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Published on: February 28, 2018
Integrative metagenomics and structural bioinformatics identify explainable gut microbial variants associated with
Nadeem Khan1, Muhammad Muneeb Nasir1, Ubair Aziz1
1School of Interdisciplinary Engineering & Sciences (SINES), National University of Sciences & Technology (NUST), Sector H-12, Islamabad, Pakistan.
Plos One
|July 10, 2026
Summary
Genomic variations in gut bacteria like Bacteroides uniformis are linked to inflammatory bowel disease (IBD). Specific mutations impair starch metabolism, potentially explaining why these beneficial microbes are depleted in Crohn's disease patients.
Area of Science:
- Microbiome research
- Genomics
- Structural bioinformatics
Background:
- Metagenomics reveals microbial shifts in inflammatory bowel disease (IBD).
- The impact of genomic variation in gut commensals on IBD pathogenesis is largely unknown.
Purpose of the Study:
- To identify disease-associated genomic variants in gut microbes using integrated metagenomic and structural analyses.
- To investigate the functional consequences of identified variants on microbial function.
Main Methods:
- Metagenomic profiling and variant calling.
- Structural bioinformatics, including protein modeling and molecular dynamics simulations.
- Analysis of single-nucleotide polymorphisms (SNPs) in associated bacteria.
Main Results:
- Identified significant negative associations between IBD (Crohn's disease and ulcerative colitis) and specific bacteria: Bacteroides uniformis, Bacteroides vulgatus, and Eubacterium rectale.
- Discovered numerous disease-specific single-nucleotide polymorphisms (SNPs), including a CD-specific Val170Leu substitution in the B. uniformis SusD protein.
- Demonstrated that this mutation reduces starch-binding affinity and impairs starch metabolism, with wild-type protein showing stable ligand retention.
Conclusions:
- Impaired starch metabolism due to SusD variation in B. uniformis may contribute to its depletion in Crohn's disease.
- Integrating metagenomics with structural bioinformatics is valuable for identifying functionally relevant microbial variants in disease states.
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