Successional Stages in Infant Gut Microbiota Maturation

After birth, microbial colonization of the infant intestinal tract is important for health later in life. However, this initial process is highly dynamic and influenced by many factors. ABSTRACT Disturbances in the primary colonization of the infant gut can result in lifelong consequences and have been associated with a range of host conditions. Although early-life factors have been shown to affect infant gut microbiota development, our current understanding of human gut colonization in early life remains limited. To gain more insights into the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (n = 303 total samples). To evaluate the gut microbiota maturation transition toward an adult configuration, we compared the microbiome composition of the infants to that of the Flemish Gut Flora Project (FGFP) population (n = 1,106). We observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, the 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 FGFP cohort clustered all infant samples within the (in adults) potentially dysbiotic Bacteroides 2 (Bact2) enterotype. We confirmed the similarities between infant gut microbial colonization and adult dysbiosis. 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. IMPORTANCE After birth, microbial colonization of the infant intestinal tract is important for health later in life. However, this initial process is highly dynamic and influenced by many factors. Studying this process in detail requires a dense longitudinal sampling effort. In the current study, the bacterial microbiota of >300 stool samples was analyzed from 8 healthy infants, suggesting that the infant gut microbial population matures along a path involving distinct microbial constellations and that the timing of these transitions is infant specific and can temporarily retrace upon external events. We also showed that the infant microbial populations show similarities to suboptimal bacterial populations in the guts of adults. These insights are crucial for a better understanding of the dynamics and characteristics of a “healthy gut microbial population” in both infants and adults and might allow the identification of intervention targets in cases of microbial disturbances or disease.

[1]  Luis Pedro Coelho,et al.  Statin therapy is associated with lower prevalence of gut microbiota dysbiosis , 2020, Nature.

[2]  J. Raes,et al.  Quantitative microbiome profiling disentangles inflammation- and bile duct obstruction-associated microbiota alterations across PSC/IBD diagnoses , 2019, Nature Microbiology.

[3]  E. Allen-Vercoe,et al.  Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health , 2019, Microbiome.

[4]  E. Kuijper,et al.  Gut Microbiota and Colonization Resistance against Bacterial Enteric Infection , 2019, Microbiology and Molecular Biology Reviews.

[5]  J. Raes,et al.  The neuroactive potential of the human gut microbiota in quality of life and depression , 2019, Nature Microbiology.

[6]  R. Gibbs,et al.  Temporal development of the gut microbiome in early childhood from the TEDDY study , 2018, Nature.

[7]  C. Huttenhower,et al.  The human gut microbiome in early-onset type 1 diabetes from the TEDDY study , 2018, Nature.

[8]  C. Lozupone,et al.  Low diversity gut microbiota dysbiosis: drivers, functional implications and recovery. , 2018, Current opinion in microbiology.

[9]  B. Finlay,et al.  Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting , 2017, The Journal of allergy and clinical immunology.

[10]  Jun Wang,et al.  Quantitative microbiome profiling links gut community variation to microbial load , 2017, Nature.

[11]  Fabian Rivera-Chávez,et al.  Oxygen as a driver of gut dysbiosis. , 2017, Free radical biology & medicine.

[12]  J. Raes,et al.  Brief Report: Dialister as a Microbial Marker of Disease Activity in Spondyloarthritis , 2017, Arthritis & rheumatology.

[13]  F. Hildebrand,et al.  Species–function relationships shape ecological properties of the human gut microbiome , 2016, Nature Microbiology.

[14]  J. Raes,et al.  Population-level analysis of gut microbiome variation , 2016, Science.

[15]  W. van Pelt,et al.  Societal Burden and Correlates of Acute Gastroenteritis in Families with Preschool Children , 2016, Scientific Reports.

[16]  Eric Z. Chen,et al.  Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease. , 2015, Cell host & microbe.

[17]  Pearl D Houghteling,et al.  Why Is Initial Bacterial Colonization of the Intestine Important to Infants' and Children's Health? , 2015, Journal of pediatric gastroenterology and nutrition.

[18]  Sumit Sharma,et al.  Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[19]  P. Bork,et al.  LotuS: an efficient and user-friendly OTU processing pipeline , 2014, Microbiome.

[20]  W. D. de Vos,et al.  The first 1000 cultured species of the human gastrointestinal microbiota , 2014, FEMS microbiology reviews.

[21]  P. Schloss,et al.  Dynamics and associations of microbial community types across the human body , 2014, Nature.

[22]  A. Hartke,et al.  The Physiology and Metabolism of Enterococci , 2014 .

[23]  H. Sokol,et al.  Ecology and metabolism of the beneficial intestinal commensal bacterium Faecalibacterium prausnitzii , 2014, Gut microbes.

[24]  M. Butel,et al.  Tolerance of Bifidobacterium human isolates to bile, acid and oxygen. , 2013, Anaerobe.

[25]  M. Espey,et al.  Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota. , 2013, Free radical biology & medicine.

[26]  Jesse R. Zaneveld,et al.  Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts , 2012, Genome research.

[27]  C. Quince,et al.  Dirichlet Multinomial Mixtures: Generative Models for Microbial Metagenomics , 2012, PloS one.

[28]  L. T. Angenent,et al.  Succession of microbial consortia in the developing infant gut microbiome , 2010, Proceedings of the National Academy of Sciences.

[29]  Eduardo P. C. Rocha,et al.  The Systemic Imprint of Growth and Its Uses in Ecological (Meta)Genomics , 2010, PLoS genetics.

[30]  Daniel B. DiGiulio,et al.  Development of the Human Infant Intestinal Microbiota , 2007, PLoS biology.

[31]  H. Flint,et al.  Lactate-Utilizing Bacteria, Isolated from Human Feces, That Produce Butyrate as a Major Fermentation Product , 2004, Applied and Environmental Microbiology.

[32]  H. Flint,et al.  The microbiology of butyrate formation in the human colon. , 2002, FEMS microbiology letters.

[33]  I. Booth,et al.  Inhibition of Escherichia coli growth by acetic acid: a problem with methionine biosynthesis and homocysteine toxicity. , 2002, Microbiology.

[34]  J. Raes,et al.  Brief Report:Dialisteras a Microbial Marker of Disease Activity in Spondyloarthritis: DIALISTERAS A MICROBIAL MARKER OF SpA DISEASE ACTIVITY , 2017 .

[35]  V. Tremaroli,et al.  Resource Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life Graphical Abstract Highlights , 2022 .