The impact of vitamin B12 deficiency on infant gut microbiota
Although physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively, less is known about their impact on developing gut microbiota. Vitamin B12 deficiency is a common micronutrient deficiency in infants. We aimed to analyze the gut microbial composition of exclusively breastfed infants aged between 4 and 6 months with and without vitamin B12 deficiency by 16S rRNA gene sequencing. In a subgroup of infants with vitamin B12 deficiency, stool samples are recollected and reanalyzed after vitamin B12 supplementation. A total of 88 infants’ stool samples (median age 4 months [IQR 4–5], 50% males) were analyzed, of which 28 (31.8%) were vitamin B12 sufficient and 60 (68.2%) were vitamin B12 insufficient. Comparisons between vitamin B12-sufficient and vitamin B12-insufficient infants revealed no evidence of differences in the microbiota. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the most abundant phyla in all groups. There was no difference between the pre- and post-treatment composition of gut microbiota.
What is Known:
• Vitamin B12 is an essential vitamin for humans and also a crucial compound for human gut microbiota.
• Vitamin B12 deficiency is common in exclusively breastfed infants.
• In contrast to the adult gut microbiota, infant gut microbiota has been shown to have decreased capacity for de novo synthesis of vitamin B12 and depend on dietary source of vitamin B12.
What is New:
• There is no difference in the gut microbial composition of vitamin B12-deficient and vitamin B12-sufficient infants.
KeywordsInfants Vitamin B12 Micronutrients Gut microbiota Breastfeeding
False discovery rate
Operational taxonomic unit
Principal coordinate analysis
P. Boran, E. Kepenekli, C. Erzik, and A. Soysal designed the study.
P. Boran and HE. Baris participated in recruitment of subjects and sample collection.
P. Boran, HE. Baris, C. Erzik, and DM. Dinh performed data analysis and interpretation.
DM. Dinh generated figures.
P. Boran and HE Baris wrote the first draft of the article.
P. Boran, HE Baris, E Kepenekli, C. Erzik, A. Soysal, and DM Dinh contributed to critical revision and approved the final manuscript.
This project was sponsored by Marmara University Scientific Research Commission, BAPKO, (SAG-A-091116-0488).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Marmara University, School of Medicine Ethics Committee, reference number: 09.2016.137) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from mothers of all individual participants included in the study.
- 7.Boran P, Yildirim S, Karakoc-Aydiner E, Ogulur I, Ozen A, Haklar G, Koc A, Akkoc T, Barlan I (2016) Vitamin B12 deficiency among asymptomatic healthy infants: its impact on the immune system. Minerva Pediatr Jan 13 [Epub ahead of print]Google Scholar
- 10.Dostal A, Lacroix C, Pham VT, Zimmermann MB, Del'homme C, Bernalier-Donadille A, Chassard C (2014) Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats. Br J Nutr 111:2135–2145. https://doi.org/10.1017/S000711451400021X CrossRefPubMedGoogle Scholar
- 14.Halicioglu O, Sutcuoglu S, Koc F, Ozturk C, Albudak E, Colak A, Sahin E, Asik Akman S (2012) Vitamin B12 and folate statuses are associated with diet in pregnant women, but not with anthropometric measurements in term newborns. J Matern Fetal Neonatal Med 25:1618–1621. https://doi.org/10.3109/14767058.2011.648244 CrossRefPubMedGoogle Scholar
- 16.Hill CJ, Lynch DB, Murphy K, Ulaszewska M, Jeffery IB, O'Shea CA, Watkins C, Dempsey E, Mattivi F, Tuohy K, Ross RP, Ryan CA, O' Toole PW, Stanton C (2017) Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET Cohort. Microbiome 5:4. https://doi.org/10.1186/s40168-016-0213-y CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB (2015) Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut 64:731–742 https://doi.org/10.1136/gutjnl-2014-307720 CrossRefGoogle Scholar
- 25.Oksanen J, Blanchet FG, Friendly M et al (2017) Vegan: Community Ecology Package. R package version 2.4-3. 2017Google Scholar
- 28.Rutayisire E, Huang K, Liu Y, Tao F (2016) The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants’ life: a systematic review. BMC Gastroenterol 16:86. https://doi.org/10.1186/s12876-016-0498-0 CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Simonyté Sjödin K, Domellöf M, Lagerqvist C, Hernell O, Lönnerdal B, Szymlek-Gay EA, Sjödin A, West CE, Lind T (2018) Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomised controlled study. Gut [Epub ahead of print] https://doi.org/10.1136/gutjnl-2018-316988 Google Scholar
- 30.Stanislawski MA, Dabelea D, Wagner BD, Iszatt N, Dahl C, Sontag MK, Knight R, Lozupone CA, Eggesbø M (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. MBio 9:e01751–e01718. https://doi.org/10.1128/MBIO.01751-18 CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Stewart CJ, Ajami NJ, O'Brien JL, Hutchinson DS, Smith DP, Wong MC, Ross MC, Lloyd RE, Doddapaneni H, Metcalf GA, Muzny D, Gibbs RA, Vatanen T, Huttenhower C, Xavier RJ, Rewers M, Hagopian W, Toppari J, Ziegler AG, She JX, Akolkar B, Lernmark A, Hyoty H, Vehik K, Krischer JP, Petrosino JF (2018) Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 562:583–588 https://doi.org/10.1038/s41586-018-0617-x CrossRefGoogle Scholar
- 34.Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227. https://doi.org/10.1038/nature11053 CrossRefPubMedPubMedCentralGoogle Scholar