Evidence map›Paper›PMID 39477928›Full record

ArticleNature communications2024

Biosynthetic enzyme analysis identifies a protective role for TLR4-acting gut microbial sulfonolipids in inflammatory bowel disease.

Ethan A Older, Jian Zhang, Zachary E Ferris, Dan Xue, Zheng Zhong, Mary K Mitchell, Michael Madden, Yuzhen Wang, Hexin Chen, Prakash Nagarkatti and 5 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Gut · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Ornithine lipids fromGut microbes · 2025
    Article
  11. Review
  12. Human gut commensalGut microbes · 2025
    Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Ethan A Older *Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, 29208, USA.ORCID 0000-0003-1281-4071
Jian Zhang *Department of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Zachary E FerrisDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, 29208, USA.
Dan XueDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, 29208, USA.
Zheng ZhongDepartment of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China.ORCID 0000-0002-1262-4115
Mary K MitchellDepartment of Biological Sciences, University of South Carolina, Columbia, South Carolina, 29208, USA.
Michael MaddenDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, 29208, USA.ORCID 0009-0008-1951-0998
Yuzhen WangDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, 29209, USA.
Hexin ChenDepartment of Biological Sciences, University of South Carolina, Columbia, South Carolina, 29208, USA.ORCID 0000-0001-9300-0859
Prakash NagarkattiDepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, 29209, USA.
Mitzi NagarkattiDepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, South Carolina, 29209, USA.
Daping FanDepartment of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina, 29209, USA.
Melissa EllermannDepartment of Biological Sciences, University of South Carolina, Columbia, South Carolina, 29208, USA.
Yong-Xin LiDepartment of Chemistry and The Swire Institute of Marine Science, The University of Hong Kong, Pokfulam Road, Hong Kong, China. yxpli@hku.hk.ORCID 0000-0003-4422-2302
Jie LiDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, 29208, USA. li439@mailbox.sc.edu.ORCID 0000-0001-7977-6749

Funding

Targeting early ceramide elevation in pre-symptomatic eczemaP20GM103641 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2012 to 2023
$20.7M
Effects of host endocannabinoid signaling on Enterobacteriaceae infectionR01AI184916 · NIAID · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI Melissa Ellermann · 2024 to 2026
$1.7M
Accessing and Expanding Natural Products Chemical Diversity by Big-data Analysis and Biosynthetic InvestigationR35GM150565 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI Jie Li · 2023 to 2026
$1.3M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R35GM150565National Science Foundation (NSF) 2239561NIAID NIH HHS R01 AI184916NIGMS NIH HHS P20 GM103641NIGMS NIH HHS R35 GM150565
6 · The paper itself

Abstract

The trillions of microorganisms inhabiting the human gut are intricately linked to human health. While specific microbes have been associated with diseases, microbial abundance alone cannot reveal the molecular mechanisms involved. One such important mechanism is the biosynthesis of functional metabolites. Here, we develop a biosynthetic enzyme-guided disease correlation approach to uncover microbial functional metabolites linked to disease. Applying this approach, we negatively correlate the expression of gut microbial sulfonolipid (SoL) biosynthetic enzymes to inflammatory bowel disease (IBD). Targeted chemoinformatics and metabolomics then confirm that SoL abundance is significantly decreased in IBD patient data and samples. In a mouse model of IBD, we further validate that SoL abundance is decreased while inflammation is increased in diseased mice. We show that SoLs consistently contribute to the immunoregulatory activity of different SoL-producing human microbes. We further reveal that sulfobacins A and B, representative SoLs, act on Toll-like receptor 4 (TLR4) and block lipopolysaccharide (LPS) binding, suppressing both LPS-induced inflammation and macrophage M1 polarization. Together, these results suggest that SoLs mediate a protective effect against IBD through TLR4 signaling and showcase a widely applicable biosynthetic enzyme-guided disease correlation approach to directly link the biosynthesis of gut microbial functional metabolites to human health.

Indexed as

Gastrointestinal MicrobiomeInflammatory Bowel DiseasesToll-Like Receptor 4AnimalsDisease Models, AnimalHumansLipopolysaccharidesMacrophagesMaleMetabolomicsMiceMice, Inbred C57BLSignal TransductionLipopolysaccharidesTLR4 protein, humanTlr4 protein, mouseToll-Like Receptor 4

Identifiers

PMID39477928
PMCPMC11525784

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.