June 5, 2019 at 19:39Microbiota. How drugs affect intestinal bacteria
We Atlas has described how working microbiota which the bacteria live in the intestines of the Russians, as the microbiota influences on the development of diseases, as well as what you can to help bowel health. We received many questions about antibiotics and decided to prepare separate material on how different drugs affect the microbiota. We talk about the most popular.
Illustration by Rentonorama
Antibiotics - a type of drugs that destroy bacteria, reduce their reproduction and spread. They are used to treat bacterial infections and only in those cases when you can not do without them. According to the type of action, antibiotics can be divided into two types: bactericidal and bacteriostatic. The former kill microorganisms, and the latter prevent them from multiplying.
Bactericides kill bacteria in different ways. Some inhibit cell wall synthesis. These include beta-lactam (penicillins, cephalosporins, carbapenems, monobactams) and vancomycins. Others, such as daptomycin, metronidazole, fluoroquinolones, nitrofurantoin, co-trimaxosole, telithromycin, inhibit bacterial enzymes and protein production. Aminoglycosides are usually bactericidal, although they can act as bacteriostats for certain strains.
Bacteriostatic inhibit the production of bacterial protein, DNA replication and other cellular processes. These include tetracyclines, sulfonamides, spectinomycin, trimethoprim, chloramphenicol, macrolides and lincosamides. These types of antibiotics help the human immune system cope with inflammation. However, high concentrations of bacteriostatics can act as bactericides, so there is no clear boundary between the groups.
Also, antibiotics are of a wide spectrum and narrowly targeted. In the first case, they hit on different types of microorganisms, in the second - only on certain strains. As a rule, if it is not known which bacterium led to the development of symptoms, then broad-spectrum antibiotics are used.
Because of the variety of species, antibiotics are difficult to study: a randomized controlled trial for each drug needs to be done, but this is unethical. In healthy people, after such therapy, the balance of bacteria will be disturbed once again, and patients who will receive a placebo instead of drugs will not be able to recover and will likely get complications from the infection. Therefore, all we have is research on mice and the results of studying molecular processes between antibiotics and microorganisms.
A study of microbiota after treatment with fluoroquinolones and beta-lactams showed that both types of antibiotics reduce the diversity of microorganisms by 25%. In addition, treatment with beta-lactams frees up space for the growth and dominance of resistant strains. A broad-spectrum antibiotic clindamycin reduces the resistance of microbiota to pathogens, which increases the risk of gastritis and diarrhea caused by Clostridium difficile.
A study of 7 different antibiotics in mice showed that cefoperazone, metronidazole, and streptomycin are associated with a high growth of the C. difficile pathogen. And the greatest bacterial growth is associated with ampicillin intake.
Often, a complex of several antibiotics is used to treat diseases. To study the effect of therapy in this case, researchers at the University of Copenhagen selected 12 men after a 4-day treatment with meropenem, gentamicin and vancomycin.
Treatment led to the almost complete destruction of microbiota. After 6 months, most species were able to recover and return to their previous levels, however, the participants still lacked 9 useful representatives of the microbiota that were in the intestine before treatment.
Antibiotics act differently on the microbiota, depending on how they enter the body. Oral administration of antibiotics stimulates the development of resistance much more than the introduction of the drug into a vein.
The response of microbiota to antibiotic treatment also depends on individual characteristics, such as age, lifestyle and the composition of bacteria in the intestine. For example, their use in newborns and infants leads to impaired development of a diverse and balanced microbiota. Antibiotics also weaken the microbiota in utero when a pregnant woman is undergoing therapy.
Researchers have come to the conclusion that antibiotics should be selected individually, like chemotherapy for cancer treatment. Algorithms are already being developed that can predict how bacteria will respond to antibiotic treatment based on microbiota patterns. Probiotic bacteria are used to restore the intestines after therapy.
Nonsteroidal anti-inflammatory drugs (NSAIDs), or simply painkillers, are used to relieve pain, reduce inflammation and lower temperature. Painkillers inhibit the production of prostaglandins - mediators that trigger an inflammation reaction in the body. Such drugs are of two types: selective and non-selective.
Non-selective inhibit the action of both enzymes that produce protaglandins - COX-1 and COX-2. Selective suppress only COX-2 and increase the risk of thrombosis and heart attack. Due to the high risk of complications, non-selective NSAIDs are now mainly used. These include ibuprofen, aspirin, naproxen, diclofenac, mefenamic acid, indomethacin. Despite similar properties, paracetamol is not an NSAID.
StudyMicrobiota samples from 155 adults who took painkillers at least once in the last 30 days showed that the type of drug, rather than the amount, is more likely to change. Ketoprofen, naproxen and ketorolac are more aggressive on the gastrointestinal tract than ibuprofen and celecosib.
In addition, the composition of the microbiota was different when NSAIDs were used together with other drugs, for example, antidepressants, laxatives, and proton pump inhibitors.
A recent mouse study found that the analgesic pain medication exacerbates the course of C. difficile infection. Scientists suggest that ibuprofen and aspirin act the same way, because these drugs have a similar mechanism of action. However, more research is needed to find out.
Research is currently underway on the relationship between aspirin and the state of microbiota. Low doses of this drug are often prescribed regularly for those who have a high risk of heart and vascular disease. On the other hand, taking aspirin increases the risk of bleeding in the digestive tract.
Antidepressants are drugs that are used to treat depression. There are different types of these drugs, but the most common are serotonin and / or norepinephrine reuptake inhibitors. It is known that intestinal microbiota affects the production of serotonin, gamma-aminobutyric acid (GABA) and dopamine - neurotransmitters, on which our mood and well-being depend.
Comparison of microbiota samples from depressed patients and healthy adults showed that the former had more Flavonifractor bacteria. Another study found that the microbiota of depressed people who took antidepressants contained fewer bacteria, Coprococcus and Dialister.
Researchin vitro demonstrate the antibacterial properties of drugs for depression. The effect of antidepressants was also studied in mice. Their preparations worsened diversity and changed the composition of intestinal bacteria.
However, this study should be treated with caution: antidepressants were injected directly into the abdomen in order to achieve certain concentrations, so the result could be affected by the stress experienced by the animals. Researchers suggest that part of the positive effect of antidepressants is due to exposure to the microbiota.
Proton pump inhibitors (PPIs) are used to treat diseases of the gastrointestinal tract. Often they are prescribed for peptic ulcer of the stomach and duodenum, dyspepsia, chronic gastritis, duodenitis and pancreatitis.
Each stomach cell contains a so-called proton pump, the activity of which depends on the production of acid for the digestion of food. Sometimes there is a lot of acid, and it begins to destroy healthy cells. Inhibitors inhibit the mechanism of acid production.
Some studies have noted that taking PPIs increases the risk of C. Difficile infection. A Japanese study showed that in patients receiving PPIs, Streptococcus is higher and Faecalibacterium is lower. The latter protect our intestines from inflammation and produce essential fatty acids for cells.
Another study compared changes in microbiota before and after a course of PPI. It turned out that patients after treatment had a higher representation of Lactobacillus, a probiotic bacterium that is usually associated with intestinal health. Researchers note that a greater presence of Lactobacillus is found in patients with type 2 diabetes and Parkinson's disease. Therefore, it remains unclear whether an increase in the proportion of bacteria is useful in this case.
The diversity of bacteria after taking PPI is reduced. Scientists suggest that this is the main reason for the increased risk of infections and inflammation after taking the drugs.
Many drugs are now available, and each microbiota can respond to them differently, reducing or, conversely, improving the properties of the drug. Perhaps in the future we will be able to select more effective drugs depending on the composition of the intestinal bacteria (as in the variants of genes in pharmacogenetics), but this is still a long way off. Most interactions between the body, bacteria, and drugs have yet to be explored.
And in the next article we’ll describe in detail how we analyze intestinal bacteria and what the “ Microbiota Genetics ” test includes .
Illustration by Rentonorama
Antibiotics
Antibiotics - a type of drugs that destroy bacteria, reduce their reproduction and spread. They are used to treat bacterial infections and only in those cases when you can not do without them. According to the type of action, antibiotics can be divided into two types: bactericidal and bacteriostatic. The former kill microorganisms, and the latter prevent them from multiplying.
Bactericides kill bacteria in different ways. Some inhibit cell wall synthesis. These include beta-lactam (penicillins, cephalosporins, carbapenems, monobactams) and vancomycins. Others, such as daptomycin, metronidazole, fluoroquinolones, nitrofurantoin, co-trimaxosole, telithromycin, inhibit bacterial enzymes and protein production. Aminoglycosides are usually bactericidal, although they can act as bacteriostats for certain strains.
Bacteriostatic inhibit the production of bacterial protein, DNA replication and other cellular processes. These include tetracyclines, sulfonamides, spectinomycin, trimethoprim, chloramphenicol, macrolides and lincosamides. These types of antibiotics help the human immune system cope with inflammation. However, high concentrations of bacteriostatics can act as bactericides, so there is no clear boundary between the groups.
Also, antibiotics are of a wide spectrum and narrowly targeted. In the first case, they hit on different types of microorganisms, in the second - only on certain strains. As a rule, if it is not known which bacterium led to the development of symptoms, then broad-spectrum antibiotics are used.
Because of the variety of species, antibiotics are difficult to study: a randomized controlled trial for each drug needs to be done, but this is unethical. In healthy people, after such therapy, the balance of bacteria will be disturbed once again, and patients who will receive a placebo instead of drugs will not be able to recover and will likely get complications from the infection. Therefore, all we have is research on mice and the results of studying molecular processes between antibiotics and microorganisms.
A study of microbiota after treatment with fluoroquinolones and beta-lactams showed that both types of antibiotics reduce the diversity of microorganisms by 25%. In addition, treatment with beta-lactams frees up space for the growth and dominance of resistant strains. A broad-spectrum antibiotic clindamycin reduces the resistance of microbiota to pathogens, which increases the risk of gastritis and diarrhea caused by Clostridium difficile.
A study of 7 different antibiotics in mice showed that cefoperazone, metronidazole, and streptomycin are associated with a high growth of the C. difficile pathogen. And the greatest bacterial growth is associated with ampicillin intake.
Often, a complex of several antibiotics is used to treat diseases. To study the effect of therapy in this case, researchers at the University of Copenhagen selected 12 men after a 4-day treatment with meropenem, gentamicin and vancomycin.
Treatment led to the almost complete destruction of microbiota. After 6 months, most species were able to recover and return to their previous levels, however, the participants still lacked 9 useful representatives of the microbiota that were in the intestine before treatment.
Antibiotics act differently on the microbiota, depending on how they enter the body. Oral administration of antibiotics stimulates the development of resistance much more than the introduction of the drug into a vein.
The response of microbiota to antibiotic treatment also depends on individual characteristics, such as age, lifestyle and the composition of bacteria in the intestine. For example, their use in newborns and infants leads to impaired development of a diverse and balanced microbiota. Antibiotics also weaken the microbiota in utero when a pregnant woman is undergoing therapy.
Researchers have come to the conclusion that antibiotics should be selected individually, like chemotherapy for cancer treatment. Algorithms are already being developed that can predict how bacteria will respond to antibiotic treatment based on microbiota patterns. Probiotic bacteria are used to restore the intestines after therapy.
Pain medication
Nonsteroidal anti-inflammatory drugs (NSAIDs), or simply painkillers, are used to relieve pain, reduce inflammation and lower temperature. Painkillers inhibit the production of prostaglandins - mediators that trigger an inflammation reaction in the body. Such drugs are of two types: selective and non-selective.
Non-selective inhibit the action of both enzymes that produce protaglandins - COX-1 and COX-2. Selective suppress only COX-2 and increase the risk of thrombosis and heart attack. Due to the high risk of complications, non-selective NSAIDs are now mainly used. These include ibuprofen, aspirin, naproxen, diclofenac, mefenamic acid, indomethacin. Despite similar properties, paracetamol is not an NSAID.
StudyMicrobiota samples from 155 adults who took painkillers at least once in the last 30 days showed that the type of drug, rather than the amount, is more likely to change. Ketoprofen, naproxen and ketorolac are more aggressive on the gastrointestinal tract than ibuprofen and celecosib.
In addition, the composition of the microbiota was different when NSAIDs were used together with other drugs, for example, antidepressants, laxatives, and proton pump inhibitors.
A recent mouse study found that the analgesic pain medication exacerbates the course of C. difficile infection. Scientists suggest that ibuprofen and aspirin act the same way, because these drugs have a similar mechanism of action. However, more research is needed to find out.
Research is currently underway on the relationship between aspirin and the state of microbiota. Low doses of this drug are often prescribed regularly for those who have a high risk of heart and vascular disease. On the other hand, taking aspirin increases the risk of bleeding in the digestive tract.
Antidepressants
Antidepressants are drugs that are used to treat depression. There are different types of these drugs, but the most common are serotonin and / or norepinephrine reuptake inhibitors. It is known that intestinal microbiota affects the production of serotonin, gamma-aminobutyric acid (GABA) and dopamine - neurotransmitters, on which our mood and well-being depend.
Comparison of microbiota samples from depressed patients and healthy adults showed that the former had more Flavonifractor bacteria. Another study found that the microbiota of depressed people who took antidepressants contained fewer bacteria, Coprococcus and Dialister.
Researchin vitro demonstrate the antibacterial properties of drugs for depression. The effect of antidepressants was also studied in mice. Their preparations worsened diversity and changed the composition of intestinal bacteria.
However, this study should be treated with caution: antidepressants were injected directly into the abdomen in order to achieve certain concentrations, so the result could be affected by the stress experienced by the animals. Researchers suggest that part of the positive effect of antidepressants is due to exposure to the microbiota.
Proton pump inhibitors
Proton pump inhibitors (PPIs) are used to treat diseases of the gastrointestinal tract. Often they are prescribed for peptic ulcer of the stomach and duodenum, dyspepsia, chronic gastritis, duodenitis and pancreatitis.
Each stomach cell contains a so-called proton pump, the activity of which depends on the production of acid for the digestion of food. Sometimes there is a lot of acid, and it begins to destroy healthy cells. Inhibitors inhibit the mechanism of acid production.
Some studies have noted that taking PPIs increases the risk of C. Difficile infection. A Japanese study showed that in patients receiving PPIs, Streptococcus is higher and Faecalibacterium is lower. The latter protect our intestines from inflammation and produce essential fatty acids for cells.
Another study compared changes in microbiota before and after a course of PPI. It turned out that patients after treatment had a higher representation of Lactobacillus, a probiotic bacterium that is usually associated with intestinal health. Researchers note that a greater presence of Lactobacillus is found in patients with type 2 diabetes and Parkinson's disease. Therefore, it remains unclear whether an increase in the proportion of bacteria is useful in this case.
The diversity of bacteria after taking PPI is reduced. Scientists suggest that this is the main reason for the increased risk of infections and inflammation after taking the drugs.
Many drugs are now available, and each microbiota can respond to them differently, reducing or, conversely, improving the properties of the drug. Perhaps in the future we will be able to select more effective drugs depending on the composition of the intestinal bacteria (as in the variants of genes in pharmacogenetics), but this is still a long way off. Most interactions between the body, bacteria, and drugs have yet to be explored.
And in the next article we’ll describe in detail how we analyze intestinal bacteria and what the “ Microbiota Genetics ” test includes .