Meta‐analyses of human gut microbes associated with obesity and IBD
Open accessAbstract
Recent studies have linked human gut microbes to obesity and inflammatory bowel disease, but consistent signals have been difficult to identify. Here we test for indicator taxa and general features of the microbiota that are generally consistent across studies of obesity and of IBD, focusing on studies involving high‐throughput sequencing of the 16S rRNA gene (which we could process using a common computational pipeline). We find that IBD has a consistent signature across studies and allows high classification accuracy of IBD from non‐IBD subjects, but that although subjects can be classified as lean or obese within each individual study with statistically significant accuracy, consistent with the ability of the microbiota to experimentally transfer this phenotype, signatures of obesity are not consistent between studies even when the data are analyzed with consistent methods. The results suggest that correlations between microbes and clinical conditions with different effect sizes (e.g. the large effect size of IBD versus the small effect size of obesity) may require different cohort selection and analysis strategies.
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The claim that the Firmicutes:Bacteroidetes ratio is altered in obesity is erroneous.
“this commonly-used but erroneous claim stems primarily from rodent-based research”
From Human microbiome myths and misconceptions (2023) · cites this paper as [26]
The Results (p. unavailable) find no statistically significant overall Firmicutes:Bacteroidetes ratio difference between obese and normal-weight humans, and the Conclusions (p. unavailable) say the ratio is not a consistent distinguishing feature across human populations. The Conclusions also note that the pattern has often been observed in animals, including rodents, but do not establish that the commonly used claim stems primarily from rodent research; calling every reported human alteration erroneous is broader than the finding. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAt least three meta-analyses report that the Firmicutes:Bacteroidetes finding is inconsistent between human studies and that there are no reproducible microbial taxonomic signatures of obesity in humans.
“there have now been at least three meta-analyses reporting that this finding is inconsistent between human studies, and that there are, in fact, no reproducible microbial taxonomic signatures of obesity in humans 25-27 .”
From Human microbiome myths and misconceptions (2023) · cites this paper as [26]
The family Oscillospiraceae produces butyrate and is negatively associated with inflammatory diseases.
“the family Oscillospiraceae, which produces butyrate (Gophna, Konikoff & Nielsen, 2017), is negatively associated with inflammatory diseases (Walters, Xu & Knight, 2014)”
From The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy (2023) · cites this paper as Walters, Xu & Knight, 2014
The Firmicutes/Bacteroidetes ratio is not always the same between studies and may be an oversimplification of phylum-level patterns in relation to host health.
“However, this is not always the same between studies [83, 84] and may be an oversimplification of phylum-level patterns in relation to host health.”
From The athletic gut microbiota (2020) · cites this paper as [83]
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- Authors
- Walters, W. A., Xu, Z., & Knight, R.
- Affiliations
- University of Colorado Boulder (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Knight, Rob
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2014-10-13
- Volume
- 588
- Issue
- 22
- Pages
- 4223-4233
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- PMC
- PMC5050012
- OpenAlex
- W2037279825
- Cited by
- 836
- References
- 54
- Citations by year
- 2026: 27 · 2025: 42 · 2024: 66 · 2023: 65 · 2022: 84 · 2021: 96 · 2020: 98 · 2019: 92 · 2018: 91 · 2017: 78 · 2016: 64 · 2015: 32 · 2014: 1
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- FEBS Letters (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health
- Crohns and Colitis Foundation of America
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- gut microbiota, obesity, inflammatory bowel disease, 16S rRNA gene, indicator taxa, microbiota transfer, effect size, cohort selection
- MeSH terms
- Animals, Feces, Humans, Obesity, Inflammatory Bowel Diseases, Sequence Analysis, RNA, Gastrointestinal Tract
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