Long-Read Metagenomic Sequencing Reveals Persistent Gut Microbiome Alterations in Children with Celiac Disease in Remission
- 1Massachusetts General Hospital
Abstract
Background: Celiac Disease (CeD) is an immune-mediated enteropathy linked to gut microbiome dysbiosis driven by dietary gluten ingestion. Although most patients achieve clinical and histologic remission on a gluten-free diet (GFD), persistent symptoms and incomplete mucosal recovery are common. While gut microbiome alterations during active CeD are well documented, taxonomic and functional shifts during histologic remission remain considerably less characterized. Methods: We utilized PacBio's HiFi long-read metagenomic sequencing to profile the gut microbiome of 21 pediatric participants with histologically confirmed CeD remission on a GFD, active CeD, and non-CeD controls. Results: High-fidelity long reads enabled reconstruction of 857 high-quality metagenome-assembled genomes and high-resolution species- and pathway-level profiling. Microbial diversity analysis showed reduced alpha-diversity in remission patients compared with controls. Differential abundance analysis revealed persistent taxonomic and functional alterations in CeD remission, indicating incomplete restoration of microbiome homeostasis. Notably, remission patients showed depletion of commensals such as Alistipes finegoldii, Bifidobacterium longum, and Bacteroides uniformis, and persistence of some inflammation-associated taxa, alongside enrichment of beneficial species, including short-chain fatty acid producers, and suppression of other inflammation-associated taxa. At the functional level, pathways related to broader metabolic homeostasis were depleted in remission, while anti-inflammatory pathways such as propionate metabolism were enriched. Conclusions: Our findings suggest a distinct microbial ecosystem during histologic remission characterized by residual taxonomic dysbiosis and functional constraints, accompanied by adaptive remodeling that may promote mucosal healing. This work advances understanding of the gut microbiome in CeD after mucosal recovery and lays the groundwork for future studies of microbiome-based therapeutic interventions.
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BibTeX
@misc{le2026longread,
title = {{Long-Read Metagenomic Sequencing Reveals Persistent Gut Microbiome Alterations in Children with Celiac Disease in Remission}},
author = {D. Le and D. M. Portik and T. Konno and M. M. Leonard and A. Miranda-Ribera and A. Fasano and A. R. Zomorrodi},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.749611},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.749611v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Long-Read Metagenomic Sequencing Reveals Persistent Gut Microbiome Alterations in Children with Celiac Disease in Remission
AU - D. Le
AU - D. M. Portik
AU - T. Konno
AU - M. M. Leonard
AU - A. Miranda-Ribera
AU - A. Fasano
AU - A. R. Zomorrodi
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.749611
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.749611v1
AB - Background: Celiac Disease (CeD) is an immune-mediated enteropathy linked to gut microbiome dysbiosis driven by dietary gluten ingestion. Although most patients achieve clinical and histologic remission on a gluten-free diet (GFD), persistent symptoms and incomplete mucosal recovery are common. While gut microbiome alterations during active CeD are well documented, taxonomic and functional shifts during histologic remission remain considerably less characterized. Methods: We utilized PacBio's HiFi long-read metagenomic sequencing to profile the gut microbiome of 21 pediatric participants with histologically confirmed CeD remission on a GFD, active CeD, and non-CeD controls. Results: High-fidelity long reads enabled reconstruction of 857 high-quality metagenome-assembled genomes and high-resolution species- and pathway-level profiling. Microbial diversity analysis showed reduced alpha-diversity in remission patients compared with controls. Differential abundance analysis revealed persistent taxonomic and functional alterations in CeD remission, indicating incomplete restoration of microbiome homeostasis. Notably, remission patients showed depletion of commensals such as Alistipes finegoldii, Bifidobacterium longum, and Bacteroides uniformis, and persistence of some inflammation-associated taxa, alongside enrichment of beneficial species, including short-chain fatty acid producers, and suppression of other inflammation-associated taxa. At the functional level, pathways related to broader metabolic homeostasis were depleted in remission, while anti-inflammatory pathways such as propionate metabolism were enriched. Conclusions: Our findings suggest a distinct microbial ecosystem during histologic remission characterized by residual taxonomic dysbiosis and functional constraints, accompanied by adaptive remodeling that may promote mucosal healing. This work advances understanding of the gut microbiome in CeD after mucosal recovery and lays the groundwork for future studies of microbiome-based therapeutic interventions.
ER -