Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts

ObjectiveCOVID-19 has had a profound impact on public health globally. However, most studies have focused on patients with long COVID or those in the acute phase of infection, with limited research on the health of individuals who have recovered from mild COVID-19. This study investigates the long-t...

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Main Authors: Da Li, Da-Ya Zhang, Shi-Ju Chen, Yan-Ting Lv, Shi-Mei Huang, Chen Chen, Fan Zeng, Run-Xiang Chen, Xiao-Dong Zhang, Jian-Xin Xiong, Fa-Di Chen, Yue-Hong Jiang, Zhai Chen, Cui-Yi Mo, Jia-Jia Chen, Xu-Li Zhu, Li-Jun Zhang, Fei-Hu Bai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1565887/full
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author Da Li
Da-Ya Zhang
Shi-Ju Chen
Yan-Ting Lv
Shi-Mei Huang
Chen Chen
Fan Zeng
Run-Xiang Chen
Xiao-Dong Zhang
Jian-Xin Xiong
Fa-Di Chen
Yue-Hong Jiang
Zhai Chen
Cui-Yi Mo
Jia-Jia Chen
Xu-Li Zhu
Li-Jun Zhang
Fei-Hu Bai
Fei-Hu Bai
author_facet Da Li
Da-Ya Zhang
Shi-Ju Chen
Yan-Ting Lv
Shi-Mei Huang
Chen Chen
Fan Zeng
Run-Xiang Chen
Xiao-Dong Zhang
Jian-Xin Xiong
Fa-Di Chen
Yue-Hong Jiang
Zhai Chen
Cui-Yi Mo
Jia-Jia Chen
Xu-Li Zhu
Li-Jun Zhang
Fei-Hu Bai
Fei-Hu Bai
author_sort Da Li
collection DOAJ
description ObjectiveCOVID-19 has had a profound impact on public health globally. However, most studies have focused on patients with long COVID or those in the acute phase of infection, with limited research on the health of individuals who have recovered from mild COVID-19. This study investigates the long-term changes in bacterial and fungal communities in individuals recovering from mild COVID-19 and their clinical relevance.MethodsHealthy individuals from Hainan Province were enrolled before the COVID-19 outbreak, along with individuals recovering from COVID-19 at 3 months and 6 months post-recovery. Stool, blood samples, and metadata were collected. Metagenomic sequencing and Internal Transcribed Spacer (ITS) analysis characterized bacterial and fungal communities, while bacterial-fungal co-occurrence networks were constructed. A random forest model evaluated the predictive capacity of key taxa.ResultsThe gut microbiota of COVID-19 recoverees differed significantly from that of healthy individuals. At 3 months post-recovery, probiotics (e.g., Blautia massiliensis and Kluyveromyces spp.) were enriched, linked to improved metabolism, while at 6 months, partial recovery of probiotics (e.g., Acidaminococcus massiliensis and Asterotremella spp.) was observed alongside persistent pathogens (e.g., Streptococcus equinus and Gibberella spp.). Dynamic changes were observed, with Acidaminococcus massiliensis enriched at both baseline and 6 months but absent at 3 months. Co-occurrence network analysis revealed synergies between bacterial (Rothia spp.) and fungal (Coprinopsis spp.) taxa, suggesting their potential roles in gut restoration. The bacterial random forest model (10 taxa) outperformed the fungal model (8 taxa) in predicting recovery status (AUC = 0.99 vs. 0.80).ConclusionThese findings highlight the significant long-term impacts of mild COVID-19 recovery on gut microbiota, with key taxa influencing metabolism and immune regulation, supporting microbiome-based strategies for recovery management.
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spelling doaj-art-7bd00f4fc2b247a984916fee3f33560c2025-08-20T03:48:23ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-05-011510.3389/fcimb.2025.15658871565887Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shiftsDa Li0Da-Ya Zhang1Shi-Ju Chen2Yan-Ting Lv3Shi-Mei Huang4Chen Chen5Fan Zeng6Run-Xiang Chen7Xiao-Dong Zhang8Jian-Xin Xiong9Fa-Di Chen10Yue-Hong Jiang11Zhai Chen12Cui-Yi Mo13Jia-Jia Chen14Xu-Li Zhu15Li-Jun Zhang16Fei-Hu Bai17Fei-Hu Bai18The Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaThe Second School of Clinical Medicine, Hainan Medical University, Haikou, ChinaDepartment of Gastroenterology, Hainan Second People’s Hospital, Wuzhishan, ChinaDepartment of Gastroenterology, Wuzhishan Center for Disease Control and Prevention, Wuzhishan, ChinaDepartment of Gastroenterology, The Second People ‘s Hospital of Ledong Li Autonomous County, Ledong Li Autonomous County, ChinaDepartment of Gastroenterology, Dongfang People’s Hospital, Dongfang, ChinaDepartment of Gastroenterology, Qionghai People’s Hospital, Qionghai, ChinaDepartment of Gastroenterology, Qionghai People’s Hospital, Qionghai, ChinaDepartmenrt of Internal Medicine, Otog Front Banner People ‘s Hospital, Otog Front Banner, ChinaHealth Management Center, The Second Affiliated Hospital of Hainan Medical University, Haikou, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou, China0Department of Gastroenterology, The Gastroenterology Clinical Medical Center of Hainan Province, Haikou, ChinaObjectiveCOVID-19 has had a profound impact on public health globally. However, most studies have focused on patients with long COVID or those in the acute phase of infection, with limited research on the health of individuals who have recovered from mild COVID-19. This study investigates the long-term changes in bacterial and fungal communities in individuals recovering from mild COVID-19 and their clinical relevance.MethodsHealthy individuals from Hainan Province were enrolled before the COVID-19 outbreak, along with individuals recovering from COVID-19 at 3 months and 6 months post-recovery. Stool, blood samples, and metadata were collected. Metagenomic sequencing and Internal Transcribed Spacer (ITS) analysis characterized bacterial and fungal communities, while bacterial-fungal co-occurrence networks were constructed. A random forest model evaluated the predictive capacity of key taxa.ResultsThe gut microbiota of COVID-19 recoverees differed significantly from that of healthy individuals. At 3 months post-recovery, probiotics (e.g., Blautia massiliensis and Kluyveromyces spp.) were enriched, linked to improved metabolism, while at 6 months, partial recovery of probiotics (e.g., Acidaminococcus massiliensis and Asterotremella spp.) was observed alongside persistent pathogens (e.g., Streptococcus equinus and Gibberella spp.). Dynamic changes were observed, with Acidaminococcus massiliensis enriched at both baseline and 6 months but absent at 3 months. Co-occurrence network analysis revealed synergies between bacterial (Rothia spp.) and fungal (Coprinopsis spp.) taxa, suggesting their potential roles in gut restoration. The bacterial random forest model (10 taxa) outperformed the fungal model (8 taxa) in predicting recovery status (AUC = 0.99 vs. 0.80).ConclusionThese findings highlight the significant long-term impacts of mild COVID-19 recovery on gut microbiota, with key taxa influencing metabolism and immune regulation, supporting microbiome-based strategies for recovery management.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1565887/fullmild COVID-19gut microbiomemetagenomic sequencingprobioticsfungal microbiotarandom forest model
spellingShingle Da Li
Da-Ya Zhang
Shi-Ju Chen
Yan-Ting Lv
Shi-Mei Huang
Chen Chen
Fan Zeng
Run-Xiang Chen
Xiao-Dong Zhang
Jian-Xin Xiong
Fa-Di Chen
Yue-Hong Jiang
Zhai Chen
Cui-Yi Mo
Jia-Jia Chen
Xu-Li Zhu
Li-Jun Zhang
Fei-Hu Bai
Fei-Hu Bai
Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts
Frontiers in Cellular and Infection Microbiology
mild COVID-19
gut microbiome
metagenomic sequencing
probiotics
fungal microbiota
random forest model
title Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts
title_full Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts
title_fullStr Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts
title_full_unstemmed Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts
title_short Long-term alterations in gut microbiota following mild COVID-19 recovery: bacterial and fungal community shifts
title_sort long term alterations in gut microbiota following mild covid 19 recovery bacterial and fungal community shifts
topic mild COVID-19
gut microbiome
metagenomic sequencing
probiotics
fungal microbiota
random forest model
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1565887/full
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