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Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling
Open accessAbstract
While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders.
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“In the gut, LPS-TLR4 signalling has been shown to both dampen intestinal immune responses to the resident microbiota during states of health5”
From Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses (2025) · cites this paper as [5]
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Metadata
- Authors
- d’Hennezel, E., Abubucker, S., Murphy, L. O., & Cullen, T. W.
- Affiliations
- Developmental and Molecular Pathways, Novartis Institutes for Biomedical Research Inc., Cambridge, Massachusetts, USA
- Corresponding author
- Cullen, Thomas W.
- ORCID
- Abubucker, Sahar
- Venue
- mSystems
- Publisher
- American Society for Microbiology
- Published
- 2017-12-26
- Volume
- 2
- Issue
- 6
- ISSN
- 2379-5077 (ISSN-L)
- PMC
- PMC5686520
- OpenAlex
- W2770311021
- Cited by
- 324
- References
- 44
- Citations by year
- 2026: 21 · 2025: 32 · 2024: 43 · 2023: 43 · 2022: 49 · 2021: 62 · 2020: 37 · 2019: 27 · 2018: 8 · 2017: 1
- FWCI
- 9.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mSystems (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Broad Institute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, lipopolysaccharide, Toll-like receptor signaling, immune tolerance, host-microbe interactions, commensal bacteria, pro-inflammatory signaling, intestinal homeostasis, inflammatory diseases
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