Predicting and Understanding the Human Microbiome’s Impact on Pharmacology

Hitchings, Reese; Kelly, Libusha

doi:10.1016/j.tips.2019.04.014

Cited by 40 publications

(29 citation statements)

References 84 publications

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“…Emerging evidences have shown that the modification of gut microbiota can drastically alter drug clinical effectiveness (Hitchings and Kelly, 2019). Recently, E. coli infection was observed to significantly reduce the absorption of orally administered enrofloxacin in broilers (Guo et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

et al. 2020

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Intestinal microbiota has been extensively studied in the context of host health benefit, and it has recently become clear that the gut microbiota influences drug pharmacokinetics and correspondingly efficacy. Intestinal microbiota dysbiosis is closely related with liver cirrhosis, especially the depletion of Lactobacillus. Therefore, the bioavailability of orally administered glycyrrhizic acid (GL) was speculated to be influenced under a pathological state. In the present study, L. murinus was isolated and screened for GL bioconversion capacity in vitro. Compared with Lactobacillus rhamnosus and Lactobacillus acidophilus, L. murinus was chosen for further investigation because it has the highest biotransformation rate. Our results showed that L. murinus could significantly improve the translocation of GL on Caco-2 cell models. Meanwhile, L. murinus was observed to have the ability to bind with the surface of Caco-2 cells and prominently downregulate the transporter gene expression level of multidrug resistance gene 1 (MDR1) and multidrug resistance protein 2 (MRP2), which were involved in the efflux of drugs. Furthermore, L. murinus was selected to be orally administred into rats in healthy and liver cirrhosis groups by a daily gavage protocol. Our data highlighted that supplements of L. murinus significantly improved the bioavailability of orally administered GL in rats, especially under a pathological condition, which may provide a novel strategy for improving the clinical therapeutic effect of liver protective drugs.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

et al. 2020

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“…10,11,33,134,135 Microbiota drug metabolism can lead to significant inter-individual pharmacokinetic variability. 136 For example, a strain of Eggerthella lenta capable of inactivating the cardiac glycoside drug digoxin is estimated to inhabit the guts of 40% of the global population. 137 Intestinal degradation of digoxin can lead to higher dose requirements of patients and make selecting a first dose difficult.…”

Section: Prediction Of Microbiome-drug Interactionsmentioning

confidence: 99%

Harnessing machine learning for development of microbiome therapeutics

et al. 2021

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The last twenty years of seminal microbiome research has uncovered microbiota's intrinsic relationship with human health. Studies elucidating the relationship between an unbalanced microbiome and disease are currently published daily. As such, microbiome big data have become a reality that provide a mine of information for the development of new therapeutics. Machine learning (ML), a branch of artificial intelligence, offers powerful techniques for big data analysis and predictionmaking, that are out of reach of human intellect alone. This review will explore how ML can be applied for the development of microbiome-targeted therapeutics. A background on ML will be given, followed by a guide on where to find reliable microbiome big data. Existing applications and opportunities will be discussed, including the use of ML to discover, design, and characterize microbiome therapeutics. The use of ML to optimize advanced processes, such as 3D printing and in silico prediction of drug-microbiome interactions, will also be highlighted. Finally, barriers to adoption of ML in academic and industrial settings will be examined, concluded by a future outlook for the field.

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“…Furthermore, the response to the same dose of biologics (mAb) in patients varies greatly due to significant variability in pharmacokinetics (PK), that is, the fate of drugs, including absorption, distribution, metabolism, and excretion in the body . The dosing regimen of biologics is normally selected based on evidence from clinical practice rather than from consideration of their PK and factors influencing individual exposure.…”

Section: Summary and Perspectivementioning

confidence: 99%

Myasthenia gravis and specific immunotherapy: monoclonal antibodies

Cai

et al. 2019

Annals of the New York Academy of Sciences

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Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as firstline treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.

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Predicting and Understanding the Human Microbiome’s Impact on Pharmacology

Cited by 40 publications

References 84 publications

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

Harnessing machine learning for development of microbiome therapeutics

Myasthenia gravis and specific immunotherapy: monoclonal antibodies

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