Gut Microbiota May Not Be Fully Restored in Recovered COVID-19 Patients After 3-Month Recovery
Yu Tian, Kai-Yi Sun, Tian-Qing Meng, Zhen Ye, Shi-Meng Guo, Zhi-Ming Li, Cheng-Liang Xiong, Ying Yin, Hong-Gang Li, Li-Quan Zhou, Yu Tian, Kai-Yi Sun, Tian-Qing Meng, Zhen Ye, Shi-Meng Guo, Zhi-Ming Li, Cheng-Liang Xiong, Ying Yin, Hong-Gang Li, Li-Quan Zhou
Abstract
Coronavirus disease 2019 (COVID-19) has infected over 124 million people worldwide. In addition to the development of therapeutics and vaccines, the evaluation of the sequelae in recovered patients is also important. Recent studies have indicated that COVID-19 has the ability to infect intestinal tissues and to trigger alterations of the gut microbiota. However, whether these changes in gut microbiota persist into the recovery stage remains largely unknown. Here, we recruited seven healthy Chinese men and seven recovered COVID-19 male patients with an average of 3-months after discharge and analyzed their fecal samples by 16S rRNA sequencing analysis to identify the differences in gut microbiota. Our results suggested that the gut microbiota differed in male recovered patients compared with healthy controls, in which a significant difference in Chao index, Simpson index, and β-diversity was observed. And the relative abundance of several bacterial species differed clearly between two groups, characterized by enrichment of opportunistic pathogens and insufficiency of some anti-inflammatory bacteria in producing short chain fatty acids. The above findings provide preliminary clues supporting that the imbalanced gut microbiota may not be fully restored in recovered patients, highlighting the importance of continuous monitoring of gut health in people who have recovered from COVID-19.
Keywords: 16S sequence; SARS-CoV-2; gut microbiota; recovered COVID-19 patient; short chain fatty acids.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2021 Tian, Sun, Meng, Ye, Guo, Li, Xiong, Yin, Li and Zhou.
Figures
References
- Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. (2020) 20:533–4. 10.1016/s1473-309930120-1
- Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. . SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. (2020) 181:271–80.e8. 10.1016/j.cell.2020.02.052
- Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. (2020) 158:1831–3 e3. 10.1053/j.gastro.2020.02.055
- Lin L, Jiang X, Zhang Z, Huang S, Zhang Z, Fang Z, et al. . Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. (2020) 69:997–1001. 10.1136/gutjnl-2020-321013
- Xie C, Jiang L, Huang G, Pu H, Gong B, Lin H, et al. . Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests. Int J Infect Dis. (2020) 93:264–7. 10.1016/j.ijid.2020.02.050
- Zhou J, Li C, Liu X, Chiu MC, Zhao X, Wang D, et al. . Infection of bat and human intestinal organoids by SARS-CoV-2. Nat Med. (2020) 26:1077–83. 10.1038/s41591-020-0912-6
- Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, et al. . Alterations of the gut microbiota in patients with COVID-19 or H1N1 influenza. Clin Infect Dis. (2020) 71:2669–78. 10.1093/cid/ciaa709
- Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. . Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. (2020) 159:944–55.e8. 10.1053/j.gastro.2020.05.048
- Zuo T, Liu Q, Zhang F, Lui GC, Tso EY, Yeoh YK, et al. . Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. (2020) 70:276–84. 10.1136/gutjnl-2020-322294
- Gou W, Fu Y, Yue L, Chen G-D, Cai X, Shuai M, et al. . Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. medRxiv. (2020). 10.1101/2020.04.22.20076091
- Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. (2016) 16:341–52. 10.1038/nri.2016.42
- Budden KF, Gellatly SL, Wood DLA, Cooper MA, Morrison M, Hugenholtz P, et al. . Emerging pathogenic links between microbiota and the gut–lung axis. Nat Rev Microbiol. (2016) 15:55–63. 10.1038/nrmicro.2016.142
- Wang J, Li F, Wei H, Lian ZX, Sun R, Tian Z. Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation. J Exp Med. (2014) 211:2397–410. 10.1084/jem.20140625
- National Health Commission of the People's Republic of China . Guidelines for COVID-19 Diagnosis and Treatment (Trial version 7). (2020). Available online at:
- Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. (2014) 30:2114–20. 10.1093/bioinformatics/btu170
- Magoc T, Salzberg SL. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics. (2011) 27:2957–63. 10.1093/bioinformatics/btr507
- Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. (2016) 165:1332–45. 10.1016/j.cell.2016.05.041
- Ferreira-Halder CV, Faria AVS, Andrade SS. Action and function of Faecalibacterium prausnitzii in health and disease. Best Pract Res Clin Gastroenterol. (2017) 31:643–8. 10.1016/j.bpg.2017.09.011
- Louis P, Young P, Holtrop G, Flint HJ. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol. (2010) 12:304–14. 10.1111/j.1462-2920.2009.02066.x
- Sencio V, Barthelemy A, Tavares LP, Machado MG, Soulard D, Cuinat C, et al. . Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production. Cell Rep. (2020) 30:2934–47.e6. 10.1016/j.celrep.2020.02.013
- Segal LN, Clemente JC, Tsay JC, Koralov SB, Keller BC, Wu BG, et al. . Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol. (2016) 1:16031. 10.1038/nmicrobiol.2016.31
- Maraki S, Papadakis IS. Rothia mucilaginosa pneumonia: a literature review. Infect Dis. (2015) 47:125–9. 10.3109/00365548.2014.980843
- Trottein F, Sokol H. Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 infection. Cell Rep. (2020) 32:107915. 10.1016/j.celrep.2020.107915
- Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, et al. . ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. (2012) 487:477–81. 10.1038/nature11228
- Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, et al. . Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature. (2009) 461:1282–6. 10.1038/nature08530
- Luhrs H, Gerke T, Muller JG, Melcher R, Schauber J, Boxberge F, et al. . Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. Scand J Gastroenterol. (2002) 37:458–66. 10.1080/003655202317316105
- Sokol H, Contreras V, Maisonnasse P, Desmons A, Delache B, Sencio V, et al. . SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota. Gut Microbes. (2021) 13:1–19. 10.1080/19490976.2021.1893113
- Miquel S, Leclerc M, Martin R, Chain F, Lenoir M, Raguideau S, et al. . Identification of metabolic signatures linked to anti-inflammatory effects of Faecalibacterium prausnitzii. mBio. (2015) 6:e00300–15. 10.1128/mBio.00300-15
- Hiippala K, Jouhten H, Ronkainen A, Hartikainen A, Kainulainen V, Jalanka J, et al. . The potential of gut commensals in reinforcing intestinal barrier function and alleviating inflammation. Nutrients. (2018) 10:988. 10.3390/nu10080988
- Walter J, Armet AM, Finlay BB, Shanahan F. Establishing or exaggerating causality for the gut microbiome: lessons from human microbiota-associated rodents. Cell. (2020) 180:221–32. 10.1016/j.cell.2019.12.025
Source: PubMed