inflammatory response

Have you ever wondered what “gut health” really means? What keeps your gut microbiome functioning properly, maintaining homeostasis, and preventing inflammation? Originating from oxygen, reactive oxygen species (ROS) that are highly reactive function as central indicators of cellular flaws and issues in the body, such as inflammation. Nai-Yun Hsu of Mount Sinai has stated that “Reactive oxygen species released by stem cells are critical in maintaining a heathy gut via maintaining proper balance of intestine barrier cell types.”

A team of researchers from the Ichan School of Medicine at Mount Sinai have gone in depth about the importance of these oxygen species for stem cell function, avoiding inflammation, and repairing wounds in a recent study. Using mice as models, the researchers were also able to conclude that microfold cells, called “m cells” regulate an organism’s gut immune response, and emerged from a loss of ROS in mice and humans.

The experiment was conducted in vino and in vitro conditions with the mice cells, and ex vivo conditions with human intestinal biopsies post-colonoscopy. Both the human intestinal biopsies and mouse cells were utilized to determine the amount of ROS in the body to support a finding. In addition to determining the amount of the oxygen species, the biopsies and mice were used to analyze the “gene expression profile” of barrier cells in intestines of mice and humans that are diagnosed with a “subtype of IBD known as ulcerative colitis.”

A decrease in these oxygen species can lead to TNF’s emergence in the body, which is a substance that attempts to maintain homeostasis in the body and avoid inflammatory diseases, like IBD and ulcerative colitis. They have concluded that losing species like NOX1, a protein that creates these species, is directly linked with inflammatory diseases like Inflammatory Bowel Disease (IBD). Judy H. Cho, MD, has stated that the study is a breakthrough “in defining the key role of oxygen species in maintaining a healthy epithelial barrier for IBD.” These reactive oxygen species are relevant to AP Bio considering the information we have learned about general biological systems and cells, which function to maintain homeostasis in the body. The mitochondria, which is an organelle of the cell covered in AP Bio, receives signals from gut bacteria that reveals inflammation. While the mitochondria is typically known as the site of cell respiration and performing reactions, new evidence has shown a relationship between the gut microbiota and mitochondria to trigger immune responses and activate barrier cell function. These processes relate to changes to the mitochondria that occur from gut-related issues in IBD patients, meaning that there is a connection to ROS.

Gut Microbiota

As a conclusion to proving the direct link between the highly reactive oxygen species and treating inflammation, these researchers encourage and plan to conduct further study on this topic, but for using “oxygen species-stem cell modulation therapy” to potentially treat IBD patients.

Ever since the initial outbreak of COVID-19, scientists have worked tirelessly to innovate and find the antidote to the virus which has infected millions and tragically killed hundreds of thousands. Such unprecedented times have led researchers to reconsider everything they already know and take intellectual risks.

An up-close visualization of the COVID-19 virus and its infamous spike proteins.

One innovator whose experimental hypothesis may save many is Angela Reiersen, a child psychiatrist from Washington University School of Medicine in St. Louis. When she fell ill with COVID-19 in March 2020, Reiersen thought back to a study she had read about the effects of the lack of the sigma-1 receptor in mice and how the lack of this receptor protein led to massive inflammation and overproduction of cytokines. Cytokines are a part of the inflammatory response that occurs when pathogens sneak past the barrier defenses of the innate immune system and permeate cells. Upon entry of a pathogen, mast cells secrete histamines and macrophages secrete these cytokines. These cytokines attract neutrophils which then digest and kill the pathogens and other cell debris. Although cytokines are crucial to a functioning immune system, overproduction of cytokines can be extremely dangerous as it can lead to septic shock, in which the immune system becomes extremely overactive. This has become the cause of death for many COVID-19 patients.

As a psychiatrist, Reiersen worked regularly with SSRIS, or selective serotonin uptake inhibitors, in the treatment of conditions like depression and obsessive compulsive disorder. SSRIs help the human brain by increasing the level of serotonin available between nerve cells, but they also activate the S1R in the Endoplasmic Reticulum. Reiersen wondered, if the lack of the S1R causes fatal levels of inflammation, can we prevent extreme inflammation from COVID-19 through the use of SSRIs?

Scientists have turned to repurposing existing drugs, like the antidepressant fluvoxamine, to prevent COVID-19 related complications.

There have been multiple studies performed to test this line of reasoning, both including and independent of Reiersen. The most notable study was performed as part of TOGETHER, an international organization seeking to test possible unorthodox treatments for COVID-19. The trial was a collaboration between researchers from McMaster University of Canada and Cardresearch, a research clinic located in Brazil. The team in Brazil located 1,497 unvaccinated adults who were deemed “high risk” for COVID complications in their first week of showing symptoms of COVID. Conducted at 11 different research sites in Brazil from January to August, the study provided participants with a 10 days supply of either 100 milligrams of fluvoxamine, an SSRI, or a placebo pill. The researchers monitored the participants for 28 days after, as well.

In the end, 15.7% of participants who were given a placebo pill ended up having major complications from COVID-19, compared to 10.1% of participants who were given fluvoxamine. The gap may seem slight, but this is because not all patients took their full dosage due to gastrointestinal complaints. However, out of patients who completed their course of medication, 66% were safe from any complications and the mortality rate was cut by 91%!

Thanks to the research of Reiersen and many others, fluvoxamine is now considered a solid treatment plan for COVID-19 infections, especially in high risk individuals. As COVID-19 continues to infect millions around the world, who knows what new scientific breakthroughs will be made?

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: inflammatory response

Can Reactive Oxygen Species Maintain Stem Cell Function and Prevent Inflammation?

How Mice and Mental Health Led to This COVID-19 Treatment Breakthrough

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