2021 article
What E. coli knows about your 1-year-old infant: Antibiotic use, lifestyle, birth mode, and siblings
Al'Abri, I. S., Durmusoglu, D., & Crook, N. (2021, June 9). CELL HOST & MICROBE, Vol. 29, pp. 854–855.
MeSH headings : Anti-Bacterial Agents / pharmacology; Asthma; Child; Environmental Exposure; Escherichia coli; Gastrointestinal Microbiome; Humans; Infant; Life Style; Siblings
TL;DR:
The causes, spread, and dynamics of ARGs and their relationship with asthma-associated microbiota in Danish children are studied and the relationship between asthma and the gut microbiota is studied.
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Source: Web Of Science
Added: June 28, 2021
The infant gut microbiota is shaped by diverse environmental exposures that alter its composition and can enrich antimicrobial resistance genes (ARGs). In this issue of Cell Host & Microbe, Li et al. (2021) studied the causes, spread, and dynamics of ARGs and their relationship with asthma-associated microbiota in Danish children. The infant gut microbiota is shaped by diverse environmental exposures that alter its composition and can enrich antimicrobial resistance genes (ARGs). In this issue of Cell Host & Microbe, Li et al. (2021) studied the causes, spread, and dynamics of ARGs and their relationship with asthma-associated microbiota in Danish children. The gut microbiota is fundamental to human health, but we lack a clear understanding of how it matures and how environmental factors modulate this process (Robertson et al., 2019Robertson R.C. Manges A.R. Finlay B.B. Prendergast A.J. The Human Microbiome and Child Growth - First 1000 Days and Beyond.Trends Microbiol. 2019; 27: 131-147Abstract Full Text Full Text PDF PubMed Scopus (228) Google Scholar). In the last decade, research has focused on understanding how the development of the gut microbiota changes in response to perturbations, especially in early life. We have learned that factors such as delivery mode, sex, exposure to antibiotics, rural versus urban lifestyle, hospitalization, and age significantly influence microbiota assembly, and consequently, human health (Stokholm et al., 2018Stokholm J. Blaser M.J. Thorsen J. Rasmussen M.A. Waage J. Vinding R.K. Schoos A.-M.M. Kunøe A. Fink N.R. Chawes B.L. et al.Maturation of the gut microbiome and risk of asthma in childhood.Nat. Commun. 2018; 9: 141Crossref PubMed Scopus (220) Google Scholar). However, the impact of these perturbations on the gut resistome is less well understood. The resistome is the collection of antibiotic resistance genes (ARGs) present in a microbial community. The overuse of antibiotics is associated with a low microbiota maturity, which can lead to metabolic disorders, malnutrition, infections, and even colon cancer (Langdon et al., 2016Langdon A. Crook N. Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation.Genome Med. 2016; 8: 39Crossref PubMed Scopus (437) Google Scholar). In addition, antibiotic treatment can lead to an increased abundance of microbes containing ARGs, facilitating future transfer of ARGs to pathogens and making treatment of infections more difficult (Ferreiro et al., 2018Ferreiro A. Crook N. Gasparrini A.J. Dantas G. Multiscale Evolutionary Dynamics of Host-Associated Microbiomes.Cell. 2018; 172: 1216-1227Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). The high density of microbes in the gut enables horizontal gene transfer and makes the study of the gut resistome particularly important. Although we know that factors such as birth mode, breastfeeding, and antibiotic use impact resistome development, we still don’t fully understand how important other environmental factors are and how they are interconnected (Stokholm et al., 2020Stokholm J. Thorsen J. Blaser M.J. Rasmussen M.A. Hjelmsø M. Shah S. Christensen E.D. Chawes B.L. Bønnelykke K. Brix S. et al.Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma.Sci. Transl. Med. 2020; 12: eaax9929Crossref PubMed Scopus (29) Google Scholar). In particular, there exists a gap in our understanding of resistome development between very early life (<1 year) (Gasparrini et al., 2016Gasparrini A.J. Crofts T.S. Gibson M.K. Tarr P.I. Warner B.B. Dantas G. Antibiotic perturbation of the preterm infant gut microbiome and resistome.Gut Microbes. 2016; 7: 443-449Crossref PubMed Scopus (57) Google Scholar, Gasparrini et al., 2019Gasparrini A.J. Wang B. Sun X. Kennedy E.A. Hernandez-Leyva A. Ndao I.M. Tarr P.I. Warner B.B. Dantas G. Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome.Nat. Microbiol. 2019; 4: 2285-2297Crossref PubMed Scopus (81) Google Scholar) and adulthood (Schwartz et al., 2020Schwartz D.J. Langdon A.E. Dantas G. Understanding the impact of antibiotic perturbation on the human microbiome.Genome Med. 2020; 12: 82Crossref PubMed Scopus (48) Google Scholar), especially in healthy individuals. To fill this gap, Li et al., 2021Li X. Stokholm J. Brejnrod A. Vestergaard G.A. Russel J. Trivedi U. Thorsen J. Gupta S. Hjelmsø M.H. Shah S.A. et al.The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition.Cell Host Microbe. 2021; 29 (this issue): 975-987Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar explored how diverse environmental factors shaped the resistomes of 662 1-year-old Danish children and the relationship of their resistomes to longer-term health impacts (Li et al., 2021Li X. Stokholm J. Brejnrod A. Vestergaard G.A. Russel J. Trivedi U. Thorsen J. Gupta S. Hjelmsø M.H. Shah S.A. et al.The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition.Cell Host Microbe. 2021; 29 (this issue): 975-987Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar). The authors identified 409 ARGs in this cohort, with 167 of them conferring resistance to multiple antibiotics. Interestingly, ARG abundance was bimodal, with one cluster of children exhibiting more abundant and diverse ARGs in their gut microbiome than the other (Figure 1). To understand the drivers of this phenomenon, the authors investigated the species that comprised each cluster. This analysis revealed that the abundance of E. coli determined cluster membership, with individuals in the “ARG high” group having a much greater abundance of intestinal E. coli. This finding agrees with previous studies that found that the microbiotas of antibiotic-treated preterm infants are dominated by Gammaproteobacteria (Gasparrini et al., 2016Gasparrini A.J. Crofts T.S. Gibson M.K. Tarr P.I. Warner B.B. Dantas G. Antibiotic perturbation of the preterm infant gut microbiome and resistome.Gut Microbes. 2016; 7: 443-449Crossref PubMed Scopus (57) Google Scholar, Gasparrini et al., 2019Gasparrini A.J. Wang B. Sun X. Kennedy E.A. Hernandez-Leyva A. Ndao I.M. Tarr P.I. Warner B.B. Dantas G. Persistent metagenomic signatures of early-life hospitalization and antibiotic treatment in the infant gut microbiota and resistome.Nat. Microbiol. 2019; 4: 2285-2297Crossref PubMed Scopus (81) Google Scholar). Removing E. coli from the analyzed samples resulted in a 10-fold reduction in ARG richness in the “ARG high” group. This work therefore prioritizes further study on the ability of intestinal E. coli to mobilize ARGs to other members of the microbiota, perhaps serving as an important “node” for ARG “traffic” in the large intestine. The authors then wondered whether the “E. coli-high” cluster was persistent across age. However, when they measured the abundance of E. coli in samples from the same individuals collected at 1 week, 1 month, 4 years, 5 years, or 6 years of age, they found no difference in E. coli levels between each cluster. This indicates that the abundance of E. coli, and perhaps ARG abundance as a consequence, is mainly influenced by transient factors such as seasons, antibiotic exposure, or ecological dynamics in the microbiota. To understand how these ARGs were acquired, the authors then examined the correlation between ARG abundance and patient metadata. Interestingly, even infants that were not treated with any antibiotics had ARGs in their microbiomes, which led the researchers to investigate whether other environmental exposures had an impact. They found that the most prominent factors in shaping the distribution of ARGs were the presence of older siblings, living environment, mode of delivery, time since antibiotic treatment, and antibiotic use 40 days before childbirth. Other factors, such antibiotic usage frequency, living in an apartment, and usage of antibiotics by pregnant mothers in the first two trimesters had a smaller role. Comparing the effects of antibiotics to other factors revealed that while all factors affect the distribution of ARGs, antibiotic use was unique because it did not change the microbiota composition. Potential explanations for this counterintuitive finding include horizontal transfer of ARGs among gut microbes in response to antibiotic exposure, or the presence of antibiotic-resistant subpopulations with the same taxonomic assignments. It is noteworthy that not all environmental exposures propel the gut microbiota to inherit the same ARGs or at the same rate. Therefore, it is possible that minimizing childhood exposure into the most influential factors may protect against ARG proliferation in the gut microbiome. Finally, the authors investigated the relationship between ARG carriage, microbiota composition, and asthma, finding that high ARG abundance was associated with a microbiota composition that increases the risk of later asthma. Additionally, samples with abundant ARGs also had lower microbiota maturity, which is a risk factor for a variety of metabolic and immunological disorders. Although more studies are needed to fully elucidate the associations between ARGs, microbiota composition, asthma, and other diseases, this study supports a microbial route to identify asthma-prone individuals. Li et al., 2021Li X. Stokholm J. Brejnrod A. Vestergaard G.A. Russel J. Trivedi U. Thorsen J. Gupta S. Hjelmsø M.H. Shah S.A. et al.The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition.Cell Host Microbe. 2021; 29 (this issue): 975-987Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar shed light on ARGs in the healthy developing gut in remarkable detail, finding that distribution of ARGs in the gut is strongly bimodal and largely based on the abundance of E.coli. It would be very fascinating to determine whether this clustering occurs in other parts of the world, or in other age groups. Additionally, the authors showed that different environmental factors can have different effects on the acquisition of ARGs, thereby setting priorities for future ARG mitigation. Interestingly, high ARG richness was correlated with low microbiota maturity and a high risk of asthma later in life, agreeing with prior studies in the nasopharyngeal microbiome (Teo et al., 2015Teo S.M. Mok D. Pham K. Kusel M. Serralha M. Troy N. Holt B.J. Hales B.J. Walker M.L. Hollams E. et al.The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.Cell Host Microbe. 2015; 17: 704-715Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar). By elucidating the risk factors for high rates of ARG acquisition during development, this study facilitates efforts to combat the rise of antimicrobial-resistant pathogens and provides a roadmap to studying these important questions in other cohorts. The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial compositionLi et al.Cell Host & MicrobeApril 21, 2021In BriefIn this comprehensive analysis of antibiotic resistance genes (ARGs) distribution in the infant gut, Li et al. show that E. coli is an extremely important reservoir of ARGs. They also reveal associations between infant gut resistome and environmental factors, gut microbiome maturation, and bacteria associated with later development of asthma. Full-Text PDF Open Archive