Bacteriophages: Viruses in Bacteria and the Gut Microbiome
Bacteriophages and the Gut Microbiome
Bacteriophages (or phages) are viruses that infect bacteria, including the ones that live in our gut. Phages don't infect our cells, but by affecting our gut bacteria they may indirectly affect our lives. They may also affect us while they are in our gut but outside cells. Influencing the types and behaviour of phages in our body might be beneficial.
Bacteria are widely studied, especially the species that directly affect our lives. The viruses that infect our cells or those of animals are also widely studied since they can make us and the animals that we care for ill. The viruses that infect bacteria haven't been given as much attention until relatively recently. Scientists are now discovering the fascinating features and variety in the bacteriophage group.
In this article, I provide an overview of phages and their activity. I also describe some of their known effects and some of their possible effects in our gut microbiome. The gut or intestinal microbiome is the community of microorganisms that lives in our digestive tract. This community influences our lives in multiple ways. Many of the effects are beneficial, but not all of them are.
Viruses are classified as living or non-living entities, depending on a researcher's point of view. They are unable to reproduce on their own. They need to infect a living cell and "force" it to make new virus particles. These leave the cell and then infect other cells.
The Structure of Viruses
Viruses consists of a coat of protein known as a capsid that encloses the genetic material, or nucleic acid. The genetic material is either DNA (deoxyribonucleic acid) or RNA (ribonucleic acid). Some viruses have a lipid coat outside the capsid.
Bacteriophages have three basic shapes, which in simple terms can be described as a head with a tail (as in the T phages), a head on its own, and a filament. Based on our current knowledge, the vast majority of phages lack a lipid coat. Their nucleic acid is double-stranded or single-stranded DNA or RNA.
The nucleic acid of phages contains genes, as it does in other organisms. A gene is a section of nucleic acid that codes for a protein. This coding ability is why genes are able to control an organism's body. A huge variety of proteins exist in living things. They contribute to both the structure and the function of the body.
In most organisms, including humans, the genes are stored in DNA and the RNA is a helper chemical in the process of protein synthesis. In some viruses, RNA stores the genes, however.
T Phages: An Interesting and Common Type
T phages were the first bacteriophages to be discovered and are very often shown as the model type. They are numbered from T1 to T7. They are sometimes said to resemble a lunar lander in appearance. The virus has a polyhedral "head" region that is attached to an elongated "tail". The tail has spikes at the bottom that resemble the legs of a lunar lander.
The virus attaches to a bacterium with its tail spikes. It then contracts the core part of its tail as it injects its nucleic acid into the bacterium. At some point in the bacterium's life cycle, the viral nucleic acid forces the cell to make new virus particles.
Though T phages receive most of the publicity with respect to bacteriophages, researchers have discovered other types. Multiple families of phages exist. A casual reader may not realize this since a T4 phage illustration is often used to represent the entire bacteriophage group. T4 is found in our gut, however. In addition, the tailed phage group seems to be the most common type living in the gut, so the viruses are relevant with respect to our lives.
A specific type of bacteriophage very often infects only one type of bacteria. It doesn't affect all bacterial species. This feature will need to be taken into account if phages become widely used in medicine.
The Lytic Cycle of Viruses
Bacterial cells (and the cells of other organisms) contain genes as well as the chemicals and structures needed to carry out the instructions in the genes. Viruses also contain genes encoding instructions, but they don't have the chemicals or the equipment needed to act on the instructions. A virus must have the help of a cell in order to reproduce.
In the lytic cycle, the viral DNA that has been injected into a bacterial cell triggers the bacterium to make new viral nucleic acid and protein and then assemble the chemicals to make new virions (individual viruses). The virions break out of the bacterial cell, destroying it in the process. The destruction of the cell is known as lysis. The process is summarized in the video above.
The Lysogenic Cycle
In some phages or in some viral infections, a lysogenic cycle takes place instead of a lytic one. In a lysogenic cycle, the viral genes are incorporated into the bacterial nucleic acid and reproduce with it. While the viral genome (gene collection) is part of the bacterial one, it's known as a prophage. It was once thought that the prophage was inactive while it remained part of the bacterium's genetic material. Researchers have discovered that this is not always the case.
If the bacterium bearing the viral genes is stimulated in an appropriate way, such as by a stress of some kind, the prophage leaves the host's DNA and triggers the host to make new virions. This is followed by lysis of the bacterium and the release of the phages. The activation of the prophage is known as induction. Finding ways to activate prophages or to force them to remain inactive might be beneficial for us.
Our Gut or Intestinal Microbiome
Our digestive tract, gastrointestinal tract, or gut is a continuous passageway that leads from the mouth to the anus. Inside the body, the wall of the digestive tract separates it from its surroundings. The wall is not a complete barrier, however. Substances pass through it in either direction.
The term "gut" with reference to the microbiome refers to the small and large intestine. Many bacteria and other microorganisms live in the gut, especially in the small intestine. Some of the bacteria have phages inside them. Bacteriophages are also found outside the bacteria after they have been released during lysis.
Most of the phages in the gut appear to be ones containing DNA, not RNA. They are much smaller than bacteria and are often difficult to study, especially when they are hiding in bacterial cells. They appear to be numerous, however.
Researchers have learned that the bacteria living in our gut can have major effects on our lives. Many scientists are studying them. Now interest in exploring the role of gut phages is increasing. They may be an important contributor to human health or disease.
The gut microbiome is a complex, interconnected ecosystem of species.— Brigham and Women's Hospital, via phys.org
Effects of Bacteriophages in the Mouse Gut
Researchers at Brigham and Women's Hospital have found that phages "can have a profound impact on the dynamics of the gut microbiome", at least in mice. The researchers used mice that had no microorganisms in their gut before the experiment was started.
The scientists added gut bacteria and phages found in humans to the intestines of the mice. They found that the phages killed the bacteria that they could infect, as was expected. They also found other changes in the bodies of the mice, however.
One observed change was that the populations of the bacterial species that weren't killed by the phages increased dramatically. There was also a change in the gut metabolome of the mice. The metabolome is the collection of chemicals (or metabolites) produced in an organism and present in a sample obtained from it, such as intestinal fluid.
By examining the gut metabolome of the mice with the added bacteria, the researchers detected an alteration in the level of neurotransmitters, bile acids, and some other molecules. Neurotransmitters are produced by our nervous system. Some are also made by certain bacteria. They control the passage of a nerve impulse from one neuron (nerve cell) to another. Bile acids or bile salts emulsify fats in the intestine, making them easier to digest. Bile acids are produced by the liver from cholesterol and exist in different forms. Some bacteria can change the form of bile acids, which may be a significant effect for us.
The investigation was performed in mice, not humans, which is an important point to consider. Nevertheless, the research might be important with respect to our intestine. The scientists plan to do more investigations in order to better understand the links between gut phages and health or disease.
Obesity and Type 2 Diabetes in Mice
Researchers at the University of Copenhagen have performed an interesting experiment. They transferred stool viruses from lean mice to mice that were following an unhealthy diet. The majority of the viruses that were transferred were phages as opposed to non-phage viruses.
The mice receiving the phages continued to eat an unhealthy diet during the experiment. Some mice eating the diet were not given transplanted viruses. The mice that received the phages gained significantly less weight over a six-week period that the mice without the phage transplant. They also had a significantly reduced chance of developing glucose intolerance. The condition includes an increased blood glucose level and is associated with type 2 diabetes.
When obese mice who were following an unhealthy diet and had glucose intolerance were given the phages, the intolerance to glucose disappeared. The researchers stress that humans with the health problem should change their lifestyle in an attempt to help their condition (and, of course, seek their doctor's advice). It's unknown whether a phage transplant will help humans or if it does when it will be available for use. Clinical trials in humans are required in order to determine the usefulness of the technique for us. The trials could be very worthwhile.
Antibacterial Foods and Phage Release
Researchers at San Diego State University have discovered some interesting information about certain foods that are often considered to be antibacterial (including oregano). In the lab, oregano and some other foods triggered the activation of prophages in certain bacteria that are found in the human gut. This caused new phages to be produced and the death of the bacteria as the phages escaped from them. The released bacteriophages were then able to attack and kill other bacteria. This may be the way or at least one way in which the foods are able to fight bacteria in our body. Once again, however, the experiment wasn't performed in humans.
The research report raises a concern. Some foods in the scientists' test list appear to be broad-spectrum antibacterials. This means that they may affect multiple kinds of gut bacteria, perhaps including helpful ones. Eating the foods in excessive amounts may therefore be harmful as well as beneficial with respect to the gut community. The researchers certainly aren't recommending that we avoid the foods, though. Discovering how the foods activate prophages (assuming they do this in our bodies) might be very useful.
Phages were discovered by Frederick Twort in 1915. He thought that his discovery may have represented a new type of virus but wasn't certain. Félix d'Hérelle made the same discovery in 1917. He declared that he had found a virus that was a parasite of bacteria. He also came up with the idea of using phages for therapy.
The discoveries about the potential benefits of phages for health problems have been made in lab animals and lab equipment. They may apply to our body as well, but we need clinical trials in order to confirm this.
An exception to the lack of evidence in the human body is a treatment called phage therapy. As its name suggests, during this therapy, a phage or a collection of phages aimed at destroying the bacteria causing an infection is administered to the patient in an appropriate way. A liquid contained suitable phages may be gargled, swallowed, or sprayed over an area, for example. The treatment is used for the treatment of gut problems and for problems outside the gut.
The therapy was developed in the country of Georgia, which is located on the border between Europe and Asia. It appears to be popular there. It has been used successfully outside of Georgia, but special permission to use the therapy is generally required in this situation. Western scientists, health professionals, and health agencies want to explore the treatment in more detail before they agree to its general use. As bacterial resistance to antibiotics increases, more scientists are investigating phage therapy.
Exploring the Role of Phages in Our Lives
Viruses are microscopic and don't consist of cells, but this doesn't mean that they are simple entities. I think the study of phages is exciting. It offers many possibilities. These include the ability to reduce the population of a target bacterium without the use of antibiotics that may affect more than one species and without increasing antibiotic resistance.
Obtaining detailed knowledge about how specific phages behave in our body and about their possible effects is important. Researchers are investigating whether our gut phages have any effect on us while they are outside bacterial cells. Evidence suggests that some types may trigger inflammation in this situation. There are uncertainties and questions related to the activities of phages in the gut, but enough research has been done to suggest that at least some of them might be very useful for us.
Scientists say that exploring the phages in our gut is not as easy as studying the bacteria that live there and that it can be a very challenging process. They are working on ways to overcome this challenge. Some of the phage types that they have discovered were unknown before their research. Learning more about bacteriophages and using them to improve our health or to obtain other benefits is a tantalizing idea.
- Information about bacteriophages from the Khan Academy
- Bacteriophage facts from the Encyclopedia Britannica
- Phages in the gut microbiome from the phys.org news service
- Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model by Bryan B.Hsu et al, Cell Host and Microbe journal
- New insights into intestinal phages from the Nature journal
- Considering the other half of the gut microbiome from the ASM (American Society for Microbiology):
- Phages from feces can fight obesity and diabetes in mice from the Medical Xpress news service
- Foods and bacteria level in the gut from the ScienceDaily news service
- Potential benefits and problems linked to phage therapy from CTV News
This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.
© 2020 Linda Crampton