The Human Microbiome and Child Growth – First 1000 Days and Beyond

Robertson, Ruairi C.; Manges, Amee R.; Finlay, B. Brett; Prendergast, Andrew J.

doi:10.1016/j.tim.2018.09.008

Cited by 566 publications

(517 citation statements)

References 115 publications

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“…For children who grow and develop in less built contexts within low‐ and middle‐income countries (LMICs), an important environmental factor that requires greater consideration is enteric pathogen exposure via household in drinking water (Kay et al, ; Morton et al, ; Robertson, Manges, Finlay & Prendergast, ). After shedding from an infected host (i.e., human or non‐human animal), enteric pathogens are transmitted by the fecal‐oral route with water serving as an important vehicle (Ashbolt, ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the gut microbiota of Nicaraguan children in a water insecure context

Piperata

Lee

Apaza

et al. 2019

American J Hum Biol

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Objectives: The gut microbiota varies across human populations. The first years of life are a critical period in its development. While delivery mode and diet contribute to observed variation, the additional contribution of specific environmental factors remains poorly understood. One factor is waterborne enteric pathogen exposure. In this pilot study, we explore the relationship between household water security and the gut microbiota of children.Methods: From Nicaraguan households (n = 39), we collected drinking water samples, as well as fecal samples from children aged one month to 5.99 years (n = 53). We tested water samples for total coliforms (CFU/mL) and the presence of common enteric pathogens. Composition and diversity of the gut microbiota were characterized by 16S rRNA sequencing. Households were classified as having drinking water that was "low" (<29 CFU/mL) or "high" (≥29 CFU/mL) in coliforms. We used permutational analyses of variance and Mann-Whitney U-tests to identify differences in the composition and diversity of the gut microbiota of children living in these two home types.Results: Insecure access led households to store drinking water and 85% tested positive for coliforms. High concentrations of Salmonella and Campylobacter were found in water and fecal samples. Controlling for age, the gut microbiota of children from high coliform homes were compositionally different and less diverse than those from low coliform homes. Conclusions:Results indicate that research exploring the ways water insecurity affects human biology should consider the gut microbiome and that investigations of inter-population variation in the gut microbial community of children should consider pathogen exposure and infection.

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Section: Introductionmentioning

confidence: 99%

Characterization of the gut microbiota of Nicaraguan children in a water insecure context

Piperata

Lee

Apaza

et al. 2019

American J Hum Biol

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“…Early life represents a critical developmental window, which lays the foundations for shortand long-term health [1,2]. Immediately after birth, the human gastrointestinal (GI) tract is colonised by a succession of microbes, up until 2-3 years of age when the 'adult' microbiota fully establishes.…”

Section: Introductionmentioning

confidence: 99%

“…Notably, several factors influence the development of the early life microbiome, including mode of delivery, host genetics, diet and drugs (e.g. antibiotics), with disturbances linked to an increasing number of immune-linked diseases including ulcerative colitis (UC), arthritis, and atopic allergy [2,4].…”

Section: Introductionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Hughes

Schofield

Dalby

et al. 2019

Preprint

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AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

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“…Perturbation of the early life HGM assembly is associated with life-long effects on the immune- and metabolic homeostasis of the host 9–12 . Breastfeeding is a key affector of the dynamics of the microbiota during infancy.…”

Section: Discussionmentioning

confidence: 99%

“…The HGM develops dynamically during infancy until a resilient adult-like community is formed after 2-3 years of life 6–8 . The early life microbiota plays a role in the maturation of the host’s endocrine, metabolic and immune system 9 , and the composition of this consortium appears to be associated with lifelong health effects 10–12 . Therefore, understanding the factors that define the HGM structure during infancy is critical for minimizing the risk for a range of metabolic, inflammatory and neurodegenerative disorders, all associated to specific HGM signatures 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Butyrate producing Clostridiales utilize distinct human milk oligosaccharides correlating to early colonization and prevalence in the human gut

Pichler

Yamada

Shuoker

et al. 2020

Preprint

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Butyrate producing Clostridiales utilize distinct human milk oligosaccharides correlating to early 2 colonization and prevalence in the human gut 3Bacterial growth studies were performed by M.J.P. Proteomic analyses were done by M.J.P and 26 E.S. Protein characterization was done by M.J.P and M.L.L. Enzymatic characterization of 27RiLe a/b 136 was performed by A.G.,To.K., M.S. and Ta.K. Mucin preparation was performed by 28 B.S. and M.J.P. Mucin glycomics were performed by B.S., C.J. and N.G.K. Protein X-ray 29 crystallography was performed by C.Y. and S.F. Metagenome analysis were performed by C.A-30 S and M.A. Experiments were designed by M.J.P and M.A.H. The manuscript was drafted by 31 M.J.P and M.A.H and finalized with contributions of all authors. 32 33 34 35 Abstract 36The early life human gut microbiota exerts life-long health effects on the host, but the mechanisms 37 underpinning its assembly remain elusive. Particularly, the early colonization of Clostridiales from 38the Roseburia-Eubacterium group, associated with protection from colorectal cancer, immune-39and metabolic disorders is enigmatic. Here we unveil the growth of Roseburia and Eubacterium 40 members on human milk oligosaccharides (HMOs) using an unprecedented catabolic apparatus. 41The described HMO pathways and additional glycan utilization loci confer co-growth with 42 Akkermansia muciniphilia via cross-feeding and access to mucin O-glycans. Strikingly, both, HMO 43and xylooligosaccharide pathways, were active simultaneously attesting an adaptation to a mixed 44HMO-solid food diet. Analyses of 4599 Roseburia genomes underscored the preponderance of 45HMO pathways and highlighted different HMO utilization phylotypes. Our revelations provide a 46 possible rationale for the early establishment and resilience of butyrate producing Clostridiales 47and expand the role of specific HMOs in the assembly of the early life microbiota. 48 49 129 R. inulinivorans, respectively. In R. inulinivorans two additional loci encoding sialic acid and 130 fucose catabolism proteins, were also upregulated ( Supplementary Fig. 3). 131 132 133 Fig. 1: Growth of R. hominis, R. inulinivorans and E. ramulus on HMOs and upregulation of core HMOs 134 utilization loci: Growth curves of R. hominis (a) and R. inulinivorans (b) on glucose, LNT, GNB, LNB, and/or purified 135 HMOs from mothers milk compared to a no-carbon source controls over 24 h. c, Growth levels of R. inulinivorans on 136 LNT, LNB, GNB and of E. ramulus on LNT within 24 h including glucose and a non-carbon source controls. d, Growth 137 of R. hominis, R. inulinivorans and E. ramulus on monosaccharides from HMOs and mucin after 24 h. The growth 138 analyses (a-d) on media supplemented with 0.5 % (w/v) carbohydrates (except for R. inulinivorans on 1% (w/v) and 139 4% (w/v) purified HMOs from mothers milk) are means of triplicates with standard deviations. e) HMO and mucin-140 derived oligo-and monosaccharides used for the growth analyses in (a-d). The core HMO utilization loci in R. hominis 141 (f) and R. in...

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The Human Microbiome and Child Growth – First 1000 Days and Beyond

Cited by 566 publications

References 115 publications

Characterization of the gut microbiota of Nicaraguan children in a water insecure context

Characterization of the gut microbiota of Nicaraguan children in a water insecure context

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Butyrate producing Clostridiales utilize distinct human milk oligosaccharides correlating to early colonization and prevalence in the human gut

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