Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

Journal of Medical Case Reports - 2021
Fengqiong Liu1, Shanliang Ye2, Xin Zhu3, Xuesong He4, Shengzhou Wang4, Yinbao Li5, Jing Lin3, Jingsu Wang4, Yonggan Lin4, Xin Ren2, Yong Li4, Zhaoqun Deng3
1Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, China
2Ganzhou Municipal Hospital, 49 Dagonglu, Ganzhou, 341000, People’s Republic of China
3Department of Laboratory Center, The Affiliated People’s Hospital of Jiangsu University, 8 Dianlilu, Zhenjiang, 212000, People’s Republic of China
4GanzhouShanjian Bio-Technology Co., Ltd., Ganzhou, China
5School of Pharmacrutical Sciences, Gannan Medical University, Ganzhou, China

Tóm tắt

Abstract Background

To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients.

 Case presentation

A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT.

 Conclusions

After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

Từ khóa


Tài liệu tham khảo

Zhou J, Li C, Zhao G, et al. Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus. Science Adv. 2017;3(11):eaao4966. https://doi.org/10.1126/sciadv.aao4966.

Openshaw PJ. Crossing barriers: infections of the lung and the gut. Mucosal Immunol. 2009;2(2):100–2. https://doi.org/10.1038/mi.2008.79.

Liang W, Feng Z, Rao S, et al. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut. 2020;69(6):1141–3. https://doi.org/10.1136/gutjnl-2020-320832.

Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. https://doi.org/10.1016/S0140-6736(20)30183-5.

Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475–81. https://doi.org/10.1016/S2213-2600(20)30079-5.

Cameron MJ, Ran L, Xu L, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007;81(16):8692–706. https://doi.org/10.1128/JVI.00527-07.

Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348(20):1986–94. https://doi.org/10.1056/NEJMoă85.

Ichinohe T, Pang IK, Kumamoto Y, et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc Natl Acad Sci USA. 2011;108(13):5354–9. https://doi.org/10.1073/pnas.1019378108.

Zuo T, Zhang F, Lui GCY, et al. Alterations in Gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020. https://doi.org/10.1053/j.gastro.2020.05.048.

Ooijevaar RE, Terveer EM, Verspaget HW, Kuijper EJ, Keller JJ. Clinical application and potential of fecal microbiota transplantation. Annu Rev Med. 2019;70:335–51. https://doi.org/10.1146/annurev-med-111717-122956.

Hensley-McBain T, Zevin AS, Manuzak J, et al. Effects of fecal microbial transplantation on microbiome and immunity in simian immunodeficiency virus-infected macaques. J Virol. 2016;90(10):4981–9. https://doi.org/10.1128/JVI.00099-16.

Kim SM, DeFazio JR, Hyoju SK, et al. Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity. Nat Commun. 2020;11(1):2354. https://doi.org/10.1038/s41467-020-15545-w.

Ekmekciu I, von Klitzing E, Neumann C, et al. Fecal microbiota transplantation, commensal Escherichia coli and Lactobacillus johnsonii strains differentially restore intestinal and systemic adaptive immune cell populations following broad-spectrum antibiotic treatment. Front Microbiol. 2017;8:2430. https://doi.org/10.3389/fmicb.2017.02430.

Wardill HR, Secombe KR, Bryant RV, Hazenberg MD, Costello SP. Adjunctive fecal microbiota transplantation in supportive oncology: emerging indications and considerations in immunocompromised patients. EBioMedicine. 2019;44:730–40. https://doi.org/10.1016/j.ebiom.2019.03.070.

Bradley KC, Finsterbusch K, Schnepf D, et al. Microbiota-driven tonic interferon signals in lung stromal cells protect from influenza virus infection. Cell Rep. 2019;28(1):245–56. https://doi.org/10.1016/j.celrep.2019.05.105.

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13. https://doi.org/10.1016/S0140-6736(20)30211-7.

Cheung KS, Hung IFN, Chan PPY, et al. Gastrointestinal manifestations of SARS-CoV-2 infection and virus load in fecal samples from a Hong Kong Cohort: systematic review and meta-analysis. Gastroenterology. 2020. https://doi.org/10.1053/j.gastro.2020.03.065.

Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 Novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020. https://doi.org/10.1001/jama.2020.1585.

Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465–9. https://doi.org/10.1038/s41586-020-2196-x.

Xu Y, Li X, Zhu B, et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med. 2020;26(4):502–5. https://doi.org/10.1038/s41591-020-0817-4.

Qi M, Jun L, Ronghui D, et al. Assessment of patients who tested positive for COVID-19 after recovery. Lancet Infect Dis. 2020. https://doi.org/10.1016/S1473-3099(20)30433-3.

Hanada S, Pirzadeh M, Carver KY, Deng JC. Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. Front Immunol. 2018;9:2640. https://doi.org/10.3389/fimmu.2018.02640.

Yildiz S, Mazel-Sanchez B, Kandasamy M, Manicassamy B, Schmolke M. Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis. Microbiome. 2018;6(1):9. https://doi.org/10.1186/s40168-017-0386-z.

Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831–3. https://doi.org/10.1053/j.gastro.2020.02.055.

Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012;487(7408):477–81. https://doi.org/10.1038/nature11228.

Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124(4):837–48. https://doi.org/10.1016/j.cell.2006.02.017.

Dethlefsen L, McFall-Ngai M, Relman DA. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature. 2007;449(7164):811–8. https://doi.org/10.1038/nature06245.

Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;562(7728):583–8. https://doi.org/10.1038/s41586-018-0617-x.

Mobeen F, Sharma V, Tulika P. Enterotype variations of the healthy human gut microbiome in different geographical regions. Bioinformation. 2018;14(9):560–73. https://doi.org/10.6026/97320630014560.

Feng Y, Duan Y, Xu Z, et al. An examination of data from the American Gut Project reveals that the dominance of the genus Bifidobacterium is associated with the diversity and robustness of the gut microbiota. MicrobiologyOpen. 2019;8(12):e939. https://doi.org/10.1002/mbo3.939.

Ferreira-Halder CV, Faria AVS, Andrade SS. Action and function of Faecalibacterium prausnitzii in health and disease. Best Pract Res Clin Gastroenterol. 2017;31(6):643–8. https://doi.org/10.1016/j.bpg.2017.09.011.

Lopez-Siles M, Duncan SH, Garcia-Gil LJ, Martinez-Medina M. Faecalibacterium prausnitzii: from microbiology to diagnostics and prognostics. The ISME journal. 2017;11(4):841–52. https://doi.org/10.1038/ismej.2016.176.

Mutlu EA, Keshavarzian A, Losurdo J, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog. 2014;10(2):e1003829. https://doi.org/10.1371/journal.ppat.1003829.

Wang F, Nie J, Wang H, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 pneumonia. J Infect Dis. 2020;221(11):1762–9. https://doi.org/10.1093/infdis/jiaa150.

Thông tin
Thông tin xuất bản

Journal of Medical Case Reports

Thông tin tác giả