Restoring Microflora Post-Antibiotic: Is it Worth Considering?

For many years, scientists have attempted to answer this question.

Doctors recommend taking antibiotics to treat various infectious diseases. However, probiotics should only be taken on a doctor’s recommendation to protect the intestine. While some experts believe that probiotics must be taken along with antibiotics, others argue that the body can cope with the consequences of treatment on its own.

Antibiotics can indeed harm the intestinal microbiome, although it typically returns to normal on its own in most cases. There is currently no convincing evidence that probiotics can effectively treat or prevent diarrhea caused by antibiotics. However, drugs containing the bacteria Lactobacillus rhamnosus GG and Saccharomyces boulardii can be used if desired.

How did the idea arise that the microbiota needs to be restored after antibiotics?

The microorganisms, including bacteria, viruses, protozoa, and others, that reside on the surface and inside the human body are collectively referred to as microbiota, microbiome, or microflora. The discovery that microorganisms inhabit the body was made by the naturalist Antonie van Leeuwenhoek in the late 17th century, when he observed bacteria in a sample of his own dental plaque under a microscope and gave them the name “animacules” or “little animals”. The term “microbiota” was later coined in the early 20th century as scientists recognized the significant role that microbes play in the body’s functioning.

Microscopic organisms can be found living in various parts of the body, such as the skin, oral cavity, respiratory and reproductive systems, and others. However, the largest number of microorganisms are located in the gastrointestinal tract (GIT), where there are over 3000 different species of bacteria and other microorganisms. These microorganisms perform various functions in the GIT.

Digestive

Intestinal microorganisms can subject proteins, fats, and carbohydrates that remain undigested in the small intestine to enzymatic breakdown. Certain substances can only be metabolized by the intestinal microflora since the body does not produce the required enzymes.

Metabolic

The intestinal microflora plays a role in synthesizing B-group vitamins and vitamin K, which is responsible for blood clotting and delivering calcium. Additionally, it participates in the metabolism of bone and connective tissues.

Protective

Bacteriocins, which are antibacterial substances synthesized by intestinal bacteria, protect the body from colonization by pathogenic microorganisms. Short-chain fatty acids, such as butyric acid, have an anti-inflammatory effect on the intestinal mucosa and reduce the permeability of the intestinal wall to harmful foreign microorganisms.

Changes in the microflora that occur for various reasons during a person’s lifetime may contribute to the development of some non-infectious diseases, such as non-alcoholic fatty liver disease.

Antibiotics are believed to indiscriminately destroy bacteria, potentially causing diseases that a healthy microbiome would protect against. Probiotics containing live beneficial microorganisms, such as lacto- and bifidobacteria, are suggested as a means of restoring the microbiome. However, this hypothesis lacks clinical evidence.

In reality, most microbiota inhabitants reside in the intestine for decades, and although their numbers may change over time, the microbiome of a healthy adult is relatively stable and can recover on its own, such as after an illness or medication intake. The differences in microflora composition between individuals are significantly greater than the changes that occur in one person’s lifetime, including after taking antibiotics.

What are the real consequences of antibiotics?

The disruption of gut microbiota due to antibiotics has been associated with the development of obesity, diabetes, hypertension, and non-infectious inflammatory bowel diseases. However, most studies examining the risk of developing these conditions while taking antibiotics have been conducted only on animals. The only well-established side effect of antibiotics in humans related to microbiota is diarrhea.

Antibiotic-associated diarrhea

Antibiotic-associated diarrhea is a type of diarrhea that occurs in connection with the use of antibiotics and has no other causes. It can start during treatment or within eight weeks after the end of the course. The main symptom is watery stool three or more times a day. The disorder usually runs a mild course and resolves within a few days without treatment.

Between 17.5% to 39% of patients taking antibiotics outside of the hospital may suffer from antibiotic-associated diarrhea. This can be a side effect of the drug itself, but not necessarily. Antibiotics alter the composition of the intestinal bacterial flora, which can lead to disturbances in carbohydrate and bile acid metabolism.

Most carbohydrates are absorbed in the small intestine, but some of them are fermented by bacteria and converted into short-chain fatty acids. When antibiotics kill bacteria, there is an excess of unused carbohydrates in the intestine, which attract water and dilute stool, causing osmotic diarrhea. As the microbiota recovers on its own, carbohydrate absorption normalizes.

The risk of developing diarrhea after antibiotics is higher for individuals who have experienced this complication during previous antibacterial treatment, those who take antibiotics for a prolonged period, such as more than one course, and those who are being treated with multiple antibacterial drugs at the same time.

Infection

The bacterium Clostridium difficile produces toxins that can lead to the development of pseudomembranous colitis, an inflammatory disease of the colon. Although it may not cause any symptoms, it is still a potential source of health complications.

As previously established, antibiotics impact the metabolic function of the microbiota, triggering a chain reaction. This suppression of normal microbiota diminishes the protective abilities of bacteria, thereby giving potentially pathogenic microorganisms free rein. Consequently, the risk of developing not only osmotic diarrhea, but also infectious diarrhea, including that caused by Clostridium difficile, increases.

The main signs of infection include:

• Experiencing diarrhea three or more times a day, which can increase to up to 15 times a day in severe cases.
• Experiencing pain and cramps in the lower abdomen.
• Having a body temperature above 38.3 °C.
• Feeling nauseous.
• Suffering from dehydration.
• Observing blood or pus in the stool.
• Experiencing a loss of appetite and weight loss.

The severity of infection symptoms can vary, and they may arise during antibiotic therapy or within 5-10 days after treatment cessation. In some cases, symptoms can appear up to 10 weeks following a course of antibiotics.

While rare in home conditions, C. difficile infections are more prevalent among hospital patients due to the bacterium’s presence on frequently-touched surfaces like bedside tables, doorknobs, and sinks. Failure to comply with hygiene practices by both patients and medical personnel increases the risk of infection.

When C. difficile infection is suspected, tests are conducted, and if the diagnosis is confirmed, antibiotics such as vancomycin or metronidazole paradoxically become part of the treatment.

In some cases, Clostridioides difficile infection may progress to a chronic form. In such instances, it may not be entirely possible to eliminate the infection, and microbiota restoration is the only viable solution. Rather than probiotics, fecal transplantation is the preferred method. Typically, healthy microbiota donors are close relatives such as spouses, parents, siblings, and adult children of elderly patients. Doctors obtain a fresh stool sample from the donor, mix it with saline, pass it through a special filter, and administer it to the patient’s intestine using colonoscopy or enema.

Which antibiotics most often cause diarrhea?

Antibiotic-associated diarrhea can result from the use of almost all antibiotics. However, certain drug groups have a higher likelihood of causing complications, including:

• Macrolides, such as clarithromycin.
• Cephalosporins, including cefdinir and cefpodoxime.
• Fluoroquinolones, such as ciprofloxacin and levofloxacin.
• Penicillins, including amoxicillin and ampicillin.

Broad-spectrum antibiotics are more likely to cause diarrhea than narrow-spectrum antibiotics due to their wider range of action.

What doctors and scientists say about the benefits of probiotics

Several clinical trials have suggested that probiotics can be effective in preventing and treating antibiotic-associated diarrhea. However, the authors of these studies often make significant methodological errors, including:

1. Using different strains of bacteria and varying dosages across studies, with some strains not well-documented.
2. Conducting many trials solely on hospitalized patients, which may not be representative of those treated at home. In both hospital and outpatient settings, doctors may use different types and dosages of antibiotics.
3. Not including a control group in some studies, instead administering a probiotic instead of a placebo.
4. Failing to track the effects of antibiotics and probiotics on individuals from different nationalities and regions, despite the knowledge that the composition of the microbiota is influenced by factors such as gender, ethnicity, and place of residence.

Therefore, it is currently not possible to draw a definitive conclusion on the use of probiotics for restoring the microflora based on the results of these studies.

For instance, a systematic review and meta-analysis of studies conducted by researchers at the University of Copenhagen found that probiotics can reduce the frequency of diarrhea by almost two times after a course of antibiotics. However, the authors of the review note that the data obtained cannot be fully trusted due to the high risk of systematic errors.

Moreover, two studies that tracked the effects of probiotics on the microbiota composition produced different results. In one study, probiotics had no effect on the microbiota composition after antibiotic intake, while in another study, researchers found that probiotics helped the microbiota recover faster after antibacterial therapy.

Official medical organizations hold diverging opinions on whether probiotics should be taken alongside antibacterial drugs.

World Gastroenterology Organisation (WGO) recommend including certain types of probiotics in clinical recommendations to prevent antibiotic-associated diarrhea. Meanwhile, American gastroenterologists believe that further research is needed before giving advice on restoring the microbiome with probiotics. On the other hand, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommends against using probiotics for the treatment and prevention of antibiotic-associated diarrhea.

How to restore intestinal function after taking antibiotics

If there is no suspicion of Clostridioides difficile infection, treating diarrhea during antibiotic therapy is unnecessary. Instead, it is enough to follow general recommendations:

• Drink more fluids, but refrain from consuming coffee, strong tea, sweet carbonated drinks, and alcohol.
• Temporarily avoid dairy products, fatty and spicy foods that may complicate the digestive process.