Antibiotics and gut flora: What do probiotic trials show?

Antibiotics save lives, and when your doctor prescribes a course, you should take it. But antibiotics do not tell the difference between the bacteria that make you ill and the billions that live peacefully in your gut.

So the question is not whether your gut flora is affected. It is. The question is how much, for how long, and whether probiotics make any difference.

It happens within a few days

In an American study, researchers followed three people for ten months while they took two courses of the antibiotic ciprofloxacin. Within three to four days the diversity of their gut flora had fallen, and its make-up had changed markedly [1].

A Danish study from the University of Copenhagen gave twelve healthy young men a powerful combination of three antibiotics for four days. Bifidobacteria and bacteria that produce butyrate largely disappeared, while other species, including some that can cause disease, grew in their place [2].

Most people recover, but not always fully

The good news: gut flora is robust. In the Danish study it looked like itself again after about a month and a half [2].

But not entirely. Nine common species that all the participants had before the course still could not be found in most of them after six months. The researchers call this a "mild yet long-lasting imprint" [2]. In the American study the flora began to return a week after the course, but the return was often incomplete, and all three ended up in a new, stable state that was different from before [1].

Two things are worth remembering: both studies are very small, and the Danish one used a combination of antibiotics that is normally only used in hospitals. They cannot tell you how long recovery takes after an ordinary course of penicillin from your GP. And the response differed from person to person [1].

Diarrhoea during the course: where probiotics have the best evidence

Diarrhoea is a common side effect of antibiotics. Here, probiotics have actually been studied thoroughly.

Children: A Cochrane review pooled 33 trials with 6,352 children. With probiotics, 8% got diarrhoea; without, 19% did. Nine children had to be treated for one child to avoid diarrhoea [3]. The effect was greatest at 5 billion CFU or more a day. Read more about what CFU means in our article on CFU and bacterial strains.
Adults: A meta-analysis of 36 placebo-controlled trials with 9,312 adults found that the risk of diarrhoea fell by 38% [4]. Side effects were no more frequent than with placebo.

This does not apply to every product, though. The European Society for Paediatric Gastroenterology (ESPGHAN) recommends only two specific types for children, Lactobacillus rhamnosus GG and the yeast Saccharomyces boulardii, and states that other strains and combinations lack sufficient evidence [5]. So the trials show that specific strains at specific doses work, not that "probiotics" as such do.

C. difficile: the effect depends on your risk

Clostridioides difficile is a bacterium that can cause severe diarrhoea, especially in older people and hospital patients after antibiotics. A Cochrane review of 39 trials with 9,955 participants found that C. difficile diarrhoea affected 1.5% with probiotics versus 4.0% without [6].

But that figure hides an important difference:

In trials where participants had more than a 5% risk of C. difficile, typically hospital patients, the rate fell from 11.6% to 3.1%. Here, 12 people had to be treated for one to avoid the illness [6].
In trials with low risk there was no measurable difference [6].

For a healthy adult taking a short course at home, the risk of C. difficile is low, and a benefit has not been shown.

Can probiotics rebuild your gut flora afterwards?

Many products promise to "rebuild your gut flora after antibiotics". That is not what the trials above measured. They measured diarrhoea, not whether the flora recovers.

An Israeli study from 2018 looked at exactly that question, and the result was surprising. Healthy volunteers were given antibiotics and then split into three groups. In those who took a multi-strain probiotic, their own gut flora came back more slowly and less completely than in those who took nothing. The group that instead got their own stool back, saved from before the course, recovered almost fully within a few days [7].

The study is small, and it has not been repeated in a large trial. Nor does it rule out that probiotics can reduce diarrhoea during the course. But it means that the claim that probiotics rebuild your gut flora after antibiotics has no evidence behind it, and that the only direct test pointed the other way.

Who should be careful?

For healthy people, the trials show no more side effects with probiotics than with placebo [4]. The Cochrane review on C. difficile found short-term use safe in patients who were not immunocompromised or severely debilitated [6].

For the sickest patients, the picture is different. In a large Canadian trial with 2,653 patients on ventilators in intensive care units, L. rhamnosus GG did not help against pneumonia or anything else the researchers measured. On the other hand, the bacterium was found in the blood or other places where it does not belong in 15 patients, against one in the placebo group [8].

If you are seriously ill, have a weakened immune system or have a catheter in a vein, talk to your doctor before taking probiotics. Read more in the article on who should not take probiotics.

What you can do

Take the course as prescribed. Do not stop early because your stomach is playing up.
If you are considering probiotics for diarrhoea, choose a strain that has been studied for that purpose rather than a product with many strains and big numbers on the label. Feel free to ask at the pharmacy or your doctor, especially for children.
Give your gut time. For most people the flora largely comes back on its own within a few weeks [2]. Varied food with fibre feeds the bacteria you have. Read more in the article on prebiotics.
Contact your doctor if during or after the course you get watery diarrhoea many times a day, a fever, stomach pain or blood in your stool.

The bottom line

Antibiotics change your gut flora within a few days.
In most people it looks like itself again after a few weeks, but some species can be missing for months.
In trials, specific probiotic strains have reduced diarrhoea during antibiotics, with the greatest effect in children and in hospital patients at high risk of C. difficile.
It has not been shown that probiotics rebuild your gut flora after a course. The only direct trial found that recovery was slower.

Sources

Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A. 2011. PMID 20847294
Palleja A et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol. 2018. PMID 30349083
Guo Q et al. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2019. PMID 31039287
Liao W et al. Probiotics for the Prevention of Antibiotic-associated Diarrhea in Adults: A Meta-Analysis of Randomized Placebo-Controlled Trials. J Clin Gastroenterol. 2021. PMID 33234881
Szajewska H et al. Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Children. J Pediatr Gastroenterol Nutr. 2016. PMID 26756877
Goldenberg JZ et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017. PMID 29257353
Suez J et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018. PMID 30193113
Johnstone J et al. Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial. JAMA. 2021. PMID 34546300

This article is general information and not medical advice.