Microbiota How do medications affect intestinal bacteria?
Atlas and I have already told how the microbiota works , what bacteria live in the intestines of Russians, how the microbiota affects the development of diseases, and how we can help the health of the intestines. We received a lot of questions about antibiotics and decided to prepare a separate material on how different drugs affect the microbiota. We talk about the most popular.
Illustration by Rentonorama
Antibiotics are a type of drugs that destroy bacteria, reduce their reproduction and distribution. They are used to treat bacterial infections and only in cases where they can not do without. According to the type of action, antibiotics can be divided into two types: bactericidal and bacteriostatic. The first kill microorganisms, and the latter do not allow them to multiply.
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-trimaxosol, telithromycin, inhibit the work of bacterial enzymes and the production of proteins. Aminoglycosides are usually bactericidal species, although they can act as bacteriostatic agents for certain strains.
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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 a person's immune system cope with inflammation. However, high concentrations of bacteriostats can act as bactericides, so there is no clear boundary between the groups.
Also, antibiotics are broad-spectrum and narrowly targeted. In the first case, they beat 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 diversity of types of antibiotics, it is difficult to study: a randomized controlled trial should be carried out for each drug, but this is unethical. In healthy people, after such therapy, the balance of bacteria will be upset once more, and patients who will receive a placebo instead of medicines will not be able to recover and are likely to get complications from infection. Therefore, all that we have is studies in mice and the results of studying molecular processes between antibiotics and microorganisms.
The study of microbiota after therapy with fluoroquinolones and beta-lactams showed that both types of antibiotics reduce the diversity of microorganisms by 25%. In addition, beta-lactam treatment makes room for the growth and dominance of resistant strains. A broad spectrum antibiotic clindamycin leads to a decrease in the resistance of the microbiota to pathogenic microorganisms, 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 largest 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, the University of Copenhagen researchers selected 12 men after 4-day treatment with meropenem, gentamicin and vancomycin.
The treatment has led to almost complete destruction of the microbiota. After 6 months, most of the species were able to recover and return to previous levels, but the participants still lacked 9 beneficial representatives of the microbiota that were in the intestines before treatment.
Antibiotics have a different effect on the microbiota, depending on the method of intake. Oral administration of antibiotics much more stimulates the development of resistance than the introduction of the drug into the vein.
The response of the 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 developmental disorders of a diverse and balanced microbiota. Also, antibiotics weaken the microbiota in utero when a pregnant woman undergoes therapy.
Researchers have come to the conclusion that antibiotics should be selected individually, like chemotherapy for cancer treatment. Already today, algorithms are being developed that will be able to predict how microbiota can predict how bacteria will react to antibiotic treatment. Probiotic bacteria are used to restore the intestines after therapy.
Non-steroidal anti-inflammatory drugs (NSAIDs), or simply painkillers, are used to relieve pain, reduce inflammation and reduce fever. Painkillers inhibit the production of prostaglandins, mediators that trigger the body’s inflammatory response. 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 does not apply to NSAIDs.
A study of microbiota samples from 155 adults who in the past 30 days took painkillers at least once showed that the type of medication is more influenced by the type of medicine than the amount. Ketoprofen, naproxen and ketorolac act more aggressively on the gastrointestinal tract than ibuprofen and celecosib.
In addition, the composition of the microbiota differed when NSAIDs were used together with other drugs, such as antidepressants, laxatives and proton pump inhibitors.
A recent study in mice revealed that the anesthetic drug indomethacin aggravates the course of C. difficile infection. Scientists suggest that ibuprofen and aspirin act in 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 intake and the state of the microbiota. Low doses of this drug are often prescribed to be taken regularly by those who have a high risk of heart and vascular diseases. On the other hand, taking aspirin increases the risk of bleeding in the gastrointestinal tract.
Antidepressants are drugs 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 the 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 of the Flavonifractor bacteria. Another study found that the microbiota of depressed people who took anti-depressants contained less Coprococcus and Dialister bacteria.
In vitro studies demonstrate the antibacterial properties of drugs for depression. The effects of antidepressants have also been studied in mice. Their drugs worsened the variety 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 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 gastric ulcer and duodenal ulcer, dyspepsia, chronic gastritis, duodenitis and pancreatitis.
Each cell of the stomach contains a so-called proton pump, on the activity of which depends on the production of acid to digest food. Sometimes it gets a lot of acid, and it starts destroying healthy cells. Inhibitors inhibit the mechanism of acid production.
Some studies indicate that ingestion of PPI increases the risk of infection with C. Difficile. A Japanese study showed that in IPP-receiving patients, the representation of Streptococcus is higher, and Faecalibacterium is lower. The latter protect our intestines from inflammation and produce the fatty acids necessary for the cells.
In another study, microbiota changes were compared before and after the course of IPP ingestion. It turned out that patients after treatment had higher representation of Lactobacillus, a probiotic bacterium that is usually associated with intestinal health. Researchers note that a large proportion 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 variety of bacteria after ingestion of IPP is reduced. Scientists suggest that this is the main cause of the increased risk of infections and inflammation after taking the drugs.
Now a lot of drugs are available, and each microbiota can react to them differently, reducing or, conversely, improving the properties of the drug. It is possible that in the future we will be able to select more effective drugs depending on the composition of the intestinal bacteria (as per gene variants in pharmacogenetics), but this is still far away. Most of the interactions between the body, bacteria and drugs have yet to be studied.
And in the next article we will describe in detail how we analyze intestinal bacteria and what the Genetics of Microbiota test includes.
Illustration by Rentonorama
Antibiotics
Antibiotics are a type of drugs that destroy bacteria, reduce their reproduction and distribution. They are used to treat bacterial infections and only in cases where they can not do without. According to the type of action, antibiotics can be divided into two types: bactericidal and bacteriostatic. The first kill microorganisms, and the latter do not allow them to multiply.
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-trimaxosol, telithromycin, inhibit the work of bacterial enzymes and the production of proteins. Aminoglycosides are usually bactericidal species, although they can act as bacteriostatic agents 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 a person's immune system cope with inflammation. However, high concentrations of bacteriostats can act as bactericides, so there is no clear boundary between the groups.
Also, antibiotics are broad-spectrum and narrowly targeted. In the first case, they beat 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 diversity of types of antibiotics, it is difficult to study: a randomized controlled trial should be carried out for each drug, but this is unethical. In healthy people, after such therapy, the balance of bacteria will be upset once more, and patients who will receive a placebo instead of medicines will not be able to recover and are likely to get complications from infection. Therefore, all that we have is studies in mice and the results of studying molecular processes between antibiotics and microorganisms.
The study of microbiota after therapy with fluoroquinolones and beta-lactams showed that both types of antibiotics reduce the diversity of microorganisms by 25%. In addition, beta-lactam treatment makes room for the growth and dominance of resistant strains. A broad spectrum antibiotic clindamycin leads to a decrease in the resistance of the microbiota to pathogenic microorganisms, 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 largest 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, the University of Copenhagen researchers selected 12 men after 4-day treatment with meropenem, gentamicin and vancomycin.
The treatment has led to almost complete destruction of the microbiota. After 6 months, most of the species were able to recover and return to previous levels, but the participants still lacked 9 beneficial representatives of the microbiota that were in the intestines before treatment.
Antibiotics have a different effect on the microbiota, depending on the method of intake. Oral administration of antibiotics much more stimulates the development of resistance than the introduction of the drug into the vein.
The response of the 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 developmental disorders of a diverse and balanced microbiota. Also, antibiotics weaken the microbiota in utero when a pregnant woman undergoes therapy.
Researchers have come to the conclusion that antibiotics should be selected individually, like chemotherapy for cancer treatment. Already today, algorithms are being developed that will be able to predict how microbiota can predict how bacteria will react to antibiotic treatment. Probiotic bacteria are used to restore the intestines after therapy.
Pain reliever
Non-steroidal anti-inflammatory drugs (NSAIDs), or simply painkillers, are used to relieve pain, reduce inflammation and reduce fever. Painkillers inhibit the production of prostaglandins, mediators that trigger the body’s inflammatory response. 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 does not apply to NSAIDs.
A study of microbiota samples from 155 adults who in the past 30 days took painkillers at least once showed that the type of medication is more influenced by the type of medicine than the amount. Ketoprofen, naproxen and ketorolac act more aggressively on the gastrointestinal tract than ibuprofen and celecosib.
In addition, the composition of the microbiota differed when NSAIDs were used together with other drugs, such as antidepressants, laxatives and proton pump inhibitors.
A recent study in mice revealed that the anesthetic drug indomethacin aggravates the course of C. difficile infection. Scientists suggest that ibuprofen and aspirin act in 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 intake and the state of the microbiota. Low doses of this drug are often prescribed to be taken regularly by those who have a high risk of heart and vascular diseases. On the other hand, taking aspirin increases the risk of bleeding in the gastrointestinal tract.
Antidepressants
Antidepressants are drugs 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 the 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 of the Flavonifractor bacteria. Another study found that the microbiota of depressed people who took anti-depressants contained less Coprococcus and Dialister bacteria.
In vitro studies demonstrate the antibacterial properties of drugs for depression. The effects of antidepressants have also been studied in mice. Their drugs worsened the variety 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 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 gastric ulcer and duodenal ulcer, dyspepsia, chronic gastritis, duodenitis and pancreatitis.
Each cell of the stomach contains a so-called proton pump, on the activity of which depends on the production of acid to digest food. Sometimes it gets a lot of acid, and it starts destroying healthy cells. Inhibitors inhibit the mechanism of acid production.
Some studies indicate that ingestion of PPI increases the risk of infection with C. Difficile. A Japanese study showed that in IPP-receiving patients, the representation of Streptococcus is higher, and Faecalibacterium is lower. The latter protect our intestines from inflammation and produce the fatty acids necessary for the cells.
In another study, microbiota changes were compared before and after the course of IPP ingestion. It turned out that patients after treatment had higher representation of Lactobacillus, a probiotic bacterium that is usually associated with intestinal health. Researchers note that a large proportion 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 variety of bacteria after ingestion of IPP is reduced. Scientists suggest that this is the main cause of the increased risk of infections and inflammation after taking the drugs.
Now a lot of drugs are available, and each microbiota can react to them differently, reducing or, conversely, improving the properties of the drug. It is possible that in the future we will be able to select more effective drugs depending on the composition of the intestinal bacteria (as per gene variants in pharmacogenetics), but this is still far away. Most of the interactions between the body, bacteria and drugs have yet to be studied.
And in the next article we will describe in detail how we analyze intestinal bacteria and what the Genetics of Microbiota test includes.
Source: https://habr.com/ru/post/454960/
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