Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment
Open accessAbstract
Background: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Results: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. Conclusions: This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis.
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A metagenomic study including inferred microbial gene content from 231 subjects and 11 additional metagenomes identified enrichment in microbial pathways for oxidative stress tolerance, immune evasion and host metabolite uptake, with corresponding depletions in SCFA biosynthesis and typical gut carbohydrate metabolism and amino acid biosynthetic processes in IBD.
“This study identified enrichment in microbial pathways for oxidative stress tolerance, immune evasion and host metabolite uptake, with corresponding depletions in SCFA biosynthesis and typical gut carbohydrate metabolism and amino acid biosynthetic processes.”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [70]
Changes in the proportions of specific taxa of gut microbiota have been observed in various disease states including obesity, inflammatory bowel disease, type 1 and type 2 diabetes mellitus, biliary disease, and intestinal cancers.
“Changes in the proportions of specific taxa of gut microbiota have been observed in various disease states, including obesity68,69, inflammatory bowel disease70, type 1 and type 2 diabetes mellitus71,72, biliary disease73, and intestinal cancers74,75 among many others.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [70]
No comprehensive model of specific microbial, molecular, and immune interactions yet exists to explain IBD onset and dynamic progression.
“no comprehensive model of specific microbial, molecular, and immune interactions yet exists to explain the disease’s onset and dynamic progression.”
From The Integrative Human Microbiome Project (2019) · cites this paper as [71]
Dynamic changes in the microbiome and host immune response during IBD were of much greater magnitude than cross-sectional differences among clinical phenotypes.
“Indeed, these dynamic changes were of much greater magnitude than were cross-sectional differences among clinical phenotypes, which have been emphasized by previous studies67,71,78,79.”
From The Integrative Human Microbiome Project (2019) · cites this paper as [71]
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- Authors
- Morgan, X. C., Tickle, T. L., Sokol, H., Gevers, D., Devaney, K. L., Ward, D. V., Reyes, J. A., Shah, S. A., LeLeiko, N., Snapper, S. B., Bousvaros, A., Korzenik, J., Sands, B. E., Xavier, R. J., & Huttenhower, C.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- Brown University (US)
- Brigham and Women's Hospital (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Huttenhower, Curtis
- ORCID
- Venue
- Genome Biology
- Published
- 2012-09-26
- Volume
- 13
- Issue
- 9
- Pages
- R79-R79
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC3506950
- OpenAlex
- W2143777796
- Cited by
- 2,713
- References
- 107
- Citations by year
- 2026: 84 · 2025: 165 · 2024: 198 · 2023: 237 · 2022: 257 · 2021: 302 · 2020: 297 · 2019: 272 · 2018: 229 · 2017: 182 · 2016: 168 · 2015: 136 · 2014: 120 · 2013: 64 · 2012: 1
- FWCI
- 41.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- National Science Foundation (1053486)
- Crohn's and Colitis Foundation of America
- Brigham and Women's Hospital
- Massachusetts General Hospital
- Brown University
- Massachusetts Institute of Technology
- Harvard University
- Crohn's and Colitis Foundation (DP000340)
- Broad Institute
- Philippe Foundation
- Fondation Bettencourt Schueller
- National Institutes of Health (ARO W911NF-11-1-0473, DBI-1053486)
- Centers for Disease Control and Prevention (DP000340)
- National Human Genome Research Institute (U54HG004969, R01HG005969)
- National Institute of General Medical Sciences (T32GM080177)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK092405, P30DK043351)
- Division of Biological Infrastructure (DBI-1053486)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD058828)
- Army Research Office (W911NF-11-1-0473, W911NF-11-1-0429, W911NF, W911NF-11)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- inflammatory bowel disease, Crohn's disease, ulcerative colitis, gut microbiota, microbial metabolism, functional metagenomics, oxidative stress pathways, carbohydrate metabolism, amino acid biosynthesis, nutrient transport, Firmicutes, Enterobacteriaceae, IBD treatment, ileal Crohn's disease, gut microbiota composition
- MeSH terms
- Amino Acids, Bacteria, Biological Transport, Humans, Intestines, Phylogeny, RNA, Ribosomal, 16S, Inflammatory Bowel Diseases, Multivariate Analysis, Linear Models, Case-Control Studies, Sequence Analysis, DNA, Oxidative Stress, Genes, rRNA, Carbohydrate Metabolism, Metagenome, Metagenomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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