"In light of the growing evidence that gut bacteria affect brain function and its diseases, we decided to examine whether they play a role in ALS," adds Prof. Eran Segal
Intestinal bacteria. "The effect of these bacteria on the brain is a new and fascinating research front"
ALS is a rare and incurable muscular dystrophy that damages the motor neurons, causing paralysis that gradually spreads to all parts of the body. From a new study in mice conducted by Weizmann Institute of Science scientists, it appears that intestinal bacteria found in our bodies may influence the development of this serious disease. As reported today in the scientific journal Nature, disease symptoms slowed after mice genetically engineered to develop an ALS-like disease were given certain strains of gut bacteria or substances secreted by these bacteria. Also, preliminary research results indicate that the findings may also be valid for people with ALS.
"Our long-term research goal is to reveal the effect of intestinal bacteria on the human body - in healthy and sick states. The effect of these bacteria on the brain is a new and fascinating research front for us," says Prof. Eran Alinev, whose group in the Department of Immunology led the research together with the group of Prof. Eran Segal from the Department of Computer Science and Applied Mathematics. "In light of the growing evidence that gut bacteria affect brain function and its diseases, we decided to examine whether they play a role in ALS," adds Prof. Segal. The post-doctoral researchers Dr. Eran Belsher and Dr. Stavros Besheards and the staff scientist Dr. Hagit Shapiro, all three from Prof. Alinev's lab, led this research, in collaboration with Dr. Dafna Rothschild, a post-doctoral researcher in Prof. Segal's lab , Dr. Mark Gutkin, director of the ALS clinic at the Hadassah Medical Center in Jerusalem, and other researchers at the Weizmann Institute of Science and beyond.
First, the scientists showed in a series of experiments that there was a worsening of the symptoms of an ALS-like disease in transgenic mice, after they received antibiotics that destroyed a significant portion of their intestinal bacteria. The scientists discovered that raising these mice in sterile conditions, without intestinal bacteria at all, is an extremely difficult task, since in their absence - their survival rates were extremely low. These findings indicated the possibility of a connection between changes in the intestinal bacteria and the acceleration of the development of ALS in mice genetically engineered to develop this disease.
The scientists isolated the strains of bacteria they found and gave them to mice prone to ALS as a kind of 'probiotic food supplement'. Some of the strains affected the disease negatively, but one strain slowed down the course of the disease and extended the lives of the mice."
Using advanced computational methods, the scientists characterized the composition of the intestinal bacteria and their mode of activity in mice with ALS and compared them to those of normal mice. They identified 11 altered bacterial strains in ALS-prone mice when their disease worsened or even before they developed distinct symptoms of the disease. The scientists isolated these strains and gave them - each strain individually - to mice with a tendency to ALS, as a kind of "probiotic food supplement", after they had been treated with antibiotics. Some strains adversely affected the disease, but one strain, Akkermansia muciniphila, slowed the course of the disease and extended the lives of the mice.
To reveal the mechanism by which this strain of bacteria affected the disease, the scientists examined thousands of small molecules secreted by the intestinal bacteria. Of all of them, they chose to focus on a molecule called nicotinamide or NAM for short: the levels of this molecule in the blood and cerebrospinal fluid of the mice with a tendency to ALS decreased after the antibiotic treatment, but increased after the mice received the Akkermansia bacteria, which secreted large amounts of the molecule. In order to confirm that NAM may indeed slow the development of the disease, the scientists continuously injected it into mice with a tendency to ALS. The condition of these mice improved significantly. Examining gene expression in the brains of these mice showed that NAM probably improved the activity of their motor neurons.
To check whether the findings in mice may also be relevant to humans, the scientists tested the gut bacteria and the levels of various substances in the blood of 37 people with ALS, and compared the results with those of their family members living with them under the same roof. Genomic analysis indicated that the composition of gut bacteria and their activity were different in ALS patients compared to healthy individuals. Furthermore, the activity of many genes involved in the production of NAM in bacteria was particularly low in ALS patients. The examination of the substances in the blood also indicated a unique and different pattern in ALS patients with a significant difference in the levels of intermediate molecules involved in the formation of NAM in these patients compared to healthy people. Finally, when the scientists tested the levels of NAM in 60 ALS patients, it became clear that these levels were low compared to healthy people - both in the blood and in the cerebrospinal fluid - and a correlation was found between the decrease in NAM levels and muscle weakness in these patients.
"These findings are only an initial step towards understanding how gut bacteria may affect ALS," says Prof. Alinev. "But in the future, it may be possible to develop new treatment methods for the disease that rely on changes in the intestinal bacteria."
Uriah Mor, Dr. Meli Dori-Bachsh, Dr. Christian Kleimeier, Claudia Morasi, Yotam Harnik, Maya Tzur, Rotam Ben Zeev, Dr. Denis Koiatkowski, Dr. Niv Zamora, Yotam Cohen and Dr. Nira participated in the study. Amar from the Department of Immunology; Noam Bar and Yitzhak Levy from the Department of Molecular Biology of the Cell and the Department of Computer Science and Applied Mathematics; Prof. Michal Schwartz from the Department of Neurobiology; Tebi Melman and Dr. Alexander Brandis from the Department of Life Sciences Research Infrastructures; Dr. Inbal Biton, Dr. Yael Kuperman, Dr. Michael Tzuri and Prof. Alon Hermlin from the Department of Veterinary Resources; Michal Sabri from the Department of Neurology, Hadassah Medical Center; Linor Elfahal and Prof. Adrian Israelson from the Department of Physiology and Cell Biology, Ben-Gurion University of the Negev; and Dr. Lisa Erika, Dr. Melin Johansson and Prof. Gunnar Hansson from the University of Gothenburg in Sweden.
About 6,000 people are diagnosed with ALS every year in the United States, most of them over the age of 40. The incidence of the disease among men is 20% higher than among women.
3 תגובות
In my opinion, the state of the immune system in ALS patients should be examined, in light of the studies that show its involvement in maintaining the normality of the nervous system.
There is a chance that patients without a genetic background suffered from a weak immune system, as well as short sleep times (sleep is essential for self-repair of nerves).
It is possible to significantly increase the bacteria Akkermansia in the intestines (x100):
1. Food or supplement containing FOS: garlic, onion, banana.
2. Normal intestinal bacteria supplement.
3. Reducing fat in food.
4. Reducing preservatives in food.
There is an Israeli researcher (in Canada) who found a connection between intestinal bacteria and fibromyalgia. These connections are interesting and what is the cause and what is the result. In the case here they seem to be aiming to show that the cause is the bacteria and the result is the outbreak of the disease.