|Year : 2022 | Volume
| Issue : 2 | Page : 73-74
Neutrophil–Lymphocyte Ratio and Dysbiosis: New Paradigm of Immunonutrition
Vera Irawany1, Marilaeta Cindryani2
1 Department of Anesthesiology and Intensive Care, Rumah Sakit Fatmawati, Jakarta, Indonesia
2 Department of Anesthesiology and Intensive Care, Universitas Indonesia, Rumah Sakit Cipto Mangunkusumo, Jakarta, Indonesia
|Date of Submission||02-Feb-2022|
|Date of Decision||23-Mar-2022|
|Date of Acceptance||28-Mar-2022|
|Date of Web Publication||09-May-2022|
Department of Anesthesiology and Intensive Care, Universitas Indonesia, Rumah Sakit Cipto Mangunkusumo, Jakarta
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Irawany V, Cindryani M. Neutrophil–Lymphocyte Ratio and Dysbiosis: New Paradigm of Immunonutrition. Bali J Anaesthesiol 2022;6:73-4
Our gastrointestinal tract is the “home” for 70% of immune cells where the process of development and maturation of these cells is influenced by the interaction of immune cells with the gut microbiota. The composition of gut microbiota can undergo changes known as dysbiosis, a decreased number of specific bacteria contributing to changes in gastrointestinal tract biodiversity that maintains physiological homeostasis of the digestive and immune system. Therefore, in dysbiosis, the development of immune cells is disrupted, and a clinically “maladaptive” immune response occurs., This response could be found in ischemic stroke in which there was an increase in T lymphocytes, which produced interleukin (IL)-17, thereby increasing injury to ischemic brain tissue. However, the activation of regulatory T cells (Treg) by producing IL-10 will suppress the production of IL-17, which aims to protect the brain from ischemia-reperfusion injury.
Neutrophil–lymphocyte ratio (NLR) is a simple inexpensive biomarker of inflammation that is often used by clinicians in daily practice. It is believed to describe the balance of innate immunity and adaptive immunity responses in infectious and inflammatory processes. The increase in neutrophils in the early phase of inflammation will be followed by a decrease in the number of lymphocytes, where sometimes accompanied by a decrease in the expression of human leukocyte antigen (HLA-DR) monocytes that causes the release of anti-inflammatory cytokines. This condition is found in sepsis as well as acute ischemic stroke or acute myocardial infarction., It is now known that the immune response and systemic inflammatory reactions are related to the levels of neutrophils and lymphocytes. Although the neutrophil and lymphocyte activity is related to gut microbiota activity, NLR is a potential to be used as a marker of dysbiosis in hospitalized patients.,
The initial phase of the inflammatory reaction occurs during the invasion of pathogens, which will activate the immune response. Innate immunity cells namely macrophages, monocytes, natural killer cells, dendritic cells, and endothelial cells will directly respond by recognizing germs through pathogen-associated molecular pattern receptors. Each microorganism has its own identity such as lipopolysaccharide for gram-negative bacteria, peptidoglycan for gram-positive bacteria, lipoteichoic acid (the component of the cell wall of gram-positive bacteria), lipopeptide (the component of many pathogenic bacteria), flagellin (the factor that makes bacteria move), and bacterial DNA. In addition, tissue damage can also activate the immune response through damage-associated molecular patterns such as burns, trauma, and necrotic tissue, which can be recognized by immune cells with similar receptors. These receptors, known as pattern recognition receptors, play as a center for recognizing danger signals in the natural immune system.,
Immunological studies have shown that microbiota are a key in T-lymphocyte cell homeostasis. Changes in microbiota diversity that occur as a direct inflammatory process of injured brain tissue have an impact on decreased T-lymphocyte cell response. The activation of regulatory T lymphocytes (Treg) cells would release anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β aimed to prevent the massive migration of inflammatory cells to the brain because of damaged blood–brain barrier. However, this condition causes the body to not respond to bacterial invasion, which resulted in sepsis.
Singh et al. found that the degree of dysbiosis is directly proportional to the level of brain tissue damage and an increase in bacterial abundance, which ultimately affects stroke outcome. It is also known that the activity of neutrophils and lymphocytes is influenced by the activity of microbiota. Acute stroke patients experiencing severe inflammation due to severe brain injury will exacerbate the dysbiosis that has occurred. The increase in the number of bacteria in the gastrointestinal tract, followed by a decrease in mucosal defenses due to dysbiosis, will increase the risk of translocation. Subsequent dysbiosis in severe acute stroke is likely to cause translocation, which will become the source of infection in organs with dysregulated immune response. This is supported by a research by Deshmukh et al., who found that the incidence of sepsis was associated with changes in composition and physiological function of microbiota. Enteric dysbiosis can trigger inflammation and injury in other organs during sepsis., Thus, it can be concluded that microbiota dysbiosis is an intermediary for sepsis in critically ill acute stroke, with causal microorganism possibilities are from the microbiota population.
The interrelated and multifaceted complexities of dysbiosis and inflammation represented by the NLR will greatly encourage critically ill experts to explore the potential advanced management in immunonutrition. It turns out that not only therapeutical drugs, but also the synergy between nutrition and pathophysiology of diseases based on a strong knowledge of immunology can provide hope for innovations in future critical care.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fay KT, Ford ML, Coopersmith CM. The intestinal microenvironment in sepsis. Biochim Biophys Acta Mol Basis Dis 2017;1863:2574-83.
Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science 2012;336:1268-73.
Hu Y, Zheng Y, Wu Y, Ni B, Shi S. Imbalance between IL-17A-producing cells and regulatory T cells during ischemic stroke. Mediators Inflamm 2014;2014:813045.
Winkler MS, Rissiek A, Priefler M, Schwedhelm E, Robbe L, Bauer A, et al
. Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNFα response: A diagnostic tool for immunosuppression? Plos One 2017;12:e0182427.
Haeusler KG, Schmidt WU, Foehring F, Meisel C, Guenther C, Brunecker P, et al
. Immune responses after acute ischemic stroke or myocardial infarction. Int J Cardiol 2012;155:372-7.
Kruger P, Saffarzadeh M, Weber AN, Rieber N, Radsak M, von Bernuth H, et al
. Neutrophils: Between host defence, immune modulation, and tissue injury. Plos Pathog 2015;11:e1004651.
Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012;486:207-14.
Singh V, Roth S, Llovera G, Sadler R, Garzetti D, Stecher B, et al
. Microbiota dysbiosis controls the neuroinflammatory response after stroke. J Neurosci 2016;36:7428-40.
Deshmukh HS, Liu Y, Menkiti OR, Mei J, Dai N, O’Leary CE, et al
. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nat Med 2014;20:524-30.
Lobo LA, Benjamim CF, Oliveira AC. The interplay between microbiota and inflammation: Lessons from peritonitis and sepsis. Clin Transl Immunology 2016;5:e90.