Journal of Translational Medicine (Mar 2025)

Gut Microbiome dysbiosis and immune activation correlate with somatic and neuropsychiatric symptoms in COVID-19 patients

  • Paula L. Scalzo,
  • Austin G. Marshall,
  • Sirena Soriano,
  • Kristen Curry,
  • Mario Dulay,
  • Timea Hodics,
  • Eamonn M. M. Quigley,
  • Todd J. Treangen,
  • María M. Piskorz,
  • Sonia Villapol

DOI
https://doi.org/10.1186/s12967-025-06348-y
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 20

Abstract

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Abstract Background Infection with SARS-CoV-2, the virus responsible for COVID-19, can lead to a range of physical symptoms and mental health challenges, including stress, anxiety, and depression. These effects are particularly pronounced in hospitalized patients, likely due to the virus’s direct and indirect impact on the nervous system. Gut dysbiosis, an imbalance in the gut microbiome, has been implicated in immune dysfunction and chronic inflammation in COVID-19 patients. However, the interactions between gut microbiome composition and the physical and mental symptoms of COVID-19 remain incompletely understood. Methods We investigated the association between physical and mental symptoms, cytokine profiles, and gut microbiota composition in 124 hospitalized COVID-19 patients. We collected data on demographics, COVID-19 severity, and mental health indicators (stress, anxiety, and depression). Gut microbiome profiling was performed using full-length 16 S rRNA gene sequencing to evaluate microbial diversity and composition. Results COVID-19 severity was categorized as low (27.4%), moderate (29.8%), or critical (42.8%). Common symptoms included fever (66.1%) and cough (55.6%), while somatic symptoms (27.3%), anxiety (27.3%), depressive symptoms (39%), and stress (80.5%) were frequently self-reported. Elevated interleukin-6 levels in severe cases highlighted systemic inflammation, reduced gut bacterial diversity, particularly among women and obese patients, correlated with higher disease severity. Notably, the genus Mitsuokella was associated with increased physical symptoms and mental distress, while Granulicatella was linked to critical illness. Conclusions Our findings reveal significant associations between mental health status, systemic inflammation, and gut dysbiosis in hospitalized COVID-19 patients. These results indicate the potential for microbiome-targeted therapies to mitigate psychological and physical complications and improve recovery outcomes in this population.

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