Early life determinants induce sustainable changes in the gut microbiome of six-year-old children

Abstract Background: Antibiotic resistance is an increasing threat to human health. The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood and clarifying these factors would inform strategies to decrease antibiotic resistance. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling was used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs.Results: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33-36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54-5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux (i.e., by pumping antibiotics out of the cell). The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically E. coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97 – 1.29)] as well as a having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12 – 1.84)] at 1 year compared to infants born vaginally. Additionally, 6 specific ARGs were at a greater relative abundance in infants delivered by cesarean section compared to vaginally delivered infants across both time points. Conclusions: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the possibility of antibiotic resistant life threatening infections.

Download Full-text

Biotic and abiotic factors influencing channel catfish egg and gut microbiome dynamics during early life stages

Aquaculture ◽

10.1016/j.aquaculture.2018.08.073 ◽

2019 ◽

Vol 498 ◽

pp. 556-567 ◽

Cited By ~ 5

Author(s):

S. Abdul Razak ◽

M.J. Griffin ◽

C.C. Mischke ◽

B.G. Bosworth ◽

G.C. Waldbieser ◽

...

Keyword(s):

Channel Catfish ◽

Gut Microbiome ◽

Early Life ◽

Abiotic Factors ◽

Life Stages ◽

Early Life Stages ◽

Biotic And Abiotic Factors ◽

Factors Influencing

Download Full-text

Early-life gut microbiome and cow’s milk allergy- a prospective case - control 6-month follow-up study

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2017.11.051 ◽

2018 ◽

Vol 25 (5) ◽

pp. 875-880 ◽

Cited By ~ 10

Author(s):

Ping Dong ◽

Jing-jing Feng ◽

Dong-yong Yan ◽

Yu-jing Lyu ◽

Xiu Xu

Keyword(s):

Gut Microbiome ◽

Early Life ◽

Case Control ◽

Cow’S Milk Allergy ◽

Cow’S Milk ◽

Milk Allergy ◽

Cow's Milk ◽

Follow Up Study ◽

Cow's Milk Allergy

Download Full-text

Joint effects of pregnancy, sociocultural, and environmental factors on early life gut microbiome structure and diversity

Scientific Reports ◽

10.1038/srep31775 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 41

Author(s):

Albert M. Levin ◽

Alexandra R. Sitarik ◽

Suzanne L. Havstad ◽

Kei E. Fujimura ◽

Ganesa Wegienka ◽

...

Keyword(s):

Environmental Factors ◽

Gut Microbiome ◽

Early Life ◽

Joint Effects

Download Full-text

Formula Supplementation of the Breastfed Infant: Assault on the Gut Microbiome

Clinical Lactation ◽

10.1891/2158-0782.5.4.128 ◽

2014 ◽

Vol 5 (4) ◽

pp. 128-132 ◽

Cited By ~ 3

Author(s):

Marsha Walker

Keyword(s):

Breast Milk ◽

Health Outcomes ◽

Milk Production ◽

Gut Microbiome ◽

Side Effect ◽

Early Life ◽

Microbial Colonization ◽

Mucosal Inflammation ◽

Maternal Milk ◽

Allergic Disorders

Although formula supplementation is well known to have detrimental effects on the duration and exclusivity of breastfeeding, on the maternal milk production, and on the health outcomes of mothers and infants, there are immediate and long-lasting effects on the infant’s gut microbiome. Breast milk is an important element modulating the metabolic and immunological programming relative to a child’s health. An unfavorable or abnormal microbial colonization during early life interferes with many functions in the gut and facilitates invasion of pathogens and foreign or harmful antigens. Alterations of the gut environment (such as from supplementation with formula) are directly responsible for mucosal inflammation and disease, autoimmunity conditions, and allergic disorders in childhood and adulthood. Clinicians and parents will benefit from knowledge of this side effect of formula supplementation.

Download Full-text

Impact of early-life rearing history on gut microbiome succession and performance of Nile tilapia

Animal Microbiome ◽

10.1186/s42523-021-00145-w ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Yale Deng ◽

Fotini Kokou ◽

Ep H. Eding ◽

Marc C. J. Verdegem

Keyword(s):

Gut Microbiome ◽

Early Life ◽

Nile Tilapia ◽

Common Garden ◽

Later Life ◽

Nutrient Digestibility ◽

Microbial Interactions ◽

Microbiome Composition ◽

Fish Gut ◽

Growth Trial

Abstract Background Fish gut microbial colonisation starts during larval stage and plays an important role in host’s growth and health. To what extent first colonisation could influence the gut microbiome succession and growth in later life remains unknown. In this study, Nile tilapia embryos were incubated in two different environments, a flow-through system (FTS) and a biofloc system (BFS); hatched larvae were subsequently cultured in the systems for 14 days of feeding (dof). Fish were then transferred to one common recirculating aquaculture system (RAS1, common garden, 15–62 dof), followed by a growth trial in another RAS (RAS2, growth trial, 63–105 dof). In RAS2, fish were fed with two types of diet, differing in non-starch polysaccharide content. Our aim was to test the effect of rearing environment on the gut microbiome development, nutrient digestibility and growth performance of Nile tilapia during post-larvae stages. Results Larvae cultured in the BFS showed better growth and different gut microbiome, compared to FTS. After the common garden, the gut microbiome still showed differences in species composition, while body weight was similar. Long-term effects of early life rearing history on fish gut microbiome composition, nutrient digestibility, nitrogen and energy balances were not observed. Still, BFS-reared fish had more gut microbial interactions than FTS-reared fish. A temporal effect was observed in gut microbiome succession during fish development, although a distinct number of core microbiome remained present throughout the experimental period. Conclusion Our results indicated that the legacy effect of first microbial colonisation of the fish gut gradually disappeared during host development, with no differences in gut microbiome composition and growth performance observed in later life after culture in a common environment. However, early life exposure of larvae to biofloc consistently increased the microbial interactions in the gut of juvenile Nile tilapia and might possibly benefit gut health.

Download Full-text

Citrus reticulatae pericarpium Extract Decreases the Susceptibility to HFD-Induced Glycolipid Metabolism Disorder in Mice Exposed to Azithromycin in Early Life

Frontiers in Immunology ◽

10.3389/fimmu.2021.774433 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hanqi Lu ◽

Yanting You ◽

Xinghong Zhou ◽

Qiuxing He ◽

Ming Wang ◽

...

Keyword(s):

Gut Microbiome ◽

High Fat Diet ◽

Early Life ◽

Underlying Mechanism ◽

Inflammatory Factors ◽

Glycolipid Metabolism ◽

Metabolism Disorder ◽

Adult Mice ◽

Gut Microbe ◽

Old Mice

BackgroundStudies have shown that gut microbe disorder in mice due to early-life antibiotic exposure promotes glycolipid metabolism disorder in adulthood. However, the underlying mechanism remains unclear and there is not yet an effective intervention or treatment for this process.PurposeThe study investigated whether early-life azithromycin (AZT) exposure in mice could promote high-fat diet (HFD)-induced glycolipid metabolism disorder in adulthood. Moreover, the effect of citrus reticulata pericarpium (CRP) extract on glycolipid metabolism disorder via regulation of gut microbiome in mice exposed to antibodies early in life were investigated.Methods and ResultsThree-week-old mice were treated with AZT (50 mg/kg/day) via drinking water for two weeks and then were fed a CRP diet (1% CRP extract) for four weeks and an HFD for five weeks. The results showed that early-life AZT exposure promoted HFD-induced glycolipid metabolism disorder, increased the levels of inflammatory factors, promoted the flora metabolism product trimethylamine N-oxide (TMAO), and induced microbial disorder in adult mice. Importantly, CRP extract mitigated these effects.ConclusionTaken together, these findings suggest that early-life AZT exposure increases the susceptibility to HFD-induced glycolipid metabolism disorder in adult mice, and CRP extract can decrease this susceptibility by regulating gut microbiome.

Download Full-text

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

Download Full-text

The Dutch Microbiome Project defines factors that shape the healthy gut microbiome

10.1101/2020.11.27.401125 ◽

2020 ◽

Cited By ~ 1

Author(s):

R. Gacesa ◽

A. Kurilshikov ◽

A. Vich Vila ◽

T. Sinha ◽

M.A.Y. Klaassen ◽

...

Keyword(s):

Mental Health ◽

Gut Microbiome ◽

Early Life ◽

Medication Use ◽

Physical And Mental Health ◽

Generational Cohort ◽

Comprehensive Overview ◽

Bacterial Composition ◽

Associated Bacteria ◽

Health And Disease

AbstractThe gut microbiome is associated with diverse diseases, but the universal signature of an (un)healthy microbiome remains elusive and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. To fill this gap, we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We then correlated this to 241 host and environmental factors, including physical and mental health, medication use, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is primarily shaped by environment and cohousing. Only ∼13% of taxa are heritable, which are enriched with highly prevalent and health-associated bacteria. By identifying 2,856 associations between microbiome and health, we find that seemingly unrelated diseases share a common signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, of which numerous early-life and current factors are particularly linked to the microbiome. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

Download Full-text