Drug–gut microbiota interactions: implications for neuropharmacology

Walsh, Jacinta; Griffin, Brendan T.; Clarke, Gerard; Hyland, Niall P.

doi:10.1111/bph.14366

Cited by 109 publications

(63 citation statements)

References 114 publications

(128 reference statements)

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“…Greater appreciation of the impacts of individual bacterial metabolites on vaginal physiology could provide important mechanistic insights into states of vaginal health and disease. It should further be noted that the expansive metabolic capacity of the microbiome can impact drug efficacy and safety, as some bacteria of the microbiome can directly metabolize xenobiotic or impact drug responses through immune‐mediated mechanisms, as suggested for immune checkpoint inhibitors used in cancer treatment .…”

Section: Introductionmentioning

confidence: 99%

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

et al. 2019

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Introduction Young women in sub‐Saharan Africa are disproportionately affected by HIV, accounting for 25% of all new infections in 2017. Several behavioural and biological factors are known to impact a young woman's vulnerability for acquiring HIV. One key, but lesser understood, biological factor impacting vulnerability is the vaginal microbiome. This review describes the vaginal microbiome and examines its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions. Discussion Although the composition of each woman's vaginal microbiome is unique, a microbiome dominated by Lactobacillus species is generally associated with a “healthy” vagina. Disturbances in the vaginal microbiota, characterized by a shift from a low‐diversity, Lactobacillus ‐dominant state to a high‐diversity non‐ Lactobacillus ‐dominant state, have been shown to be associated with a range of adverse reproductive health outcomes, including increasing the risk of genital inflammation and HIV acquisition. Gardnerella vaginalis and Prevotella bivia have been shown to contribute to both HIV risk and genital inflammation. In addition to impacting HIV risk, the composition of the vaginal microbiome affects the vaginal concentrations of some antiretroviral drugs, particularly those administered intravaginally, and thereby their efficacy as pre‐exposure prophylaxis (PrEP) for HIV prevention. Although the role of rectal microbiota in HIV acquisition in women is less well understood, the composition of this compartment's microbiome, particularly the presence of species of bacteria from the Prevotellaceae family likely contribute to HIV acquisition. Advances in technologies have facilitated the study of the genital microbiome's structure and function. While next‐generation sequencing advanced knowledge of the diversity and complexity of the vaginal microbiome, the emerging field of metaproteomics, which provides important information on vaginal bacterial community structure, diversity and function, is further shedding light on functionality of the vaginal microbiome and its relationship with bacterial vaginosis (BV), as well as antiretroviral PrEP efficacy. Conclusions A better understanding of the composition, structure and function of the microbiome is needed to identify opportunities to alter the vaginal microbiome and prevent BV and reduce the risk of HIV acquisition.

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Section: Introductionmentioning

confidence: 99%

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

et al. 2019

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“…It is used for the treatment of a wide range of cancers including colorectal, colon, breast, ovarian, liver, gastrointestinal and head and neck cancer . It exhibits antibacterial activity and augments the bactericidal effect of antibiotics . 5‐FU has been reported to be used in topical preparations for the treatment of malignant skin cancers .…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of lanthanum (III) and europium (III) 5‐fluorouracil complexes on Caco‐2 cell line

El‐Maali

Wahman

Aly

et al. 2020

Applied Organom Chemis

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Lanthanide complexes are of increasing importance in cancer diagnosis and therapy. In the present study 1:1 and 1:3 solid complexes of La (III)–5‐FU (5‐fluorouracil) were prepared and characterized. In solution, the formation of 1:1 La (III) and Eu (III) complexes enabled the enhancement of 5‐FU's effectiveness. Binding constants of the 1:1 complexes of both metals were estimated using spectrophotometry and HPLC with fluorescence detection methods. The thermodynamic parameters ΔG°, ΔH°and ΔS°were calculated using differential scanning calorimetry. Evaluation of the cytotoxic activity of the 1:1 La (III)‐ and Eu (III)–5‐FU complexes was performed through two methodologies, trypan blue for cell viability where La (III)‐ and Eu (III)–5‐FU complexes were found to have 52,000 and 80,000 dead cells, respectively, and via flow cytometric analysis to measure the apoptotic values, which were found to be 59.87 and 86.86% respectively.

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“…Evidences suggest that drugs can affect the functions and composition of the gut microbiome 3–5 . Increasing studies are focused on drug-microbiome interactions 1, 6 . In vitro gut microbiome culturing models are rapid, and cost-efficient approaches for studying drug-microbiome interactions and are increasingly applied to microbiome studies 7–11 .…”

Section: Introductionmentioning

confidence: 99%

Growth phase-dependent responses of an in vitro gut microbiome to metformin

Zhang

Ning

et al. 2020

Preprint

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In vitro gut microbiota models are often used to study drug-microbiome interaction. Similar to culturing individual microbial strains, the biomass accumulation of in vitro gut microbiota follows a logistic growth curve. Current studies on in vitro gut microbiome responses introduce drug stimulation during different growth stages, e.g. lag phase or stationary phase. However, in vitro gut microbiota in different growth phases may respond differently to same stimuli. Therefore, in this study, we used a 96-deep well plate-based culturing model (MiPro) to culture the human gut microbiota. Metformin, as the stimulus, was added at the lag, log and stationary phases of growth. Microbiome samples were collected at different time points for optical density and metaproteomic functional analysis. Results show that in vitro gut microbiota responded differently to metformin added during different growth phases, in terms of the growth curve, alterations of taxonomic and functional compositions. The addition of drugs at log phase leads to the greatest decline of bacterial growth. Metaproteomic analysis suggested that the strength of the metformin effect on the gut microbiome functional profile was ranked as lag phase > log phase > stationary phase. Our results showed that metformin added at lag phase resulted in a significantly reduced abundance of the Clostridiales order as well as an increased abundance of the Bacteroides genus, which was different from stimulation during the rest of the growth phase.Metformin also resulted in alterations of several pathways, including energy production and conversion, lipid transport and metabolism, translation, ribosomal structure and biogenesis. Our results indicate that the timing for drug stimulation should be considered when studying drugmicrobiome interactions in vitro.

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Drug–gut microbiota interactions: implications for neuropharmacology

Cited by 109 publications

References 114 publications

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

Anticancer activity of lanthanum (III) and europium (III) 5‐fluorouracil complexes on Caco‐2 cell line

Growth phase-dependent responses of an in vitro gut microbiome to metformin

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