254 - The fungal intestinal microbiota predict the development of bronchopulmonary dysplasia in very low birthweight newborns

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 254
Publication Number: 254.34

Kent A. Willis, The University of Alabama at Birmingham, Birmingham, AL, United States; Mary Silverberg, University of Alabama School of Medicine, Birmingham, AL, United States; Ahmed Abdelgawad, UAB, Mountain Brook, AL, United States; Isaac Martin, University of Alabama at Birmingham, Birmingham, AL, United States; Kosuke Tanaka, The University of Alabama at Birmingham, Birmingham, AL, United States; Brian A. Halloran, University of Alabama at Birmingham, Birmingham, AL, United States; Erin Myers, University of California-Irvine, Long Beach, CA, United States; Charitharth Vivek Lal, University of Alabama at Birmingham, Birmingham, AL, United States; Namasivayam Ambalavanan, University of Alabama School of Medicine, Birmingham, AL, United States; Tamas Jilling, University of Alabama at Birmingham, Birmingham, AL, United States; Laura Tipton, Chaminade University of Honolulu, Honolulu, HI, United States; Joseph F. Pierre, University of Wisconsin-Madison, Madison, WI, United States; Ajay J. Talati, UTHSC, Memphis, TN, United States

Presenting Author(s)

Kent A. Willis, MD (he/him/his)

Assistant Professor
The University of Alabama at Birmingham
Birmingham, Alabama, United States

Background: Bronchopulmonary dysplasia (BPD) is the most severe lung disease affecting preterm infants. Alterations in gut microbial communities can contribute to multiple lung diseases, but the role of the gut microbiome in the pathogenesis of BPD remains unknown. Despite previous research into the bacterial microbiome, a role for the gut fungal microbiome (mycobiome) in the development of BPD has not been previously reported.

Objective:

To test if the composition of the intestinal mycobiome predicts the risk to develop BPD in very low birthweight infants.

Design/Methods:

We performed a prospective, observational cohort study to evaluate the fecal microbiota of very low birthweight infants (< 1500 g, n = 147). This study compared infants with BPD or the post-prematurity respiratory disease (PPRD), which encompasses none to mild BPD, by bacterial 16S and fungal ITS2 ribosomal RNA sequencing. To test the potential causative relationship between gut dysbiosis and BPD, we used fecal microbiota transplant in an antibiotic-pseudohumanized mouse model.

Results: From the 100 infants from which gut microbiome samples were successfully sequenced, 65 eventually developed PPRD, 37 BPD, and 7 died prior to adjudication. Infants that developed BPD showed a clear fungal dysbiosis as compared to infants with PPRD (p = 0.0451, Shannon Diversity, p = 0.0113, Chao1, Fig. 1A, p = 0.0219, PERMANOVA, Fig. 1B), that was more pronounced than differences identified in the multikingdom microbiome (p = 0.4, Shannon Diversity, p = Chao1, Fig. 1C, and p = 0.0229, PERMANOVA, Fig. 1D. Differential fungal and bacterial genera with FDR < 0.05 by negative binomial regression are shown in Fig. 1E). Experimentally, on successful colonization in mice, the gut microbiota from infants with BPD augmented lung injury in the offspring of recipient animals; altering both lung structure (p < 0.0001, ANOVA mean linear intercept and p < 0.001, ANOVA, radial alveolar counts) and function (p = 0.01, ANOVA, resistance; p = 0.008, ANOVA, compliance) as compared to PPRD-colonized mice.

Conclusion(s):

We present one of the first reports of the multikingdom microbiome in premature neonates. Our results from a human cohort and mouse model suggest differences in the intestinal mycobiome may precede and anticipate the eventual development of BPD. Examining the multikingdom microbiome may be important to understand how the gut-lung axis impacts respiratory disease.