The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Microbiota-Modulated Metabolites Shape the Intestinal Microenvironment by Regulating NLRP6 Inflammasome Signaling
Open accessAbstract
Host-microbiome co-evolution drives homeostasis and disease susceptibility, yet regulatory principles governing the integrated intestinal host-commensal microenvironment remain obscure. While inflammasome signaling participates in these interactions, its activators and microbiome-modulating mechanisms are unknown. Here, we demonstrate that the microbiota-associated metabolites taurine, histamine, and spermine shape the host-microbiome interface by co-modulating NLRP6 inflammasome signaling, epithelial IL-18 secretion, and downstream anti-microbial peptide (AMP) profiles. Distortion of this balanced AMP landscape by inflammasome deficiency drives dysbiosis development. Upon fecal transfer, colitis-inducing microbiota hijacks this microenvironment-orchestrating machinery through metabolite-mediated inflammasome suppression, leading to distorted AMP balance favoring its preferential colonization. Restoration of the metabolite-inflammasome-AMP axis reinstates a normal microbiota and ameliorates colitis. Together, we identify microbial modulators of the NLRP6 inflammasome and highlight mechanisms by which microbiome-host interactions cooperatively drive microbial community stability through metabolite-mediated innate immune modulation. Therefore, targeted "postbiotic" metabolomic intervention may restore a normal microenvironment as treatment or prevention of dysbiosis-driven diseases.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“free taurine generated by deconjugation can enhance the activation of the NLRP6 inflammasome and thereby increase production of IL-18 by the intestinal epithelium, which supports epithelial barrier function and maintenance (Levy et al., 2015).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Levy et al., 2015
In the citing paper
“Spermine and the monoamine histamine both inhibit activation of the NLRP6 inflammasome, a protein complex expressed by epithelial cells that regulates IL-18 secretion.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Levy et al., 2015
In the citing paper
“Levy et al. recently reported that exogenous polyamines can reduce the release of IL-18, a cytokine that promotes epithelial repair and barrier function.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Levy et al., 2015
In the citing paper
“taurine, another microbial metabolite that derives from host-produced bile acids (see below), counteracts the effects of spermine and histamine, indicating a finely tuned balance of opposing bacterial stimuli (Levy et al., 2015).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Levy et al., 2015
In the citing paper
“NLRP6 inflammasome signaling is co-modulated by microbiota-derived metabolites, which regulates epithelial IL-18 secretion and AMP expression profiles.71”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [71]
In the citing paper
“NLRP6 KO mice show dysbiosis and increased incidence of inflammation-associated CRC [135,136,137].”
From Gut Microbiota and Cancer: From Pathogenesis to Therapy (2019) · cites this paper as [136]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100
Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
Ivanov, I. I., Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., et al. (2009) · Cell · doi:10.1016/j.cell.2009.09.033 · Cited by 4,554
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251
Interactions Between the Microbiota and the Immune System
Hooper, L. V., Littman, D. R., & Macpherson, A. J. (2012) · Science · doi:10.1126/science.1223490 · Cited by 4,173
Human Genetics Shape the Gut Microbiome
Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J. T., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.053 · Cited by 3,164
Data, information, knowledge and principle: back to metabolism in KEGG
Kanehisa, M. I., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1076 · Cited by 3,103
Flagged first, then by citations
1 of the 51 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Interaction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947
Inflammasomes: mechanism of assembly, regulation and signalling
Broz, P., & Dixit, V. M. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.58 · Cited by 3,500
Pyroptosis: Mechanisms and Diseases
Yu, P., Zhang, X., Liu, N., Tang, L., Peng, C., & Chen, X. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00507-5 · Cited by 2,353
The microbiome and innate immunity
Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016) · Nature · doi:10.1038/nature18847 · Cited by 2,012
Self-citationDysbiosis and the immune system
Levy, M., Kolodziejczyk, A. A., Thaiss, C. A., & Elinav, E. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.7 · Cited by 1,769
Metadata
- Authors
- Levy, M., Thaiss, C. A., Zeevi, D., Dohnalová, L., Zilberman-Schapira, G., Mahdi, J. A., David, E., Savidor, A., Korem, T., Herzig, Y., Pevsner-Fischer, M., Shapiro, H., Christ, A., Harmelin, A., Halpern, Z., Latz, E., Flavell, R. A., Amit, I., Segal, E., & Elinav, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Ben-Gurion University of the Negev (IL)
- University of Bonn (DE)
- Tel Aviv University (IL)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Segal, Eran
- Elinav, Eran
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 163
- Issue
- 6
- Pages
- 1428-1443
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5665753
- OpenAlex
- W2188593832
- Cited by
- 960
- References
- 51
- Citations by year
- 2026: 63 · 2025: 67 · 2024: 95 · 2023: 106 · 2022: 109 · 2021: 112 · 2020: 96 · 2019: 108 · 2018: 69 · 2017: 78 · 2016: 51 · 2015: 3
- FWCI
- 29.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (P30CA016359)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK034989)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- gut microbiota, NLRP6 inflammasome, host-microbiome interactions, taurine, histamine, spermine, IL-18, antimicrobial peptides, dysbiosis, colitis, fecal microbiota transplantation, postbiotics, innate immune modulation, intestinal epithelium
- MeSH terms
- Animals, Colitis, Colon, Germ-Free Life, Mice, Inbred C57BL, Receptors, Cell Surface, Taurine, Inflammatory Bowel Diseases, Signal Transduction, Interleukin-18, Antimicrobial Cationic Peptides, Mice, Inflammasomes, Microbiota, Dysbiosis
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
