TY - JOUR

T1 - Gut dysbiosis narrative in psoriasis: matched-pair approach identifies only subtle shifts correlated with elevated fecal calprotectin

AU - Юнусбаев, Баязит Булатович

AU - Юнусбаева, Миляуша Мусиевна

AU - Данилов, Лаврентий Глебович

PY - 2024

Y1 - 2024

N2 - Many studies 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 of 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, observed microbial changes correlate with moderately elevated calprotectin, albeit at levels not enough to diagnose ongoing inflammation. Hence, sources of elevated inflammatory markers in patients’ intestines remain unclear and warrant further investigation to clarify their cause-and-effect relationship with the disease.

AB - Many studies 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 of 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, observed microbial changes correlate with moderately elevated calprotectin, albeit at levels not enough to diagnose ongoing inflammation. Hence, sources of elevated inflammatory markers in patients’ intestines remain unclear and warrant further investigation to clarify their cause-and-effect relationship with the disease.

KW - Gut Microbiota

KW - Dysbiosis

KW - Low-grade Inflammation

KW - Psoriasis

KW - Lactate

M3 - Article

JO - Microbiology spectrum

JF - Microbiology spectrum

SN - 2165-0497

ER -