Evidence map›Paper›PMID 38280374›Full record

ArticleCell2024

Gut complement induced by the microbiota combats pathogens and spares commensals.

Meng Wu, Wen Zheng, Xinyang Song, Bin Bao, Yuanyou Wang, Deepshika Ramanan, Daping Yang, Rui Liu, John C Macbeth, Elyza A Do and 14 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
16.6field-weighted citation impact, top 1% of its field
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

63 citing papers in PubMed, 72 citations in OpenAlex.

  1. Bridging the gap:Gut microbes · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. The island biology of the host microbiome.Trends in microbiology · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. Pan-Metabolomics Repository Mapping of the Carnitine Landscape.bioRxiv : the preprint server for biology · 2026
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 1 country.

Meng WuDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Wen ZhengDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Xinyang SongDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Bin BaoDivision of Gastroenterology, Boston Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Yuanyou WangProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Deepshika RamananDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Daping YangDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Rui LiuDepartment of Microbiology & Plant Pathology, University of California, Riverside, CA 92521, USA.
John C MacbethDepartment of Microbiology & Plant Pathology, University of California, Riverside, CA 92521, USA.
Elyza A DoDepartment of Microbiology & Plant Pathology, University of California, Riverside, CA 92521, USA.
Warrison A AndradeGenentech LLC, South San Francisco, CA 94080, USA.
Tiandi YangDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Hyoung-Soo ChoDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Francesca S GazzanigaDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Marit IlvesDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Daniela CoronadoDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Charlotte ThompsonDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Saiyu HangGenentech LLC, South San Francisco, CA 94080, USA.
Isaac M ChiuDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Jeffrey R MoffittProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Ansel HsiaoDepartment of Microbiology & Plant Pathology, University of California, Riverside, CA 92521, USA.
John J MekalanosDepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Christophe BenoistDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA.
Dennis L KasperDepartment of Immunology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dennis_kasper@hms.harvard.edu.
Harvard University · USUniversity of California, Riverside · USBoston Children's Hospital · US

Funding

Genetic analysis of toxinogenesis of Vibrio choleraeR37AI018045 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI John Joseph Mekalanos · 1989 to 2026
$12.8M
Vibrio cholerae antinitrosative stress defenses and gut microbiome interactionR01AI157106 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HSIAO, ANSEL, ZHU, JUN · 2020 to 2024
$4.0M
Elucidating the Structural Requirements for Next-Gen Glycoconjugate VaccinesR01AI148273 · NIAID · HARVARD MEDICAL SCHOOL · PI KASPER, DENNIS L. · 2020 to 2024
$3.0M
Nociceptor neuron regulation of gastrointestinal barrier protection and host defenseR01DK127257 · NIDDK · HARVARD MEDICAL SCHOOL · PI CHIU, ISAAC MING-CHENG · 2021 to 2024
$2.2M
Gut microbiome-mediated small-molecule signaling and resistance to invading microorganismsR35GM124724 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI HSIAO, ANSEL · 2017 to 2021
$1.8M
Gut complement system: Induction and protection against enteric infectionR01AI181938 · NIAID · HARVARD MEDICAL SCHOOL · PI Dennis L. Kasper · 2025 to 2026
$1.6M
Identifying gut bacterial molecules and mechanisms that promote an anti-tumor response to immunotherapyK22CA258960 · NCI · HARVARD MEDICAL SCHOOL · PI GAZZANIGA, FRANCESCA SMYLIE · 2022 to 2024
$559k
Tetraacylated lipid A enhancement of checkpoint blocking cancer immunotherapyR21CA287104 · NCI · HARVARD MEDICAL SCHOOL · PI KASPER, DENNIS L. · 2024 to 2025
$436k
NCI NIH HHS K22 CA258960NCI NIH HHS R21 CA287104NIAID NIH HHS R01 AI148273NIAID NIH HHS R01 AI157106NIAID NIH HHS R01 AI181938NIAID NIH HHS R37 AI018045NIDDK NIH HHS R01 DK127257NIGMS NIH HHS R35 GM124724
6 · The paper itself

Abstract

Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein, we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization and is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host's specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as an innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.

Indexed as

Complement C3Intestinal MucosaMicrobiotaAnimalsHumansMiceNeutrophilsStromal CellsComplement C3complement C3gut complement systeminnate immunityisolated lymphoid folliclesmicrobiomemicrobiotastromal cells

Identifiers

PMID38280374
PMCPMC10922926
OpenAlexW4391254288

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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.