Chemical imaging of energetic intestine microbes. After transient incubation with heavy water, tradition medium and a drug, numerous chemical bonds (right here C–D and C–H) within the stool pattern are proven in yellow and inexperienced, their ratio in yellow-purple (left). Chosen microbes are detected in the identical picture part with fluorescence-labelled oligonucleotide probes in cyan. The exercise of the detected microbes will be decided based mostly on the quantity of C–D bonds. Credit score: Nature Microbiology (2024). DOI: 10.1038/s41564-024-01853-0
A brand new examine has revealed that the broadly prescribed Parkinson’s illness drug entacapone considerably disrupts the human intestine microbiome by inducing iron deficiency.
The findings, printed in Nature Microbiology, present new insights into the often-overlooked influence of human-targeted medicine on the microbial communities that play a crucial position in human well being.
The analysis was carried out inside the framework of the Cluster of Excellence “Microbiomes drive Planetary Health,” and included scientists from the College of Vienna, in collaboration with the College of Southampton, Aalborg College and Boston College.
Whereas it’s effectively established that antibiotics can considerably disrupt the human intestine microbiome, rising analysis reveals that a variety of human-targeted medicine—significantly these used to deal with neurological circumstances—may profoundly have an effect on the microbial communities dwelling in our our bodies.
Regardless of their supposed therapeutic results on completely different organs, these medicine can inadvertently disrupt the stability of intestine microbes, resulting in potential well being penalties.
Till now, most research investigating these interactions relied both on affected person cohort analyses affected by many confounding elements or on experiments utilizing remoted intestine micro organism, which don’t totally seize the complexity of the human microbiome.
A novel examine design to research drug–bug interactions
Utilizing a novel experimental strategy, the worldwide group studied the consequences of two medicine—entacapone and loxapine, a medicine for schizophrenia—on fecal samples from wholesome human donors. They incubated the samples with therapeutic concentrations of those medicine, then analyzed the influence on the microbial communities utilizing superior molecular and imaging methods, together with heavy water labeling mixed with Stimulated Raman Spectroscopy (SRS).
The group found that loxapine and much more so entacapone severely inhibited many microbiome members, whereas E. coli dramatically expanded within the presence of entacapone.
“The results were even more striking when we examined microbial activity, rather than just their abundance,” defined Fatima Pereira, lead creator of the examine and former Postdoctoral researcher on the College of Vienna. “The heavy water-SRS method allowed us to observe the subtle yet significant changes in the gut microbiome, which are often missed in traditional abundance-based measurements.”
Entacapone induces iron hunger, favors pathogenic microbes
The researchers hypothesized that entacapone would possibly intrude with iron availability within the intestine, a vital useful resource for a lot of microbes. Their experiments confirmed that including iron to fecal samples containing entacapone counteracted the drug’s microbiome-altering results.
Additional investigation revealed that E. coli, which thrived beneath these circumstances, carried a extremely environment friendly iron-uptake system (enterobactin siderophore). This method allowed the micro organism to beat iron hunger and proliferate, even within the presence of the drug.
“By showing that entacapone induces iron deficiency, we have uncovered a new mechanism of drug-induced gut dysbiosis, in which the drug selects for E. coli and other potentially pathogenic microbes well adapted to iron limiting conditions,” mentioned Michael Wagner, scientific director of the Excellence Cluster and vice-head of the Middle for Microbiology and Environmental Techniques Science (CeMESS) on the College of Vienna.
Wider implications for drug-microbiome interactions
This discovery has broader implications for understanding how different human-targeted medicine would possibly have an effect on the intestine microbiome. A number of medicine, together with entacapone, comprise metal-binding catechol teams, suggesting that this mechanism might be a extra widespread pathway for drug-induced microbiome alterations.
The findings additionally current a possibility to mitigate the unintended effects of medicine like entacapone. By making certain enough iron availability to the massive gut, it could be doable to scale back dysbiosis and the gastrointestinal points that usually accompany Parkinson’s illness remedy.
“The next step is to explore how we can modify drug treatments to better support the gut microbiome,” mentioned Wagner. “We are looking at strategies to selectively deliver iron to the large intestine, where it can benefit the microbiome without interfering with drug absorption in the small intestine.”
Extra info:
Fátima C. Pereira et al, The Parkinson’s illness drug entacapone disrupts intestine microbiome homoeostasis through iron sequestration, Nature Microbiology (2024). DOI: 10.1038/s41564-024-01853-0
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Parkinson’s drug adjustments the intestine microbiome for the more serious as a result of iron deficiency, examine reveals (2024, November 21)
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