Understanding Infant Gut Microbiome and Clinical Microbiology Informatics

Understanding Infant Gut Microbiome and Clinical Microbiology Informatics

October 29th, 2024|Nutrition

The infant gut microbiome refers to the diverse collection of microorganisms found in the gastrointestinal tract of newborns and infants, typically those aged 1 to 23 months.? This microbial community is composed of different microorganisms, including bacteria, viruses, fungi, parasites, archaea, and other microbes. Generally, the human gut microbiome is fundamental in shaping the health and well-being of individuals throughout their lifespan. Overall, the human gut microbiome plays a vital role in influencing health and well-being throughout life, and its significance is particularly heightened during infancy—a crucial stage that sets the groundwork for long-term health.

Significance of Microbiome in Infant Health

Existing literature has emphasized the importance of the gut microbiome in infants, highlighting its impact on various aspects of health and illness. Gut microbiota plays three critical roles: protective, metabolic, and trophic. First, gut microorganisms act as a barrier against the growth of harmful pathogens. Second, they are crucial for digesting and metabolizing colostrum, breast milk, formula, and complementary foods in infants, as well as a wide range of foods in adults. They assist in breaking down toxins and drugs, synthesizing vitamins, and absorbing ions. Its tropic function includes the support that the microbiome provides in the growth and differentiation of the epithelial cells in the intestinal lining and helps maintain immune homeostasis, including tolerance to food antigens. With adequate colonization of the gut in an individual, the gut is in a state of eubiosis, populated by a diverse array of microorganisms and marked by oral tolerance to commensal bacteria and benign antigens. Inadequate colonization during this early period, however, may lead to dysbiosis (or an imbalance between commensal and pathogenic organisms) which may increase susceptibility to a variety of immune-related pathogenic states, and other adverse metabolic-related disorders such as cardiovascular diseases (CVDs), cancers, respiratory diseases, etc.

Determinants of Gut Microbiota in Infant Health

Numerous elements contribute to the development of an infant’s gut microbiota which includes maternal diet, mode of delivery (vaginal birth vs. cesarean section), feeding method (breastfeeding vs. formula feeding), antibiotic exposure, and introduction to complementary foods as elaborated upon in the sections as follows:

Maternal Diet

Existing literature has reported an association between maternal diet, both during pregnancy and while breastfeeding, on the development of the infant gut microbiome. In 2021, Fan et al. examined the effect of maternal fruit and vegetable consumption on the infant gut microbiome at two months postpartum and found an increased abundance of the beneficial genera Cutibacterium, Parabacteroides, and Lactococcus in the gut of infants whose mothers had high gestational consumption of fruits and vegetables as compared to those with low gestational consumption of fruits and vegetables. Another study was conducted by Williams et al. (2017) who studied the associations between maternal nutrient intake and the milk microbiome in a cohort of 21 women between 2 and 6 months postpartum. Reportedly, the relative abundance of Lactobacillus was negatively associated with maternal consumption of thiamine, niacin, folate, vitamin B-6, and chromium. Additionally, the relative abundance of Proteobacteria was positively associated with a nutrient-rich diet and intake of various fatty acids. They also found that milk from mothers with male infants had higher Streptococcus and lower Staphylococcus than milk from mothers with female infants.

Mode of Delivery

?In infants delivered vaginally, their gut microbiota closely resembles their mothers’ vaginal microbiota, which is primarily dominated by Lactobacillus, Prevotella, and Sneathia. In contrast, infants born via cesarean section tend to have gut microbiota that more closely resembles skin microbiota, dominated by Staphylococcus, Corynebacterium, and Propionibacterium. The gut microbiota of infants born via cesarean section exhibits a notable underrepresentation of Bacteroides, a trend that persists for three to four months postnatally. Pioneering studies indicate that those delivered by elective cesarean section display particularly low bacterial diversity and are at high risk of developing immune disorders, including allergic rhinitis, asthma, and celiac disease as compared to newborns delivered vaginally.

Antibiotic Exposure

The administration of antibiotics during early life exerts significant effects on the development of the gut microbiota. In infants, the use of antibiotics results in a compositional shift characterized by an increased prevalence of proteobacteria and a concomitant reduction in Actinobacteria populations. This alteration not only diminishes the overall diversity of the microbiota but also favors the emergence of drug-resistant bacterial strains. Epidemiological surveys indicate that early-life antibiotic exposure is correlated with an elevated risk of developing allergic diseases, including asthma, atopic disorders, eczema, and type 1 diabetes.

Exclusive Breast-Feeding vs Formulae Feeding

The gut microbiome of infants nourished with human milk markedly diverges from that of those fed formula. Notably, formula feeding in term infants has been linked to increased microbial diversity. Studies have consistently reported elevated levels of Bifidobacteria—crucial constituents of a healthy microbiota—in breastfed infants compared to their formula-fed peers. Consequently, there are discernible differences in the levels of fecal short-chain fatty acids (SCFAs), the principal metabolites derived from the fermentation of human milk oligosaccharides (HMOs), with breastfed infants exhibiting higher concentrations.

Introduction to Complementary Feeding

The introduction of complementary foods, particularly those rich in indigestible carbohydrates (eg: cellulose, hemicellulose, pectin, etc), precipitates a substantial transition in the gut microbial community, shifting from a Bifidobacterium-dominant profile to one characterized by increased prevalence of Bacteroidetes and Firmicutes. Notably, the specific taxa present before and after this dietary shift may differ. By approximately three years of age, the composition and diversity of the gut microbiota closely approximate those observed in adults. In the absence of significant perturbations—such as prolonged dietary modifications, dysbiosis associated with disease, or antibiotic intervention—these microbiotas tend to maintain a relatively stable equilibrium throughout adulthood.

Scope of Clinical Microbial Informatics: Future Directions

Clinical microbiology informatics is the use of information (e.g., data, knowledge, and results) and information tools (e.g., software, databases, and rules) in the “science and service dealing with detection, identification, and antimicrobial susceptibility testing” of clinically relevant microbes and the communication of these results to clinicians. Technology enables the scientific community to bridge the divide between health informatics and bioinformatics, enhancing our understanding of health and the microbiome. The evolution of genome sequencing technologies and metagenomic analysis has equipped researchers to examine microorganisms, their roles, and their interactions in both natural ecosystems and industrial settings. The swift advancement of high-throughput, culture-independent analytical techniques has generated vast experimental data, greatly enhancing the study of the human microbiome. For instance, Sindi et al 2022 collected stool samples from ten infants of caucasian mothers (before and after the maternal dietary invention) and shotgun metagenomic sequencing was used to characterize the gut microbiome composition and function of exclusively breastfed infants. Reportedly, short-term maternal dietary interventions (reduced fat and sugar diet) during lactation could significantly alter the functional potential of the gut microbiome of breastfed infants. Thus, it can be said that modern microbiology research is increasingly embracing high-throughput techniques and big data methods, which offer quicker, more unbiased, and reproducible results compared to traditional studies that often rely on limited data or labour-intensive experimental approaches.

References

1. Tanaka, M.; Nakayama, J. Development of the gut microbiota in infancy and its impact on health in later life. Allergol. Int. 2017, 66, 515–522.
2. Turroni, F.; Milani, C.; Duranti, S.; Lugli, G.A.; Bernasconi, S.; Margolles, A.; Di Pierro, F.; Van Sinderen, D.; Ventura, M. The infant gut microbiome is a microbial organ influencing host well-being. Ital. J. Pediatr. 2020, 46, 16.
3. Mehta, S.; Huey, S.L.; McDonald, D.; Knight, R.; Finkelstein, J.L. Nutritional Interventions and the Gut Microbiome in Children. Annu. Rev. Nutr. 2021, 41, 479–510.
4. Yang, I., Corwin, E. J., Brennan, P. A., Jordan, S., Murphy, J. R., & Dunlop, A. (2016). The Infant Microbiome: Implications for Infant Health and Neurocognitive Development. Nursing Research, 65(1), 76–88. https://doi.org/10.1097/NNR.0000000000000133.
5. Walker WA. Initial intestinal colonization in the human infant and immune homeostasis. Annals of Nutrition and Metabolism. 2013;63:8–15.
6. Renz H, Brandtzaeg P, Hornef M. The impact of perinatal immune development on mucosal homeostasis and chronic inflammation. Nature Reviews Immunology. 2012;12:9–23.
7. Penders, J., Thijs, C., Vink, C., Stelma, F. F., Snijders, B., Kummeling, I., Van Den Brandt, P. A., & Stobberingh, E. E. (2006). Factors influencing the composition of the intestinal microbiota in early infancy. PEDIATRICS, 118(2), 511–521. https://doi.org/10.1542/peds.2005-2824.
8. A. Langdon, N. Crook, G. Dantas (2016). The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation Genome Med, 8 (2016), p. 39.
9. A.M. Moore, S. Ahmadi, S. Patel, M.K. Gibson, B. Wang, M.I. Ndao, et al.(2015) Gut resistome development in healthy twin pairs in the first year of life Microbiome, 3, p. 27.
10. T. Yatsunenko, F.E. Rey, M.J. Manary, I. Trehan, M.G. Dominguez-Bello, M. Contreras, et al. Human gut microbiome viewed across age and geography Nature, 486 (2012), pp. 222-227.
11. M. Fallani, S. Amarri, A. Uusijarvi, R. Adam, S. Khanna, M. Aguilera, et al. (2011). Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centers Microbiology, 157, pp. 1385-1392
12. Ma J., Li Z., Zhang W., Zhang C., Zhang Y., Mei H., Zhuo N., Wang H., Wang L., Wu D. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: A study of 91 term infants. Sci. Rep. 2020;10:15792. doi: 10.1038/s41598-020-72635-x.
13. Chong, H. Y., Tan, L. T., Law, J. W., Hong, K. W., Ratnasingam, V., Ab Mutalib, N. S., Lee, L. H., & Letchumanan, V. (2022). Exploring the Potential of Human Milk and Formula Milk on Infants’ Gut and Health. Nutrients, 14(17), 3554. https://doi.org/10.3390/nu14173554
14. Salli K., Anglenius H., Hirvonen J., Hibberd A.A., Ahonen I., Saarinen M.T., Tiihonen K., Maukonen J., Ouwehand A.C. The effect of 2′-fucosyllactose on simulated infant gut microbiome and metabolites; a pilot study in comparison to GOS and lactose. Sci. Rep. 2019;9:13232. doi: 10.1038/s41598-019-49497-z.
15. Penders, J., Thijs, C., Vink, C., Stelma, F. F., Snijders, B., Kummeling, I., Van Den Brandt, P. A., & Stobberingh, E. E. (2006). Factors influencing the composition of the intestinal microbiota in early infancy. PEDIATRICS, 118(2), 511–521. https://doi.org/10.1542/peds.2005-2824
16. Sindi, A. S., Stinson, L. F., Lean, S. S., Chooi, Y., Leghi, G. E., Netting, M. J., Wlodek, M. E., Muhlhausler, B. S., Geddes, D. T., & Payne, M. S. (2022). Effect of a reduced fat and sugar maternal dietary intervention during lactation on the infant gut microbiome. Frontiers in Microbiology, 13. https://doi.org/10.3389/fmicb.2022.900702.
17. Fan H., Tung Y., Yang Y., Hsu J., Lee C., Chang T., Su E., Hsieh R., Chen Y. Maternal Vegetable and Fruit Consumption during Pregnancy and Its Effects on Infant Gut Microbiome. (2021) Nutrients. ;13:1559. doi: 10.3390/nu13051559.
18. Williams J.E., Carrothers J.M., Lackey K.A., Beatty N.F., York M.A., Brooker S.L., Shafii B., Price W.J., Settles M.L., McGuire M.A., et al. Human Milk Microbial Community Structure Is Relatively Stable and Related to Variations in Macronutrient and Micronutrient Intakes in Healthy Lactating Women. J. Nutr. 2017;147:1739–1748. doi: 10.3945/jn.117.248864.
19. Thomson RB, Jr, Wilson ML, Weinstein MP. 2010. The clinical microbiology laboratory director in the United States hospital setting. J. Clin. Microbiol. 48:3465–3469. 10.1128/JCM.01575-10

Written by

Dr. Priyanka Arora?1, Nikita Arya 2

1. Academic Coordinator at the Foundation of Healthcare Technologies Society
2. Public Health Researcher at the Foundation of Healthcare Technologies Society