we attempted to find the cause of undetectable bacteria in milk.MethodsA total of 17 healthy pregnant women and 17 infants were enrolled in this study. Fecal samples were collected from full-term pregnant women. Milk samples and infant fecal samples were collected on the 14th postnatal day. Breast milk and fecal samples were examined using 16S rRNA sequencing technology. Pregnant women and infants were grouped according to milk with or without bacteria. To compare the differences in gut microbiota and clinical characteristics between groups.ResultsBacteria were detected in 11 breast milk samples, and the bacterial detection rate was 64.7%. Infants fed with bacterial milk showed higher Shannon index and Simpson index (P = 0.020, P = 0.048), and their relative abundance of Lachnospirales, Lachnospiraceae and Eggerthellaceae was markedly higher. In addition, there were more bacterial associations in the co-occurrence network of infants fed with bacterial milk. Pregnant women with sterile and bacterial breast milk showed no significant differences in their clinical characteristics, and microbial composition and diversity.ConclusionsSome breast milk from healthy postpartum women failed to be sequenced due to low microbial DNA quantities or is sterile. Research is needed to explore the reasons for this phenomenon. Infants fed with bacterial milk had higher Alpha diversity and more complex microbiota networks. These findings provide novel insight into milk microbiota and infant gut microbiota.

Characterization and Comparison of Ocular Surface Microbiome in Newborns.

The ocular microbiome is of fundamental importance for immune eye homeostasis, and its alteration would lead to an impairment of ocular functionality. Little evidence is reported on the composition of the ocular microbiota of term infants and on the impact of antibiotic prophylaxis. Methods: A total of 20 conjunctival swabs were collected from newborns at birth and after antibiotic treatment. Samples were subjected to 16S rRNA sequencing via system MiSeq Illumina. The data were processed with the MicrobAT software and statistical analysis were performed using two-way ANOVA. Results: Antibiotic prophylaxis with gentamicin altered the composition of the microbiota. In detail, a 1.5- and 2.01-fold reduction was recorded for Cutibacterium acnes (C. acnes) and Massilia timonae (M. timonae), respectively, whereas an increase in Staphylococcus spp. of 6.5 times occurred after antibiotic exposure. Conclusions: Antibiotic prophylaxis altered the ocular microbiota whose understanding could avoid adverse effects on eye health.

A Randomized Controlled Trial of Dietary Rice Bran Intake on Microbiota Diversity, Enteric Dysfunction, and Fecal Secretory IgA in Malian and Nicaraguan Infants

ABSTRACTBackgroundMalnutrition and diarrhea are leading causes of death in children aged <5 y. Rice bran is a nutrient-dense prebiotic available globally.ObjectivesThe objective of this secondary analysis was to evaluate the effects of daily rice bran supplementation on environmental enteric dysfunction (EED) markers, total fecal secretory IgA (sIgA), and microbiota in infants at high risk of malnutrition.MethodsSix-month-old Malian and Nicaraguan infants were randomly assigned to control or daily rice bran supplementation cohorts (1 to 5 g/d). Feces were collected monthly for 6 mo to evaluate fecal sIgA, markers of EED, and microbiota diversity. Statistical methods included linear mixed models, generalized mixed models, Spearman correlation, and Wilcoxon rank-sum tests.ResultsSix-month-old Malian infants had significantly elevated sIgA (4.0× higher, P < 0.001), fecal myeloperoxidase (31.6× higher, P < 0.001), fecal α1-antitrypsin (1.8× higher, P = 0.006), and lower fecal neopterin (0.13× higher, P < 0.001) than the age-matched Nicaraguan infants. In the Nicaraguan rice bran cohort from 6 to 12 mo of age, there was a significant decrease in sIgA concentrations (0.4×, P < 0.05) and a correlation between sIgA and the EED marker α1-antitrypsin (0.523, P < 0.0001) at 12 mo of age. In Malian infants, daily rice bran ingestion resulted in decreased EED scores (0.71×, P = 0.02) and a stable sIgA concentration over time. The rice bran group of Malian infants also had correlation between sIgA and the EED marker neopterin (0.544, P < 0.001) at 12 mo of age and a significant (P < 0.05) increase in microbiota α-diversity at a younger age (9 mo with rice bran compared with 10 mo in control group), which supports earlier microbiota maturation.ConclusionsThese results support rice bran as a functional food ingredient targeting gut mucosa in children at high-risk of malnutrition.

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.

The Complex Link and Disease Between the Gut Microbiome and the Immune System in Infants

The human gut microbiome is important for human health. The development of stable microbial communities in the gastrointestinal tract is closely related to the early growth and development of host immunity. After the birth of a baby, immune cells and the gut microbiome mature in parallel to adapt to the complex gut environment. The gut microbiome is closely linked to the immune system and influences each other. This interaction is associated with various diseases in infants and young children, such as asthma, food allergies, necrotizing colitis, obesity, and inflammatory bowel disease. Thus, the composition of the infant gut microbiome can predict the risk of disease development and progression. At the same time, the composition of the infant gut microbiome can be regulated in many ways and can be used to prevent and treat disease in infants by modulating the composition of the infant gut microbiome. The most important impacts on infant gut microbiota are maternal, including food delivery and feeding. The differences in the gut microbiota of infants reflect the maternal gut microbiota, which in turn reflects the gut microbiota of a given population, which is clinically significant.

#49 Nasal microbiota differences in young infants are associated with early childhood irritability

Abstract Background The etiology and pathophysiology of childhood mental health are poorly understood. Early childhood irritability is a transdiagnostic marker that portends significant risk for subsequent mental health problems. Robust evidence demonstrates irritability can be quantified early in infancy. The early life microbiome is implicated in defining health trajectories including neurodevelopment. In contrast to the gut microbiome, however, a relationship between the infant nasal microbiome and early childhood irritability remains undefined. We sought to investigate associations between the nasal microbiota of infants &amp;lt;60 days of age and early childhood irritability. Method This case-control study included infants with archived respiratory nasal samples collected for routine clinical care at ≤60 days of age from an emergency department visit (1/2016-5/2019). Parents completed an online survey when children were 14-42 months of age that included questions about medical history, development, and irritability (Multidimensional Assessment of Preschool Disruptive Behavior, MAP-DB). The upper quartile of the MAP-DB Temper Loss Score was classified as high dysregulation. Additional clinical data were collected from the electronic health record. DNA extracted from archived viral media specimens were subjected to 16S rRNA gene (V3-V4 region) next generation sequencing (NGS). Ecological diversity and differential taxon analysis were performed. Results Seventy-two children were initially included, with 16 categorized as high dysregulation. The median age at nasal sample collection was 30 days (IQR 14-44), and age at parent survey was 28 months (IQR 19-31). Fifty-weight percent of the cohort was white, 6% Black, 6% Asian, 20% other, and 25% identified as Lantine ethnicity. The infants were 49% female sex, 77% were born by vaginal delivery, and 43% had a virus identified at time of nasal sample. After removal of extraction/PCR contaminants, taxa present only or at higher levels in media, and samples with &amp;lt;80 sequences, the final microbiota comparison dataset was n=33 children, 7 with high dysregulation. Alpha-diversity (Shannon index) was lower in the high dysregulation group (p=0.0031 pre-background taxa removal, p=0.1288 post-correction, Figure 1A-B). Of the 18 taxa that were compared, Haemophilus, Streptococcus, Staphylococcus, and Gardnerella were significantly less abundant in the high dysregulation group (false discovery corrected significance q&amp;lt;0.005, Figure 1C). Parasutterella was more abundant in a subset of the high dysregulation group. Conclusion Differences in the nasal microbiota of infants, decreased diversity and abundance of certain respiratory bacteria, are associated with early childhood irritability, a marker of mental health risk. Further study may provide mechanistic insights and potentially guide new risk assessment or treatment options.

Antibiotic treatments to mothers during the perinatal period leaving hidden trouble on infants

Antibiotic application during the perinatal period is unavoidable in the clinic, but the potential effects on mothers and infants remain unknown. Herein, 25 breast milk samples from mothers who received cefuroxime (CXM) or CXM + cefoxitin (CFX) treatments and fecal samples from their infants were collected to investigate the undesirable effects of antibiotics on the microbiota of mothers and neonates. Furthermore, five fecal samples of infants, whose mothers had antibiotic treatments, were collected at a 6-month postpartum follow-up visit to evaluate the long-term effects on infants’ gut microbiota. Moreover, the relative abundance of antibiotic resistance genes (ARGs) in fecal samples was compared to investigate the transfer of ARGs in the infant gut microbiota. The results indicated that the antibiotic treatments had no influence on the microbiota of breast milk. The dominant bacterial phyla in the fecal samples changed to Firmicutes and Proteobacteria after antibiotic treatments, while the bacterial community showed a recuperative trend at the follow-up visits. In addition, the abundance of ARGs in the infant gut microbiota demonstrated a declining trend in the CXM- and CXM + CFX-treated groups, while ARG abundance presented a significant increasing trend after a 6-month recovery period.Conclusion: Antibiotic treatments for mothers during the perinatal period disturb the gut microbiota in neonates. The infants’ gut microbiota would partly return to their initial state after rehabilitation, but the transfer of ARGs would leave the hidden trouble of antibiotic resistance. Overall, the data presented here can help to guide the scientific use of antibiotics during the perinatal period and provide potential approaches to mitigate the negative consequences.What is Known:• Antibiotic application during the perinatal period is unavoidable in the clinic.• Misuse of antibiotics can cause various unintended consequences, especially for antibiotic resistance.What is New:• Antibiotic treatments had no influence on the microbiota of breast milk but greatly disturbed the gut microbiota composition in infants.• The gut microbiota in infants would partly return to its initial state after rehabilitation but the transfer of ARGs would leave the hidden trouble of antibiotic resistance.

Development of gut microbiota during the first 2 years of life

Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.

Comparison of the Gut Microbiota in Healthy Infants With Different Delivery Modes and Feeding Types: A Cohort Study.

To compare the gut microbiota of healthy infants based on specific interactions of delivery modes and feeding types, we recruited 62 healthy babies who were followed up for 2 years from our previous cohort study of 91 infants (the rest were lost to follow-up). They were exclusively fed breast milk or specific formulas for more than 4 months after birth. The fecal bacterial composition was tested at 40 days, 3 months, and 6 months of age. Solid foods were introduced from 4 to 6 months of age and thus did not affect the microbiota before 4 months of age. According to the different delivery modes (i.e., vaginal delivery, VD, or cesarean section delivery, CS) and feeding types (i.e., breast-fed, br, or formula-fed, fo), the infants were assigned to four different groups, namely, the VD-br, VD-fo, CS-br, and CS-fo groups. We found that at 40 days of age, the α diversity (reported as the Shannon index) was lower in the br infants than in the fo infants. At 3 months of age, the α diversity was significantly lower in the CS-br group, although significant differences were not observed after solid food introduction. Bifidobacterium represented the most predominant genus in all groups at all time points, followed by Enterobacteriaceae. At 40 days of age, the abundance of Bifidobacterium was much higher in the CS-br group than in the CS-fo group but did not differ between the VD-br and VD-fo groups. The differences in Bifidobacterium disappeared at 3 and 6 months of age among the different groups. At 40 days of age, the abundance of Streptococcus and Enterococcus was much lower in the br infants than in the CS-fo group. At 3 months of age, Enterococcus was significantly lower in the CS-br group than in the fo infants, although for infants delivered by VD, the difference between feeding types was not significant. The specific interaction of delivery modes and feeding types has a large impact on the infants' gut microbiota. Breastfeeding and VD may decrease the potential adverse effects of formula feeding or CS delivery on gut microbiota, thus leading to a more stable and beneficial gut environment for infants.

A synbiotics, long chain polyunsaturated fatty acids, and milk fat globule membranes supplemented formula modulates microbiota maturation and neurodevelopment

The critical window of concurrent developmental paths of the nervous system and gut microbiota in infancy provides an opportunity for nutritional interventions with potential health benefits later in life. We compared the dynamics of gut microbiota maturation and explored its association with neurodevelopment at 12 months and 4 years of age in 170 full-term healthy infants fed a standard formula (SF) or a new formula (EF) based on standard formula supplemented with synbiotics, long chain polyunsaturated fatty acids (LC-PUFA) and bovine milk fat globule membranes (MFGM), including a breastfed reference group (BF). Using Dirichlet Multinomial Modelling, we characterized three microbial enterotypes (Mixed, anaerobic and aerobic profile; Bact, Bacteroides-dominant; Firm, Firmicutes-enriched) and identified a new enterotype dominated by an unidentified genus within Lachnospiraceae (U_Lach). Enterotypes were associated with age (Mixed with baseline, U_Lach with month 6, Bact and Firm with months 12 and 18). Trajectories or timely enterotype shifts in each infant were not random but strongly associated with type of feeding. Trajectories in SF shifted from initial Mixed to U_Lach, Bact or Firm at month. Microbiota maturation in EF split into a fast trajectory as in SF, and a slow trajectory with Mixed to U_Lach, Bact or Firm transitions at months 12 or 18, as in BF. EF infants with slow trajectories were more often in-home reared and born by vaginal delivery to mothers with pre-pregnancy lean BMI. At 12 months of age, language and expressive language scores were significantly higher in EF infants with fast trajectories than in BF. Neurodevelopmental outcomes were similar between EF infants with slow trajectories and BF at 12 months and 4 years of age. Feeding a synbiotics, LC-PUFA and MFGM supplemented formula in a specific infant environment promoted probiotic growth and retarded gut microbiota maturation with similar neurodevelopment outcomes to breastfed infants. NCT02094547.

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.

The ecology and antimicrobial resistance of Staphylococci colonising neonates

Coagulase Negative Staphylococci (CoNS) are common commensals of human skin, account for nearly 20% of the microbiota in infants and are thought to promote early immune responses in healthy babies. However, CoNS are opportunistic pathogens and in the UK between 2005 and 2014 were responsible for 57% of episodes of Late Onset Sepsis (LOS). In neonatal intensive care units (NICUs) this is a major concern and antiseptics are used to prevent vascular catheter infections. Chlorhexidine (CHX) and Octenidine (OCT) are the most common agents used for skin antisepsis, but evidence is emerging of antiseptic tolerance amongst CoNS. We undertook a longitudinal survey of CoNS from skin and rectal swabs isolated from babies in two NICUs from countries with different antiseptic regimens (UK and Germany). Over 1000 isolates were characterised for antimicrobial susceptibility and sequenced. The most frequent species isolated were S. epidermidis and S. haemolyticus with similar strain types present in both units. Reduced susceptibility to CHX and OCT was observed in UK isolates (where CHX is used), compared to German isolates (where OCT is used). Analysis of genome data using GWAS and clustering techniques has identified loci associated with antimicrobial susceptibility. Comparison of isolates taken on admission and thereafter, demonstrated that babies acquired isolates with decreased antiseptic tolerance after admission. This data provides new information about the phylogeny of CoNS in NICUs and suggest different potentials for selection of resistance between antiseptics commonly used in neonatal care.

Human milk oligosaccharides induce acute yet reversible compositional changes in the gut microbiota of conventional mice linked to a reduction of butyrate levels.

Human Milk Oligosaccharides (HMOs) are glycans with prebiotic properties known to drive microbial selection in the infant gut, which in turn influences immune development and future health. Bifidobacteria are specialized in HMO degradation and frequently dominate the gut microbiota of breastfed infants. However, some species of Bacteroidaceae also degrade HMOs, which may prompt selection also of these species in the gut microbiota. To investigate to what extent specific HMOs affect the abundance of naturally occurring Bacteroidaceae species in a complex mammalian gut environment, we conducted a study in 40 female NMRI mice administered three structurally different HMOs, namely 6'sialyllactose (6'SL, n = 8), 3-fucosyllactose (3FL, n = 16), and Lacto-N-Tetraose (LNT, n = 8), through drinking water (5%). Compared to a control group receiving unsupplemented drinking water (n = 8), supplementation with each of the HMOs significantly increased both the absolute and relative abundance of Bacteroidaceae species in faecal samples and affected the overall microbial composition analyzed by 16srRNA amplicon sequencing. The compositional differences were mainly attributed to an increase in the relative abundance of the genus Phocaeicola (formerly Bacteroides) and a concomitant decrease of the genus Lacrimispora (formerly Clostridium XIVa cluster). During a 1-week washout period performed specifically for the 3FL group, this effect was reversed. Short-chain fatty acid analysis of faecal water revealed a decrease in acetate, butyrate and isobutyrate levels in animals supplemented with 3FL, which may reflect the observed decrease in the Lacrimispora genus. This study highlights HMO-driven Bacteroidaceae selection in the gut environment, which may cause a reduction of butyrate-producing clostridia.

Effects of a Formula with scGOS/lcFOS (9:1) and Glycomacropeptide (GMP) Supplementation on the Gut Microbiota of Very Preterm Infants.

Microbial colonization of very preterm (VPT) infants is detrimentally affected by the complex interplay of physiological, dietary, medical, and environmental factors. The aim of this study was to evaluate the effects of an infant formula containing the specific prebiotic mixture of scGOS/lcFOS (9:1) and glycomacropeptide (GMP) on the composition and function of VPT infants’ gut microbiota. Metagenomic analysis was performed on the gut microbiota of VPT infants sampled at four time points: 24 h before the trial and 7, 14, and 28 days after the trial. Functional profiling was aggregated into gut and brain modules (GBMs) and gut metabolic modules (GMMs) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Enterococcus faecium, Escherichia coli, Klebsiella aerogenes, and Klebsiella pneumoniae were dominant species in both the test group and the control group. After the 4-week intervention, the abundance of Bifidobacterium in the test group was significantly increased. We found two GBMs (quinolinic acid synthesis and kynurenine degradation) and four GMMs (glutamine degradation, glyoxylate bypass, dissimilatory nitrate reduction, and preparatory phase of glycolysis) were significantly enriched in the test group, respectively. The results of this study suggested that formula enriched with scGOS/lcFOS (9:1) and GPM is beneficial to the intestinal microecology of VPT infants.

Profiling Growth Patterns of Human Gut Microbes in Response to Preterm Human Milk and Formula

BackgroundThe infant gut microbiota undergoes significant fluxes in microbial composition during the first few years of life. The intestine is colonized shortly after birth with facultative anaerobes, like as Enterococcus, Enterobacter, Streptococcus, and Staphylococcus, which reduce the intestinal oxygen content and create niches for strict anaerobes, like Bifidobacteria, Bacteroides, and Clostridia. The dominant factors which influence the infant gut composition are gestational age and diet. The gut microbiota of preterm infants is characterized by limited microbial diversity and increased levels of facultative anaerobes such as Enterococci, Staphylococci, and Enterbacteriacea (Enterobacter, Escherichia, and Klebsiellaspp.). The gut microbiota is also highly influenced by diet, specifically formula and human milk use. The intake of human milk is associated with increased Bifidobacteria, while the intake of formula correlates with increased Enterobacteriaceae. This study aimed to analyze next‐generation products including preterm formula, human milk‐oligosaccharide term formula, and preterm breastmilk using a culture‐based model.Methods &amp; ResultsWe cultured 8 different Bifidobacteria, 8 Lactobacilli, 8 Streptococcus, 3 Enterococci and 4 Klebsiella strains in a fully defined bacteria media and monitored growth and pH after 20 hrs of anaerobic incubation. Significant differences were identified in strain growth and culture pH between human milk and formula. Human milk significantly elevated the growth of all Bifidobacteria and Lactobacilli. In contrast, human milk supported the growth of three Streptococci and only nominally supported pathobiont Enterococci and Klebsiella strains. Preterm formula elevated the majority of Bifidobacteria and Lactobacilli, as well as several Streptococci. Interestingly, preterm and full‐term formula significantly enhanced the growth of pathobiont strains. Full‐term formula only supported the growth certain commensal microbes, which was in marked contrast to human milk and preterm formula. Using computational modeling, a correlation was observed with human milk oligosaccharide (HMO) degrading glycosyl hydrolase profiles in the genomes of commensal microbes with human milk, but not with formula; confirming the HMO preference of our representative infant commensal microbes.ConclusionsThese findings indicate a unique profile of growth in response to human milk and formula. Since alterations in the infant gut microbiota have linked to childhood health and development, understanding how bacteria differentially utilize whole milk or formula may provide insights into which microbes drive diet‐related microbiota shifts.

Developing a synbiotic biotherapy to prevent allergic responses to food

Abstract Over the past generation, the prevalence of food allergies has risen dramatically, but the development of treatments has lagged. The commensal gut microbiome is critically involved in regulating allergic responses to food. Our laboratory has described a humanized model of cow’s milk allergy (CMA) in which germ-free mice are colonized with feces from healthy or CMA infants and sensitized to the cow’s milk allergen b-lactoglobulin (BLG). The healthy infant microbiota and specifically a single Clostridial species, Anaerostipes caccae, protect against the development of anaphylaxis, while the CMA microbiota does not induce this protection. We isolated a novel sub-strain of A. caccae (A. caccae_lahuc) from the feces of a healthy infant, sequenced its genome, and characterized its growth on various substrates in vitro. A. caccae_lahuc produces high concentrations of butyrate, a key immunoregulatory molecule in the gut which we hypothesize is critical to its protective impact. A. caccae_lahuc engrafts readily into the dysbiotic CMA microbiota, but co-delivery with lactulose is required for measurable butyrate production in vivo. Lactulose undergoes primary degradation by bacteria in the CMA feces which release small metabolites that A. caccae_lahuc can ferment into butyrate. Preliminary data show that this novel synbiotic biotherapy (A. caccae_lahuc + lactulose) prevents allergic responses to BLG in CMA-colonized mice as measured by serum mMCPT-1 and core body temperature upon challenge, and type 2 cytokine production in BLG-stimulated splenocytes. Further exploration into the mechanisms behind this therapeutic effect will contribute toward the larger goal of developing bacterial biotherapeutics against food allergies.

Association Between Trajectory Patterns of Body Mass Index Change Up to 10 Months and Early Gut Microbiota in Preterm Infants.

Recent research suggests that gut microbiota plays an important role in the occurrence and development of excessive weight and obesity, and the early-life gut microbiota may be correlated with weight gain and later growth. However, the association between neonatal gut microbiota, particularly in preterm infants, and excessive weight and obesity remains unclear. To evaluate the relationship between gut microbiota and body mass index (BMI) growth trajectories in preterm infants, we examined microbial composition by performing 16S rDNA gene sequencing on the fecal samples from 75 preterm infants within 3 months after birth who were hospitalized in the neonatal intensive care unit of Hunan Children’s Hospital from August 1, 2018 to October 31, 2019. Then, we collected their physical growth information during 0–10 months. Latent growth mixture models were used to estimate growth trajectories of infantile BMI, and the relationship between the gut microbiota and the BMI growth trajectories was analyzed. The results demonstrated that there were 63,305 and 61 operational taxonomic units in the higher BMI group (n = 18), the lower BMI group (n = 51), and the BMI catch-up group (n = 6), respectively. There were significant differences in the abundance of the gut microbiota, but no significant differences in the diversity of it between the lower and the higher BMI group. The BMI growth trajectories could not be clearly distinguished because principal component analysis showed that gut microbiota composition among these three groups was similar. The three groups were dominated by Firmicutes and Proteobacteria in gut microbiota composition, and the abundance of Lactobacillus in the higher BMI group was significantly different from the lower BMI group. Further intervention experiments and dynamic monitoring are needed to determine the causal relationship between gut microbiota differences and the BMI change.

Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents.

Gut microbiota maturation coincides with nervous system development. Cross-sectional data suggest gut microbiota of individuals with and without attention deficit hyperactivity disorder (ADHD) differs. We hypothesized that infant gut microbiota composition is associated with later ADHD development in our on-going birth cohort study, WHEALS. Gut microbiota was profiled using 16S ribosomal RNA and the internal transcribed spacer region 2 (ITS2) sequencing in stool samples from 1 month and 6 months of age. ADHD was defined by parent-reported or medical record doctor diagnosis at age 10. A total of 314 children had gut microbiota and ADHD data; 59 (18.8%) had ADHD. After covariate adjustment, bacterial phylogenetic diversity (p = 0.017) and bacterial composition (unweighted UniFrac p = 0.006, R2 = 0.9%) at age 6 months were associated with development of ADHD. At 1 month of age, 18 bacterial and 3 fungal OTUs were associated with ADHD development. At 6 months of age, 51 bacterial OTUs were associated with ADHD; 14 of the order Lactobacillales. Three fungal OTUs at 6 months of age were associated with ADHD development. Infant gut microbiota is associated with ADHD development in pre-adolescents. Further studies replicating these findings and evaluating potential mechanisms of the association are needed. Cross-sectional studies suggest that the gut microbiota of individuals with and without ADHD differs. We found evidence that the bacterial gut microbiota of infants at 1 month and 6 months of age is associated with ADHD at age 10 years. We also found novel evidence that the fungal gut microbiota in infancy (ages 1 month and 6 months) is associated with ADHD at age 10 years. This study addresses a gap in the literature in providing longitudinal evidence for an association of the infant gut microbiota with later ADHD development.