Fecal human β-defensin-2 (hBD-2) levels and gut microbiota patterns in preterm neonates with different feeding patterns
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Abstract
Background and Objectives: Human β-defensin-2 (hBD-2) is an essential antibacterial peptide involved in innate immunity and is expressed in breast milk and intestinal mucosa. The aim of this study was to investigate fecal hBD-2 levels and gut microbiota in preterm neonates with different feeding patterns.
Materials and Methods: This study was cross-sectionally designed and included 44 preterm neonates categorized into four groups as follows: breast milk only, breast milk predominant, formula milk predominant, formula milk only. The study was conducted at the Neonatology Ward, National Center Hospital Cipto Mangunkusumo, Jakarta from November 2016 to April 2017. hBD-2 levels were measured by ELISA. Intestinal bacteria were quantified by qPCR.
Results: hBD-2 levels were significantly different between groups (one-way ANOVA, p=0.004) and the highest value of hBD-2 was found in the formula milk predominant group (344.87±61.2 ng/mL). hBD-2 levels were positively correlated with feeding pattern (Spearman correlation test, p=0.009, r=0.391). There were no significant differences in the total number of specific intestinal microbiota (Bifidobacterium, Lactobacillus and Klebsiella) among groups (one-way ANOVA, p>0.05). Interestingly, the formula milk only group had the highest amount of Klebsiella compared with other groups. hBD-2 levels were not correlated with the quantity of Bifidobacterium, Lactobacillus and Klebsiella (Pearson correlation test, p>0.05).
Conclusion: hBD-2 levels were significantly higher in the formula milk predominant group compared with the breast milk only group. Gut microbiota patterns showed that Bifidobacterium and Lactobacillus were higher in the breast milk only group, while Klebsiella was higher in formula milk group, although this difference was not statistically significant.
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27. O’Neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, et al. Expression and regulation of the human β-defensins hbd-1 and hbd-2 in intestinal epithelium. J Immunol 1999; 163: 6718-6724.
28. Witthoft T, Pilz CS, Fellermann K, Nitschke M, Stange EF, Ludwig D. Enhanced human β-defensin-2 (hbd-2) expression by corticosteroids is independent of nf-kappab in colonic epithelial cells (Caco2). Dig Dis Sci 2005; 50:1252-1259.
29. Schwiertz A, Gruhl B, Lobnitz M, Michel P, Radke M, Blaut M. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res 2003; 54:393-399.
30. Abdulkadir B, Nelson A, Skeath T, Marrs EC, Perry JD, Cummings SP, et al. Routine use of probiotics in preterm infants: Longitudinal impact on the microbiome and metabolome. Neonatology 2016; 109:239-247.
31. Wall R, Ross RP, Ryan CA, Hussey S, Murphy B, Fitzgerald GF. Role of gut microbiota in early infant development. Clin Med Pediatrr 2009; 3:45-54.
32. Wold AE, Adlerbeth I. Breast feeding and the intestinal microflora of the infant—implications for protection against infectious diseases. Adv Exp Med Biol 2000; 478:77-93.
33. Jiménez E, Delgado S, Maldonado A, Arroyo R, Albújar M, García N, et al. Staphylococcus epidermidis: a differential trait of the fecal microbiota of breast-fed infants. BMC Microbiol 2008; 8:143.
34. Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and human milk. Pediatr Res 2007; 61:2-8.
35. Parra-Llorca A, Gormaz M, Alcantara C, Cernada M, Nunez-Ramiro A, Vento M, et al. Preterm gut microbiome depending on feeding type: significance of donor human milk. Front Microbiol 2018; 9:1376.
36. Neu J. Preterm infant nutrition, gut bacteria, and necrotizing enterocolitis. Curr Opin Clin Nutr Metab Care 2015; 18:285-288.
37. Albenberg L, Esipova TV, Judge CP, Bittinger K, Chen J, Laughlin A, et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota in humans and mice. Gastroenterology 2014; 147:1055-1063.
2. Howson CP, Kinney MV, McDougall L, Lawn JE. Born too soon: preterm birth matters. Reprod Health 2013; 10:S1.
3. Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet 2008; 371:261-269.
4. Jobe AH, Hillman N, Polglase G, Kramer BW, Kallapur S, Pillow J. Injury and inflammation from resuscitation of the preterm infant. Neonatology 2008; 94, 190-196.
5. Melville JM, Bischof RJ, Meeusen EN, Westover AJ, Moss TJ. Changes in fetal thymic immune cell populations in a sheep model of intrauterine inflammation. Reprod Sci 2012; 19:740-747.
6. Strunk T, Currie A, Richmond P, Simmer K, Burgner D. Innate immunity in human newborn infants: prematurity means more than immaturity. J Matern Fetal Neonatal Med 2011; 24:25-31.
7. Siggers J, Sangild PT, Jensen TK, Siggers RH, Skovgaard K, Støy AC, et al. Transition from parenteral to enteral nutrition induces immediate diet-dependent gut histological and immunological responses in preterm neonates. Am J Physiol Gastrointest Liver Physiol 2011; 301:G435-445.
8. Guaraldi F, Salvatory G. Effect of breast and formula feeding on gut microbiota shaping in nwborns. Front Cell Infect Microbiol 2012; 2:94.
9. Jenke ACW, Zilbauer M, Postberg J, Wirt S. Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis. Pediatr Res 2012; 72:513-520.
10. Grave GD, Nelson SA, Walker WA, Moss RL, Dvorak B, Hamilton FA, et al. New therapies and preventive approaches for necrotizing enterocolitis: report of a research planning workshop. Pediatr Res 2007; 62:510-514.
11. Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am 2013; 60:49-74.
12. Blewett HJH, Cicalo MC, Holland CD, Field CJ. The immunological components of human milk. Adv Food Nutr Res 2008; 54:45-80.
13. Pattel RM, Denning PW. Intestinal microbiota and its relationship with necrotizing enterocolitis. Pediatr Res 2015; 78: 232-238.
14. Newman TB, Draper D, Puopolo KM, Wi S, Escobar GJ. Combining immature and total neutrophil counts to predict early onset sepsis in term and late preterm newborns: use of the I/T2. Pediatr Infect Dis J 2014; 33:798-802.
15. Wang TY, Wang L, Zhang JH, Dong WH. A simplified universal genomic DNA extraction protocol suitable for PCR. Genet Mol Res 2011; 10:519-525.
16. Wang IK, Lai HC, Yu CJ, Liang CC, Chang CT, Kuo HL, et al. Real-time PCR analysis of the intestinal microbiotas in peritoneal dialysis patients. Appl Environ Microbiol 2012;78:1107-1112
17. Haarman M, Knol J. Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium species in infants receiving a prebiotic infant formula. Appl Environ Microbiol 2005; 71:2318-2324.
18. Haarman M, Knol J. Quantitative real-time PCR analysis of fecal Lactobacillus species in infants receiving a prebiotic infant formula. Appl Environ Microbiol 2006; 72: 2359-2365.
19. Vazquez L, Guadamuro L, Giganto F, Mayo B, Florez AB. Development and use of a real-time quantitative PCR method for detecting and quantifying equol-producing bacteria in human faecal samples and slurry cultures. Front Microbiol 2017; 8:1155.
20. Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent ductus arteriosus in preterm infants. Pediatrics 2016; 137: 10.1542/peds.2015-3730.
21. Clyman RI, Couto J, Murphy GM. Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all? Semin Perinatol 2012; 36:123-129.
22. Baricelli J, Rocafull MA, Vazquez D, Bastidas B, Baez-Ramirez E, Thomas LE. Β-defensin-2 in breast milk displays a broad antimicrobial activity against pathogenic bacteria. J Pediatr (Rio J) 2015; 91:36-43.
23. Patel AL, Kim JH. Human milk and necrotizing enterocolitis. Semin Pediatr Surg 2018; 27:34-38.
24. Cobo ER, Chadee K. Antimicrobial human β-defensins in the colon and their role in infectious and non-infectious diseases. Pathogens 2013; 2:177-192.
25. Frye M, Bargon J, Lembcke B, Wagner TO, Gropp R. Differential expression of human alpha- and β-defensins mrna in gastrointestinal epithelia. Eur J Clin Invest 2000; 30:695-701.
26. Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger K, Fellermann K, et al. Inducible and constitutive β-defensins are differentially expressed in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 2003; 9:215-223.
27. O’Neil DA, Porter EM, Elewaut D, Anderson GM, Eckmann L, Ganz T, et al. Expression and regulation of the human β-defensins hbd-1 and hbd-2 in intestinal epithelium. J Immunol 1999; 163: 6718-6724.
28. Witthoft T, Pilz CS, Fellermann K, Nitschke M, Stange EF, Ludwig D. Enhanced human β-defensin-2 (hbd-2) expression by corticosteroids is independent of nf-kappab in colonic epithelial cells (Caco2). Dig Dis Sci 2005; 50:1252-1259.
29. Schwiertz A, Gruhl B, Lobnitz M, Michel P, Radke M, Blaut M. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res 2003; 54:393-399.
30. Abdulkadir B, Nelson A, Skeath T, Marrs EC, Perry JD, Cummings SP, et al. Routine use of probiotics in preterm infants: Longitudinal impact on the microbiome and metabolome. Neonatology 2016; 109:239-247.
31. Wall R, Ross RP, Ryan CA, Hussey S, Murphy B, Fitzgerald GF. Role of gut microbiota in early infant development. Clin Med Pediatrr 2009; 3:45-54.
32. Wold AE, Adlerbeth I. Breast feeding and the intestinal microflora of the infant—implications for protection against infectious diseases. Adv Exp Med Biol 2000; 478:77-93.
33. Jiménez E, Delgado S, Maldonado A, Arroyo R, Albújar M, García N, et al. Staphylococcus epidermidis: a differential trait of the fecal microbiota of breast-fed infants. BMC Microbiol 2008; 8:143.
34. Newburg DS, Walker WA. Protection of the neonate by the innate immune system of developing gut and human milk. Pediatr Res 2007; 61:2-8.
35. Parra-Llorca A, Gormaz M, Alcantara C, Cernada M, Nunez-Ramiro A, Vento M, et al. Preterm gut microbiome depending on feeding type: significance of donor human milk. Front Microbiol 2018; 9:1376.
36. Neu J. Preterm infant nutrition, gut bacteria, and necrotizing enterocolitis. Curr Opin Clin Nutr Metab Care 2015; 18:285-288.
37. Albenberg L, Esipova TV, Judge CP, Bittinger K, Chen J, Laughlin A, et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota in humans and mice. Gastroenterology 2014; 147:1055-1063.
| Files | ||
| Issue | Vol 11 No 2 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v11i2.1081 | |
| Keywords | ||
| Human B-defensin-2 Intestinal microbiota pattern Preterm neonates | ||
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How to Cite
1.
Corebima B, Rohsiswatmo R, Gayatri P, Patole S. Fecal human β-defensin-2 (hBD-2) levels and gut microbiota patterns in preterm neonates with different feeding patterns. Iran J Microbiol. 2019;11(2):151-159.
