Journal
MICROBIOME
Volume 8, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40168-020-00906-w
Keywords
Microbiota; Celiac disease; Multi-omics analysis; gut microbiome
Categories
Funding
- NIH NIDDK [DK104344, DK109620, K23DK122127]
- Nutrition Obesity Research Center at Harvard [P30-DK040561]
- Thrasher Research Fund
- Mucosal Immunology and Biology Research Center at Massachusetts General Hospital
Ask authors/readers for more resources
BackgroundCeliac disease (CD) is an autoimmune digestive disorder that occurs in genetically susceptible individuals in response to ingesting gluten, a protein found in wheat, rye, and barley. Research shows that genetic predisposition and exposure to gluten are necessary but not sufficient to trigger the development of CD. This suggests that exposure to other environmental stimuli early in life, e.g., cesarean section delivery and exposure to antibiotics or formula feeding, may also play a key role in CD pathogenesis through yet unknown mechanisms. Here, we use multi-omics analysis to investigate how genetic and early environmental risk factors alter the development of the gut microbiota in infants at risk of CD.ResultsToward this end, we selected 31 infants from a large-scale prospective birth cohort study of infants with a first-degree relative with CD. We then performed rigorous multivariate association, cross-sectional, and longitudinal analyses using metagenomic and metabolomic data collected at birth, 3months and 6months of age to explore the impact of genetic predisposition and environmental risk factors on the gut microbiota composition, function, and metabolome prior to the introduction of trigger (gluten). These analyses revealed several microbial species, functional pathways, and metabolites that are associated with each genetic and environmental risk factor or that are differentially abundant between environmentally exposed and non-exposed infants or between time points. Among our significant findings, we found that cesarean section delivery is associated with a decreased abundance of Bacteroides vulgatus and Bacteroides dorei and of folate biosynthesis pathway and with an increased abundance of hydroxyphenylacetic acid, alterations that are implicated in immune system dysfunction and inflammatory conditions. Additionally, longitudinal analysis revealed that, in infants not exposed to any environmental risk factor, the abundances of Bacteroides uniformis and of metabolite 3-3-hydroxyphenylproprionic acid increase over time, while those for lipoic acid and methane metabolism pathways decrease, patterns that are linked to beneficial immunomodulatory and anti-inflammatory effects.ConclusionsOverall, our study provides unprecedented insights into major taxonomic and functional shifts in the developing gut microbiota of infants at risk of CD linking genetic and environmental risk factors to detrimental immunomodulatory and inflammatory effects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available