An antibiotic with no side effects could be on the horizon. Scientists say they have identified compounds that reduce the risk of nausea, indigestion, bloating and diarrhoea.
It opens the door to an antidote that saves certain microbes - without interfering with the drugs' destruction of harmful bugs. Antibiotics wipe out gut bacteria both good and bad - which can have long lasting health consequences.
The findings are based on an analysis of the effects of 144 different antibiotics on the microbiome - trillions of bacteria that live in our intestines. They boost digestion, provide nutrients and metabolites and work with the immune system to fend off illness.
Co-author Dr Ulrike Lober, of the Max-Delbruck-Centre for Molecular Medicine in Berlin, said: "This Herculean undertaking by an international team has identified a novel approach. It combines antibiotics with a protective antidote to help keep the gut microbiome healthy and reduce the harmful side effects of antibiotics without compromising their efficiency."
Antibiotics can damage these microbial communities, resulting in an imbalance that can lead to recurrent gastrointestinal problems caused by Clostridioides difficile infections. It can trigger obesity, allergies, asthma and other immunological or inflammatory diseases.
Using state of the art techniques Dr Lisa Maier, of the European Molecular Biology Laboratory in Heidelberg and colleagues investigated the collateral cost for the first time. They identified which antibiotics affect which types of bacterial species.
The breakthrough could help combat resistance to the drugs - one of the biggest threats facing mankind, according to the World Health Organisation.
What the study found
The study systematically analysed the growth and survival of 27 different bacterial species commonly found in the gut following treatment with the various antibiotics. It also assessed the minimal inhibitory concentration (MIC) required to stop bacteria from growing for over 800 antibiotic-bacteria combinations.
The results revealed the majority of gut bacteria had slightly higher MICs than disease-causing bacteria, suggesting that at commonly used antibiotic concentrations, most would not be affected. But two widely used antibiotic classes – tetracyclines and macrolides – stopped healthy bacteria growing at much lower concentrations than those required to stop the growth of disease-causing bacteria.
They also killed more than half of the gut bacterial species they tested - potentially altering the gut microbiome composition for a long time. Drugs interact differently across different bacterial species. So a second drug could be used to protect the gut microbes.
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The researchers combined the antibiotics erythromycin and doxycycline with a set of 1,197 pharmaceuticals to identify suitable drugs that would protect two abundant gut bacterial species (Bacteriodes vulgatus and Bacteriodes uniformis). Several promising candidates included the anticoagulant dicumarol, the gout medication benzbromarone and two anti-inflammatory drugs, tolfenamic acid and diflunisal.
Importantly, these drugs did not compromise the effectiveness of the antibiotics against disease-causing bacteria. Further experiments showed that these antidote drugs also protected natural bacterial communities derived from human stool samples and in living mice.
'Promising findings'
Dr Lober added: "Despite our promising findings, further research is needed to identify optimum and personalised combinations of antidote drugs and to exclude any potential long-term effects on the gut microbiome."
She presented the findings at the European Congress of Clinical Microbiology & Infectious Diseases in Copenhagen, Denmark.
