Many non-antibiotic pharmaceutical drugs harm your gut biome

It is not only antibiotics that devastate our microbial biome

Pharmaceutical drugs may promote pathogens

The four most harmful drug categories

Results / outcomes

References

It is not only antibiotics that devastate our microbial biome

A quarter of all pharmaceutical drugs affect the growth of bacteria in your body, according to a 2018 study. (1) Drugs were selected from all therapeutic classes, including antipsychotics, proton-pump inhibitors such as omeprazole, calcium-channel blockers, antihistamines, painkillers, hormone mimickers and anti-cancer drugs. The researchers screened more than 1,000 marketed drugs against 40 representative gut bacterial strains. They found that 24% of the drugs they tested inhibited the growth of at least one strain of common representative gut bacteria. The worst offenders were the chemically diverse group of antipsychotics.

The researchers also found that the same bacterial species were often susceptible to both antibiotics and some of the drugs tested, so the bacteria have common pharmaceutical resistance mechanisms. This means the gut bacteria of patients consuming drugs like painkillers or proton-pump inhibitors might evolve a resistance that they then pass on to a pathogen that subsequently infects the body. There is therefore a risk that non-antibiotic drugs can promote antibiotic resistance.

Our body's microbiome plays a vital role in our health. In particular, the gut microbiome affects our immune system and our digestion. Upsets of the biome have been linked to a host of diseases including autoimmune diseases, obesity, digestive disorders, asthma and numerous psychological and brain disorders.

Another study published in October 2019 (3) found that the gut microbiome is at high risk of damage from pharmaceutical drugs in eighteen commonly used drug groups. This study shows that pharmaceutical drugs are even more harmful to the biome than earlier research indicated.

The term "gut microbiome" refers to the whole of the microbial population in the gut. The gut biome is an essential and health-giving "organ" in the human body. It comprises 40 trillion bacteria, viruses and fungi, with the bacteria belonging to over two thousand species in a healthy individual.

The composition of the gut bacteria is different between different individuals and population groups, conspicuously affected by food patterns, excessive hygiene and by medications (especially antibiotics).

In the last two decades several studies have shown that the health of the gut microbiome directly affects numerous chronic modern degenerative diseases such as obesity, diabetes, liver disease, cancer, depression, dementia, autism and other neurological disorders.

The harmful effects of pharmaceutical drug use range from changes in the relative proportions of different beneficial and potentially harmful bacterial species to alterations in genes and the cellular metabolism of the bacteria themselves.

The outcomes measured by the study included harmful intestinal infections and microbiome-linked conditions such as the risk of obesity and depression. It also found that pharmaceutical drugs in another eight categories promoted antibiotic resistance.

The researchers examined the effects of using drugs from forty one pharmaceutical categories on three groups of people: a control group representative of the general population; a group with inflammatory bowel disease (IBD) and a third group containing individuals with IBD as well as healthy controls. They compared 1,880 faecal samples from the three groups, analysing differences in the composition of the gut microbiota and the bacteria cellular metabolism induced by the drugs. They looked at the effects of using a single drug, and of multiple drugs used together.

Pharmaceutical drugs may promote pathogens

These non-antibiotic drugs not only inhibit good bacteria, but they may also promote the growth of harmful bacteria and other microbes. For example, a study found that the top diabetes drug metformin works by encouraging the growth of certain bacteria, particularly Akkermansia and Bifidobacterium. (2) Athanasios Typas, commenting on the more recent study (1), suggested that some pharmaceutical drugs work by affecting gut microbes - a possibility the drug originators and pharmaceutical companies have been largely unaware of until now.

"This 25% estimate is likely to be valid even if we include more drugs in the screen," said Kiran Patil, one of the scientists in study (1). He also drew attention to the wide range of drugs tested.

Athanasios Typas said both pathogens and good bacteria were affected by the drugs, with the good bacteria being worst affected. "Most non-antibiotics target one or a handful of species from the species we tested. But there are 40 non-antibiotics that target 10 or more species" Typas noted.

Patil and Typas said that non-antibiotic drugs that affect gut microbiomes had more antibiotic-like side effects, such as gastrointestinal problems. Their findings may help explain some of the terrible side effects of pharmaceutical drugs.

A study published in 2019 found that many pharmaceutical drugs are even more harmful than this research indicates.

The four most harmful drug categories

The study identified four drug categories that had the greatest impact on the gut microbiome:

• Antibiotics are used by more than one in three Europeans every year. Antibiotics wreck the gut biome, often for life.
• Proton pump inhibitors (PPIs). PPIs are used to treat digestive disorders such as heartburn, flatulence, oesophageal metaplasia and gastroesophageal reflux, which affect between 11% and 24% of the European population. PPIs are also used to treat peptic ulcers which occur after an overgrowth of Helicobacter pylori in the stomach lining. The study found that PPI users had increased numbers of bacteria in the upper digestive tract because of the reduced acidity, as well as increased levels of fatty acid synthesis within the gut lumen.
• Laxatives are used to relieve or prevent constipation, from which 17% of European adults suffer.
• Metformin is used to treat type 2 diabetes, from which 10% of the adult European population suffer. This drug category causes an increase in the level of the bacterium Escherichia coli, leading to harmful pathogenic infection.

Results / outcomes

The researchers also found that another seven drug groups caused significant changes to the gut bacterial populations. For example, a class of antidepressant called selective serotonin reuptake inhibitor (SSRIs) caused a spike in the potentially pathological bacterial species Eubacterium ramulus. Another example: oral steroids caused an abundance of methane-producing bacteria, promoting overweight / obesity / a high body mass index.

The researchers found that the efficiency and toxicity of pharmaceutical drugs are influenced by the patient's gut biome, as well as affecting it. The interaction between different drugs and the gut biome is also significant and complex. With each patient having their own individualised cocktail of drugs and medications, and their own and unique gut biome, the prescription of drugs for a particular patient by their doctor is virtually done in the dark. According to the lead researcher, "this study highlights the importance of considering the role of the gut microbiota when designing treatments and also points to new hypotheses that could explain certain side-effects associated with medication use."

References

1. Lisa Maier, Mihaela Pruteanu, Michael Kuhn, Georg Zeller, Anja Telzerow, Exene Erin Anderson, Ana Rita Brochado, Keith Conrad Fernandez, Hitomi Dose, Hirotada Mori, Kiran Raosaheb Patil, Peer Bork, Athanasios Typas. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. Published 19 March 2018. doi:10.1038/nature25979.

2. Forslund, K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262-266 (2015)

3. Vich Vila, Arnau. et al. Impact of 41 commonly used drugs on the composition, metabolic function and resistome of the gut microbiome. Presentation at UEG Week, Barcelona, October, 2019.