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Gut microbial metabolites such as short-chain fatty acids rule our immune system and might have therapeutic roles in the Corona Virus Diseases. Production of these metabolites particularly butyrate is indispensable for its hostility against viral diseases. This viral disease, predominantly initiated from the Wuhan city, China in the year 2019 has its mechanism in the host cells that embrace the binding of the spike protein with the angiotensin converting enzyme-2 (ACE2) receptors of the hosts via damaging the alveolar epithelial type 2 cells leading to inflammations and butyrate and its derivatives play a significant role in suppressing these factors, thereby act as a potential therapeutic target.
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Current Trends in Pharmaceutical Research 2020 Vol 7 Issue 1
© Dibrugarh University www.dibru.ac.in/ctpr ISSN: 2319-4820 (Print)
2582-
4783 (Online)
*E-mail: priyanka.sarkar14@gmail.com
Opinion Paper
CAN MICROBIAL SCFA, BUTYRATE BE THE ALTERNATE
SAVIOR AGAINST COVID-19?
Priyanka Sarkar1*, Sudarshana Borah2, H. K. Sharma2
1Wellcome-DBT (Indian Alliance) Lab, Institute of Translational Research, Asian
Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad-500032, India
2Department of Pharmaceutical Sciences, Faculty of Science and Engineering,
Dibrugarh University, Dibrugarh-786004, India
Abstract
Gut microbial metabolites such as short-chain fatty acids rule our immune system
and might have therapeutic roles in the Corona Virus Diseases. Production of these
metabolites particularly butyrate is indispensable for its hostility against viral
diseases. This viral disease, predominantly initiated from the Wuhan city, China in
the year 2019 has its mechanism in the host cells that embrace the binding of the
spike protein with the angiotensin converting enzyme-2 (ACE2) receptors of the
hosts via damaging the alveolar epithelial type 2 cells leading to inflammations and
butyrate and its derivatives play a significant role in suppressing these factors,
thereby act as a potential therapeutic target.
Keywords: Gut microbiome; metabolite; anti-inflammatory; SCFA
Short Chain Fatty Acids (SCFAs) including butyrate, propionate, and acetate are
produced by the gut microbes, which help in the regulation of the host immune
system. Recently, orally administered SCFAs showed promising anti-inflammatory
effects [1]. SCFAs may also act as potential therapeutics in Corona Virus Disease,
2019 (COVID19) management. The COVID19, which was primarily originated
from the Wuhan city, China in the year 2019 and drastically spread around the
world with more than 5,000,599 positive cases and 325,156 mortality as on date [2].
The common symptoms include fever, dry cough, and difficulty to breath in most
Microbial metabolites as immunotherapies against viral diseases
12
cases and headache, muscle pain, diarrhea, loss of smell and taste in a few [3, 4].
The entry mechanism of the virus in the host cells includes the binding of the spike
protein with the angiotensin converting enzyme -2 (ACE2) receptors of the hosts
followed by damaging the alveolar epithelial type 2 cells causing inflammation of
the epithelial linings of the lungs [4]. The patients suffering from the disease have
further been observed to have reduced CD8T and CD4 T- cell population, which is
important to maintain the host immunity [4]. Also the dysregulation of IFN-γ has
been reported in the cases [4]. SCFAs especially butyrate may be considered as
therapeutic agents in this context. Several studies have suggested the potential role
of SCFAs in the maintenance of the functions of CD4-T cells and antigen
presenting cells [5]. Luu et al., in 2018, have shown the potential impact of butyrate
and propionate (to a lesser amount) in direct modulation of the CD8+ cytotoxic T
lymphocytes (CTLs) and Tc17 cells gene expressions. Moreover, the authors also
reported the significant effect of butyrate in elevation of the CTLs mediated
expressions of IFN-γ and granzyme B and molecular switch of Tc17 cells towards
the CTL phenotype as well, engaging the specific SCFA-receptors e.g. GPR41 and
GPR43. Butyrate has also been found to inhibit histone-deacetylases in CD8-T cells
affecting its gene expression, which might have significant implications in the
adoptive antiviral immunity of the host [6]. COVID19 has also been found to
damage the alveolar epithelial cells followed by inflammation [4]. Studies have
shown the effect of SCFAs especially butyrate and propionate in controlling the
inflammation by inducing FOXP3 [7]. Also, these are found to promote regulatory
T cells and suppression of Th2 responses. Additionally, butyrate treatment also
observed to attenuate lung inflammation and mucus production in the mice model
[7].
Sarkar et al.
13
Fig. 1: Prospective protective mechanism of butyrate and its derivatives.
Moreover, the derivative of butyrate viz.; sodium butyrate has also been found to
play a major role in suppressing the angiotensin-II expression [8]. These findings
provide possible therapeutic strategies for 2019-nCoV by using the butyrate,
although detailed research is needed before concluding about the drug target (Fig.
1). Additionally, a suitable dosage regimen should be designed within the
therapeutic window for human use, along with a suitable drug delivery system.
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How to cite this article:
Sarkar P, Borah S, Sharma HK. Can microbial SCFA, Butyrate be the alternate Savior
against COVID-19?, Curr. Trends Pharm. Res., 2020, 7 (1): 11-14.
... По мнению ведущих мировых специалистов, хотя текущие рекомендации по применению пробиотиков при COVID-19 и основаны на косвенных доказательствах, пробиотики и бактериальные метаболиты (бутират, пропионат) могут рассматриваться как эффективное адъювантное терапевтическое средство у пациентов с коронавирусной инфекцией [204,205,206,214]. ...
... Пробиотики на основе хорошо изученных и безопасных штаммов Lactobacillus spp. и Bifi dumbacterium spp., оказывающих противовоспалительные и иммуномодулирующие эффекты, могут быть использованы для поддержания баланса кишечной микробиоты, снижения частоты и тяжести вирусных инфекций дыхательных путей, предотвращения вторичной бактериальной инфекции у пациентов с COVID-19 [204,205,206]. ...
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Smell and taste dysfunction in patients with COVID-19
  • M S Xydakis
  • P D Mobaraki
  • E H Holbrook
  • U W Geisthoff
  • C Bauer
  • C Hautefort
  • P Herman
  • G T Manley
  • D M Lyon
  • C Hopkins
Xydakis MS, Mobaraki PD, Holbrook EH, Geisthoff UW, Bauer C, Hautefort C, Herman P, Manley GT, Lyon DM, Hopkins C. Smell and taste dysfunction in patients with COVID-19. Lancet Infect. Dis. 2020; doi: https://doi.org/10.1016/S1473-3099(20)30293
Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate
  • M Luu
  • K Weigand
  • F Wedi
  • C Breidenbend
  • H Leister
  • S Pautz
  • T Adikary
  • A Sekruna
Luu M, Weigand K, Wedi F, Breidenbend C, Leister H, Pautz S, Adikary T, Sekruna A. Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate. Sci. Rep. 2018; 8(1):1-0.
Butyrate attenuates lung inflammation by negatively modulating Th9 cells
  • Vieira Rds
  • A Castoldi
  • P J Basso
  • M I Hiyane
  • Nos Camara
  • R R Almeida
Vieira RdS, Castoldi A, Basso PJ, Hiyane MI, Camara NOS, Almeida RR. Butyrate attenuates lung inflammation by negatively modulating Th9 cells. Front. Immunol. 2019; 10: 1-14.