Evidence map›Paper›PMID 34283837›Full record

ArticlePloS one2021

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.

Cassandra Velasco, Christopher Dunn, Cassandra Sturdy, Vladislav Izda, Jake Martin, Alexander Rivas, Jeffrey McNaughton, Matlock A Jeffries

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Commensal skin bacteria interact with the innate immune system to promote tail regeneration in Xenopus laevis tadpoles.Developmental dynamics : an official publication of the American Association of Anatomists · 2026
    Article
  2. Osteoarthritis as a systemic disease.Nature reviews. Rheumatology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Biofilm-Associated Infections in Chronic Wounds and Their Management.Advances in experimental medicine and biology · 2023
    Article
  9. Manipulating the microbiome alters regenerative outcomes in Xenopus laevis tadpoles via lipopolysaccharide signalling.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2022
    Article
  10. Review
  11. Review
  12. Lifestyle Medicine Approach to Wound Management.American journal of lifestyle medicine
    Article
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

8 authors at 3 institutions in 1 country.

Cassandra VelascoUniversity of Oklahoma Health Sciences Center, Department of Internal Medicine, Division of Rheumatology, Immunology, and Allergy, Oklahoma City, Oklahoma, United States of America.
Christopher DunnUniversity of Oklahoma Health Sciences Center, Department of Internal Medicine, Division of Rheumatology, Immunology, and Allergy, Oklahoma City, Oklahoma, United States of America.
Cassandra SturdyOklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, Oklahoma City, Oklahoma, United States of America.
Vladislav IzdaOklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, Oklahoma City, Oklahoma, United States of America.ORCID 0000-0002-7561-2699
Jake MartinOklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, Oklahoma City, Oklahoma, United States of America.
Alexander RivasUniversity of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
Jeffrey McNaughtonUniversity of Oklahoma Health Sciences Center, Department of Internal Medicine, Division of Rheumatology, Immunology, and Allergy, Oklahoma City, Oklahoma, United States of America.
Matlock A JeffriesUniversity of Oklahoma Health Sciences Center, Department of Internal Medicine, Division of Rheumatology, Immunology, and Allergy, Oklahoma City, Oklahoma, United States of America.ORCID 0000-0001-9516-4312
Oklahoma Medical Research Foundation · USUniversity of Oklahoma Health Sciences Center · USUniversity of Arkansas for Medical Sciences · US

Funding

Visualizing insulin actions on neuronal metabolism and function using fluorescent biosensorsP20GM125528 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Marisol Castillo-Castrejon · 2019 to 2026
$17.8M
Peripheral blood mononuclear cell epigenetic associations in and biomarkers for knee osteoarthritis development and progression.R01AR076440 · NIAMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI BHUTANI, NIDHI, JEFFRIES, MATLOCK · 2020 to 2025
$3.6M
An integrative study of circulating leukocyte composition, epigenetic patterns, and functional consequences in knee osteoarthritis.K08AR070891 · NIAMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI JEFFRIES, MATLOCK · 2017 to 2021
$862k
Intraarticular microbial DNA as a novel mediator of osteoarthritisR61AR078075 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JEFFRIES, MATLOCK · 2020 to 2021
$861k
Intraarticular microbial DNA as a novel mediator of osteoarthritisR33AR078075 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JEFFRIES, MATLOCK · 2022 to 2022
$437k
NIAMS NIH HHS K08 AR070891NIAMS NIH HHS R01 AR076440NIAMS NIH HHS R33 AR078075NIAMS NIH HHS R61 AR078075NIGMS NIH HHS P20 GM125528
6 · The paper itself

Abstract

objectiveAdult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation.

methodsWe orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt.

resultsTransplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25±0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm-final ear hole size], mean±SEM), whereas MRL-vehicle mice healed well (1.4±0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74±0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3±0.1 vs. MRL-vehicle 1.4±0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63±0.03mm, mean±SEM vs. B6-vehicle control:0.25±0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice.

conclusionIn this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.

Indexed as

Gastrointestinal MicrobiomeMice, Inbred C57BLWound HealingAnimalsCecumEarFecal Microbiota TransplantationFemaleMaleMice

Identifiers

PMID34283837
PMCPMC8291702
OpenAlexW3183774523

What OpenQuestion holds

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LicenceCC BY
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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.