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Emerging research: Epigenetics and the microbiome

Infant health research

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The following studies explore emerging and growing evidence that genetics, prenatal environments, delivery modes and early postnatal environments including feeding method can affect the infant microbiome, with significant implications for the infant immune system and both short- and long-term health outcomes. Find out more in our Breastfeeding and Relationship Building course

Altered Gut Microbiome and Fecal Immune Phenotype in Early Preterm Infants With Leaky Gut

Intestinal barrier immaturity is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. This study investigated the fecal cytokine profile and gut microbiota in a cohort of 40 early preterm infants <33-weeks-gestation to identify immune markers of intestinal barrier maturation. Results demonstrated the critical role of both immunological and microbiological factors in the early development of intestinal barrier that collectively shape the intestinal microenvironment influencing gut homeostasis and postnatal intestinal maturation in early preterm newborns.

Lemme-Dumit Jose M., et al. 2022. Altered Gut Microbiome and Fecal Immune Phenotype in Early Preterm Infants With Leaky Gut. Frontiers in Immunology. Volume 13.  DOI 10.3389/fimmu.2022.815046

Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut

Findings from this study demonstrate that breastmilk-promoted Bifidobacterium species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective aromatic lactic acids (indolelactic acid, phenyllactic acid and 4-hydroxyphenyllactic acid) via a previously unrecognised aromatic lactate dehydrogenase (ALDH), suggesting that these microbial metabolites may impact immune function in early life

Laursen, M.F., Sakanaka, M., von Burg, N. et al. Bifidobacterium species associated with breastfeeding produce aromatic lactic acids in the infant gut. Nat Microbiol 6, 1367–1382 (2021). https://doi.org/10.1038/s41564-021-00970-4

Frequent use of antimicrobial drugs in early life shifts bacterial profiles in saliva

The Finnish Health in Teens study (Fin-HIT) is a cohort study including over 11,000 Finnish adolescents. In the most recent Fin-HIT study, researchers tried to find the associations of lifelong AMs use with saliva microbiota diversity and composition in preadolescents. They used data from 808 randomly selected children in the Fin-HIT cohort with objective register data on AM purchases from the Social Insurance Institution of Finland (KELA). Results found that on average, the children had 7.4 AM purchases during their lifespan until on average 12 years. The four most commonly used AMs were amoxicillin (43.7 %), azithromycin (24.9 %), amoxicillin-clavulanate (18.7 %) and phenoxymethylpenicillin (6.8 %). The strongest associations were presented with azithromycin that is used for example to middle ear infections, strep throat and pneumonia.

University of Helsinki. “Frequent use of antimicrobial drugs in early life shifts bacterial profiles in saliva.” ScienceDaily. ScienceDaily, 24 August 2020. <www.sciencedaily.com/releases/2020/08/200824105926.htm>.

Composition and variation of the human milk microbiota are influenced by maternal and early-life factors

This study of 393 mother-infant dyads from the CHILD cohort explored the factors affecting the complex community of bacteria in breastmilk, which may in turn help seed the infant gut microbiota.  Researchers found that milk microbiota composition and diversity were associated with maternal factors (BMI, parity, and mode of delivery), breastfeeding practices, and other milk components in a sex-specific manner. Causal modeling identified mode of breastfeeding as a key determinant of milk microbiota composition. Specifically, providing pumped breastmilk was consistently associated with multiple microbiota parameters including enrichment of potential pathogens and depletion of bifidobacteria. The findings also support the hypothesis that infant oral cavity, rather than mother’s own gut microbiome, impacts the milk microbiota.

Moossavi, S, Sepehri, S, Robertson, B, et al (2019). Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host & Microbe, doi.org/10.1016/j.chom.2019.01.011.

Read a summary of this study: https://www.gutmicrobiotaforhealth.com/en/a-new-study-sheds-light-on-maternal-and-infant-factors-that-shape-breast-milk-microbiome/

Infant Feeding and the Developmental Origins of Chronic Disease in the CHILD Cohort: Role of Human Milk Bioactives and Gut Microbiota

This article provides a useful summary of recent studies exploring potential links between early life exposures and the development of chronic diseases such as allergies, asthma and obesity. In particular, the studies highlight the potential for infant feeding method to impact the infant gut microbiota and so later health. Summaries of some of the studies featured in this article can be found on this page, as well as on our asthma and overweight/obesity research pages.

Azad, M, (2019). Infant Feeding and the Developmental Origins of Chronic Disease in the CHILD Cohort: Role of Human Milk Bioactives and Gut Microbiota. Breastfeeding Medicine, doi.org/10.1089/bfm.2019.0029

Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children

This study of infants from the KOALA Birth Cohort found that breastfeeding duration in early life and pre-school dietary lifestyle correlated with the composition and functional competences of the gut microbiota in children at school age. The researchers’ findings also suggest that distinct metabolic responses to dietary lifestyle are strongly governed by the composition and functional potentials of the gut microbiota, implying that stratification of children according to gut microbiota enterotypes may well be included in future investigations on the relationship between dietary intake and metabolic health in children.

Zhong, H, Penders, J, Shi, Z, et al, (2019). Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children. Microbiome, doi.org/10.1186/s40168-018-0608-z

Early life gut microbiome as an obesity and type 1 diabetes predictor

This article highlights three studies recently published which explore the impact of the gut microbiome on health. One study (Stanislawski et al) found an association between early life gut microbiota, particularly at two years of age, and BMI at age 12 in a Norwegian prospective cohort. The other two studies were part of The Environmental Determinants of Diabetes in the Young (TEDDY) study, exploring the development of type 1 diabetes (T1D). One study (Stewart et al) found that receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure and that birth mode was also significantly associated with the microbiome during the developmental phase. The researchers found subtle associations between microbial taxonomy and the development of islet autoimmunity or T1D. The other study (Vatanen et al) found that children who developed T1D later in childhood had different microbial features than those who didn’t develop it; for example the gut microbiome of children who did not develop T1D later in childhood contained more genes related to fermentation and short-chain fatty acid production, whose protective role in metabolic conditions have been shown previously. The findings suggest that the early life gut microbiome may help identify children who are at risk of obesity or T1D and may support prevention efforts.

https://www.gutmicrobiotaforhealth.com/en/early-life-gut-microbiome-as-an-obesity-and-type-1-diabetes-predictor/

Stanislawski, M, Dabelea, D, Wagner, B, et al, (2018). Gut Microbiota in the First 2 Years of Life and the Association with Body Mass Index at Age 12 in a Norwegian Birth Cohort. American Society for Microbiology, DOI: 10.1128/mBio.01751-18

Stewart, C, Ajami, N, et al (2018). Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature, doi.org/10.1038/s41586-018-0617-x

Vatanen, T, Franzosa, E, Schwager, R, et al (2018). The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature, doi.org/10.1038/s41586-018-0620-2

Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations

This study performed a meta-analysis of seven microbiome studies (1825 stool samples from 684 infants) to compare the gut microbiota of exclusively breastfed (EBF) and non-EBF infants across populations. The authors found that compared with EBF infants, non-EBF infants had increased microbial diversity and microbiota age, and altered microbial composition and functions. EBF was found to have a protective effect on the infant gut microbiota during diarrheal episodes, and gut microbiota differences between EBF and non-EBF infants persisted after 6 months. The researchers conclude that the findings help explain some mechanisms of short and long-term benefits of exclusive breastfeeding.

Nahn T. Ho, Fan Li et al, (2018). Meta-analysis of effects of exclusive breastfeeding on infant gut microbiota across populations, Nature Communications, 9, Article number: 4169

Association of exposure to formula in the hospital and subsequent infant feeding practices with gut microbiota and risk of overweight in the first year of life

This study found that among 1087 infants from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort, earlier cessation of breastfeeding and supplementation with formula (more so than complementary foods) were associated with a dose-dependent increase in risk of overweight by age 12 months; this association was partially explained by specific gut microbiota features at 3 to 4 months. Subtle but significant microbiota differences were observed after brief exposure to formula limited to the birth hospital stay, but these differences were not associated with overweight.

Forbes, J, Azad, B, et al, (2018). Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life. JAMA Paediatrics, doi:10.1001/jamapediatrics.2018.1161

A causal mechanism for childhood acute lymphoblastic leukaemia

This review explores the multifactorial causation of childhood acute lymphoblastic leukaemia (ALL). It argues that there are three stages to the development of the disease: an initial genetic mutation that takes place in the womb; a lack of exposure to microbes in the first year of life; a childhood infection which can cause immune system malfunction. The study highlights the important role that microbes play in determining health outcomes, as well as the value of breastfeeding in supporting the development of these microbes in an infant’s gut.

Greaves, Mel, (2018). A causal mechanism for childhood acute lymphoblastic leukaemia, Nature Reviews Cancer, doi.org/10.1038/s41568-018-0015-6

Further analysis of this review available here: https://www.bbc.co.uk/news/amp/health-44199844

Older research 

  • Association between breast milk bacterial communities and establishment and development of the infant gut microbiome

Pannaraj, P.S. et al (2017), Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome. JAMA Pediatrics, doi:10.1001/jamapediatrics.2017.0378

  • The microbiome in early life: implications for health outcomes

Tamburini, S, et al (2016). The microbiome in early life: implications for health outcomes, Nature Medicine, doi: 10.1038/nm.4142

  • Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses

Dahlen, HG, et al (2016). Childbirth and consequent atopic disease: emerging evidence on epigenetic effects based on the hygiene and EPIIC hypotheses, BMC Pregnancy and Childbirth, https://doi.org/10.1186/s12884-015-0768-9

  • The infant microbiome development: mom matters

Mueller, NT, et al (2014), The infant microbiome development: mom matters, Trends in Molecular Medicine, DOI: https://doi.org/10.1016/j.molmed.2014.12.002

  • Cesarean Section and Chronic Immune Disorders

Sevelsted, A, et al (2014). Cesarean Section and Chronic Immune Disorders, Pediatrics, doi:10.1542/peds.2014-0596

  • Epigenetic effects of human breast milk

Verduci, E, et al (2014). Epigenetic Effects of Human Breast Milk, Nutrients, doi:  10.3390/nu6041711 

  • Natural Childbirth and Breastfeeding as Preventive Measures of Immune- Microbiome Dysbiosis and Misregulated Inflammation

Dietert, RR (2013). Natural Childbirth and Breastfeeding as Preventive Measures of Immune-Microbiome Dysbiosis and Misregulated Inflammation. Journal of Infectious Diseases & Preventive Medicine, doi: 10.4172/2329-8731.1000103

  • An overview of epigenetics in nursing

Clark, A, et al (2013). An overview of epigenetics in nursing, The Nursing Clinics of North America, doi: 10.1016/j.cnur.2013.08.004

Related research and further reading