Gut dysbiosis narrative in psoriasis: matched-pair approach identifies only subtle shifts correlated with elevated fecal calprotectin

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-28
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yunusbayev B, Bogdanova A, Nadyrchenko N, Danilov L, Bogdanov V, Sergeev G, Altinbaev R, Bilalov F, Yunusbaeva M
Journal
Microbiology spectrum
Year
2025
Keywords:
dysbiosis, gut microbiota, lactate, low-grade Inflammation, psoriasis
UNLABELLED: Many studies have reported gut microbiome alterations in psoriasis patients, suggesting dysbiosis. While evidence for dysbiosis and its link to pathogenesis remains inconclusive, murine models of psoriasis suggest that gut microbiome alterations develop in response to psoriasis-like inflammation. Hence, the dominant narrative about gut microbiome alterations' impact on disease should be evaluated critically with more data and a well-powered approach. In this case-control study, we used deep sequencing of fecal samples from 53 psoriasis patients and 47 healthy donors to reconstruct the strain/species-level content of the gut microbiome. Unlike previous studies, we first identified matched pairs for each patient with healthy donors to adjust for microbiome variability and increase power. We found no evidence for depleted gut community diversity and apparent divergence in structure between patients and healthy individuals. However, our matched-pair approach identified a subtle but systematic increase in select bacteria among patients, e.g., Megasphaera elsdenii and Eubacterium CAG 180. We next showed that these enriched species were correlated with elevated biomarkers of intestinal and systemic inflammation and liver function. Functionally, one of the top species, Megasphaera elsdenii, is a potent lactate utilizer in the context of intestinal lactic acidosis and inflammation. While our findings hardly support overt dysbiosis in the large intestine, the observed microbial changes correlate with moderately elevated calprotectin, albeit at levels not enough to diagnose ongoing inflammation. Hence, the sources of elevated inflammatory markers in patients' intestines remain unclear and warrant further investigation to clarify their cause-and-effect relationship with the disease. IMPORTANCE: With sufficient taxonomic resolution and sample size, this study critically evaluates new and published data on the gut microbiome in psoriasis patients. It shows that observed taxonomic changes in patients are modest and do not meet strict criteria for gut dysbiosis, at least in the large intestine. Instead, observed taxonomic changes in psoriasis patients can be explained by the microbial response to possible low-grade inflammation with unknown localization in the intestine and unclear impact on the host. The authors point out that published endoscopic data point to the small intestine as the site of gut inflammation. Therefore, further research focused on the small intestine would be informative to clarify the hypothetical gut-psoriasis link.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-3-28

Curated date: 2025/03/24

Curator: Tosin

Revision editor(s): Tosin

Subjects

Location of subjects
Russian Federation
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
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
Psoriasis Other and unspecified pityriasis,OTHER PSORIASIS,Other psoriasis and similar disorders,Other psoriasis and similar disorders (disorder),Other psoriasis and similar disorders excluding psoriatic arthropathy,Palmoplantaris Pustulosis,PITYRIASIS NEC & NOS,PSORIAS RELATED DIS NEC,Psoriases,psoriasis,Psoriasis and similar disorders,Psoriasis and similar disorders (disorder),Psoriasis and similar disorders (navigational concept),Psoriasis and similar disorders NOS,Psoriasis and similar disorders NOS (disorder),Pustular Psoriasis of Palms and Soles,PUSTULAR PSORIASIS OF PALMS SOLES,Pustulosis of Palms and Soles,PUSTULOSIS OF PALMS SOLES,Pustulosis Palmaris et Plantaris,Psoriasis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy adult donors
Group 1 name Corresponds to the case (exposed) group for case-control studies
Psoriasis patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Psoriasis
Group 0 sample size Number of subjects in the control (unexposed) group
47
Group 1 sample size Number of subjects in the case (exposed) group
53
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Prior antibiotic use

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).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
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
sex

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-28

Curated date: 2025/03/24

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 2

Description: Differentially abundant bacteria in case-control matched pairs

Abundance in Group 1: increased abundance in Psoriasis patients

NCBI Quality ControlLinks
Bacteroides xylanisolvens
Catenibacterium mitsuokai
Eubacterium sp. CAG:180
Megasphaera elsdenii
Prevotella sp. AM42-24
Rothia mucilaginosa
[Clostridium] leptum

Revision editor(s): Tosin

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-28

Curated date: 2025/03/24

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 2

Description: Differentially abundant bacteria in case-control matched pairs

Abundance in Group 1: decreased abundance in Psoriasis patients

NCBI Quality ControlLinks
Bacteroides salyersiae
Blautia obeum CAG:39
Dialister sp. CAG:357
Haemophilus sp. HMSC71H05
Lachnospira eligens
Parasutterella excrementihominis
Roseburia inulinivorans

Revision editor(s): Tosin

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-3-28

Curated date: 2025/03/24

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-28

Curated date: 2025/03/24

Curator: Tosin

Revision editor(s): Tosin, Svetlana up

Source: Figure S6

Description: Differentially abundant bacterial species inferred using the linear discriminant analysis, LEfSe

Abundance in Group 1: increased abundance in Psoriasis patients

NCBI Quality ControlLinks
Acidaminococcus
Bacteroides finegoldii
Bacteroides xylanisolvens
Deltaproteobacteria
Desulfovibrionaceae
Desulfovibrionales
Dialister invisus
Eubacterium sp. CAG:180
Holdemanella
Holdemanella biformis
Megasphaera
Megasphaera elsdenii
Prevotella sp. AM42-24

Revision editor(s): Tosin, Svetlana up

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-28

Curated date: 2025/03/24

Curator: Tosin

Revision editor(s): Tosin, Svetlana up

Source: Figure S6

Description: Differentially abundant bacterial species inferred using the linear discriminant analysis, LEfSe

Abundance in Group 1: decreased abundance in Psoriasis patients

NCBI Quality ControlLinks
Dialister
Dialister sp. CAG:357
Eubacterium ventriosum
Fusobacteriales
Fusobacteriia
Fusobacteriota
Lachnospira eligens
Proteobacteria bacterium CAG:139
Roseburia inulinivorans
Sutterellaceae
unclassified Pseudomonadota

Revision editor(s): Tosin, Svetlana up