No abstract

The gut microbiota has emerged as a key modulator of cancer treatment responses in terms of both efficacy and toxicity. This effect is clearly mediated by processes impacting the activation and modulation of immune responses. More recently, the ability to regulate chemotherapeutic drug metabolism has also emerged as a key driver of response, although the direct mechanisms have yet to be fully elucidated. Through fermentation, the gut microbiota can produce several types of metabolites, including short-chain fatty acids (SCFAs). SCFAs play an important role in maintaining epithelial barrier functions and intestinal homeostasis, with recent work suggesting that SCFAs can modulate response to cancer treatments and influence both anti-tumor immune response and inflammatory-related side effects. In this review, we will discuss the importance of SCFAs and their implications for cancer treatment response and toxicities.

Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation reflects a current lack of authoritative guidance on reporting standards that would facilitate replication efforts and ultimately reproducible science. We therefore systematically reviewed all FMT protocols used in mouse models with the goal of formulating recommendations on the reporting of preclinical FMT protocols. Search strategies were applied across three databases (PubMed, EMBASE, and Ovid Medline) until June 30, 2020. Data related to donor attributes, stool collection, processing/storage, recipient preparation, administration, and quality control were extracted. A total of 1753 papers were identified, with 241 identified for data extraction and analysis. Of the papers included, 92.5% reported a positive outcome with FMT intervention. However, the vast majority of studies failed to address core methodological aspects including the use of anaerobic conditions (91.7% of papers lacked information), storage (49.4%), homogenization (33.6%), concentration (31.5%), volume (19.9%) and administration route (5.3%). To address these reporting limitations, we developed the Guidelines for Reporting Animal Fecal Transplant (GRAFT) that guide reporting standards for preclinical FMT. The GRAFT recommendations will enable robust reporting of preclinical FMT design, and facilitate high-quality peer review, improving the rigor and translation of knowledge gained through preclinical FMT studies.

Mounting evidence suggests the gut microbiome in uences radiotherapy e cacy and toxicity by modulating immune signalling. However, its contribution to radiotherapy outcomes in head and neck cancer (HNC) is yet to be investigated. This study, therefore, aimed to uncover associations between an individual's pre-therapy gut microbiota and i) severity of radiotherapy-induced oral mucositis (OM), and ii) recurrence risk in patients with HNC. MethodsIn this prospective pilot study, 20 patients with HNC scheduled to receive radiotherapy or chemoradiotherapy were recruited. Stool samples were collected before treatment and microbial composition was analysed using 16S rRNA gene sequencing. OM severity was assessed using the NCI-CTCAE scoring system. Patients were also followed for 12 months of treatment completion to assess tumour recurrence. ResultsOverall, 80% of the patients were male with a median age of 65.5 years. 53% experienced mild/moderate OM while 47% developed severe OM. Further, 18% experienced tumour relapse within 1 year of treatment completion. A pre-treatment microbiota enriched of Eubacterium, Victivallis, and Ruminococcus was associated with severe OM. Conversely, a higher relative abundance of immunomodulatory microbes Faecalibacterium, Prevotella, and Phascolarctobacterium was associated with a lower risk of tumour recurrence. ConclusionOur results indicate that a patient's gut microbiota composition at the start of treatment is linked to OM severity and recurrence risk. We now seek to validate these ndings to determine their ability to predict treatment outcomes in HNC, with the goal of using this data to inform second-generation microbial therapeutics to optimise treatment outcomes for patients with HNC.

Oral mucositis (OM) is one of the most common and debilitating oral complications of cancer treatments including chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. It is associated with severe pain and difficulties in chewing, swallowing, and speech. This leads to impairment of basic oral functions and could result in unplanned treatment interruption or modification. As such, OM negatively impacts both patients' quality of life as well as tumor prognostic outcomes. Understanding pathways underlying OM pathogenesis help identify new targets for intervention or prevention. The pathophysiology of OM has been widely studied over past decades with several pathways related to oxidative stress, inflammation, and molecular and cellular signaling being implicated. In this mini-review, we will discuss the emerging role of the oral-gut microbiome axis in the development of OM. Particularly, we will elaborate on how the alterations in the oral and gut microbiota as well as intestinal dysfunction caused by cancer treatments could contribute to the pathogenesis of OM. Further, we will briefly discuss the potential methods for targeting the oral-gut microbiome axis to improve OM outcomes.