24 Apr Drugs and Gut Health: a brief review of antibiotics, immune suppressants and pain killers
The use of prescribed medication is on the rise. But, are we getting any healthier?
Australians are consuming massive amounts of prescription drugs, including antibiotics, opioids and other pain killers as well as other drugs. The overuse of some of these prescription drugs may bring negative consequences to your health.
Antibiotic use and abuse
According to official figures, more than 30 million antibiotic prescriptions were handed out in 2014 to about half of the Australian population. Compared to European countries, for example, Australia has the eight highest rate of antibiotic use. Below are some key facts about antibiotics,
Antibiotics can be defined as any compound that can either kill bacteria or slow down its growth. There are thousands of different antibiotic compounds available. In Australia, the three most prescribed antibiotics are amoxicillin, cefalexin and amoxicillin–clavulanate1.
Antibiotics work by targeting specific components of the bacterial cell, like the bacterial cell wall or proteins responsible for bacterial growth. A key characteristic of antibiotics is that they only target the bacterial cells and not our own cells.
A major problem with the overuse of antibiotics is resistance. Ever since the development of the first antibiotics, bacteria have evolved resistance. Antibiotic resistance occurs because bacteria evolve random mutations every time they reproduce, and, by pure chance, some of these mutations will give bacteria resistance to the antibiotic. Furthermore, antibiotic-resistant bacteria can transfer this trait to other bacteria, making them resistant too.
Superbugs in Australia
- As a result of the constant development of new antibiotics and the formation of new strains of bacteria that resist them, today we are facing the development of superbugs.
- Escherichia coli, for example, is a common pathogen that is highly capable of developing antibiotic resistance. When treating patients with ampicillin or amoxicillin alone, about 50% of cases develop resistant bacteria. For the antibiotics amoxicillin-clavulanate, this rate was 20%1.
How antibiotics affect our gut
- Even a short-term course of antibiotics can alter the composition of the gut microbiota (GM), causing long-lasting dysbiosis.
- In response to antibiotic treatment, our GM experiences a reduction in the number of microbial species, which significantly hinders the many functions of the GM and increases the chances of pathogens entering our body2.
Drugs for pain
Another important group of drugs that is commonly prescribed in Australia involve opioids. According to recent numbers from the Australian Institute of Health and Welfare around 3.1 million Australians were prescribed opioids between 2016-2017. Below are some key facts about these drugs.
Opioids are a group of pain-relieving drugs prescribed in cases of extreme pain. They can be naturally derived or synthetic. Naturally derived opioids are extracted from the opium or bread seed poppy, Papaver somniferum, an ornamental plant with a long history of use as medicine and food. The most common opioid prescribed in Australia is oxycodone, given to 1.3 million Australians, followed by codeine and tramadol, prescribed to 1.7 million and 600,000 people, respectively.
Opioids work in a very specific way. They bind to a special group of nerve cells that a part of the opioid system, involved in the regulation of mood, pain relief, mood regulation and stress response. Neural cells in this system can be found throughout the central and peripheral nervous system, the gastrointestinal tract, and the immune system. Opioids work by binding to cellular components called receptors, which affects the function of the cell and result in a slowing down of the transmission of messages between neurons. In practice, this translate into a reduction of pain, as well as other side effects, such as euphoria and, in many cases, addiction to the medication3.
The problem with opioids
A major problem is that opioids are addictive and cause all sorts of health problems. About 11% of all Australians aged 14 and over report using opioids in an illegal manner. In recent years hospitalizations due to opioid poisoning have risen by 25%, according to official figures. It is estimated that about 3 people die every day from opioid-related problems in Australia.
Another consequence of chronic opioid use is dysregulation of the stress response system, leading to symptoms like hyperarousal, attentional dysfunctions, and increased anxiety4-6. Mood disorders, such as disordered mood states, social isolation, depression-like behaviours, aggression, anxiety and other problems7 are also linked to opioid abuse.
How opioids affect the gut
chronic use of opioids significantly affects the gut and the gut microbiota, affecting the integrity of the gut epithelial barriers, affecting gut homeostasis and causing dysbiosis8. Studies have suggested potential mechanisms through which alterations to the gut microbiota can affect symptoms related to opioid use. These include neuroinflammation8-9, bacterial metabolites10-12, serotonin modulation13-14 and by affecting microbial diversity15.
Suppressing your immune system
Another important type of drugs are immunosuppressants (IS), used to treat severe allergic reactions as well as autoimmune and transplant-related diseases.
Immunosuppressants, also known as anti-rejection drugs, have the basic goal of inhibiting the immune system, hence preventing the damaging effects of immune attacks against our own healthy cells. Some common immunosuppressant are corticosteroids, Janus kinase inhibitors, Calcineurin, IMDH and mTOR inhibitors, biologics, and monoclonal antibodies.
Immunosuppressants drugs work by targeting different immune pathways or immune cells. For example, the drug tacrolimus is an inhibitor of calcineurin, an enzyme responsible for the production of T-cells, a key type of immune cell. By weakening or inhibiting parts of the immune response, symptoms from allergies or autoimmune diseases are expected to become significantly milder.
What conditions do they treat?
Immunosuppressants are commonly prescribed for people with autoimmune conditions like psoriasis, lupus, rheumatoid arthritis, Crohn’s disease or multiple sclerosis. Also, people undergoing an organ transplant almost always are prescribed immunosuppressants, as this is the only way to prevent the immune system to attack the foreign organ.
The problem with Immunosuppressants
An important issue with these drugs involves the negative consequences of a weakened immune system, like increased chances of getting infections, development of more severe infections, and prolonged time to recover from a disease. In addition, immunosuppressant drugs have significant side effects, including fever or chills, back pain, problems urinating, and fatigue.
Also, certain immunosuppressants increase your chances of developing cancer. For example, studies have found that some immunosuppressants increase the risk of developing skin cancer on patients suffering from with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD)16-17.
Immunosuppressants and the gut
A potentially negative interaction between the GM and IS involves how microbes process certain chemicals. For example, a study found that gut bacteria reduced the effectiveness of the immunosuppressant drug Tracolimus, by metabolising the drug into less efficacious components18. Other studies suggest similar interactions and caution about the need to learn more about the link between GM and immunoregulatory drugs19-20.
Immunosuppressants can also alter the GM composition and favour the overgrowth of pathogenic bacteria, as demonstrated in one study21. The study found that treatment with IS led to changes in microbial composition. For example, single treatment with the drug Prednisolone reduced observed levels of the bacterial group Bacteroidetes, and increased levels of Firmicutes in stool samples. Treatment with Prednisolone, tacrolimus, and mycophenolate, three IS drugs, resulted in overgrowth of a pathogenic strain of Escherichia coli.
Do you have health problems requiring the use of antibiotics, pain killers or immunosuppressants? Do you suffer from gut problems, mood disorders, fatigue or sleep issues? Depending on your condition, there might be better approaches to deal with your underlying problems. At AUSCFM we employ comprehensive testing of your stools, blood, urine and gut microbiota, to obtain a complete picture of your current health and identify the best treatments.
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- Australian Commission on Safety and Quality in Health Care (ACSQHC). AURA 2016: first Australian report on antimicrobial use and resistance in human health. Sydney: ACSQHC, 2016. Read it!
- Lange K, Buerger M, Stallmach A, Bruns T. Effects of antibiotics on gut microbiota. Digestive Diseases. 2016;34(3):260-8. Read it!
- Toubia T, Khalife T. The Endogenous Opioid System: Role and Dysfunction Caused by Opioid Therapy. Clinical obstetrics and gynecology. 2019 Mar 1;62(1):3-10. Read it!
- Valentino RJ, Van Bockstaele E. Endogenous opioids: the downside of opposing stress. Neurobiology of stress. 2015 Jan 1;1:23-32. Read it!
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- Xu GP, Van Bockstaele E, Reyes B, Bethea T, Valentino RJ. Chronic morphine sensitizes the brain norepinephrine system to corticotropin-releasing factor and stress. Journal of Neuroscience. 2004 Sep 22;24(38):8193-7. Read it!
- Lutz PE, Kieffer BL. Opioid receptors: distinct roles in mood disorders. Trends in neurosciences. 2013 Mar 1;36(3):195-206. Read it!
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- Erny D, de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V. Host microbiota constantly control maturation and function of microglia in the CNS. Nature neuroscience. 2015 Jul;18(7):965. Read it!
- Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nature Reviews Immunology. 2016 Jun;16(6):341-52. Read it!
- Wall R, Cryan JF, Ross RP, Fitzgerald GF, Dinan TG, Stanton C. Bacterial neuroactive compounds produced by psychobiotics. InMicrobial endocrinology: The microbiota-gut-brain axis in health and disease 2014 (pp. 221-239). Springer, New York, NY. Read it!
- Thomas CM, Hong T, Van Pijkeren JP, Hemarajata P, Trinh DV, Hu W, Britton RA, Kalkum M, Versalovic J. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PloS one. 2012;7(2). Read it!
- O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural brain research. 2015 Jan 15;277:32-48. Read it!
- Van De Wouw M, Stilling RM, Peterson VL, Ryan FJ, Hoban AE, Shanahan F, Clarke G, Claesson MJ, Dinan TG, Cryan JF, Schellekens H. Host microbiota regulates central nervous system serotonin receptor 2C editing in rodents. ACS chemical neuroscience. 2019 Aug 15;10(9):3953-60. Read it!
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- Scott FI. Immunosupressants and biologics increase skin cancer risk. Reactions. 2015 Dec;1580:7-5. Read it!
- Scott FI, Mamtani R, Brensinger CM, Haynes K, Chiesa-Fuxench ZC, Zhang J, Chen L, Xie F, Yun H, Osterman MT, Beukelman T. Risk of nonmelanoma skin cancer associated with the use of immunosuppressant and biologic agents in patients with a history of autoimmune disease and nonmelanoma skin cancer. JAMA dermatology. 2016 Feb 1;152(2):164-72. Read it!
- Guo Y, Crnkovic CM, Won KJ, Yang X, Lee JR, Orjala J, Lee H, Jeong H. Commensal gut bacteria convert the immunosuppressant tacrolimus to less potent metabolites. Drug Metabolism and Disposition. 2019 Mar 1;47(3):194-202. Read it!
- Dery KJ, Kadono K, Hirao H, Górski A, Kupiec-Weglinski JW. Microbiota in organ transplantation: An immunological and therapeutic conundrum?. Cellular Immunology. 2020 Feb 27:104080. Read it!
- Lam KN, Alexander M, Turnbaugh PJ. Precision medicine goes microscopic: engineering the microbiome to improve drug outcomes. Cell host & microbe. 2019 Jul 10;26(1):22-34. Read it!
- Tourret J, Willing BP, Dion S, MacPherson J, Denamur E, Finlay BB. Immunosuppressive treatment alters secretion of ileal antimicrobial peptides and gut microbiota, and favors subsequent colonization by uropathogenic Escherichia coli. Transplantation. 2017 Jan 1;101(1):74-82. Read it!