(199) Persistent immaturity of the developing gut microbiome in infants with cystic fibrosis

Thursday, November 3, 2022

12:45 PM – 1:25 PM ET

Presenting Author(s)

PS

Paige Salerno

PhD Candidate
Dartmouth College
Lebanon, New Hampshire, United States

Co-Author(s)

AV

Adrian Verster

United States
CP

Courtney Price

United States
RV

Rebecca Valls

United States
Kaitlyn Barrack

PhD Candidate
Dartmouth College, United States
GO

George O'Toole

United States
JM

Juliette Madan

United States
BR

Benjamin Ross

United States

Background: The cystic fibrosis (CF) infant gut microbiome is characterized by the altered abundance of beneficial bacterial taxa coincident with a developmental delay in maturation in the first year of life [1]. However, there is an inflection point of microbiome stability after 12 months of age in healthy infants [1, 2]. We sought to explore the functional capacity of the CF gut past the first year of life to understand how gut microbiome dysbiosis affects long-term health in CF.

Methods: We performed whole genome shotgun sequencing on 192 stool samples from 40 infants with CF through 3 years of age and compared metagenomic taxonomic and functional profiles with published data including 4,003 samples from 714 infants [1-6]. We then employed supervised and unsupervised machine learning methods to understand the developmental trajectory and key contributing taxa [1, 7, 8].

Results: Our analysis revealed persistent delays in microbiome development in CF through 36 months of life. We identified distinct developmental community states through which the CF microbiome failed to transition, defined by depleted levels of immune-modulatory taxa including Bacteroides and members of the phylum Firmicutes known to produce short chain fatty acids (SCFAs) [9].

Conclusions: In sum, we have identified key developmentally-delayed microbiome states in the gut of infants with CF that could be targeted by future microbiota-directed therapeutic interventions to improve gut and systemic health in CF.

Acknowledgements:

References: [1] Hayden HS, Eng A, Pope CE, Brittnacher MJ, Vo AT, Weiss EJ, et al. Fecal dysbiosis in infants with cystic fibrosis is associated with early linear growth failure. Nat Med. 2020;26(2):215-21.

[2] Yassour M, Vatanen T, Siljander H, Hämäläinen A-M, Härkönen T, Ryhänen SJ, et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Microbiome. 2016;8 (343).

[3] Backhed F, Roswall J, Peng Y, Feng Q, Jia H, Kovatcheva-Datchary P, et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015;17(5):690-703.

[4] Kostic AD, Gevers D, Siljander H, Vatanen T, Hyotylainen T, Hamalainen AM, et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe. 2015;17(2):260-73.

[5] Stewart CJ, Ajami NJ, O'Brien JL, Hutchinson DS, Smith DP, Wong MC, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562(7728):583-8.

[6] Vatanen T, Kostic AD, d'Hennezel E, Siljander H, Franzosa EA, Yassour M, et al. Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans. Cell. 2016;165(4):842-53.

[7] Holmes I, Harris K, Quince C. Dirichlet multinomial mixtures: generative models for microbial metagenomics. PLoS One. 2012;7(2):e30126.

[8] Beghini F, McIver LJ, Blanco-Miguez A, Dubois L, Asnicar F, Maharjan S, et al. Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. Elife. 2021;10.

[9] Parada Venegas D, De la Fuente MK, Landskron G, Gonzalez MJ, Quera R, Dijkstra G, et al. Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front Immunol. 2019;10:277.

(199) ­Persistent immaturity of the developing gut microbiome in infants with cystic fibrosis

Presenting Author(s)

Co-Author(s)

(199) Persistent immaturity of the developing gut microbiome in infants with cystic fibrosis