Systems to model the personalized aspects of microbiome health and gut dysbiosis

Matthewman, Cristina; Narin, Alexandra; Huston, Hannah; Hopkins, Christopher E.

doi:10.1016/j.mam.2022.101115

Cited by 7 publications

(6 citation statements)

References 186 publications

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“…The alpha diversity mainly refers to the species diversity and abundance of a single sample, while the beta diversity refers to the difference in species diversity between groups [21]. Furthermore, the intestinal flora of healthy people will maintain a relatively stable level in adulthood [22,23], and low-intensity exercise may not necessarily lead to changes in the richness and diversity of the intestinal flora (alpha and/or beta diversity) [17]. Therefore, as far as the results of this study were concerned, moderate exercise intervention seemed to have no significant influence on the intestinal flora diversity of the control group students, but the effect was indeed obvious for students with sleep disorders.…”

Section: Discussionmentioning

confidence: 99%

Exercise Interventions Improved Sleep Quality through Regulating Intestinal Microbiota Composition

Qiu

Gong

et al. 2022

IJERPH

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(1) Background: Sleep quality is closely related to the physical and mental health of college students. The objectives of this study were to obtain data on the sleep quality of university students and to investigate the relationship between intestinal flora and the improvement in sleep quality through exercise intervention. (2) Methods: Here, 11 university students with a body mass index (BMI) ≤ 18 and Pittsburgh Sleep Quality Index (PSQI) ≥ 7 were selected as experimental subjects, and another 11 healthy people were recruited as control subjects. The experimental group and control group were each intervened with exercise for 8 weeks. We used 16SrDNA sequencing technology to analyze the variations of the intestinal flora and the relation of the variations and sleep quality improvement between the experimental group and the control group before and after the exercise intervention. (3) Results: The differences in gut flora composition between people with sleep disorders and healthy people were statistically significant (p < 0.05). Before and after the exercise intervention, the differences were also statistically significant (p < 0.05) in people with sleep disorders. The sleep-disordered population had a larger proportion compared with the healthy population (p < 0.05). Blautia and Eubacterium hallii were microbe markers in the sleep-disordered population before and after the exercise intervention, while there was no microbe marker found in the healthy population. (4) Conclusions: The increase in Blautia and Eubacterium hallii, and the decrease in Agathobacter are associated with healthy sleep. Gut flora may be related to sleep disorders. Exercise intervention can improve sleep quality while changing the diversity of the gut flora, and exercise intervention targeting the gut flora is a new concept for preventing and treating sleep disorders.

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Section: Discussionmentioning

confidence: 99%

Exercise Interventions Improved Sleep Quality through Regulating Intestinal Microbiota Composition

Qiu

Gong

et al. 2022

IJERPH

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“…fish), whose physiology and host-microbiota relationships are, in some aspects, common with mammals. As they can be used in large numbers and are less expensive than rodents, they are well suited for screening similar to those carried out in vitro (Erkosar et al, 2013;Dirksen et al, 2016;Garc ıa-Gonz alez et al, 2017;Scott et al, 2017;Catron et al, 2019;Douglas, 2019;Ericsson, 2019;Kumar et al, 2020;Ludington and Ja, 2020;Poupet et al, 2020;Lu et al, 2021;Radeke and Herman, 2021;Matthewman et al, 2023). As with any result obtained from a simple model, it must then be confirmed in a complex system with close similarity to humans to enable extrapolation.…”

Section: Assaysmentioning

confidence: 99%

“…As with any result obtained from a simple model, it must then be confirmed in a complex system with close similarity to humans to enable extrapolation. In this context, one should not forget the large animal models such as pigs, often dismissed for cost reasons yet interesting thanks to their physiological proximity to humans and the possibility of simulating human pathologies (Zhang et al, 2013;Clayton et al, 2018;Coelho et al, 2018;Vlasova et al, 2018;Ericsson, 2019;Matthewman et al, 2023).…”

Section: Assaysmentioning

confidence: 99%

Gut Microbiome Integration in Drug Discovery and Development of Small Molecules

Jimonet,

Druart,

Blanquet-Diot

et al. 2024

Drug Metab Dispos

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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.

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“…Initial studies established the role of the microbiota in modifying the efficacy of certain drugs. One such study identified Levodopa, a treatment involved in Parkinson’s disease, as undergoing microbial transformation (Matthewman et al 2022 ). Two bacteria isolated from the gut, Enterococcus faecalis and Eggerthela lenta , were found to metabolize Levodopa before it crossed the blood–brain barrier, ultimately rendering it ineffective (Maini Rekdal et al 2019 ).…”

Section: Role Of the Microbiomementioning

confidence: 99%

Exploring the influence of the microbiome on the pharmacology of anti-asthmatic drugs

Chan,

Ghadieh,

Irfan

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals’ pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.

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Systems to model the personalized aspects of microbiome health and gut dysbiosis

Cited by 7 publications

References 186 publications

Exercise Interventions Improved Sleep Quality through Regulating Intestinal Microbiota Composition

Exercise Interventions Improved Sleep Quality through Regulating Intestinal Microbiota Composition

Gut Microbiome Integration in Drug Discovery and Development of Small Molecules

Exploring the influence of the microbiome on the pharmacology of anti-asthmatic drugs

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