Develop mini review on :

The use of human microbiota as potential candidates for therapeutic use in viral infections. Your review
should cover these elements and not more than 2000 words. 

 Introduction on microbiome and human immune system

 Types of viruses and viral-related infectious diseases
 Components of innate and adaptive immunity
 Mechanism on how microbiota shape the immune system
 Factors contribute to microbiota colonization
 FDA-approved microbiome or related metabolites as therapy
 Conclusion of your OWN idea on how you may contribute to policymakers to incorporate your
review to the betterment of current infectious disease management in Malaysia.

Answer :

The human microbiota which refers to the microorganisms living in and on the human body has
been suggested as a potential candidate for therapeutic use in viral infections. Every human has an entirely
unique microbiota network that was originally determined by one’s DNA which includes bacteria, viruses,
fungi, and parasites. (Simon et al., 2019). During delivery in the birth canal, it is the first exposure to
microbes in an infant along through the mother's breast milk. Thereafter, environmental exposures and
diets might modify one's microbiome to either be healthy or harmful in developing diseases in the future.
(Ursell et al., 2012). Marchesi and Ravel (2015) found that microbiome refers to the entire habitat and
surrounding environmental conditions of a given microbiota and their collective genomes which can be
found in the gut, skin, and respiratory tract. It is said to have a crucial role in maintaining human health and
in shaping the human immune system which defenses against harmful pathogens or vice versa.

Nowadays, viral infections are a significant threat either to health or the economy throughout the
world which range from mild to severe and in the short term or long term. Some of these infections may
also cause mortality. A viral infection or the viral life cycle is started by the interaction between the viral
capsid and the host cell-specific receptors. After entering the target cell, the viral nucleic acid sequence
amplification, and viral particles are generated and then exit from the cell. (Bron P.A. et al., 2017). Some
viruses incorporate the viral genome in the host cell genome and persistently infect the host during the
process cycle. For example, Human Immunodeficiency Virus (HIV) and Hepatitis viruses. Meanwhile, most
viruses are rapidly eliminated from the host and remain only in transient infection.

The most common viral infections are Upper Respiratory Infections that spread from person to
person in contact with infected droplets. Examples are adenovirus, influenza viruses, and severe acute
respiratory syndrome coronavirus-2 (SARS-CoV-2) which may cause high-grade fever, cough, nasal
congestion, and sore throat. Secondly, Gastrointestinal infections which are transmitted by the oral-fecal
route cause gastroenteritis with vomiting and diarrhea. Examples are Rotavirus, Norovirus, and
Enteroviruses. Thirdly, Hepatic infection or liver inflammation which caused by Hepatitis A, B, C, D, and E
viruses in which each virus causes a specific type of hepatitis. These viruses are transmitted via infected
body secretions or blood (Hepatitis B, C, and D) and oral-fecal route (Hepatitis A, and E). Next, spinal cord
infection disease due to poliovirus, cervix cancer due to human papillomavirus (HPV), Acquired
Immunodeficiency Syndrome (AIDS) due to Human Immunodeficiency Virus (HIV), and Neurologic
infections such as Encephalitis due to arboviruses which transmitted from mosquitoes. (Laura D Kramer,
2021).

The human immune system comprises innate and adaptive immunity which both works together to
combat pathogens and to protect from infections. Innate immunity is a nonspecific multi-layered set of
reactions with an immediate defense mechanism against pathogens. (Medzhitov, 2007). The epithelial cells
in mucosal surfaces and phagocytic cells mediated the innate immune response which detects the
presence of pathogens through pattern recognition receptors (PRRs). (Holt and Strickland, 2008). Thus,
results in cellular defense mechanism activation in which production of secreted pro-inflammatory
cytokines, immune cells recruitment to the infection site, and anti-microbicidal mechanism activation such
as antimicrobial peptides production known as defensins. Hence, toll-like receptor (TLR) and non toll-like
receptor pattern recognition receptors combination will be triggered during the infection. (Lee and Kim,
2007). Adaptive immunity is a slower or delayed but highly pathogen-specific defense mechanism involving
the specific immune cells activation known as T-cells. The activation of adaptive immunity causes the
antibody production known as B-cells in which the infected host cells are killed by cytotoxic T-cells (CD8)
with helper T-cell (CD4) mediated actions. (Erf, 2004). As a result, memory B-cells and memory T-cells are
produced which provide long-term specific protection against pathogens with the same antigens infections.

The microbiota plays an important role in shaping the immune system by regulating the
development and immune cell function. Besides, it also helps to regulate the immune response and helps
to protect against pathogens by competing with them for space and nutrients. For instance, certain gut
bacteria stimulate the regulatory T-cells production which modulates the immune response in order to
prevent excessive inflammation. Moreover, gut bacteria also can modulate the function of the dendritic cells
which initiate adaptive immunity. The mechanism by which the microbiota shapes the immune system is
complex and not fully understood. However, several mechanisms have been proposed which are the
maturation of immune cells, the production of antibodies, regulation of inflammation in which the
microbiome can influence the balance of pro-inflammatory and anti-inflammatory cytokines that play an
important role in the immune response to pathogens, tolerance induction in which the microbiome help to
establish immune tolerance to harmless antigens and prevent the development of autoimmune diseases,
and metabolite production in which the gut microbiome is also capable of producing molecules like short-
chain fatty acids that are important for the maintenance of the intestinal epithelial barrier and have an effect
on immune cells as well.

The colonisation and composition of the microbiota are dynamic and can be affected by both
internal and external factors which can work together to shape the human microbiome. There are several
factors that contribute to the colonisation of the microbiota in the human body including genetics which
makes up an individual and can influence the composition and diversity of their microbiota, mode of
delivery such as birth via vaginal vs. cesarean section that can affect the initial colonisation of the
microbiota in infants, diet which can greatly influence the composition and diversity of the microbiota
because a high fiber diet and fermented foods can promote the growth of beneficial bacteria, while a diet
high in processed and sugary foods can lead to an imbalance in the microbiota, antibiotic use which can
disrupt the balance of the microbiota leading to overgrowth of harmful bacteria and reducing the diversity of
the microbiome, age in which the composition and diversity of the microbiota can change throughout an
individual's lifespan with the elderly having a different microbial profile than young adults. Besides, lifestyle
factors such as stress, smoking, alcohol consumption and lack of physical activity can also affect the
microbiota. Other than that, geography or environmental factors such as climate, water source and
sanitation can also play a role in shaping the microbiota. Other factors such as skin pH, hormonal changes,
and exposure to pollutants can also affect the colonisation of the microbiota.

The use of microbiome-derived therapies is a promising area of research. Currently, there are
several FDA-approved therapies that target the microbiome including VSL#3 probiotics and fecal
microbiota transplantation (FMT). VSL#3 probiotics contain eight different strains of live bacterias that when
ingested in sufficient amounts can provide health benefits for ulcerative colitis and Irritable Bowel
Syndrome (IBS) management. FMT is a procedure in which fecal material from a healthy individual is
transplanted into the gut of a patient with a gut disorder. Besides, Synthetic human secretin in which a
naturally-occurring hormone that is produced by the small intestine in response to food as a diagnostic aid
for pancreas function. Metronidazole gel is an antibiotic gel that is used to treat bacterial vaginosis as a
topical treatment for this condition. Next is Rifaximin which is an antibiotic for the traveler's diarrhea
treatment caused by E. coli and for hepatic encephalopathy management.

In a nut shell, the human microbiome plays a crucial role in maintaining human health and in
shaping the immune system which has the potential to be used as a therapeutic tool in the management of
viral infections. However, further research is needed to fully understand the mechanisms by which the
microbiome shapes the immune system and to develop effective therapies. To contribute to policymakers in
Malaysia, I would suggest further funding for research in this area and incorporating microbiome-based
therapies into the current infectious disease management guidelines. The use of microbiome-based
therapies for the treatment of viral infections is an area of active research and there are a number of
therapies that are in development or being tested in clinical trials. I would also recommend educating the
public on the importance of maintaining a healthy microbiome as it is important to consider the impact of
environmental and lifestyle factors on the microbiome.

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words
References :

- Ashton Harper, Vineetha Vijayakumar, Arthur C. Ouwehand, Jessica ter Haar, David Obis, Jordi

Espadaler, Sylvie Binda, Shrilakshmi Desiraju and Richard Day. (12 February 2021). Viral
Infections, the Microbiome, and Probiotics. Front. Cell. Infect. Microbiol.,Sec. Microbiome in Health
and Disease.
https://doi.org/10.3389/fcimb.2020.596166
- Gebrayel, P., Nicco, C., Al Khodor, S. et al. (2020). Microbiota medicine: towards clinical
revolution. J Transl Med 20, 111.
https://doi.org/10.1186/s12967-022-03296-9
- Grace A. Ogunrinola, John O. Oyewale, Oyewumi O. Oshamika, Grace I. Olasehinde. (2020). The
Human Microbiome and Its Impacts on Health, International Journal of Microbiology, Article ID
8045646, 7 pages, 2020.

https://doi.org/10.1155/2020/8045646

- Hou, K., Wu, ZX., Chen, XY. et al. (2022). Microbiota in health and diseases. Sig Transduct Target
Ther 7, 135 (2022).
https://doi.org/10.1038/s41392-022-00974-4
- Laura D Kramer. (Jun, 2021). Types of Viral Disorders. MSD Manuals.
https://www.msdmanuals.com/professional/infectious-diseases/viruses/types-of-viral-
disorders#top
- Michael H. Kogut, Annah Lee, Elizabeth Santin. (2020). Microbiome and pathogen interaction with
the immune system,Poultry Science,Volume 99, Issue 4,Pages 1906-1913,ISSN 0032-579.
https://doi.org/10.1016/j.psj.2019.12.011
- Yuan, L., Hensley, C., Mahsoub, H. M., Ramesh, A. K., & Zhou, P. (2020). Microbiota in viral
infection and disease in humans and farm animals. Progress in molecular biology and translational
science, 171, 15–60.
https://doi.org/10.1016/bs.pmbts.2020.04.005