Role of the gut microbiome in cardiovascular drug response: The potential for clinical application

Steiner, Heidi E.; Gee, Kevin; Giles, Jason B.; Knight, Hayley; Hurwitz, Bonnie; Karnes, Jason H.

doi:10.1002/phar.2650

Cited by 9 publications

(6 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… • Bioaccumulation of common drugs has been shown to be a common feature of commensal gut microbes 295 . This may in turn modify the drug dosage received by a patient, preventing clinical improvement 296 . Microbiome modulation to delete species that impact specific drugs may enhance patient response.…”

Section: Methods Of Microbiome-based Interventions Their Rationales A...mentioning

confidence: 99%

Microbiome-based interventions to modulate gut ecology and the immune system

et al. 2022

View full text Add to dashboard Cite

The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.

show abstract

Section: Methods Of Microbiome-based Interventions Their Rationales A...mentioning

confidence: 99%

Microbiome-based interventions to modulate gut ecology and the immune system

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The combination of an individual's genetic profiles with personal microbiome information will be a key driver toward stratification into human subpopulations (e.g. according to responder status or bioavailability status) and eventually a more accurate prediction of drug efficacy at the individual level (Steiner et al, 2022).…”

Section: Gut Microbiome Integration In Drug Discovery and Developmentmentioning

confidence: 99%

Gut Microbiome Integration in Drug Discovery and Development of Small Molecules

Jimonet,

Druart,

Blanquet-Diot

et al. 2024

Drug Metab Dispos

View full text Add to dashboard Cite

Human microbiomes, particularly in the gut, could have a major impact on the efficacy and toxicity of drugs. However, gut microbial metabolism is often neglected in the drug discovery and development process. Medicen, a Paris-based human health innovation cluster, has gathered more than 30 international leading experts from pharma, academia, biotech, clinical research organizations, and regulatory science to develop proposals to facilitate the integration of microbiome science into drug discovery and development. Seven subteams were formed to cover the complementary expertise areas of 1) pharma experience and case studies, 2) in silico microbiome-drug interaction, 3) in vitro microbial stability screening, 4) gut fermentation models, 5) animal models, 6) microbiome integration in clinical and regulatory aspects, and 7) microbiome ecosystems and models. Each expert team produced a state-of-the-art report of their respective field highlighting existing microbiome-related tools at every stage of drug discovery and development. The most critical limitations are the growing, but still limited, drug-microbiome interaction data to produce predictive models and the lack of agreed-upon standards despite recent progress. In this paper we will report on and share proposals covering 1) how microbiome tools can support moving a compound from drug discovery to clinical proof-of-concept studies and alert early on potential undesired properties stemming from microbiome-induced drug metabolism and 2) how microbiome data can be generated and integrated in pharmacokinetic models that are predictive of the human situation. Examples of drugs metabolized by the microbiome will be discussed in detail to support recommendations from the working group. SIGNIFICANCE STATEMENTGut microbial metabolism is often neglected in the drug discovery and development process despite growing evidence of drugs' efficacy and safety impacted by their interaction with the microbiome. This paper will detail existing microbiome-related tools covering every stage of drug discovery and development, current progress, and limitations, as well as recommendations to integrate them into the drug discovery and development process.

show abstract

“…Relevant to the present study, the gut microbiota is widely recognized as a key player in the metabolism of drugs . Extensive interactions between gut microbes and medications have been shown in vitro , with microbes possessing capacities to affect drug metabolism via gene, enzyme, and metabolite modification . For example, Eggerthella lenta produces glycoside reductase that inactivates the cardiac medication digoxin in the absence of arginine .…”

mentioning

confidence: 91%

“…5 Extensive interactions between gut microbes and medications have been shown in vitro 6,7 with microbes possessing capacities to affect drug metabolism via gene, enzyme, and metabolite modification. 8 For example, Eggerthella lenta produces glycoside reductase that inactivates the cardiac medication digoxin in the absence of arginine. 9 At the same time, medication use can also affect the gut microbiota and its diversity in CMD.…”

mentioning

confidence: 99%

Microbial Features Linked to Medication Strategies in Cardiometabolic Disease Management

Shearer,

Shah,

Shen-Tu

et al. 2024

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Human gut microbiota are recognized as critical players in both metabolic disease and drug metabolism. However, medication−microbiota interactions in cardiometabolic diseases are not well understood. To gain a comprehensive understanding of how medication intake impacts the gut microbiota, we investigated the association of microbial structure with the use of single or multiple medications in a cohort of 134 middle-aged adults diagnosed with cardiometabolic disease, recruited from Alberta's Tomorrow Project. Predominant cardiometabolic prescription medication classes (12 total) were included in our analysis. Multivariate Association with Linear Model (MaAsLin2) was employed and results were corrected for age, BMI, sex, and diet to evaluate the relationship between microbial features and single-or multimedication use. Highly individualized microbiota profiles were observed across participants, and increasing medication use was negatively correlated with α-diversity. A total of 46 associations were identified between microbial composition and single medications, exemplified by the depletion of Akkermansia muciniphila by β-blockers and statins, and the enrichment of Escherichia/Shigella and depletion of Bacteroides xylanisolvens by metformin. Metagenomics prediction further indicated alterations in microbial functions associated with single medications such as the depletion of enzymes involved in energy metabolism encoded by Eggerthella lenta due to β-blocker use. Specific dual medication combinations also had profound impacts, including the depletion of Romboutsia and Butyriciocccus by statin plus metformin. Together, these results show reductions in bacterial diversity as well as species and microbial functional potential associated with both single-and multimedication use in cardiometabolic disease.

show abstract

Role of the gut microbiome in cardiovascular drug response: The potential for clinical application

Cited by 9 publications

References 96 publications

Microbiome-based interventions to modulate gut ecology and the immune system

Microbiome-based interventions to modulate gut ecology and the immune system

Gut Microbiome Integration in Drug Discovery and Development of Small Molecules

Microbial Features Linked to Medication Strategies in Cardiometabolic Disease Management

Contact Info

Product

Resources

About