There is growing concern about microbial resistance to antibiotics. The World Health Organisation has recently labelled antibiotic resistance as one of the greatest threats to public health. Australia has one of the highest use of antibiotics in the world with over 19 million prescriptions written very year. There is emerging concern that antibiotics also have a significant impact on the gastrointestinal microbiome. Using DNA sequencing of the gut microbiome has shown that the damaging effect on the gut microbes is far worse than previously believed.
There are times when antibiotic treatment is the best, and sometimes, the only option that is available. The use of antibiotics has saved countless lives. However, as reported in the Medical Journal of Australia in 2014, doctors are prescribing antibiotics for new adult cases of acute bronchitis at a staggering 90.6% of the time. A rate that has steadily increased over a 15-year period, despite evidence, guidelines, and campaign efforts stating that the antibiotic prescribing rate should be zero.
Impact of Antibiotics on Gut Bacteria
Of all the factors that can impact the gut microbiome, antibiotics have the greatest effect. The older research using microbiology culture techniques, where the gut flora is grown first and then identified, suggested that changes in the gut flora would change for up to 40 days. Other changes that have been reported:
- overgrowth of already-present microorganisms, such as fungi (e.g. Candida) or Clostridium difficile
- overgrowth of these organisms is a frequent cause of antibiotic-associated diarrhoea, and in some cases can cause severe life threatening infection
- decrease the production of short chain fatty acids (SCFAs), which are important for electrolyte balance in the gut, maintenance of pH, improving colonic and hepatic blood flow, increasing the absorption of calcium, increasing the absorptive capacity of the small intestine, and maintaining integrity of the mucus lining of the gut
- increased susceptibility to intestinal pathogens and a lower number of pathogens is required to cause an infection
- decreased therapeutic effect of some medicinal herbs and phytoestrogen-rich foods as the activity of many medicinal herbs depends on their bacterial enzymatic metabolism in the colon
Source: Long-term impacts of antibiotic exposure on the human intestinal microbiota. Jernberg C, Lofmark S, Edlund C, et al. Microbiology 2010;156:3216-3223.
New research utilising more sensitive molecular analysis techniques has revealed:
- antibiotic resistant gut flora can persist for up to 4 years after antibiotic treatment
- alterations in gut flora can last significantly longer than previously believed. For example, changes in gut flora persist for 18 – 24 months after use of the antibiotic clindamycin and 4 years after triple therapy for Helicobacter pylori infection
- some gut bacteria never recover, even after a single dose of antibiotics
- antibiotics that are active against Gram-positive and Gram-negative bacteria will have the greatest impact on the gut flora
- it is interesting to note that the salivary microbiota composition remains relatively stable
The potential for antibiotics to influence the gut microflora is dependent on its spectrum of antimicrobial activity, rate of absorption, dosage and length of therapy. Antimicrobials that are poorly absorbed will have a greater effect than those that are well absorbed. However, even those that are well absorbed, if they are then excreted in their active forms via the bile, saliva or intestinal mucosa, they can still cause considerable damage.
Recent research has shown that individuals who had taken only one course of antibiotics had significantly lower serum concentrations of enterolactone up to 16 months post-antibiotic use compared to individuals who refrained taking antibiotics during the same time period. Enterolactone is produced in the gut as a result of microbial action on specific plant based fibres called lignans. This has clinical importance due to recent studies showing correlations between high serum enterolactone concentrations and protection from cardiovascular mortality and breast cancer.
With this in mind, it is interesting that this long-term change in microbiota composition is rarely taken into account when practitioners order and receive stool test results for their patients. Have antibiotics have been used recently or over the last 12 months? How many courses of antibiotics were taken? What type of antibiotic was used? It is not unusual to hear of patients receiving results of their stool test and are then recommended a course or courses of antibiotics to treat pathogens detected in the stool test. Repeat stool testing is performed sometimes within months of completing antibiotic treatment. I have seen the results of some of these tests and although the primary pathogen may have been eliminated, the composition of the beneficial flora has been severely compromised and new pathogens have appeared to become a problem.
Long-term Systemic Effects of Antibiotics
- antibiotic exposure in the first year of life may increase the risk of subsequent eczema by up to 40%. Broad spectrum antibiotics have an even greater effect. Each subsequent course of antibiotics may increase the risk by a further 7%
- animal studies have shown that antibiotics may increase the risk of obesity
- there is a 3-fold increase in inflammatory bowel disease in children who received seven or more courses of antibiotics, compared to those that received none
- there may be an increased risk of developing autoimmune diseases. Although some autoimmune diseases are thought to be triggered by infections, a recent study suggests that certain antibiotics used to treat these infections, may also trigger autoimmune diseases
- alarmingly, antibiotic use may increase the risk of cancer. The risk of certain cancers was more than 1.5 times more prevalent in individuals with six or more antibiotic prescriptions, compared to those with the lowest exposure
What to do if Antibiotic Treatment is Required?
There will always be some time in life that a course of antibiotics will be required. So what can we do to minimise the impact on the microflora? Like most, until recently I believed that there is no point in giving probiotics with antibiotics as the antibiotics would make them ineffective. There is mounting evidence that probiotics can be used with antibiotics by reducing their adverse effects, improve antibiotic function and enhance mucosal immunity. The evidence for the use of probiotics with antibiotics includes:
- reducing the risk of antibiotic induced superinfections in the gut and vagina
- secreting antibacterial substances that lower pathogenic bacteria and disrupt biofilms, enhancing the effect of antibiotics
- enhancing mucosal immunity, which in turn helps to remove pathogenic organisms at the mucosal layer in the gut
Post Antibiotic Gut Treatment
Immediately following a course of antibiotics a broad spectrum, high potency probiotic blend should be taken. The minimum effective dose is not known; however, it is recommended that probiotics containing 500 million to 1 billion colony forming units (CFU)/day be taken. Some studies recommend up to 450-900 billion CFU/day.
There have not been any specific studies on how long probiotics should be taken post-antibiotic treatment. This would depend on the strength of the antibiotic used, the length of treatment with antibiotics and the state of the gastrointestinal tract. There is limited research on probiotics taken over 28 days or more following antibiotic treatment, and some that show that taking probiotics over just 10-14 days can have a positive effect.