Novel Insights into the Infant Gut Microbiome and Host–Microbe Interactions

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 32380

Special Issue Editor

Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61801, USA
Interests: infant; microbiome; breastfeeding; human milk; oligosaccharide

Special Issue Information

Dear Colleagues,

In recent years, data from large longitudinal cohorts have informed our understanding of the temporal development of the gut infant microbiome and the key determinants of that process. However, less is known about the temporal development and composition of the phages, fungi, and archaea in the gut microbiota and in/on other body sites in infancy. Additionally, a major gap exists in our understanding of host-microbe interactions in infancy that underlie long-term programming of infant cognitive, immune, and metabolic programming.

The aim of this Microorganisms Special Issue is to provide deep insights into the latest developments of research dedicated to the defining the function of the infant microbiota. Articles that describe novel aspects of metabolomics, probiotics, bacteriophage, and host-microbe interactions in humans are particularly sought, but mechanistic work in animal models is also desired.

The manuscripts included in this Special Issue should provide a foundation to expand our current understanding of the complex interactions between the host and is commensal microbiota and may suggest interventions to address dysbiosis in early life to support infant development.

Prof. Dr. Sharon M. Donovan
Guest Editor

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Keywords

  • infant
  • microbiome
  • nutrition
  • host–microbe interactions
  • metabolome

Published Papers (10 papers)

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Research

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19 pages, 1579 KiB  
Article
Microbial Interrelationships across Sites of Breastfeeding Mothers and Infants at 6 Weeks Postpartum
by Erin C. Davis, Mei Wang and Sharon M. Donovan
Microorganisms 2022, 10(6), 1155; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms10061155 - 02 Jun 2022
Cited by 2 | Viewed by 1685
Abstract
Infancy is a critical life stage for the establishment of the gut microbiome. Human milk contains a unique microbial ecosystem that serves as a continuous source of commensal bacteria for the infant. However, the origin of the human milk microbiota, how it is [...] Read more.
Infancy is a critical life stage for the establishment of the gut microbiome. Human milk contains a unique microbial ecosystem that serves as a continuous source of commensal bacteria for the infant. However, the origin of the human milk microbiota, how it is influenced by breastfeeding exclusivity, and its role in infant gut microbiota assembly are not clear. To interrogate these questions, we examined the relationships among fecal, oral, breast skin, and human milk microbiota of 33 exclusively breastfeeding (EBF) and mixed-feeding (MF; human milk + infant formula) mother–infant pairs at 6 weeks postpartum. Here, we show that MF infants have a significantly more diverse oral microbiome comprised of lower relative abundances of Streptococcus and Gemella and higher abundances of Veillonella. Using both SourceTracker2 and FEAST, we demonstrate breast skin and infant saliva as the principal contributing sources to the human milk microbiota. Of the sampled sites, human milk and maternal stool were predicted to contribute the largest fraction to the infant fecal microbiome, but the majority of the community was estimated to arise from unknown sources. Lastly, we identified twenty-one significant co-occurrence relationships between bacteria in human milk and on other maternal and infant body sites. These results demonstrate several unique microbial interrelationships between breastfeeding dyads, providing insight into potential mechanisms of microbial assembly in early life. Full article
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13 pages, 2425 KiB  
Article
Effect of Environmental Exposures on the Gut Microbiota from Early Infancy to Two Years of Age
by Kameron Y. Sugino, Tengfei Ma, Nigel Paneth and Sarah S. Comstock
Microorganisms 2021, 9(10), 2140; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9102140 - 13 Oct 2021
Cited by 9 | Viewed by 2092
Abstract
The gut microbiota undergoes rapid changes during infancy in response to early-life exposures. We have investigated how the infant gut bacterial community matures over time and how exposures such as human milk and antibiotic treatment alter gut microbiota development. We used the LonGP [...] Read more.
The gut microbiota undergoes rapid changes during infancy in response to early-life exposures. We have investigated how the infant gut bacterial community matures over time and how exposures such as human milk and antibiotic treatment alter gut microbiota development. We used the LonGP program to create predictive models to determine the contribution of exposures on infant gut bacterial abundances from one month to two years of age. These models indicate that infant antibiotic use, human milk intake, maternal pre-pregnancy BMI, and sample shipping time were associated with changes in gut microbiome composition. In most infants, Bacteroides, Lachnospiraceae unclassified, Faecalibacterium, Akkermansia, and Phascolarctobacterium abundance increased rapidly after 6 months, while Escherichia, Bifidobacterium, Veillonella, and Streptococcus decreased in abundance over time. Individual, time-varying, random effects explained most of the variation in the LonGP models. Multivariate association with linear models (MaAsLin) displayed partial agreement with LonGP in the predicted trajectories over time and in relation to significant factors such as human milk intake. Multiple factors influence the dynamic changes in bacterial composition of the infant gut. Within-individual differences dominate the temporal variations in the infant gut microbiome, suggesting individual temporal variability is an important feature to consider in studies with a longitudinal sampling design. Full article
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17 pages, 2203 KiB  
Article
Human Milk Oligosaccharide-Stimulated Bifidobacterium Species Contribute to Prevent Later Respiratory Tract Infections
by Shaillay Kumar Dogra, Francois-Pierre Martin, Dominique Donnicola, Monique Julita, Bernard Berger and Norbert Sprenger
Microorganisms 2021, 9(9), 1939; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9091939 - 12 Sep 2021
Cited by 21 | Viewed by 2855
Abstract
(1) Background: Human milk oligosaccharides (HMOs) may support immune protection, partly via their action on the early-life gut microbiota. Exploratory findings of a randomized placebo-controlled trial associated 2′fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) formula feeding with reduced risk for reported bronchitis and lower respiratory [...] Read more.
(1) Background: Human milk oligosaccharides (HMOs) may support immune protection, partly via their action on the early-life gut microbiota. Exploratory findings of a randomized placebo-controlled trial associated 2′fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT) formula feeding with reduced risk for reported bronchitis and lower respiratory tract illnesses (LRTI), as well as changes in gut microbiota composition. We sought to identify putative gut microbial mechanisms linked with these clinical observations. (2) Methods: We used stool microbiota composition, metabolites including organic acids and gut health markers in several machine-learning-based classification tools related prospectively to experiencing reported bronchitis or LRTI, as compared to no reported respiratory illness. We performed preclinical epithelial barrier function modelling to add mechanistic insight to these clinical observations. (3) Results: Among the main features discriminant for infants who did not experience any reported bronchitis (n = 80/106) or LRTI (n = 70/103) were the 2-HMO formula containing 2′FL and LNnT, higher acetate, fucosylated glycans and Bifidobacterium, as well as lower succinate, butyrate, propionate and 5-aminovalerate, along with Carnobacteriaceae members and Escherichia. Acetate correlated with several Bifidobacterium species. By univariate analysis, infants experiencing no bronchitis or LRTI, compared with those who did, showed higher acetate (p < 0.007) and B. longum subsp. infantis (p ≤ 0.03). In vitro experiments demonstrate that 2′FL, LNnT and lacto-N-tetraose (LNT) stimulated B. longum subsp. infantis (ATCC15697) metabolic activity. Metabolites in spent culture media, primarily due to acetate, supported epithelial barrier protection. (4) Conclusions: An early-life gut ecology characterized by Bifidobacterium-species-driven metabolic changes partly explains the observed clinical outcomes of reduced risk for bronchitis and LRTI in infants fed a formula with HMOs. (Trial registry number NCT01715246.). Full article
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17 pages, 2837 KiB  
Article
Variation in Human Milk Composition Is Related to Differences in Milk and Infant Fecal Microbial Communities
by Ryan M. Pace, Janet E. Williams, Bianca Robertson, Kimberly A. Lackey, Courtney L. Meehan, William J. Price, James A. Foster, Daniel W. Sellen, Elizabeth W. Kamau-Mbuthia, Egidioh W. Kamundia, Samwel Mbugua, Sophie E. Moore, Andrew M. Prentice, Debela G. Kita, Linda J. Kvist, Gloria E. Otoo, Lorena Ruiz, Juan M. Rodríguez, Rossina G. Pareja, Mark A. McGuire, Lars Bode and Michelle K. McGuireadd Show full author list remove Hide full author list
Microorganisms 2021, 9(6), 1153; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9061153 - 27 May 2021
Cited by 27 | Viewed by 4765
Abstract
Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, [...] Read more.
Previously published data from our group and others demonstrate that human milk oligosaccharide (HMOs), as well as milk and infant fecal microbial profiles, vary by geography. However, little is known about the geographical variation of other milk-borne factors, such as lactose and protein, as well as the associations among these factors and microbial community structures in milk and infant feces. Here, we characterized and contrasted concentrations of milk-borne lactose, protein, and HMOs, and examined their associations with milk and infant fecal microbiomes in samples collected in 11 geographically diverse sites. Although geographical site was strongly associated with milk and infant fecal microbiomes, both sample types assorted into a smaller number of community state types based on shared microbial profiles. Similar to HMOs, concentrations of lactose and protein also varied by geography. Concentrations of HMOs, lactose, and protein were associated with differences in the microbial community structures of milk and infant feces and in the abundance of specific taxa. Taken together, these data suggest that the composition of human milk, even when produced by relatively healthy women, differs based on geographical boundaries and that concentrations of HMOs, lactose, and protein in milk are related to variation in milk and infant fecal microbial communities. Full article
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19 pages, 1383 KiB  
Article
Bovine Milk Oligosaccharides and Human Milk Oligosaccharides Modulate the Gut Microbiota Composition and Volatile Fatty Acid Concentrations in a Preclinical Neonatal Model
by Mei Wang, Marcia H. Monaco, Jonas Hauser, Jian Yan, Ryan N. Dilger and Sharon M. Donovan
Microorganisms 2021, 9(5), 884; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9050884 - 21 Apr 2021
Cited by 13 | Viewed by 3019
Abstract
Milk oligosaccharides (OS) shape microbiome structure and function, but their relative abundances differ between species. Herein, the impact of the human milk oligosaccharides (HMO) (2′-fucosyllactose [2′FL] and lacto-N-neotetraose [LNnT]) and OS isolated from bovine milk (BMOS) on microbiota composition and volatile fatty acid [...] Read more.
Milk oligosaccharides (OS) shape microbiome structure and function, but their relative abundances differ between species. Herein, the impact of the human milk oligosaccharides (HMO) (2′-fucosyllactose [2′FL] and lacto-N-neotetraose [LNnT]) and OS isolated from bovine milk (BMOS) on microbiota composition and volatile fatty acid (VFA) concentrations in ascending colon (AC) contents and feces was assessed. Intact male piglets received diets either containing 6.5 g/L BMOS (n = 12), 1.0 g/L 2′FL + 0.5 g/L LNnT (HMO; n = 12), both (HMO + BMOS; n = 10), or neither (CON; n = 10) from postnatal day (PND) 2 to 34. Microbiota were assessed by 16S rRNA gene sequencing and real-time PCR, and VFA were measured by gas chromatography. The microbiota was affected by OS in an intestine region-specific manner. BMOS reduced (p < 0.05) microbial richness in the AC, microbiota composition in the AC and feces, and acetate concentrations in AC, regardless of HMO presence. HMO alone did not affect overall microbial composition, but increased (p < 0.05) the relative proportion of specific taxa, including Blautia, compared to other groups. Bacteroides abundance was increased (p < 0.05) in the AC by BMOS and synergistically by BMOS + HMO in the feces. Distinct effects of HMO and BMOS suggest complementary and sometimes synergistic benefits of supplementing a complex mixture of OS to formula. Full article
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19 pages, 1756 KiB  
Article
A Mediation Analysis to Identify Links between Gut Bacteria and Memory in Context of Human Milk Oligosaccharides
by Stephen A. Fleming, Jonas Hauser, Jian Yan, Sharon M. Donovan, Mei Wang and Ryan N. Dilger
Microorganisms 2021, 9(4), 846; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9040846 - 15 Apr 2021
Cited by 6 | Viewed by 2512
Abstract
Elucidating relationships between the gut and brain is of intense research focus. Multiple studies have demonstrated that modulation of the intestinal environment via prebiotics or probiotics can induce cognitively beneficial effects, such as improved memory or reduced anxiety. However, the mechanisms by which [...] Read more.
Elucidating relationships between the gut and brain is of intense research focus. Multiple studies have demonstrated that modulation of the intestinal environment via prebiotics or probiotics can induce cognitively beneficial effects, such as improved memory or reduced anxiety. However, the mechanisms by which either act remain largely unknown. We previously demonstrated that different types of oligosaccharides affected short- and long-term memory in distinct ways. Given that the oligosaccharide content of human milk is highly variable, and that formula-fed infants typically do not consume similar amounts or types of oligosaccharides, their potential effects on brain development warrant investigation. Herein, a mediation analysis was performed on existing datasets, including relative abundance of bacterial genera, gene expression, brain volume, and cognition in young pigs. Analyses revealed that numerous bacterial genera in both the colon and feces were related to short- and/or long-term memory. Relationships between genera and memory appeared to differ between diets. Mediating variables frequently included GABAergic and glutamatergic hippocampal gene expression. Other mediating variables included genes related to myelination, transcription factors, brain volume, and exploratory behavior. Overall, this analysis identified multiple pathways between the gut and brain, with a focus on genes related to excitatory/inhibitory neurotransmission. Full article
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15 pages, 1525 KiB  
Article
The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota
by Shen Jean Lim, Miriam Aguilar-Lopez, Christine Wetzel, Samia V. O. Dutra, Vanessa Bray, Maureen W. Groer, Sharon M. Donovan and Thao Ho
Microorganisms 2021, 9(2), 278; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9020278 - 29 Jan 2021
Cited by 7 | Viewed by 2820
Abstract
The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA [...] Read more.
The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota. Full article
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20 pages, 2417 KiB  
Article
Assessing the Multivariate Relationship between the Human Infant Intestinal Exfoliated Cell Transcriptome (Exfoliome) and Microbiome in Response to Diet
by Kejun He, Sharon M. Donovan, Ivan V. Ivanov, Jennifer S. Goldsby, Laurie A. Davidson and Robert S. Chapkin
Microorganisms 2020, 8(12), 2032; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms8122032 - 18 Dec 2020
Cited by 7 | Viewed by 3313
Abstract
Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly influencing the health and well-being of the host. In addition to the standard differential expression analysis of host genes to assess the complex cross-talk between [...] Read more.
Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly influencing the health and well-being of the host. In addition to the standard differential expression analysis of host genes to assess the complex cross-talk between environment (diet), microbiome, and host intestinal physiology, data-driven integrative approaches are needed to identify potential biomarkers of both host genes and microbial communities that characterize these interactions. Our findings demonstrate that the complementary application of univariate differential gene expression analysis and multivariate approaches such as sparse Canonical Correlation Analysis (sCCA) and sparse Principal Components Analysis (sPCA) can be used to integrate data from both the healthy infant gut microbial community and host transcriptome (exfoliome) using stool derived exfoliated cells shed from the gut. These approaches reveal host genes and microbial functional categories related to the feeding phenotype of the infants. Our findings also confirm that combinatorial noninvasive -omic approaches provide an integrative genomics-based perspective of neonatal host-gut microbiome interactions. Full article
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Review

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22 pages, 1753 KiB  
Review
Nurturing the Early Life Gut Microbiome and Immune Maturation for Long Term Health
by Shaillay Kumar Dogra, Cheong Kwong Chung, Dantong Wang, Olga Sakwinska, Sara Colombo Mottaz and Norbert Sprenger
Microorganisms 2021, 9(10), 2110; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9102110 - 07 Oct 2021
Cited by 28 | Viewed by 5411
Abstract
Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization [...] Read more.
Early life is characterized by developmental milestones such as holding up the head, turning over, sitting up and walking that are typically achieved sequentially in specific time windows. Similarly, the early gut microbiome maturation can be characterized by specific temporal microorganism acquisition, colonization and selection with differential functional features over time. This orchestrated microbial sequence occurs from birth during the first years of age before the microbiome reaches an adult-like composition and function between 3 and 5 years of age. Increasingly, these different steps of microbiome development are recognized as crucial windows of opportunity for long term health, primarily linked to appropriate immune and metabolic development. For instance, microbiome disruptors such as preterm and Cesarean-section birth, malnutrition and antibiotic use are associated with increased risk to negatively affect long-term immune and metabolic health. Different age discriminant microbiome taxa and functionalities are used to describe age-appropriate microbiome development, and advanced modelling techniques enable an understanding and visualization of an optimal microbiome maturation trajectory. Specific microbiome features can be related to later health conditions, however, whether such features have a causal relationship is the topic of intense research. Early life nutrition is an important microbiome modulator, and ‘Mother Nature’ provides the model with breast milk as the sole source of nutrition for the early postnatal period, while dietary choices during the prenatal and weaning period are to a large extent guided by tradition and culture. Increasing evidence suggests prenatal maternal diet and infant and child nutrition impact the infant microbiome trajectory and immune competence development. The lack of a universal feeding reference for such phases represents a knowledge gap, but also a great opportunity to provide adequate nutritional guidance to maintain an age-appropriate microbiome for long term health. Here, we provide a narrative review and perspective on our current understanding of age-appropriate microbiome maturation, its relation to long term health and how nutrition shapes and influences this relationship. Full article
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Other

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6 pages, 469 KiB  
Opinion
Metaproteomics—An Advantageous Option in Studies of Host-Microbiota Interaction
by Oleg Karaduta, Zeljko Dvanajscak and Boris Zybailov
Microorganisms 2021, 9(5), 980; https://0-doi-org.brum.beds.ac.uk/10.3390/microorganisms9050980 - 30 Apr 2021
Cited by 11 | Viewed by 2134
Abstract
Gut microbiome contributes to host health by maintaining homeostasis, increasing digestive efficiency, and facilitating the development of the immune system. Manipulating gut microbiota is being recognized as a therapeutic target to manage various chronic diseases. The therapeutic manipulation of the intestinal microbiome is [...] Read more.
Gut microbiome contributes to host health by maintaining homeostasis, increasing digestive efficiency, and facilitating the development of the immune system. Manipulating gut microbiota is being recognized as a therapeutic target to manage various chronic diseases. The therapeutic manipulation of the intestinal microbiome is achieved through diet modification, the administration of prebiotics, probiotics, or antibiotics, and more recently, fecal microbiome transplantation (FMT). In this opinion paper, we give a perspective on the current status of application of multi-omics technologies in the analysis of host-microbiota interactions. The aim of this paper was to highlight the strengths of metaproteomics, which integrates with and often relies on other approaches. Full article
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