Development of the intestinal microbiome in cystic fibrosis in early life
ABSTRACT Cystic fibrosis (CF) is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infections in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00046-23 |
| _version_ | 1797730334629953536 |
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| author | Courtney E. Price Thomas H. Hampton Rebecca A. Valls Kaitlyn E. Barrack George A. O’Toole Juliette C. Madan Modupe O. Coker |
| author_facet | Courtney E. Price Thomas H. Hampton Rebecca A. Valls Kaitlyn E. Barrack George A. O’Toole Juliette C. Madan Modupe O. Coker |
| author_sort | Courtney E. Price |
| collection | DOAJ |
| description | ABSTRACT Cystic fibrosis (CF) is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infections in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here, we describe the longitudinal development of the gut microbiome in a cohort of children with CF (cwCF) from birth through early childhood (0–4 years of age) using 16S rRNA gene amplicon sequencing of stool samples as a surrogate for the gut microbiota. Similar to healthy populations, alpha diversity of the gut microbiome increases significantly with age, but diversity plateaus at ~2 years of age for this CF cohort. Several taxa that have been associated with dysbiosis in CF change with age toward a more healthy-like composition; notable exceptions include Akkermansia, which decreases with age, and Blautia, which increases with age. We also examined the relative abundance and prevalence of nine taxa associated with CF lung disease, several of which persist across early life, highlighting the possibility of the lung being seeded directly from the gut early in life. Finally, we applied the Crohn’s Dysbiosis Index to each sample, and found that high Crohn’s-associated dysbiosis early in life (<2 years) was associated with significantly lower Bacteroides in samples collected from 2 to 4 years of age. Together, these data comprise an observational study that describes the longitudinal development of the CF-associated gut microbiota and suggest that early markers associated with inflammatory bowel disease may shape the later gut microbiota of cwCF. IMPORTANCE Cystic fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth has not been thoroughly studied. Here, we describe an observation study following the development of the gut microbiome of cwCF throughout the first 4 years of life, during the critical window of both gut microbiome and immune development. Our findings indicate the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease. |
| first_indexed | 2024-03-12T11:42:47Z |
| format | Article |
| id | doaj.art-aa0b0337d724452394ed04389ec97a6d |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-12T11:42:47Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-aa0b0337d724452394ed04389ec97a6d2023-08-31T14:26:40ZengAmerican Society for MicrobiologymSphere2379-50422023-08-018410.1128/msphere.00046-23Development of the intestinal microbiome in cystic fibrosis in early lifeCourtney E. Price0Thomas H. Hampton1Rebecca A. Valls2Kaitlyn E. Barrack3George A. O’Toole4Juliette C. Madan5Modupe O. Coker6Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USADepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USADepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USADepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USADepartment of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USADepartment of Pediatrics, Children’s Hospital at Dartmouth, Dartmouth Health , Lebanon, New Hampshire, USADepartment of Epidemiology, Geisel School of Medicine at Dartmouth , Hanover, New Hampshire, USAABSTRACT Cystic fibrosis (CF) is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infections in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here, we describe the longitudinal development of the gut microbiome in a cohort of children with CF (cwCF) from birth through early childhood (0–4 years of age) using 16S rRNA gene amplicon sequencing of stool samples as a surrogate for the gut microbiota. Similar to healthy populations, alpha diversity of the gut microbiome increases significantly with age, but diversity plateaus at ~2 years of age for this CF cohort. Several taxa that have been associated with dysbiosis in CF change with age toward a more healthy-like composition; notable exceptions include Akkermansia, which decreases with age, and Blautia, which increases with age. We also examined the relative abundance and prevalence of nine taxa associated with CF lung disease, several of which persist across early life, highlighting the possibility of the lung being seeded directly from the gut early in life. Finally, we applied the Crohn’s Dysbiosis Index to each sample, and found that high Crohn’s-associated dysbiosis early in life (<2 years) was associated with significantly lower Bacteroides in samples collected from 2 to 4 years of age. Together, these data comprise an observational study that describes the longitudinal development of the CF-associated gut microbiota and suggest that early markers associated with inflammatory bowel disease may shape the later gut microbiota of cwCF. IMPORTANCE Cystic fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth has not been thoroughly studied. Here, we describe an observation study following the development of the gut microbiome of cwCF throughout the first 4 years of life, during the critical window of both gut microbiome and immune development. Our findings indicate the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease.https://journals.asm.org/doi/10.1128/msphere.00046-23cystic fibrosisgutmicrobiomeCrohn’s disease |
| spellingShingle | Courtney E. Price Thomas H. Hampton Rebecca A. Valls Kaitlyn E. Barrack George A. O’Toole Juliette C. Madan Modupe O. Coker Development of the intestinal microbiome in cystic fibrosis in early life mSphere cystic fibrosis gut microbiome Crohn’s disease |
| title | Development of the intestinal microbiome in cystic fibrosis in early life |
| title_full | Development of the intestinal microbiome in cystic fibrosis in early life |
| title_fullStr | Development of the intestinal microbiome in cystic fibrosis in early life |
| title_full_unstemmed | Development of the intestinal microbiome in cystic fibrosis in early life |
| title_short | Development of the intestinal microbiome in cystic fibrosis in early life |
| title_sort | development of the intestinal microbiome in cystic fibrosis in early life |
| topic | cystic fibrosis gut microbiome Crohn’s disease |
| url | https://journals.asm.org/doi/10.1128/msphere.00046-23 |
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