Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen.
Animals
Biodiversity
Biomarkers
Biopsy
Chronic Disease
Diarrhea
/ complications
Disease Models, Animal
Disease Susceptibility
Dysbiosis
/ complications
Gastrointestinal Microbiome
/ immunology
Growth Disorders
/ etiology
Immunity, Mucosal
/ genetics
Immunohistochemistry
Intestinal Mucosa
/ immunology
Lymphocyte Count
Macaca mulatta
Metagenome
Metagenomics
/ methods
Transcriptome
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
09
02
2021
accepted:
19
05
2021
revised:
13
05
2021
pubmed:
24
6
2021
medline:
22
1
2022
entrez:
23
6
2021
Statut:
ppublish
Résumé
Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea. We show that growth faltering in the presence or absence of active diarrhea is associated with a heightened systemic and mucosal pro-inflammatory state centered in the colon. Moreover, polyclonal stimulation of colonic lamina propria leukocytes resulted in a dampened cytokine response, indicative of immune exhaustion. We also detected a functional and taxonomic shift in the luminal microbiome across multiple gut sites including the migration of Streptococcus and Prevotella species between the small and large intestine, suggesting a decompartmentalization of gut microbial communities. Our studies provide valuable insight into the outcomes of diarrheal diseases and growth faltering not attainable in humans and lays the groundwork to test interventions in a controlled and reproducible setting.
Identifiants
pubmed: 34158595
doi: 10.1038/s41385-021-00418-2
pii: S1933-0219(22)00206-9
pmc: PMC8379072
mid: NIHMS1707048
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1113-1126Subventions
Organisme : NIH HHS
ID : P51 OD011092
Pays : United States
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007319
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI141346
Pays : United States
Informations de copyright
© 2021. The Author(s).
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