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Kurath-Koller, S.
Changes of intestinal microbiota composition and diversity in very low birthweigt infants related to strategies of NEC prophylaxis
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2021. pp. 107 [OPEN ACCESS]
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Authors Med Uni Graz:
Kurath-Koller Stefan
Advisor:
Gorkiewicz Gregor
Moissl-Eichinger Christine
Resch Bernhard
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Abstract:
Background At the Division of Neonatology, Department of Pediatrics, Medical University Graz, a unique regimen for prophylaxis of necrotizing enterocolitis (NEC) in preterm infants <1500g birth weight is used. This regimen includes the combined use of antibiotics, mycostatics and probiotics, as well as a structured feeding regimen. The incidence of NEC in preterm infants treated by this regimen has been shown to be as low as 0.7% when treatment was initiated at the first day of life, compared to international incidence rates reported to be about 5.1%. We hypothesized that differences in hospital regimens influence diversity and composition of intestinal microbiota development. Thus, intestinal microbial diversity and abundance as well as development of the intestinal microbiome within the first two weeks of life were analyzed from stool samples. Methods The doctoral thesis was carried out as a prospective controlled triplecenter cohort study in preterm infants with a birth weight <1500g (i.e. very low birth weight, VLBW). Partizipating centers were located in south eastern Austria (NICU, Department of Pediatrics, Medical University Graz; NICU, Department of Pediatrics, General Hospital of Klagenfurt; NICU, Department of Pediatrics, General Hospital of Leoben). At the Division of Neonatology, Department of Pediatrics, General Hospital of Klagenfurt a different probiotic supplement containing different strains and a different feeding strategy are used. Furthermore, oral antibiotics are not routinely used. At the Department of Pediatrics, General Hospital of Leoben no probiotic supplements are used but antibiotics, mycostatics and feeding regimens adhere to the Graz protocol. Seven stool samples from each of the 54 included infants, 18 from each center, collected every other day throughout the first two weeks of life, were analyzed by 16srRNA analysis. All 378 samples were analyzed at the Core Facility for Molecular Biology at the Medical University of Graz. Data was processed and interpreted with the help of biostatisticians and statisticians, as well as specialists of the Interactive Microbiome Research Unit Graz. Results Regarding gestational age, birth weight, APGAR scores and oxygen demand, nostatistical differences were found between the three groups. Overall, 2029 different taxa were detected, showing a predominance of the probiotic genera Lactobacillus and Bifidobacterium, and further comprising Enterococcus and Staphylococcus. With the use of probiotic supplementation, an earlier increase in bacterial load was found. Although predominating in samples from infants who were supplemented with probiotics, Lactobacillus and Bifidobacterium contributed only marginally to the intestinal microbiome if no probiotics supplementation was administered. However, some infants did not respond to probiotics supplementation. By the end of the second week of life microbial diversity in samples of all partizipating centers showed a similar pattern. Microbial samples from all centers clustered significantly, yet varied from each other. Conclusion The administration of probiotics supplementation in very low birth weight preterm infants seems to be safe. Furthermore, it seems to initiate an earlier increase in bacterial load with a predominance of probiotic strains, which might be essential for the prevention of neonatal morbidities and NEC. Meconium samples were found not to be sterile but already containing bacterial DNA. Oral antibiotics did not influence the development of the stool microbiome in a negative way, and did not interfere with probiotics colonization despite combined use. Hospital regimens lead to centerspecific and distinct clustering as a microbial hallmark.

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