Have you ever noticed that you feel ‘sick to your stomach’ when you are nervous? Or have you ever had a ‘gut feeling’ about something? Well, a recent study on probiotics has added another potential piece to the gut-brain connection puzzle to help us understand how and why our emotions are so intimately involved with our digestive systems. A team of scientists in Canada looked at the effects of supplementation with Lactobacillus rhamnosus on both the brains and behavior of mice.
As most of you reading this blog probably know, probiotics are good bacteria that are specifically defined as live micro-organisms that, when administered in adequate amounts, confer a beneficial physiological effect on the host. The study in Canada elucidated a previously unknown benefit of these little bacteria. Apparently, supplementation with Lactobacillus rhamnosus significantly increased the number of GABA receptors in certain areas of the brain, reduced the amount of corticosterone produced by the adrenal glands and reduced certain anxiety and stress related behaviors in mice. Since this study was performed on mice, we cannot immediately assume that the results of this study are applicable to a human population but it is certainly a step in the right direction towards a randomized control trial with human subjects in the near future.
The main inhibitory (which can also loosely be described as the main anti-anxiety) neurotransmitter in the brain is GABA (gamma-aminobutyric acid). Anti-anxiety medications such as Xanax and Valium reduce anxiety by enhancing the effects of GABA in the brain. Since the Lactobacillus rhamnosus increased the number of GABA receptors in certain areas of the brain, the overall effect of supplementation was a decrease in anxiety levels. The researchers did not stop once they determined that the probiotics were affecting the number of receptors; they wanted to understand HOW the probiotics were affecting receptor expression. They hypothesized that the probiotics were somehow ‘communicating’ with the brain via the vagus nerve.
The vagus nerve, also known as Cranial Nerve Ten (CN X), is responsible for almost all parasympathetic stimulation in the body. Our autonomic nervous system has two parts that work in tandem – the sympathetic, or ‘fight or flight,’ portion and the parasympathetic, or ‘rest and digest,’ portion. During digestion it is the vagus nerve that slows the heart rate, decreases blood flow to the extremities, increases blood flow to the digestive tract and promotes digestion. To test their hypothesis, the researchers cut the vagus nerve just above the digestive tract in some of the mice. After the subdiaphragmatic vagotomies were performed, they determined that the positive changes that occurred as a result of probiotic supplementation were not seen in the mice without a vagus nerve innervating their digestive tracts. So, it does appear that their hypothesis was correct and the probiotics are somehow using the vagus nerve in the gut as a way to ‘communicate’ with and affect change in the brain. They point out that they do not understand the molecular mechanism by which the probiotics affect the vagus nerve but they hope that future studies will resolve the mystery.
The authors of the study state "it is worth noting that the majority of studies on the microbiome-gut-brain axis are rodent-based", and future validation of the role of this axis in modulation in behavior is now warranted. Nonetheless, our current studies offer the intriguing opportunity of developing unique microbial-based strategies for the adjunctive treatment of stress-related psychiatric disorders.’ At the very least, everyone should be taking a probiotic during and after taking a prescription antibiotic to replenish their highly beneficial population of good bacteria. If you want to increase your intake of probiotics, they can be found in supplements and in fermented foods such as kombucha, yogurt and kimchi. Yum!!
Laura Firetag ND Student Bastyr University
References:
1. Bravo, Javier. "Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA Receptor Expression in a Mouse Via the Vagus Nerve ." Proceedings of the National Academy of Sciences of the United States of America. 108.38 (2011): 16050-55. Print.
Labels: anxiety, axis, gut health, lactobacillus, probiotic
In one of the most exciting studies that I have seen lately, researchers have reported that a novel therapy has resulted in the complete remission of Chronic Lymphocytic Leukemia (CLL) in two patients. CLL is the most common form of leukemia in the Western hemisphere and there are over 10,000 new cases diagnosed annually in the United States. So far three patients have received the novel therapy and the details about one of the patients were reported in the New England Journal of Medicine and discussed in an article in the New York Times.
Our immune systems have several types of cells that work together to keep us healthy. Two of the most important cells are the B cells and the T cells. CLL is a cancer that affects the B cell population. The main purpose of B cells is to produce antibodies to tag infectious agents so that the other cells of the immune system can then recognize and destroy them. T cells, on the other hand, can directly kill pathogens such as tumor cells or cells that have been infected with a virus by recognizing certain proteins on the surface of the pathogenic cells. B cells express a unique protein on their surface that does not exist on any other cell in the human body. The protein on the B cells is known as the CD19 protein. Researchers at the University of Pennsylvania thought that if they were able to ‘teach’ the T cells of CLL patients to recognize the CD19 protein on the cancerous B cells then maybe the T cells would destroy the cancerous cells.
The idea of genetically programming T cells was initially developed by Dr. Zelig Eshhar in Israel in the 1980’s. Dr. Eshhar was able to add new genes to the genome of the T cells and create something called a ‘chimeric antigen receptor’ on the surface of the T cell which could then recognize the desired protein. 30 years later, the current study used this technology to create T cells that recognize the CD19 protein on the cancerous B cells. Surprisingly, the researchers used a disabled form of the Human Immunodeficiency Virus (HIV) to introduce the necessary genes to the T cells since HIV naturally targets T cells.
The patient described in the New England Journal of Medicine was first diagnosed with CLL in 1996 and had several clinical successes using chemotherapy treatments for more than 10 years. By 2010, the patient had no options left and was enrolled in the Phase 1 clinical trial at the University of Pennsylvania. The researchers removed a billion of the patient’s T cells and then ‘educated’ them to attack the CD19 protein using the disabled HIV. Once all of the cells were educated, they were reintroduced into the patient over the course of three days.
Fourteen days after the first infusion, the patient began to experience chills and a low grade fever which eventually exacerbated to a 102.5 oF fever. The patient was diagnosed with tumor lysis syndrome syndrome 22 days after the first infusion. Tumor lysis syndrome occurs when the cancerous cells are being destroyed at a very high rate. The symptoms of tumor lysis syndrome are caused primarily by two events. First, the molecules (known as cytokines) that are released by the T Cells to kill the cancerous cells cause flu-like symptoms. Secondly, the destroyed cancer cells themselves overwhelm the body with metabolic waste products. The kidneys are especially wounded by the excessive amount of waste product. Fortunately the patient was able to survive the tumor lysis syndrome and, ‘on day 23, there was no evidence of CLL in the bone marrow.’ By day 31, a CT scan showed that the patient’s lymph nodes were no longer enlarged.
Overall, the doctors calculated that the HIV-educated T cells killed off TWO POUNDS of cancer cells. The treatment also killed all healthy B cells so now the patient has to receive intravenous immune globulin regularly to supplement for the loss of antibody production, a condition known as hypogammaglobulinemia. Fortunately, hypogammaglobulinemia is manageable clinically and so far the patient has not had any significant symptoms due to his lack of B cells and antibodies.
While it seems as though this treatment could easily be applied to all cancers that is not necessarily the case. This treatment works for CLL because only B cells are involved in CLL and it is possible to survive without B cells. In liver or pancreatic cancer, the cancerous cells usually have most, if not all, of the same surface proteins as healthy cells and therefore if this treatment were to be used for the aforementioned cancers, it is possible that the entire organ could be attacked rather than just the tumor. Unfortunately, it is not possible to live without a liver or a pancreas. Also, sometimes there are proteins that are expressed in multiple areas in the body. If there was a protein on the cancerous pancreatic cells that was not found on healthy pancreatic cells it is possible that the protein might be expressed elsewhere in the body. It might be expressed in healthy colon cells or healthy heart cells. In this situation, the T cells educated to recognize the protein would attack the cancerous pancreatic cells and the healthy cells of the colon or the heart. There are many other possible dangers to consider as well when applying this treatment to other cancers.
It is also important to remember that this novel therapy has only been used in three patients so far. Two patients experienced a complete remission while one experienced a partial remission and then passed away.
According to Dr. June, the next step is to administer this treatment to a larger set of patients with randomization to determine if the treatment is as effective as it appears to be. I know I will be eagerly awaiting the results.
References:
1) 1. Porter, David et al. "Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia." New England Journal of Medicine. 365.8 (2011): 725-33. Print.
2) 2. Grady, Denise. "An Immune System Trained to Kill Cancer." New York Times 12 09 2011. .
3) 3. Ferri, Fred. 2011 Ferri's Clinical Advisor. Philadelphia, PA: Mosby, Inc., 2011. 621. Print.
Labels: cancer prevention, t cells
The basic ingredients for this recipe are:
1-1.5 lbs. of fresh organic carrots (washed, unpeeled, and sliced)
2-3 tablespoons of organic butter, ghee, olive oil, or coconut oil
(your choice!)
1-1.5 teaspoons of fresh organic ginger (grated or minced)
The instructions for this recipe are:
- In a saucepan, warm the butter or ghee. Then add in the carrots and ginger. And gently sauté under medium heat for 3-5 minutes while stirring.
- This next step is optional, but allows for variety and creativity. If you’d like you may add in other spices such as cumin, cloves, cinnamon, cardamom, nutmeg, orange rind, cayenne, turmeric, black pepper, sea salt, curry, wine, and even coconut rinds.
- Then cover and allow to simmer for 5-10 minutes under low heat.
Happy October!
Cindy Azevedo, ND Student, University of Bridgeport
Labels: carrots, ginger, heart health, recipes
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