Gut microbiota modulation of chemotherapy efficacy and toxicity

Alexander, James L.; Wilson, Ian D.; Teare, Julian; Marchesi, Julian R.; Nicholson, Jeremy K.; Kinross, James

doi:10.1038/nrgastro.2017.20

Cited by 688 publications

(620 citation statements)

References 103 publications

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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 now known that cancer treatments cause a raft of changes to the microbiome and host innate immune system . There is significant heterogeneity in the microbiome and in immune function, and as such, this emergent data represents a chance to personalise cancer treatment, and allow the identification of patients at risk of severe symptoms .…”

Section: Introductionmentioning

confidence: 99%

The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity

Secombe

Coller

Gibson

et al. 2018

Intl Journal of Cancer

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Chemotherapy-induced gastrointestinal toxicity (CIGT) occurs in up to 80% of all patients undergoing cancer treatment, and leads to symptoms such as diarrhoea, abdominal bleeding and pain. There is currently limited understanding of how to predict an individual patient's risk of CIGT. It is believed the gut microbiome and its interactions with the host's innate immune system plays a key role in the development of this toxicity and potentially other toxicities, however comprehensive bioinformatics modelling has not been rigorously performed. The innate immune system is strongly influenced by the microbial environment and vice-versa. Ways this may occur include the immune system controlling composition and compartmentalisation of the microbiome, the microbiome affecting development of antigen-presenting cells, and finally, the NLRP6 inflammasome orchestrating the colonic host-microbiome interface. This evidence calls into question the role of pre-treatment risk factors in the development of gastrointestinal toxicity after chemotherapy. This review aims to examine evidence of a bidirectional interaction between the gut microbiome and innate immunity, and how these interactions occur in CIGT. In the future, knowledge of these interactions may lead to improved personalised cancer medicine, predictive risk stratification methods and the development of targeted interventions to reduce, or even prevent, CIGT severity.

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“…i. Microbiota-Derived Trace Amines. There is a growing recognition of the role of the commensal microbiota in health and disease, including neurologic and psychiatric disorders (Dinan and Cryan, 2015;Fung et al, 2017), cancer and its chemotherapy (Alexander et al, 2017;Roy and Trinchieri, 2017), metabolic disorders (Sonnenburg and Bäckhed, 2016;Brunkwall and Orho-Melander, 2017), and immune disorders (Honda and Littman, 2016;Thaiss et al, 2016;Fung et al, 2017;Luo et al, 2017). Prokaryotes contain a large array of decarboxylase enzymes, many of which include L-amino acids in their substrate profile (Zheng et al, 2011;Nelson et al, 2015).…”

Section: Vertebrate Trace Aminesmentioning

confidence: 99%