Evidence map›Paper›PMID 40961935›Full record

ArticleCell host & microbe2025

Gut microbiota and metabolites drive chronic sickle cell disease pain in mice.

Amanda M Brandow, Samantha N Atkinson, Zulmary Manjarres, Vanessa L Ehlers, McKenna L Pratt, Iti Mehta, Sruthi Mudunuri, Aishwarya Kappagantu, Stephanie I Shiers, Khadijah Mazhar and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Dyslipidemia is a metabolic hallmark of acute pain in sickle cell disease.medRxiv : the preprint server for health sciences · 2026
    Article
  3. Article
  4. Article
  5. Sulfolipid-1 fromJournal of neurophysiology · 2026
    Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Amanda M BrandowDepartment of Pediatrics, Division of Hematology/Oncology, Bone Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Samantha N AtkinsonCenter for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Zulmary ManjarresDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Vanessa L EhlersDepartment of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
McKenna L PrattDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Iti MehtaDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Sruthi MudunuriDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Aishwarya KappagantuDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Stephanie I ShiersDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Khadijah MazharDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Mackenzie A SimmsDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA; Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Sahar AlhendiDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Anagha SheshadriDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Anna M CervantesSouthwest Transplant Alliance, Dallas, TX 75231, USA.
Jeffrey C ReeseSouthwest Transplant Alliance, Dallas, TX 75231, USA.
Diana Tavares-FerreiraDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Ishwarya SankaranarayananDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Mandee K SchaubDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Tyler B WaltzDepartment of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Michael HaywardCenter for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Dianise M Rodríguez GarcíaDepartment of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Gregory DussorDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Nita H SalzmanCenter for Microbiome Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Department of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Kelli L PalmerDepartment of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA.
Cheryl L StuckyDepartment of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Theodore J PriceDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA.
Katelyn E SadlerDepartment of Neuroscience, The University of Texas at Dallas, Richardson, TX 75080, USA; Center for Advanced Pain Studies, The University of Texas at Dallas, Richardson, TX 75080, USA. Electronic address: katelyn.sadler@utdallas.edu.

Funding

Mechanistic underpinnings of chronic low back painU19NS130608 · NINDS · UNIVERSITY OF TEXAS DALLAS · PI Theodore J Price · 2022 to 2026
$13.6M
Nociceptive Mechanisms Underlying Sickle Cell PainR01NS070711 · NINDS · MEDICAL COLLEGE OF WISCONSIN · PI Bonnie N Dittel, Cheryl Louise Stucky · 2009 to 2026
$8.7M
Pain Mechanisms in Fabry DiseaseR37NS108278 · NINDS · MEDICAL COLLEGE OF WISCONSIN · PI STUCKY, CHERYL LOUISE · 2019 to 2025
$5.6M
Investigating the role of the microbiome and inflammation in acute and chronic pain in patients with sickle cell diseaseR01HL142657 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI BRANDOW, AMANDA M · 2018 to 2022
$3.7M
Intestinal Enterococcal Dynamics: Modeling Host-Commensal and Host-Pathogen InteractionsR35GM122503 · NIGMS · MEDICAL COLLEGE OF WISCONSIN · PI SALZMAN, NITA H · 2017 to 2021
$2.7M
The Inflammatory Index as a Biomarker for Pain in Patients with Sickle Cell DiseaseR61NS114954 · NINDS · MEDICAL COLLEGE OF WISCONSIN · PI BRANDOW, AMANDA M · 2019 to 2019
$2.7M
The Inflammatory Index as a Biomarker for Pain in Patients with Sickle Cell DiseaseR33NS114954 · NINDS · MEDICAL COLLEGE OF WISCONSIN · PI BRANDOW, AMANDA M · 2023 to 2024
$1.3M
Peripheral Sensitization as a Novel Mechanism for Pain in Sickle Cell DiseaseK23HL114636 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI BRANDOW, AMANDA M · 2013 to 2017
$752k
Sickle cell disease gut dysbiosis effects on CNS pain processingR00HL155791 · NHLBI · UNIVERSITY OF TEXAS DALLAS · PI SADLER, KATELYN · 2023 to 2025
$747k
Sickle cell disease gut dysbiosis effects on CNS pain processingK99HL155791 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI SADLER, KATELYN · 2021 to 2022
$230k
NHLBI NIH HHS K23 HL114636NHLBI NIH HHS K99 HL155791NHLBI NIH HHS R00 HL155791NHLBI NIH HHS R01 HL142657NIGMS NIH HHS R35 GM122503NINDS NIH HHS R01 NS070711NINDS NIH HHS R33 NS114954NINDS NIH HHS R37 NS108278NINDS NIH HHS R61 NS114954NINDS NIH HHS U19 NS130608
6 · The paper itself

Abstract

Individuals with sickle cell disease (SCD) suffer from debilitating chronic pain that does not have a clear etiology. Recent 16S ribosomal RNA gene sequencing studies revealed gut dysbiosis in individuals with SCD. It is unclear, however, whether these intestinal microbial changes contribute to chronic SCD pain. Using transgenic SCD mice, we determined that chronic SCD pain is alleviated following fecal microbiota transplantation from healthy controls, specifically by increasing the relative abundance of probiotic Akkermansia muciniphila. Reciprocally, transplantation of the SCD gut microbiome induced persistent pain in wild-type recipients via bilirubin-vagus nerve TRPM2 signaling. Biospecimens from individuals with SCD and spatial transcriptomic analysis of human nodose ganglia tissue identified additional bacterial species and neuronally expressed transcripts that should be explored as novel SCD analgesic targets.

Indexed as

Anemia, Sickle CellChronic PainGastrointestinal MicrobiomeAkkermansiaAnimalsDisease Models, AnimalDysbiosisFecal Microbiota TransplantationFemaleHumansMaleMiceMice, TransgenicProbioticsTRPM Cation ChannelsVerrucomicrobiaTRPM Cation ChannelsAkkermansiabilirubinmicrobiomepainsickle cell diseaseTRPM2vagus nerve

Identifiers

PMID40961935
PMCPMC12448112

What OpenQuestion holds

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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.