Evidence map›Paper›PMID 41412123›Full record

ArticleCell2026

Gut microbiota promotes immune tolerance at the maternal-fetal interface.

Julia A Brown, Mohammed Amir, Shui Yu, Daniel S H Wong, Jinghua Gu, Uthra Balaji, Christopher N Parkhurst, Seunghee Hong, Lucy R Hart, Hannah C Carrow and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Julia A BrownGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Mohammed AmirGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Shui YuGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Daniel S H WongGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA.
Jinghua GuGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Uthra BalajiGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Christopher N ParkhurstJill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10065, USA.
Seunghee HongDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
Lucy R HartGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Hannah C CarrowGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA.
Mamadou A BahImmunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA.
Aparna AnanthanarayananGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Katherine Z SanidadGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Mengze LyuJill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10065, USA; Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10065, USA.
Anisa SiddikovaGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA.
Marina Lima Silva SantosGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Inna SerganovaMeyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; Department of Medicine, Division of Hematology & Medical Oncology, Weill Cornell Medicine, New York, NY 10065, USA.
Gretchen E DiehlImmunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA; Immunology Program of the Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Josef AnratherThe Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065, USA.
Naohiro InoharaRogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Gregory F SonnenbergImmunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY 10065, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, NY 10065, USA.
Virginia PascualGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA.
Melody Y ZengGale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine, New York, NY 10065, USA; Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School, New York, NY 10065, USA; Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: myz4001@med.cornell.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Institutional Career Development CoreKL2TR002385 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI YUAN-SHAN ZHU · 2017 to 2026
$13.3M
J. NRSA Training CoreTL1TR002386 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Genevieve Giny Fouda Amou ou · 2017 to 2026
$5.8M
Orchestrating intestinal immunity through microbiota-CX3CR1+ cell interactions R01AI125264 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI GRETCHEN E DIEHL · 2017 to 2026
$4.1M
Immune regulation of intestinal health and diseaseR01AI123368 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Gregory F Sonnenberg · 2016 to 2026
$3.6M
Image-guided Trp-IDO/TDO-Kyn-AHR pathway inhibition, combined with immunotherapyR01CA249294 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI KESHARI, KAYVAN R, MERGHOUB, TAHA · 2021 to 2025
$2.6M
Megakaryocyte regulation by the gut microbiomeR01HL169989 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Melody Y Zeng · 2023 to 2026
$2.6M
Multidisciplinary Research Training in Gastroenterology and HepatologyT32DK116970 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI Randy S Longman · 2019 to 2026
$2.3M
Exploiting tumor metabolism to optimize T cell therapyR50CA221810 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Inna Serganova · 2018 to 2026
$1.6M
Immune regulation by the gut microbiome at the maternal-fetal interfaceR01HD110118 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI ZENG, MELODY Y · 2022 to 2024
$1.3M
Microbial Regulation of Microglial FunctionK08MH130773 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI PARKHURST, CHRISTOPHER NEAL · 2022 to 2025
$782k
Role of gut microbiota-induced IgG in enteric host defenseK01DK114376 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI ZENG, MELODY Y · 2018 to 2022
$758k
NCATS NIH HHS KL2 TR002385NCATS NIH HHS TL1 TR002386NCI NIH HHS K99 CA290052NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA249294NCI NIH HHS R21 CA270998NCI NIH HHS R50 CA221810NHLBI NIH HHS R01 HL169989NIAID NIH HHS R01 AI123368NIAID NIH HHS R01 AI125264NICHD NIH HHS F32 HD112151NICHD NIH HHS R01 HD110118NIDDK NIH HHS K01 DK114376NIDDK NIH HHS T32 DK116970NIMH NIH HHS K08 MH130773
6 · The paper itself

Abstract

Immune tolerance at the maternal-fetal interface (MFI) is required for fetal development. Excessive maternal interferon-gamma (IFN-γ) and interleukin-17 (IL-17) are linked to pregnancy complications, but the regulation of maternal IFN-γ and IL-17 at the MFI is poorly understood. Here, we demonstrate a gut-placenta immune axis in pregnant mice in which the absence or perturbation of gut microbiota dysregulates maternal IFN-γ and IL-17 responses at the MFI, resulting in fetal resorption. Microbiota-dependent tryptophan derivatives suppress IFN-γ+ and IL-17+ T cells at the MFI by priming myeloid-derived suppressor cells (MDSCs) and gut-derived RORγt+ regulatory T cells (Tregs), respectively. The tryptophan derivative indole-3-carbinol, or tryptophan-metabolizing Lactobacillus murinus, rebalances the T cell response at the MFI and reduces fetal resorption in germ-free mice. Furthermore, MDSCs, RORγt+ Tregs, and microbiota-dependent tryptophan derivatives are dysregulated at the MFI in human recurrent miscarriage cases. Together, our findings identify microbiota-dependent immune tolerance mechanisms that promote fetal development.

Indexed as

Gastrointestinal MicrobiomeImmune ToleranceMaternal-Fetal ExchangeAbortion, HabitualAnimalsFemaleHumansInterferon-gammaInterleukin-17MiceMice, Inbred C57BLMyeloid-Derived Suppressor CellsNuclear Receptor Subfamily 1, Group F, Member 3PlacentaPregnancyT-Lymphocytes, RegulatoryInterferon-gammaInterleukin-17Nuclear Receptor Subfamily 1, Group F, Member 3Tryptophanaryl hydrocarbon receptorgut microbiotagut-placenta axismaternal-fetal immune toleranceMDSCsmetabolitesT cellsTregstryptophan

Identifiers

PMID41412123
PMCPMC12904261

What OpenQuestion holds

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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 OpenQuestion graph.