Gut Microbiota as a Key Player in Health and Disease with a Focus on Long-Term Alterations in Post-COVID

Authors:
  • ABAna Bačić
    Ana Bačić
  • TGTijana Gmizić
    Tijana Gmizić
  • TTTea Takić
    Tea Takić
  • MZMarija Zdravković
    Marija Zdravković
  • MBMarija Branković
    Marija Branković
  • MRMirjana Rajilić-Stojanović
    Mirjana Rajilić-Stojanović

Abstract
Introduction: Gut microbiota plays a critical role in health and may contribute to post-COVID manifestations, as alterations in microbial communities have been observed in affected individuals. This study aimed to identify microbial and biochemical signatures in post-COVID individuals after an extended period following acute infection. Methods: A total of 90 subjects were recruited, divided into three equal groups: post-COVID, fully recovered individuals, and healthy controls. The post-COVID group was further stratified by symptom duration and severity. Fecal microbiota was analyzed using 16S rRNA gene sequencing (V3-V4 region), with differential abundance assessed through LEfSE. Biochemical parameters were measured using the Mindray BS800 system. Spearman’s correlation was applied to explore associations between taxonomic groups and biochemical markers. Results: Several microbial taxa exhibited positive correlations with high-density lipoprotein (HDL) levels and negative associations with non-HDL lipid parameters and CRP, highlighting their potential role in health. Individuals with a history of COVID-19 showed a significantly lower relative abundance of Phascolarctobacterium, Slackia, Enterorhabdus, and Senegalimassilia (p < 0.05, LDA >2) compared to healthy controls. In participants with post-COVID symptoms, Eggerthella was significantly enriched, with Holdemania, Gemella, and two uncultured Lachnospiraceae showing a trend toward higher abundance. Severe post-COVID cases showed higher Parasutterella abundance, while long-lasting symptoms (>1 year) were associated with Dialister enrichment and Phascolarctobacterium depletion compared to controls and fully recovered individuals. Conclusion: Gut microbiota alterations were observed in post-COVID individuals even after a prolonged period following acute infection, suggesting a potential link between microbial imbalance and lingering symptoms, though causality cannot be confirmed.

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