Successional stages in infant gut microbiota maturation

Background: Disturbances in the primary colonization of the infant gut can result in life-long consequences and have been associated with a range of host conditions. Although early life factors have been shown to affect the infant gut microbiota development, our current understanding of the human gut colonization in early life remains limited. To gain more insights in the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (total number of samples, n=303). To evaluate gut microbiota maturation transition towards an adult configuration, we compared the microbiome composition of the infants to the Flemish Gut Flora Project population (n=1,106). Results: We observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, genus predominance was observed to shift from Escherichia over Bifidobacterium to Bacteroides. Both disease and antibiotic treatment were observed to be associated occasionally with gut microbiota maturation stage regression, a transient setback in microbiota maturation dynamics. Although the studied microbiota trajectories evolved to more adult-like constellations, microbiome community typing against the background of the Flemish Gut Flora Project (FGFP) cohort clustered all infant samples within the (in adults) potentially dysbiotic Bact2 enterotype. Conclusion: We confirmed similarities between infant gut microbial colonization and adult dysbiosis. A profound knowledge about the primary gut colonization process in infants might provide crucial insights into how the secondary colonization of a dysbiotic adult gut can be redirected.

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Maternal effects on early-life gut microbiome maturation in a wild nonhuman primate

10.1101/2021.11.06.467515 ◽

2021 ◽

Author(s):

Alice Baniel ◽

Lauren Petrullo ◽

Arianne Mercer ◽

Laurie Reitsema ◽

Sierra Sams ◽

...

Keyword(s):

Maternal Effects ◽

Gut Microbiome ◽

Early Life ◽

Amplicon Sequencing ◽

Microbial Colonization ◽

Fecal Samples ◽

Microbiome Composition ◽

16S Rrna Amplicon Sequencing ◽

Gut Colonization ◽

First Time

Early-life gut microbial colonization is an important process shaping host physiology, immunity and long-term health outcomes in humans and other animals. However, our understanding of this dynamic process remains poorly investigated in wild animals, where developmental mechanisms can be better understood within ecological and evolutionary relevant contexts. Using 16s rRNA amplicon sequencing on 525 fecal samples from a large cohort of infant and juvenile geladas (Theropithecus gelada), we characterized gut microbiome maturation during the first three years of life and assessed the role of maternal effects in shaping offspring microbiome assembly. Microbial diversity increased rapidly in the first months of life, followed by more gradual changes until weaning. As expected, changes in gut microbiome composition and function with increasing age reflected progressive dietary transitions: in early infancy when infants rely heavily on their mother's milk, microbes that facilitate milk glycans and lactose utilization dominated, while later in development as graminoids are progressively introduced into the diet, microbes that metabolize plant complex polysaccharides became dominant. Furthermore, the microbial community of nursing infants born to first-time (primiparous) mothers was more "milk-oriented" compared to similarly-aged infants born to experienced (multiparous) mothers. Comparisons of matched mother-offspring fecal samples to random dyads did not support vertical transmission as a conduit for these maternal effects, which instead could be explained by slower phenotypic development (and associated slower gut microbiome maturation) in infants born to first-time mothers. Together, our findings highlight the dynamic nature of gut colonization

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Impact of Delivery Mode on Infant Gut Microbiota

Annals of Nutrition and Metabolism ◽

10.1159/000518498 ◽

2021 ◽

pp. 1-9

Author(s):

Katri Korpela

Keyword(s):

Gut Microbiota ◽

Epidemiological Studies ◽

Microbial Colonization ◽

Hospital Environment ◽

Delivery Mode ◽

Normal Birth ◽

Gut Colonization ◽

Intrapartum Antibiotic ◽

First Year Of Life

Microbial colonization of the neonate is an important feature of normal birth. The gut microbiota has a central role in the programming of the host’s metabolism and immune function, with both immediate and long-term health consequences. During vaginal birth, the infant is exposed to diverse maternal microbes, of which specific faecal microbes colonize the infant’s gut. C-section eliminates the infant’s contact with maternal microbes, preventing vertical transmission of gut microbes. Consequently, infants are colonized by bacteria from the environment, including potential pathogens from the hospital environment. Recent studies have shown that intrapartum antibiotic exposure has a C-section-like effect on the infant gut microbiota. While the composition of the gut microbiota largely normalizes during the first year of life, epidemiological studies suggest that the aberrant early microbial exposures have long-term immunological and metabolic consequences. Because of the high prevalence of procedures that prevent normal gut microbiota development, effective methods to normalize the gut microbiota of neonates are urgently needed. Even more importantly, attention should be paid to the microbiota imbalance in C-section-born and antibiotic-exposed infants in clinical practice. Breastfeeding and probiotics are particularly important for infants with disrupted gut colonization.

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Levels of Predominant Intestinal Microorganisms in 1 Month-Old Full-Term Babies and Weight Gain During the First Year of Life

Nutrients ◽

10.3390/nu13072412 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2412

Author(s):

Sonia González ◽

Marta Selma-Royo ◽

Silvia Arboleya ◽

Cecilia Martínez-Costa ◽

Gonzalo Solís ◽

...

Keyword(s):

Weight Gain ◽

Gut Microbiota ◽

Early Life ◽

Later Life ◽

Full Term ◽

First Year ◽

Term Infants ◽

Term Newborns ◽

Infant Weight Gain ◽

First Year Of Life

The early life gut microbiota has been reported to be involved in neonatal weight gain and later infant growth. Therefore, this early microbiota may constitute a target for the promotion of healthy neonatal growth and development with potential consequences for later life. Unfortunately, we are still far from understanding the association between neonatal microbiota and weight gain and growth. In this context, we evaluated the relationship between early microbiota and weight in a cohort of full-term infants. The absolute levels of specific fecal microorganisms were determined in 88 vaginally delivered and 36 C-section-delivered full-term newborns at 1 month of age and their growth up to 12 months of age. We observed statistically significant associations between the levels of some early life gut microbes and infant weight gain during the first year of life. Classifying the infants into tertiles according to their Staphylococcus levels at 1 month of age allowed us to observe a significantly lower weight at 12 months of life in the C-section-delivered infants from the highest tertile. Univariate and multivariate models pointed out associations between the levels of some fecal microorganisms at 1 month of age and weight gain at 6 and 12 months. Interestingly, these associations were different in vaginally and C-section-delivered babies. A significant direct association between Staphylococcus and weight gain at 1 month of life was observed in vaginally delivered babies, whereas in C-section-delivered infants, lower Bacteroides levels at 1 month were associated with higher later weight gain (at 6 and 12 months). Our results indicate an association between the gut microbiota and weight gain in early life and highlight potential microbial predictors for later weight gain.

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Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets

International Journal of Molecular Sciences ◽

10.3390/ijms21020503 ◽

2020 ◽

Vol 21 (2) ◽

pp. 503 ◽

Cited By ~ 4

Author(s):

Quanhang Xiang ◽

Xiaoyu Wu ◽

Ye Pan ◽

Liu Wang ◽

Chenbin Cui ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Relative Abundance ◽

Early Life ◽

System Development ◽

Fecal Microbiota ◽

Microbial Colonization ◽

Life Period ◽

Weaning Stress ◽

Immune System Development

Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a “window of opportunity” for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.

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Effects of Antibiotic Treatment with Piperacillin/Tazobactam versus Ceftriaxone on the Composition of the Murine Gut Microbiota.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01504-20 ◽

2020 ◽

Author(s):

Carola Venturini ◽

Bethany Bowring ◽

Alicia Fajardo-Lubian ◽

Carol Devine ◽

Jonathan Iredell

Keyword(s):

Gut Microbiota ◽

Generation Cephalosporin ◽

Multidrug Resistant ◽

Individual Variability ◽

Gut Microflora ◽

Third Generation ◽

Fecal Microbiome ◽

Microbiome Composition ◽

Gut Colonization ◽

The Impact

Effective antimicrobial stewardship requires a better understanding of the impact of different antibiotics on the gut microflora. Studies in humans are confounded by large inter-individual variability and difficulty in identifying control cohorts. However, controlled murine models can provide valuable information. Here, we examine the impact of a penicillin-like antibiotic (piperacillin-tazobactam, TZP) or a third-generation cephalosporin (ceftriaxone, CRO) on the murine gut microbiota by analysis of changes in fecal microbiome composition by 16S-rRNA amplicon sequencing and standard microbiology. Colonization resistance to multidrug resistant Escherichia coli ST131 and Klebsiella pneumoniae ST258 was also tested. Changes in microbiome composition and a significant (p< 0.05) decrease in diversity occurred in all treated mice, but dysbiosis was more marked and prolonged after CRO exposure with a persistent rise in Proteobacteria. Enterobacteriaceae blooms occurred in all antibiotic treated mice, but for TZP, unlike CRO, these were only significant under direct antibiotic pressure. At the height of dysbiosis after antibiotic termination, the murine gut was highly susceptible to colonization with both multidrug resistant enterobacterial pathogens. Co-habitation of treated mice with untreated individuals had a notable mitigating effect on dysbiosis of treated guts. The administration of a third-generation cephalosporin caused a more severe dysbiosis in the murine gut microflora, when compared to a penicillin/β-lactam inhibitor combination with comparable activity against medically important virulent bacteria. At the height of dysbiosis, both antibiotic treatments equally led to microbial imbalance associated with loss of resistance to gut colonization by antibiotic-resistant pathogens.

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Impact of Yeast-Derived β-Glucans on the Porcine Gut Microbiota and Immune System in Early Life

Microorganisms ◽

10.3390/microorganisms8101573 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1573

Author(s):

Hugo de Vries ◽

Mirelle Geervliet ◽

Christine A. Jansen ◽

Victor P. M. G. Rutten ◽

Hubèrt van Hees ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Immune Function ◽

Early Life ◽

Microbial Colonization ◽

Control Treatment ◽

Microbiota Composition ◽

Tissue Samples ◽

Immune Parameters ◽

Weaning Piglets

Piglets are susceptible to infections in early life and around weaning due to rapid environmental and dietary changes. A compelling target to improve pig health in early life is diet, as it constitutes a pivotal determinant of gut microbial colonization and maturation of the host’s immune system. In the present study, we investigated how supplementation of yeast-derived β-glucans affects the gut microbiota and immune function pre- and post-weaning, and how these complex systems develop over time. From day two after birth until two weeks after weaning, piglets received yeast-derived β-glucans or a control treatment orally and were subsequently vaccinated against Salmonella Typhimurium. Faeces, digesta, blood, and tissue samples were collected to study gut microbiota composition and immune function. Overall, yeast-derived β-glucans did not affect the vaccination response, and only modest effects on faecal microbiota composition and immune parameters were observed, primarily before weaning. This study demonstrates that the pre-weaning period offers a ‘window of opportunity’ to alter the gut microbiota and immune system through diet. However, the observed changes were modest, and any long-lasting effects of yeast-derived β-glucans remain to be elucidated.

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The Bifidogenic Effect Revisited—Ecology and Health Perspectives of Bifidobacterial Colonization in Early Life

Microorganisms ◽

10.3390/microorganisms8121855 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1855

Author(s):

Himanshu Kumar ◽

Maria Carmen Collado ◽

Harm Wopereis ◽

Seppo Salminen ◽

Jan Knol ◽

...

Keyword(s):

Caesarean Section ◽

Early Life ◽

Evolutionary Ecology ◽

Fecal Microbiota ◽

Microbial Colonization ◽

Parallel Mechanisms ◽

Microbiome Composition ◽

Adverse Health Outcomes ◽

Microbial Strains ◽

Life Type

Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria’s saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health.

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The impact of early life gut colonization on metabolic and obesogenic outcomes: what have animal models shown us?

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174415001518 ◽

2015 ◽

Vol 7 (1) ◽

pp. 15-24 ◽

Cited By ~ 17

Author(s):

J. G. Wallace ◽

W. Gohir ◽

D. M. Sloboda

Keyword(s):

Animal Models ◽

Gut Microbiota ◽

Early Life ◽

Maternal Obesity ◽

Communicable Disease ◽

Critical Periods ◽

Early Life Adversity ◽

Gut Colonization ◽

Increased Risk ◽

The Impact

The rise in the occurrence of obesity to epidemic proportions has made it a global concern. Great difficulty has been experienced in efforts to control this growing problem with lifestyle interventions. Thus, attention has been directed to understanding the events of one of the most critical periods of development, perinatal life. Early life adversity driven by maternal obesity has been associated with an increased risk of metabolic disease and obesity in the offspring later in life. Although a mechanistic link explaining the relationship between maternal and offspring obesity is still under investigation, the gut microbiota has come forth as a new factor that may play a role modulating metabolic function of both the mother and the offspring. Emerging evidence suggests that the gut microbiota plays a much larger role in mediating the risk of developing non-communicable disease, including obesity and metabolic dysfunction in adulthood. With the observation that the early life colonization of the neonatal and postnatal gut is mediated by the perinatal environment, the number of studies investigating early life gut microbial establishment continues to grow. This paper will review early life gut colonization in experimental animal models, concentrating on the role of the early life environment in offspring gut colonization and the ability of the gut microbiota to dictate risk of disease later in life.

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Deviations in the Gut Microbiota of Neonates Affected by Maternal Group B Streptococcus Infection

10.21203/rs.3.rs-117284/v1 ◽

2020 ◽

Author(s):

Yue-feng Li ◽

Xue-lei Gong ◽

Su-xiang Chen ◽

Ke-jian Wang ◽

Yan-hua Jiang

Keyword(s):

Discriminant Analysis ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Early Life ◽

Bacterial Species ◽

Group B Streptococcus ◽

Healthy Controls ◽

Linear Discriminant ◽

Gut Colonization ◽

Group B

Abstract Background: Group B Streptococcus (GBS) infection is the leading cause of septicemia, meningitis, and pneumonia in neonates. Aberrant gut colonization in early life may predispose children to various diseases in adulthood. However, the associations between gut microbial changes and GBS infection is still unclear.Methods: We adopted a new microarray-based technique on neonatal meconium samples collected from 13 participants with mother’s GBS infection/colonization in vaginas and 73 uninfected controls.Results: The composition and diversity of meconium microbiota in GBS group were similar to that of healthy controls. However, we identified several specific taxa that were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p<0.05, LDA>2.0). Particularly, the relative abundance of Lactobacillus paracasei was significantly reduced, indicating a role in GBS infection.Conclusions: Our study presented a series of bacterial species affected by GBS, thus providing novel evidence in support of initial intestinal microbiota dysbiosis in the neonates with mother’s GBS infection/colonization.

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Gut Microbiota Composition in Healthy Japanese Infants and Young Adults Born by C-Section

Annals of Nutrition and Metabolism ◽

10.1159/000490841 ◽

2018 ◽

Vol 73 (Suppl. 3) ◽

pp. 4-11 ◽

Cited By ~ 9

Author(s):

Ravinder Nagpal ◽

Yuichiro Yamashiro

Keyword(s):

Young Adults ◽

Gut Microbiota ◽

Gut Microbiome ◽

Early Life ◽

Microbial Colonization ◽

Natural Phenomenon ◽

Microbiota Composition ◽

Infant Gut Microbiome ◽

Gut Microbiota Composition ◽

Japanese Infants

Our gut microbiome plays a fundamental role in our health and disease. The microbial colonization of human gut begins immediately at birth and is an indispensable natural process that modulates our physiology and immunity. Recent studies are elegantly revealing how and when these microbes colonize the gut and what elements could potentially influence this natural phenomenon. The vertical mother-to-baby transmission of microbes is a crucial factor for normal development and maturation of newborn’s immune, metabolic as well as neurological health. This important and delicate process of gut microbiota development may be impacted by various factors such as birth mode, type of feeding, gestational age at birth, antibiotics exposure in early life, surrounding environment and hygiene settings, and so on. Perturbations in early life gut microbial colonization have been associated with the development of several diseases such as diabetes, obesity, asthma, allergies, celiac disease, neurodevelopmental disorders, and so on. However, it remains unclear whether predisposition to these diseases is due to the lack of acquisition of the mother’s (vaginal and perianal) microbes during birth or because of abnormal exposure to unsolicited bacteria. Hence, studies are required to scrutinize the colonization pattern of infant gut microbiome in context to birth mode and also to elucidate how long these differences could persist. In these contexts, we review and discuss some of the findings obtained from recent investigation of the gut microbiota composition in healthy Japanese infants and young adults born vaginally or by C-section.

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