The microbiota is composed of commensal bacteria and other microorganisms that live on the epithelial barriers of the host. The commensal microbiota is important for the health and survival of the organism. Microbiota influences physiological functions from the maintenance of barrier homeostasis locally to the regulation of metabolism, haematopoiesis, inflammation, immunity and other functions systemically. The microbiota is also involved in the initiation, progression and dissemination of cancer both at epithelial barriers and in sterile tissues. Recently, it has become evident that microbiota, and particularly the gut microbiota, modulates the response to cancer therapy and susceptibility to toxic side effects. In this Review, we discuss the evidence for the ability of the microbiota to modulate chemotherapy, radiotherapy and immunotherapy with a focus on the microbial species involved, their mechanism of action and the possibility of targeting the microbiota to improve anticancer efficacy while preventing toxicity.

Microbiota: a key orchestrator of cancer therapy.

The Human Gut Microbiome: From Association to Modulation

We thank the scientists and technical staff of the Luxembourg Centre for Systems Biomedicine and Center for Applied Nanobioscience and Medicine, particularly Matthew Barrett and Brett Duane for their excellent technical assistance and engineering support We are grateful to Francois Bernardin, Nathalie Nicot and Laurent Vallar for the microarray analysis; Aidos Baumuratov for imaging support; Linda Wampach for HuMiX illustrations; and Anna Heintz-Buschart for fruitful discussions This work was supported by an ATTRACT programme grant (ATTRACT/A09/03), a CORE programme grant (CORE/11/BM/1186762), a European Union Joint Programming in Neurodegenerative Diseases grant (INTER/JPND/12/01) and a Proof-of-Concept grant (PoC-15/11014639) to PW, Accompany Measures mobility grant (12/AM2c/05) to PW and PS, an INTER mobility grant to PS (INTER/14/7516918), and an Aide a la Formation Recherche (AFR) postdoctoral grant (AFR/PDR 2013-1/BM/5821107) as well as a CORE programme grant (CORE/14/BM/8066232) to JVF, all funded by the Luxembourg National Research Fund (FNR) This work was further supported by a grant attributed to CS-D by the 'Fondation Recherche sur le SIDA du Luxembourg' Bioinformatics analyses presented in this paper were carried out in part using the HPC facilities of the University of Luxembourg (http://hpcunilu)

/pdf/a-microfluidics-based-in-vitro-model-of-the-gastrointestinal-1b7z9ei6ja.pdf

A microfluidics-based in vitro model of the gastrointestinal human-microbe interface.

The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host-microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.

/pdf/a-complex-human-gut-microbiome-cultured-in-an-anaerobic-30r4q6hmb9.pdf

A Complex Human-Gut Microbiome Cultured in an Anaerobic Intestine-on-a-Chip

Background:Exposure to inorganic and organic arsenic compounds is a major public health problem that affects hundreds of millions of people worldwide. Exposure to arsenic is associated with cancer ...

Arsenic and Environmental Health: State of the Science and Future Research Opportunities

Awareness is growing concerning the potential role of the oral microbiota in radiotherapy-induced side effects like mucositis. In a small-scale patient study, we used denaturing gradient gel electrophoresis to visualize the shifts in the oral microbial community during radiotherapy. Samples of the first weeks of irradiation clustered together and towards the end of the therapy the richness decreased (-14 %) and the oral microbial community became dominated by a small fraction of species. The shifts at the level of the buccal mucosa and the tongue were correlated with different clinical parameters and a significant correlation between shifts in the buccal microbial community and the patients’ normal oral functioning (pain, nutrition) was observed. By monitoring the microbial shifts during therapy, the role of the microbiota can be further elucidated and treatment regimes can be adapted, increasing patients’ quality of life during therapy.

https://www.jscimedcentral.com/InfectiousDiseases/infectiousdiseases-2-1013.pdf

Dynamic shifts in the oral microbiome during radiotherapy

The major component in the pathogenesis of oral radiation-induced mucositis is progressive epithelial hypoplasia and eventual ulceration Irradiation inhibits cell proliferation, while cell loss at the surface continues We conceived to slow down this desquamation by increasing intercellular adhesion, regulated by the E-cadherin/catenin complex We investigated if 8-prenylnaringenin (8-PN) or tamoxifen (TAM) decrease the shedding of irradiated human buccal epithelial cells in vitro and thus delay the ulcerative phase of radiation-induced mucositis in vivo In vitro, aggregates of buccal epithelial cells were irradiated and cultured in suspension for 11 days 8-PN or TAM were investigated regarding their effect on cell shedding In vivo, the lower tongue surface of mice was irradiated with graded single doses of 25 kV X-rays The incidence, latency, and duration of the resulting mucosal ulcerations were analyzed after topical treatment with 8-PN, TAM or solvent 8-PN or TAM prevented the volume reduction of the irradiated cell aggregates during the incubation period This was the result of a higher residual cell number in the treated versus the untreated irradiated aggregates In vivo, topical treatment with 8-PN or TAM significantly increased the latency of mucositis from 109 to 121 and 124 days respectively, while the ulcer incidence was unchanged 8-PN and TAM prevent volume reduction of irradiated cell aggregates in suspension culture In the tongues of mice, these compounds increase the latency period This suggests a role for these compounds for the amelioration of radiation-induced mucositis in the treatment of head and neck tumors

8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis

The impact of irradiation on host-microbe crosstalk is still underexplored. By use of an in vitro oral mucosa model, we show an impact of irradiation on epithelial wound healing depending on the microbial composition and functionality. 454-pyrosequencing analyses pointed to a slight increase in abundance of Rothia, Granulicatella and Gemella in our model after irradiation. Further research is needed to unravel the effects of irradiation on the oral microbiota and the host-microbe interactions more in detail.

https://biblio.ugent.be/publication/7017244/file/7017245.pdf

Tine De Ryck

Papers

Dynamic shifts in the oral microbiome during radiotherapy

8-prenylnaringenin and tamoxifen inhibit the shedding of irradiated epithelial cells and increase the latency period of radiation-induced oral mucositis

Effects of Irradiation on Epithelial Wound Healing and Microbial Diversity in an in-vitro Oral Mucosa Model