Early-life period (≤ 1 month after birth) is critical for determining long- and short-term health of neonates. Composition of neonates’ gut microbiota varies greatly between individuals whose development is influenced by various factors including differences in maternal diet and lifestyle during pregnancy, related to population and ethnicity. Balanced microbial composition can create symbiosis among commensal microbes, immunomodulatory compound production, and subsequent immune response regulation. Unbalanced microbiota composition, characterized by more pathogenic organism, less diversity, and less resistance to disease, is called dysbiosis. Probiotic bacteria are a bacteria group contributing to the balance of neonates’ gut microbiota. Probiotic bacterial strains, such as Lactobacillus, Bifidobacterium and Streptococcus strains, are present in neonatal meconium microbiota. Meconium, a biological material formed during pregnancy, is a useful source of information in describing in utero microbial environment. This review aims to describe probiotic potential in profile composition of neonates’ microbiota meconium of multiple ethnicities as marker of neonates’ health level. Molecular-based sequencing method, such as Next-Generation Sequencing (NGS), is the preferred method for analyzing complex microbiota communities, such as gut microbiota. Neonatal meconium samples are collected and DNA extractions are carried out, then the target genes are amplified by PCR. The amplicons obtained are sequenced and characterized to determine the presence of potential probiotic strains in sample. Whether the probiotic strains can be used to measure neonates’ health level during period of growth and development is also described. Those probiotic strains could be developed as microbial therapeutic agent in gastrointestinal tract disorder therapy.
Alcon-giner, C. et al. (2017). Optimisation of 16S rRNA gut microbiota profiling of extremely low birth weight infants. BMC Genomics, 18(841), 1–15.
Angelakis, E. (2017). Weight gain by gut microbiota manipulation in productive animals. Microb. Pathogenesis 106, 162–170
Atarashi, K. et al. (2011). Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337–341.
Atya, A. K. Al et al. (2015) ‘Probiotic potential of Enterococcus faecalis strains isolated from meconium’, frontiers in Microbiology, 6(April).
Bain, C.C. et al. (2014). Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nature Immunology 15, 929–937.
Bajaj, B.K., Claes, I.J., Lebeer, S. (2015). Functional mechanisms of probiotics. Journal of Microbiology, Biotechnology and Food Sciences, 4, 321–327.
Barnes, M.J. and Powrie, F. (2009). Regulatory T cells reinforce intestinal homeostasis. Immunity 31, 401–411
Belkaid, Y and Hand, T.W. (2014). Role of the microbiota in immunity and inflammation. Cell 157, 121–141.
Bene, K.P. et al. (2017). Lactobacillus reuteri surface mucus adhesins upregulate inflammatory responses through interactions with innate C-Type lectin receptors. Frontiers in Microbiology 8, 321
Bennett, C.L. et al. (2001). The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nature Genetics 27, 20–21.
Bermudez-Brito, M., et al. (2012). Human intestinal dendritic cells decrease cytokine release against Salmonella infection in the presence of Lactobacillus paracasei upon TLR activation. PLoS One 7, e43197
Besser, J. et al. (2018) ‘Next-generation sequencing technologies and their application to the study and control of bacterial infections’, Clinical Microbiology and Infection, 24(4), 335–341.
Bimczok, D. et al. (2015). Human gastric epithelial cells contribute to gastric immune regulation by providing retinoic acid to dendritic cells. Mucosal Immunology, 8, 533–544
Birarra, M. K., Heye, T. B., and Shibeshi, W. (2017) ‘Assessment of drug-related problems in pediatric ward of Zewditu Memorial Referral Hospital, Addis Ababa, Ethiopia’, International Journal of Clinical Pharmacy, 39(5), 1039–1046.
Bleich, A. and Fox, J.G. (2015). The Mammalian Microbiome and its importance in laboratory animal research. ILAR Journal, 56, 153–158.
Boyle, R. J., Robins-browne, R. M., and Tang, M. L. K. (2018) ‘Probiotic use in clinical practice : what are the risks ?’, The American Journal of Clinical Nutrition, 83(April), 1256–1264.
Brittan, J.L. and Nobbs, A.H. (2015). Group B Streptococcus pili mediate adherence to salivary glycoproteins. Microbes and Infection, 17, 360–368.
Butel, M.-J., Waligora- Dupriet, A.-J., and Wydau-Dematteis, S. (2018) ‘The developing gut microbiota and its consequences for health’, Journal of Developmental Origins of Health and Disease, (May).
Byrd, D. A. et al. (2020) ‘Elucidating the role of the gastrointestinal microbiota in racial and ethnic health disparities’, Genome Biology, 21(1), 192.
Campos, C. A. et al. (2006) ‘Preliminary characterization of bacteriocins from Lactococcus lactis , Enterococcus faecium and Enterococcus mundtii strains isolated from turbot ( Psetta maxima ) q’, Food Research International, 39, 356–364.
Caporaso, J. G. et al. (2012). Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. The ISME Journal, 6(8), 1621–1624.
Clarke, G. et al. (2019) ‘Gut reactions: Breaking down xenobiotic–microbiome interactions’, Pharmacological Reviews, 71(2), 198–224. Cleary, B. et al. (2016) ‘Detection of low-abundance bacterial strains in metagenomic datasets by eigengenome partitioning’, HHS Public Access, 33(10), 1053–1060.
Clemente, J.C., Ursell, L.K., Parfrey, L.W., and Knight, R. (2012). The impact of the gut microbiota on human health: an integrative view. Cell 148, 1258–1270.
Collado, M. C., Rautava, S., Aakko, J., and Isolauri, E. (2016). Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Nature Publishing Group, (February), 1–13.
de Agüero, M.G. et al. (2016). The maternal microbiota drives early postnatal innate immune development. Science 351, 1296–1302.
Desai, M.S. et al. (2016). A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167(5):1339–1353.
Diggikar, S. (2019) ‘Neonatal Microbiome: A Complex, Invisible Organ and Its Evolving Role in Neonatal Illness and Beyond’, Journal of Clinical Neonatology, 5–9.
Dwivedi, M., Kumar, P., Laddha, N.C., and Kemp, E.H. (2016). Induction of regulatory T cells: a role for probiotics and prebiotics to suppress autoimmunity. Autoimmunity Reviews, 15, 379–392.
ECDC/EMEA (2009). Joint Technical Report. The Bacterial Challenge: Time to React; European Centre for Disease Control: Stockholm, Sweden, September 2009.
Earle, K.A. et al. (2015). Quantitative imaging of gut microbiota spatial organization. Cell Host & Microbe 18(4):478–488.
Fabricatore, A. N. et al. (2011) ‘Intentional weight loss and changes in symptoms of depression : a systematic review and meta-analysis’, International Journal of Obesity, 1–14.
Fakruddin, M., Hossain, N., and Ahmed, M. M. (2017) ‘Antimicrobial and antioxidant activities of Saccharomyces cerevisiae IFST062013 , a potential probiotic’, BMC Complementary and Alternative Medicine, 1–11.
Fijan, S. (2016) ‘Antimicrobial Effect of Probiotics against Common Pathogens’, INTECH, (Probiotics and Prebiotics in Human Nutrition and Health).
Franzosa, E. A. et al. (2014) ‘Relating the metatranscriptome and metagenome of the human gut’, PNAS.
Gassler, N. (2017). Paneth cells in intestinal physiology and pathophysiology. World Journal of Gastrointestinal Pathophysiology, 8, 150.
Goodrich, J. K. et al. (2014) ‘Conducting a Microbiome Study’, Cell, 158(2), 250–262.
Goodwin, S., Mcpherson, J. D. and Mccombie, W. R. (2016) ‘Coming of age : ten years of next- generation sequencing technologies’, Nature Publishing Group, 17(6), 333–351.
Gosalbes, M. J. et al. (2013) ‘Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants’, Clinical and Experimental Allergy, 43(2), 198–211.
Goto, Y. et al. (2014). Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science, 345, 1254009
Gratz, I.K. and Campbell, D.J. (2014). Organ-specific and memory treg cells: specificity, development, function, and maintenance. Front. Immuno. 5, 333.
Groer, M. W., Luciano, A. A., Dishaw, L. J., Ashmeade, T. L., Miller, E., and Gilbert, J. A. (2014). Development of the preterm infant gut microbiome : a research priority. Microbiome, 1–8.
Gupta, R. W. et al. (2013). Histamine-2 Receptor Blockers Alter the Fecal Microbiota in Premature Infants. JPGN, 56(4), 397–400.
Hasan, N. and Yang, H. (2019) ‘Factors affecting the composition of the gut microbiota, and its modulation’, PeerJ, 2019(8), 1–31.
Heilig, H.G., Zoetendal, E.G., Vaughan, E.E., Marteau, P., Akkermans, A.D., and de Vos, W.M. (2002). Molecular diversity of Lactobacillus spp. and other lactic acid bacteria in the human intestine as determined by specific amplification of 16S ribosomal DNA. Applied and Environmental Microbiology, 68(1), 114–23.
Hojo, K., Nagaoka, S., Murata, S., Taketomo, N., Ohshima, T., and Maeda, N. (2007). Reduction of vitamin K concentration by salivary Bifidobacterium strains and their possible nutritional competition with Porphyromonas gingivalis. Journal of Applied Microbiology, 103, 1969–1974
Hooper, L.V., Littman, D.R., and Macpherson, A.J. (2012). Interactions between the microbiota and the immune system. Science, 336, 1268–1273
Hugenholtz, P. and Pace, N. R. (1996). Identifying microbial diversity in the natural environment : a molecular phylogenetic approach. Trends in Biotechnology, 14(96), 190–197.
Jostins, L. et al. (2012) ‘Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease’, Nature, 490(7422), 119–124.
Kankainen, M. et al. (2009). Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human-mucus binding protein. Proceedings of the National Academy of Sciences, USA 106, 17193–1719
Kau, A.L. et al. (2015). Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Science Translational Medicine, 7, 276ra24.
Kaushik, J. K. et al. (2009) ‘Functional and Probiotic Attributes of an Indigenous Isolate of Lactobacillus plantarum’, PLoS One, 4(12).
Konieczna, P. et al. (2012). Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. Gut 61, 354–366.
Kook, S. et al. (2019) ‘Isolation and characterization of five novel probiotic strains from Korean infant and children faeces’, PLoS One, 1–17.
Lécuyer, E. et al. (2014). Segmented filamentous bacterium uses secondary and tertiary lymphoid tissues to induce gut IgA and specific T helper 17 cell responses. Immunity, 40, 608–620.
Lebeer, S., Vanderleyden, J., and De Keersmaecker, S.C.J. (2010). Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nature Reviews Microbiology, 8, 171–184
Lee, Y.K. and Mazmanian, S.K. (2010). Has the microbiota played a critical role in the evolution of the adaptive immune system? Science, 330, 1768–1773.
Luo, C. et al. (2015) ‘ConStrains identifies microbial strains in metagenomic datasets’, Nature Biotechnology.
Mack, D.R., Michail, S., Wei, S., McDougall, L., and Hollingsworth, M.A. (1999). Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression.American Journal of Physiology-Gastrointestinal and Liver, 276, G941–G950
Malik, A. et al. (2020). Clinical characteristics and clinical outcomes influence the cultivable-bacteria composition of the meconium of Indonesian neonates, Heliyon. [Manuscript].
Mantis, N.J., Rol, N., and Corthésy, B. (2011). Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunology, 4, 603–611.
Marshall, K. (1977). Advances in Microbial Ecology. (R. M. Atlas, B. B. Jforgensen, J. H. Slater, & K. M. Editor, Eds.) (Vol. 9). Kensington, Australia: MICROBIAL ECOLOGY Advances in Volume 9 Edited by K. C. Marshall University of New South Wales Kensington, New South Wales, Australia SPRINGER SCIENCE+ BUSINESS MEDIA, LLC.
Ma, T., Suzuki, Y., and Guan, L. L. (2018) ‘Dissect the mode of action of probiotics in affecting host-microbial interactions and immunity in food producing animals’, Veterinary Immunology and Immunopathology, 205, 35–48. Marißen, J. et al. (2019) ‘Efficacy of Bifidobacterium longum, B. infantis and Lactobacillus acidophilus probiotics to prevent gut dysbiosis in preterm infants of 28 + 0 – 32 + 6 weeks of gestation : a randomised , placebo- trial : the PRIMAL Clinical Study protocol’, BMJ Open, 9, 1–9.
Matamoros, S., Gras-leguen, C., Vacon, L., Potel, G., and Cochetiere, M. D. La. (2013). Development of intestinal microbiota in infants and its impact on health. Human Microbiome, 1–7.
Morais, J. et al. (2020) ‘Extremely preterm neonates have more Lactobacillus in meconium than very preterm neonates–the in utero microbial colonization hypothesis’, Gut Microbes, 12(1), 1–9.
Morgan, X. C. and Huttenhower, C. (2012) ‘Chapter 12 : Human Microbiome Analysis’, PLoS Computational Biology, 8(12).
Mueller, N. T. et al. (2017) ‘Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure, Composition and Predicted Metabolic Function’, Genes, 8(364).
Muñoz-Atienza, E. et al. (2013). Antimicrobial activity, antibiotic susceptibility and virulence factors of lactic acid bacteria of aquatic origin intended for use as probiotics in aquaculture. BMC Microbiology, 13, 15.
Nagpal, R. et al. (2016) ‘Sensitive quantitative analysis of the meconium bacterial microbiota in healthy term infants born vaginally or by cesarean section’, Frontiers in Microbiology, 7(DEC), 1–9.
O’Mahony, C. et al. (2008). Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-κB activation. PLOS Pathogens, 4, e1000112.
O’Sullivan, D.J. (1999). Methods for the analysis of the intestinal microflora. In: Tannock, G.W. (Ed.), Probiotics: A Critical 1997. Analysis of fecal populations of bifidobacteria and Review, Horizon Scientific Press, Norfolk, UK, 23–44.
Ohland, C.L. and MacNaughton, W.K. (2010). Probiotic bacteria and intestinal epithelial barrier function. American Journal of Physiology-Gastrointestinal and Liver, 298, G807–G819.
Okai, S. et al. (2016). High-affinity monoclonal IgA regulates gut microbiota and prevents colitis in mice. Nature Microbiology, 1, 16103.
Proft, T. and Baker, E.N. (2009). Pili in Gram-negative and Gram-positive bacteria—structure, assembly and their role in disease. Cellular and Molecular Life Sciences, 66, 613.
Round, J.L. and Mazmanian, S.K. (2010). Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proceedings of the National Academy of Sciences USA 107, 12204–12209.
Russo, E., Taddei, A., Ringressi, M.N., Ricci, F., and Amedei, A. (2016). The interplay between the microbiome and the adaptive immune response in cancer development. Therapeutic Advances in Gastroenterology, 9, 594–605.
Rosser, E.C. et al. (2014). Regulatory B cells are induced by gut microbiota–driven interleukin-1β and interleukin-6 production. Nature Medicine, 20, 1334–1339.
Rintala, A. et al. (2017) ‘Gut Microbiota Analysis Results Are Highly Dependent on the 16S rRNA Gene Target Region , Whereas the Impact of DNA Extraction Is Minor’, Journal of Biomolecular Techniques, 28, 19–30.
Sakai, F. et al. (2014). Lactobacillus gasseri SBT2055 induces TGF-b expression in dendritic cells and activates TLR2 signal to produce IgA in the small intestine. PLoS One 9, e105370.
Sarangi, A. N., Goel, A., and Aggarwal, R. (2019) ‘Methods for Studying Gut Microbiota : A Primer for Physicians’, Journal of Clinical and Experimental Hepatology, 9(1), 62–73.
Schlee, M., Harder, J., Köten, B., Stange, E.F., Wehkamp, J., and Fellermann, K. (2008). Probiotic lactobacilli and VSL#3 induce enterocyte β-defensin 2. Clinical & Experimental Immunology, 151, 528–535.
Schlee, M., Wehkamp, J., Altenhoefer, A., Oelschlaeger, T.A., Stange, E.F., and Fellermann, K. (2007). Induction of human β-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated throuah flagellin. Infection and Immunity, 75, 2399–2407.
Shaw, M.H., Kamada, N., Kim, Y.G., and Núñez, G. (2012). Microbiota-induced IL-1β, but not IL-6, is critical for the development of steady-state TH17 cells in the intestine. Journal of Experimental Medicine, 209, 251– 258.
Shokryazdan, P. et al. (2014) ‘Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains’.
Sihotang, S. and Fachrial, E. (2020) ‘Isolasi, identifikasi dan karakterisasi bakteri probiotik dari mekonium isolation, identification and characterization of probiotic bacteria from meconium’, Jurnal Kedokteran STM (Sains dan Teknologi Medik), 3(2), 82–90.
Smolinska, S., Groeger, D., and O’Mahony, L. (2017). Biology of the microbiome 1: interactions with the host immune response. Gastroenterology Clinics of North America, 46, 19–35
Stearns, J. C. et al. (2017) ‘Ethnic and diet-related differences in the healthy infant microbiome’, Genome Medicine, 9(23), 1–12.
Tannock, G.W. (1999). Identification of lactobacilli and bifidobacteria. In: Probiotics: A Critical Review, Horizon Scientific Environ. Microbiology, 64, 4816–4819. Press, Norfolk, UK, 45–56
Tsai, Y.T., Cheng, P.C., and Pan, T.M. (2012). The immunomodulatory effects of lactic acid bacteria for improving immune functions and benefits. Applied Microbiology and Biotechnology, 96, 853–862.
Turroni, F. et al. (2014). Expression of sortase-dependent pili of Bifidobacterium bifidum PRL2010 in response to environmental gut conditions. FEMS Microbiology Letters, 357, 23–33.
Varankovich, N.V., Nickerson, M.T., and Korber, D.R. (2015). Probiotic-based strategies for therapeutic and prophylactic use against multiple gastrointestinal diseases. Frontiers in Microbiology, 6, 685.
Viladomiu, M. et al. (2017). IgA-coated E. coli enriched in Crohn’s disease spondyloarthritis promote TH17- dependent inflammation. Science Translational Medicine, 9, eaaf9655.
Weaver, C.T., Harrington, L.E., Mangan, P.R., Gavrieli, M., and Murphy, K.M. (2006). Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity, 24, 677–688.
White, J. R., Nagarajan, N., and Pop, M. (2009) ‘Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples’, PLoS Computational Biology, 5(4).
Xu, J. et al. (2020) ‘Ethnic diversity in infant gut microbiota is apparent before the introduction of complementary diets’, Gut Microbes, 1–12.
Yan, F., Cao, H., Cover, T.L., Whitehead, R., Washington, M.K., and Polk, D.B. (2007). Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology,132, 562–575.
Zavisic, G. et al. (2019) ‘Probiotic potential of Lactobacillus fermentum G-4 originated from newborns meconium’, Journal of the Serbian Chemical Society, 2020(February).
Zhao, Q. and Elson, C.O. (2018). Adaptive immune education by gut microbiota antigens. Immunology, 154, 28–37.
Oktaviyani, Devi; 'Alawiyyah, Raden Zulfa; Nusaiba, Putri; and Malik, Amarila
"A Review: Composition of Neonatal Meconium Microbiota and Its Role for Potential Probiotic,"
Pharmaceutical Sciences and Research: Vol. 8:
1, Article 6.
Available at: https://scholarhub.ui.ac.id/psr/vol8/iss1/6