Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice

Study information

Needs review

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

38589392

DOI Digital object identifier for electronic documents.

https://doi.org/10.1038/s41467-024-47072-3

URI

Authors

Dokoshi T, Chen Y, Cavagnero KJ, Rahman G, Hakim D, Brinton S, Schwarz H, Brown EA, O'Neill A, Nakamura Y, Li F, Salzman NH, Knight R, Gallo RL

Journal

Nature communications

Year

2024

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Experiment 1

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Curated date: 2024/11/06

Curator: Prolific

Revision editor(s): Prolific, KateRasheed

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Skin wound Skin wound,skin wound

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Control group(mice without skin wounds)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Experimental group/Wound (with skin wounds)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Experimental group of mice subjected to either dermal injury or skin injury

Group 0 sample size Number of subjects in the control (unexposed) group: 32

Group 1 sample size Number of subjects in the case (exposed) group: 32

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: DESeq2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Matched on Factors on which subjects have been matched on in a case-control study: age, sex

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: increased

Signature 1

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Curated date: 2024/11/12

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Source: Figure 3D

Description: Differential abundance of bacterial species between the group with skin wounds and the control group (without skin injuries).

Abundance in Group 1: increased abundance in Experimental group/Wound (with skin wounds)

NCBI	Quality Control	Links
Adlercreutzia caecimuris
Adlercreutzia equolifaciens
Adlercreutzia mucosicola
Akkermansia muciniphila
Bacteroides fragilis CAG:47
Bacteroides thetaiotaomicron
Bifidobacterium pseudolongum
Enterococcus faecalis
Firmicutes bacterium ASF500
Lachnospiraceae bacterium A2
Lachnospiraceae bacterium A4
Lachnospiraceae bacterium M18-1
Lactobacillus acidophilus
Lactobacillus gasseri
Parasutterella excrementihominis
Phocaeicola vulgatus CAG:6
Anaerotruncus sp. G3
Dorea sp. 5-2
Lachnospiraceae bacterium 3-1
Lachnospiraceae bacterium MD308
Oscillibacter sp. 1-3

Revision editor(s): Prolific, KateRasheed

Signature 2

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Curated date: 2024/11/12

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Source: Figure 3D

Description: Differential abundance of bacterial species between the group with skin wounds and the control group (without skin injuries).

Abundance in Group 1: decreased abundance in Experimental group/Wound (with skin wounds)

NCBI	Quality Control	Links
Curtobacterium flaccumfaciens
Dubosiella newyorkensis
Escherichia coli
Ligilactobacillus murinus
Mammaliicoccus lentus
Pediococcus damnosus
Ralstonia pickettii
Saccharomonospora viridis
Saccharopolyspora rectivirgula
Serratia marcescens
Shouchella clausii
Staphylococcus xylosus
Thermoactinomyces sp. Gus2-1

Revision editor(s): Prolific, KateRasheed

Experiment 2

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Curated date: 2024/12/20

Curator: KateRasheed

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Control group

Group 1 name Corresponds to the case (exposed) group for case-control studies: Experimental group/Wound (after skin wounding)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Experimental group of mice who were subjected to either dermal injury or skin injury.

Group 0 sample size Number of subjects in the control (unexposed) group: 5

Group 1 sample size Number of subjects in the case (exposed) group: 5

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances