Evidence map›Paper›PMID 41027803›Full record

ArticleAnnals of the rheumatic diseases2026

Short-chain fatty acids and their gut microbial pathways distinguish rheumatoid arthritis in discordant monozygotic twins.

Rebecca B Blank, Kevin Bu, Xinyuan Zhang, Weixi Chen, Ian Cunningham, Jeremy Sokolove, Lauren Lahey, Adriana Heguy, Rhina Medina, Carles Ubeda and 7 more

Abstract readTwin Study
In one paragraph

Article in Annals of the rheumatic diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Rebecca B BlankDivision of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.
Kevin BuDepartment of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
Xinyuan ZhangDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.
Weixi ChenDivision of Biostatistics, Department of Population Health, NYU School of Medicine, New York, New York, USA.
Ian CunninghamDivision of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.
Jeremy SokoloveStanford University School of Medicine, Stanford, California, USA.
Lauren LaheyStanford University School of Medicine, Stanford, California, USA.
Adriana HeguyDepartment of Pathology, NYU School of Medicine, New York, New York, USA.
Rhina MedinaDivision of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA.
Carles UbedaFundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, FISABIO, Valencia, Spain; CIBER en Epidemiología y Salud Pública, Madrid, Spain.
Renuka R NayakRheumatology Division, Department of Medicine, University of California, San Francisco, California, USA; Veterans Affairs Medical Center, San Francisco, California, USA.
Jiyuan HuDivision of Biostatistics, Department of Population Health, NYU School of Medicine, New York, New York, USA.
Adam CantorDepartment of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
Jakleen LeeDepartment of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
Frances M K WilliamsDepartment of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, UK.
Jose C ClementeDepartment of Genetics and Genomic Sciences, Precision Immunology Institute, Icahn School of Medicine at Mt. Sinai, New York, New York, USA.
Jose U ScherDivision of Rheumatology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA; NYU Colton Center for Autoimmunity, NYU Grossman School of Medicine, New York, New York, USA. Electronic address: Jose.scher@nyulangone.org.

Funding

Project-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5M
Micro-TeACH (Microbiome Technology and Analytic Center Hub)UC2AR081034 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jose C Clemente, ADRIANA HEGUY · 2022 to 2026
$4.6M
Employing the gut microbiome to accelerate effective initiation of rheumatoid arthritis therapyR01AR074500 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Renuka Rajendra Nayak, Jose U. Scher · 2019 to 2026
$4.1M
Translational Basic and Clinical Research Training in RheumatologyT32AR069515 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jill P Buyon, Jose U. Scher · 2017 to 2026
$2.9M
The impact of the gut microbiome on rheumatoid arthritis treatmentK08AR073930 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NAYAK, RENUKA RAJENDRA · 2018 to 2022
$981k
Investigate the Role of Gut Microbiota in the Development of Type 1 Diabetes Using TEDDY StudyR03DK138490 · NIDDK · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HU, JIYUAN · 2024 to 2025
$339k
Human Gut Microbiome as Modulator of Drug Response in Inflammatory ArthritisR03AR072182 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SCHER, JOSE U. · 2017 to 2018
$170k
CSRD VA I01 CX002557NCATS NIH HHS UL1 TR001445NIAMS NIH HHS K08 AR073930NIAMS NIH HHS R01 AR074500NIAMS NIH HHS R03 AR072182NIAMS NIH HHS T32 AR069515NIAMS NIH HHS UC2 AR081034NIDDK NIH HHS R03 DK138490Wellcome Trust
6 · The paper itself

Abstract

objectivesAlthough genetic risk factors, such as HLA-DRB1 alleles, contribute to the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other factors are involved in disease development. Further, the relative contribution of nongenetic elements in identical twins has not been characterised. Here, we aimed to characterise host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multiomics approach.

methodsEight pairs of MZ twins discordant for RA (N = 16) were enrolled in the United States (US). The gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and plasma proteins were measured in both plasma and faeces. Levels of short-chain fatty acids (SCFAs) from serum and faeces were quantified using gas chromatography mass spectrometry (GC-MS). Metagenomic data from a UK twin registry (TwinsUK) (N = 14) were used to validate findings in the US population.

resultsAlthough microbiome diversity and composition did not differ between twins, we observed a significant decrease in the SCFA-producing bacteria Blautia faecis and significantly lower concentrations of faecal butyrate and propionate in affected RA twins in the US. TwinsUK showed a similar reduction in the SCFA-producers Gemmiger formicilis and Faecalicatena fissicatena, as well as bacterial SCFA metabolism pathways.

conclusionsMultiomics biomarkers differentiate MZ twins discordant for RA. Faecal butyrate and propionate, as well as SCFA-producing bacteria, were decreased in affected twins. We found a similar decrease in SCFA-producing taxa in affected twins in a geographically distinct cohort in the UK. Our results suggest that, if further validated in larger cohorts, multiomics approaches may improve our understanding of RA pathogenesis and, potentially, contribute to more accurate diagnostics and coadjuvant therapies.

Indexed as

Arthritis, RheumatoidFatty Acids, VolatileGastrointestinal MicrobiomeTwins, MonozygoticAdultAgedBiomarkersFecesFemaleHumansMaleMiddle AgedBiomarkersFatty Acids, Volatile

Identifiers

PMID41027803
PMCPMC13636000

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Registered trials

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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.