'Just Google it'-A scoping review of online mental health resources for survivors of breast cancer.

OBJECTIVE: As the Internet is a ubiquitous resource for information, we aimed to replicate a patient's Google search to identify and assess the quality of online mental health/wellbeing materials available to support women living with or beyond cancer. METHODS: A Google search was performed using a key term search strategy including search strings 'cancer', 'wellbeing', 'distress' and 'resources' to identify online resources of diverse formats (i.e., factsheet, website, program, course, video, webinar, e-book, podcast). The quality evaluation scoring tool (QUEST) was used to analyse the quality of health information provided. RESULTS: The search strategy resulted in 283 resources, 117 of which met inclusion criteria across four countries: Australia, USA, UK, and Canada. Websites and factsheets were primarily retrieved. The average QUEST score was 10.04 (highest possible score is 28), indicating low quality, with 92.31% of resources lacking references to sources of information. CONCLUSIONS: Our data indicated a lack of evidence-based support resources and engaging information available online for people living with or beyond cancer. The majority of online resources were non-specific to breast cancer and lacked authorship and attribution.

Role of mucositis in predicting gut microbiota composition in people with cancer.

PURPOSE OF REVIEW: Disruption of the precious ecosystem of micro-organisms that reside in the gut - the gut microbiota - is rapidly emerging as a key driver of adverse side effects/toxicities caused by numerous anti-cancer agents. Although the contribution of the gut microbiota to these toxicities is understood with ever increasing precision, the cause of microbial disruption (dysbiosis) remains poorly understood. Here, we discuss current evidence on the cause(s) of dysbiosis after cancer therapy, positioning breakdown of the intestinal mucosa (mucositis) as a central cause. RECENT FINDINGS: Dysbiosis in people with cancer has historically been attributed to extensive antibiotic use. However, evidence now suggests that certain antibiotics have minimal impacts on the microbiota. Indeed, recent evidence shows that the type of cancer therapy used predicts microbiota composition independently of antibiotics. Given most anti-cancer drugs have modest effects on microbes directly, this suggests that their impact on the gut microenvironment, in particular the mucosa, which is highly vulnerable to cytotoxicity, is a likely cause of dysbiosis. Here, we outline evidence that support this hypothesis, and discuss the associated clinical implications/opportunities. SUMMARY: The concept that mucositis dictates microbiota compositions provides two important implications for clinical practice. Firstly, it reiterates the importance of prioritising the development of novel mucoprotectants that preserve mucosal integrity, and indirectly support microbial stability. Secondly, it provides an opportunity to identify dysbiotic events and associated consequences using readily accessible, minimally invasive biomarkers of mucositis such as plasma citrulline.

The Degree of Inulin Polymerization Is Important for Short-Term Amelioration of High-Fat Diet (HFD)-Induced Metabolic Dysfunction and Gut Microbiota Dysbiosis in Rats.

Inulin, a non-digestible polysaccharide, has gained attention for its prebiotic properties, particularly in the context of obesity, a condition increasingly understood as a systemic inflammatory state linked to gut microbiota composition. This study investigates the short-term protective effects of inulin with different degrees of polymerization (DPn) against metabolic health deterioration and gut microbiota alterations induced by a high-fat diet (HFD) in Sprague Dawley rats. Inulin treatments with an average DPn of 7, 14, and 27 were administered at 1 g/kg of bodyweight to HFD-fed rats over 21 days. Body weight, systemic glucose levels, and proinflammatory markers were measured to assess metabolic health. Gut microbiota composition was analyzed through 16S rRNA gene sequencing. The results showed that inulin27 significantly reduced total weight gain and systemic glucose levels, suggesting a DPn-specific effect on metabolic health. The study also observed shifts in gut microbial populations, with inulin7 promoting several beneficial taxa from the Bifidobacterium genera, whilst inducing a unique microbial composition compared to medium-chain (DPn 14) and long-chain inulin (DPn: 27). However, the impact of inulin on proinflammatory markers and lipid metabolism parameters was not statistically significant, possibly due to the short study duration. Inulin with a higher DPn has a more pronounced effect on mitigating HFD-induced metabolic health deterioration, whilst inulin7 is particularly effective at inducing healthy microbial shifts. These findings highlight the benefits of inulin as a dietary adjuvant in obesity management and the importance of DPn in optimizing performance.

Supporting gut health with medicinal cannabis in people with advanced cancer: potential benefits and challenges.

The side effects of cancer therapy continue to cause significant health and cost burden to the patient, their friends and family, and governments. A major barrier in the way in which these side effects are managed is the highly siloed mentality that results in a fragmented approach to symptom control. Increasingly, it is appreciated that many symptoms are manifestations of common underlying pathobiology, with changes in the gastrointestinal environment a key driver for many symptom sequelae. Breakdown of the mucosal barrier (mucositis) is a common and early side effect of many anti-cancer agents, known to contribute (in part) to a range of highly burdensome symptoms such as diarrhoea, nausea, vomiting, infection, malnutrition, fatigue, depression, and insomnia. Here, we outline a rationale for how, based on its already documented effects on the gastrointestinal microenvironment, medicinal cannabis could be used to control mucositis and prevent the constellation of symptoms with which it is associated. We will provide a brief update on the current state of evidence on medicinal cannabis in cancer care and outline the potential benefits (and challenges) of using medicinal cannabis during active cancer therapy.

From hype to hope: Considerations in conducting robust microbiome science.

Microbiome science has been one of the most exciting and rapidly evolving research fields in the past two decades. Breakthroughs in technologies including DNA sequencing have meant that the trillions of microbes (particularly bacteria) inhabiting human biological niches (particularly the gut) can be profiled and analysed in exquisite detail. This microbiome profiling has profound impacts across many fields of research, especially biomedical science, with implications for how we understand and ultimately treat a wide range of human disorders. However, like many great scientific frontiers in human history, the pioneering nature of microbiome research comes with a multitude of challenges and potential pitfalls. These include the reproducibility and robustness of microbiome science, especially in its applications to human health outcomes. In this article, we address the enormous promise of microbiome science and its many challenges, proposing constructive solutions to enhance the reproducibility and robustness of research in this nascent field. The optimisation of microbiome science spans research design, implementation and analysis, and we discuss specific aspects such as the importance of ecological principals and functionality, challenges with microbiome-modulating therapies and the consideration of confounding, alternative options for microbiome sequencing, and the potential of machine learning and computational science to advance the field. The power of microbiome science promises to revolutionise our understanding of many diseases and provide new approaches to prevention, early diagnosis, and treatment.

More than a small adult brain: Lessons from chemotherapy-induced cognitive impairment for modelling paediatric brain disorders.

Childhood is recognised as a period of immense physical and emotional development, and this, in part, is driven by underlying neurophysiological transformations. These neurodevelopmental processes are unique to the paediatric brain and are facilitated by augmented rates of neuroplasticity and expanded neural stem cell populations within neurogenic niches. However, given the immaturity of the developing central nervous system, innate protective mechanisms such as neuroimmune and antioxidant responses are functionally naïve which results in periods of heightened sensitivity to neurotoxic insult. This is highly relevant in the context of paediatric cancer, and in particular, the neurocognitive symptoms associated with treatment, such as surgery, radio- and chemotherapy. The vulnerability of the developing brain may increase susceptibility to damage and persistent symptomology, aligning with reports of more severe neurocognitive dysfunction in children compared to adults. It is therefore surprising, given this intensified neurocognitive burden, that most of the pre-clinical, mechanistic research focuses exclusively on adult populations and extrapolates findings to paediatric cohorts. Given this dearth of age-specific research, throughout this review we will draw comparisons with neurodevelopmental disorders which share comparable pathways to cancer treatment related side-effects. Furthermore, we will examine the unique nuances of the paediatric brain along with the somatic systems which influence neurological function. In doing so, we will highlight the importance of developing in vitro and in vivo paediatric disease models to produce age-specific discovery and clinically translatable research.

Supportive Care in Pediatric Oncology: Opportunities and Future Directions.

The optimization of outcomes for pediatric cancer patients relies on the successful advancement of supportive care to ease the treatment burden and mitigate the long-term impacts of cancer therapy. Advancing pediatric supportive care requires research prioritization as well as the development and implementation of innovations. Like the prevailing theme throughout pediatric oncology, there is a clear need for personalized or precision approaches that are consistent, evidence-based, and guided by clinical practice guidelines. By incorporating technology and datasets, we can address questions which may not be feasible to explore in clinical trials. Now is the time to listen to patients' voices by using patient-reported outcomes (PROs) to ensure that their contributions and experiences inform clinical care plans. Furthermore, while the extrapolation of knowledge and approaches from adult populations may suffice in the absence of pediatric-specific evidence, there is a critical need to specifically understand and implement elements of general and developmental pediatrics like growth, nutrition, development, and physical activity into care. Increased research funding for pediatric supportive care is critical to address resource availability, equity, and disparities across the globe. Our patients deserve to enjoy healthy, productive lives with optimized and enriched supportive care that spans the spectrum from diagnosis to survivorship.

Autologous Faecal Microbiota Transplantation to Improve Outcomes of Haematopoietic Stem Cell Transplantation: Results of a Single-Centre Feasibility Study.

Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual's own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. The stool was collected prior to starting first line therapy. Patients who progressed to HSCT were offered FMT via 3 × retention enemas before day +5 (HSCT = day 0). The feasibility was determined by the recruitment rate, number and volume of enemas administered, and the retention time. Longitudinally collected stool samples were also collected to explore the influence of auto-FMT using 16S rRNA gene sequencing. n = 4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25 (1-3) enemas 43.67 (25-50) mL total, retained for an average of 60.78 (10-145) min. No adverse events (AEs) attributed to the FMT were identified. Although the minimum requirements were met for the volume and retention of auto-FMT, the recruitment was significantly impacted by the logistical challenges of the pretherapy stool collection. This ultimately undermined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.

Exercise and the gut microbiome: implications for supportive care in cancer.

PURPOSE: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population. METHODS: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors. RESULTS: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists. CONCLUSIONS: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.

Self-emulsifying drug delivery systems (SEDDS) disrupt the gut microbiota and trigger an intestinal inflammatory response in rats.

Self-emulsifying drug delivery systems (i.e. SEDDS, SMEDDS and SNEDDS) are widely employed as solubility and bioavailability enhancing formulation strategies for poorly water-soluble drugs. Despite the capacity for SEDDS to effectively facilitate oral drug absorption, tolerability concerns exist due to the capacity for high concentrations of surfactants (typically present within SEDDS) to induce gastrointestinal toxicity and mucosal irritation. With new knowledge surrounding the role of the gut microbiota in modulating intestinal inflammation and mucosal injury, there is a clear need to determine the impact of SEDDS on the gut microbiota. The current study is the first of its kind to demonstrate the detrimental impact of SEDDS on the gut microbiota of Sprague-Dawley rats, following daily oral administration (100 mg/kg) for 21 days. SEDDS comprising a lipid phase (i.e. Type I, II and III formulations according to the Lipid Formulation Classification Scheme) induced significant changes to the composition and diversity of the gut microbiota, evidenced through a reduction in operational taxonomic units (OTUs) and alpha diversity (Shannon's index), along with statistically significant shifts in beta diversity (according to PERMANOVA of multi-dimensional Bray-Curtis plots). Key signatures of gut microbiota dysbiosis correlated with the increased expression of pro-inflammatory cytokines within the jejunum, while mucosal injury was characterised by significant reductions in plasma citrulline levels, a validated biomarker of enterocyte mass and mucosal barrier integrity. These findings have potential clinical ramifications for chronically administered drugs that are formulated with SEDDS and stresses the need for further studies that investigate dose-dependent effects of SEDDS on the gastrointestinal microenvironment in a clinical setting.

From Pathogenesis to Intervention: The Importance of the Microbiome in Oral Mucositis.

Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, affecting up to 80% of patients. Its aetiology centres on the initial destruction of epithelial cells and the increase in inflammatory signals. These changes in the oral mucosa create a hostile environment for resident microbes, with oral infections co-occurring with OM, especially at sites of ulceration. Increasing evidence suggests that oral microbiome changes occur beyond opportunistic infection, with a growing appreciation for the potential role of the microbiome in OM development and severity. This review collects the latest articles indexed in the PubMed electronic database which analyse the bacterial shift through 16S rRNA gene sequencing methodology in cancer patients under treatment with oral mucositis. The aims are to assess whether changes in the oral and gut microbiome causally contribute to oral mucositis or if they are simply a consequence of the mucosal injury. Further, we explore the emerging role of a patient's microbial fingerprint in OM development and prediction. The maintenance of resident bacteria via microbial target therapy is under constant improvement and should be considered in the OM treatment.

Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy.

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy's cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3/g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.

Active glucose transport varies by small intestinal region and oestrous cycle stage in mice.

NEW FINDINGS: What is the central question of this study? Body mass and food intake change during the female ovarian cycle: does glucose transport by the small intestine also vary? What is the main finding and its importance? We have optimised Ussing chamber methodology to measure region-specific active glucose transport in the small intestine of adult C57BL/6 mice. Our study provides the first evidence that jejunal active glucose transport changes during the oestrous cycle in mice, and is higher at pro-oestrus than oestrus. These results demonstrate adaptation in active glucose uptake, concurrent with previously reported changes in food intake. ABSTRACT: Food intake changes across the ovarian cycle in rodents and humans, with a nadir during the pre-ovulatory phase and a peak during the luteal phase. However, it is unknown whether the rate of intestinal glucose absorption also changes. We therefore mounted small intestinal sections from C57BL/6 female mice (8-9 weeks old) in Ussing chambers and measured active ex vivo glucose transport via the change in short-circuit current (∆Isc ) induced by glucose. Tissue viability was confirmed by a positive ∆Isc response to 100 µM carbachol following each experiment. Active glucose transport, assessed after addition of 5, 10, 25 or 45 mM d-glucose to the mucosal chamber, was highest at 45 mM glucose in the distal jejunum compared to duodenum and ileum (P < 0.01). Incubation with the sodium-glucose cotransporter 1 (SGLT1) inhibitor phlorizin reduced active glucose transport in a dose-dependent manner in all regions (P < 0.01). Active glucose uptake induced by addition of 45 mM glucose to the mucosal chamber in the absence or presence of phlorizin was assessed in jejunum at each oestrous cycle stage (n = 9-10 mice per stage). Overall, active glucose uptake was lower at oestrus compared to pro-oestrus (P = 0.025). This study establishes an ex vivo method to measure region-specific glucose transport in the mouse small intestine. Our results provide the first direct evidence that SGLT1-mediated glucose transport in the jejunum changes across the ovarian cycle. The mechanisms underlying these adaptations in nutrient absorption remain to be elucidated.

Exposure of anti-infective drugs and the dynamic changes of the gut microbiota during gastrointestinal mucositis in autologous stem cell transplant patients: a pilot study.

Gastrointestinal mucositis could potentially compromise drug absorption due to functional loss of mucosa and other pathophysiological changes in the gastrointestinal microenvironment. Little is known about this effect on commonly used anti-infectives. This study aimed to explore the association between different stages of gastrointestinal mucositis, drug exposure, and gut microbiota. A prospective, observational pilot study was performed in HSCT patients aged ≥ 18 years receiving anti-infectives orally. Left-over blood samples and fecal swabs were collected from routine clinical care until 14 days after HSCT to analyze drug and citrulline concentrations and to determine the composition of the gut microbiota. 21 patients with a median age of 58 (interquartile range 54-64) years were included with 252 citrulline, 155 ciprofloxacin, 139 fluconazole, and 76 acyclovir concentrations and 48 fecal swabs obtained. Severe gastrointestinal mucositis was observed in all patients. Due to limited data correlation analysis was not done for valacyclovir and fluconazole, however we did observe a weak correlation between ciprofloxacin and citrulline concentrations. This could suggest that underexposure of ciprofloxacin can occur during severe mucositis. A follow-up study using frequent sampling rather than the use of left-over would be required to investigate the relationship between gastrointestinal mucositis, drug exposure, and gut microbiome.

Contribution of TLR4 to colorectal tumor microenvironment, etiology and prognosis.

PURPOSE: Toll-like receptor 4 (TLR4) is increasingly recognized for its ability to govern the etiology and prognostic outcomes of colorectal cancer (CRC) due to its profound immunomodulatory capacity. Despite widespread interest in TLR4 and CRC, no clear analysis of current literature and data exists. Therefore, translational advances have failed to move beyond conceptual ideas and suggestions. METHODS: We aimed to determine the relationship between TLR4 and CRC through a systematic review and analysis of published literature and datasets. Data were extracted from nine studies that reported survival, CRC staging and tumor progression data in relation to TLR4 expression. Primary and metastatic tumor samples with associated clinical data were identified through the Cancer Genome Atlas (TCGA) database. RESULTS: Systematic review identified heterogeneous relationships between TLR4 and CRC traits, with no clear theme evident across studies. A total of 448 datasets were identified through the TCGA database. Analysis of TCGA datasets revealed TLR4 mRNA expression is decreased in advanced CRC stages (P < 0.05 for normal vs Stage II, Stage III and Stage IV). Stage-dependent impact of TLR4 expression on survival outcomes were also found, with high TLR4 expression associated with poorer prognosis (stage I vs III (HR = 4.2, P = 0.008) and stage I vs IV (HR = 11.3, P < 0.001)). CONCLUSION: While TLR4 mRNA expression aligned with CRC staging, it appeared to heterogeneously regulate survival outcomes depending on the stage of disease. This underscores the complex relationship between TLR4 and CRC, with unique impacts dependent on disease stage.

Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota.

Aims: We performed a randomized, placebo-controlled trial, RIBOGUT, to study the effect of 2 weeks supplementation with either 50 or 100 mg/d of riboflavin on (i) Faecalibacterium prausnitzii abundance, (ii) gut microbiota composition, (iii) short-chain fatty acid (SCFA) profiles, and (iv) the satiety and gut hormones. Results: Neither dose of riboflavin, analyzed separately, impacted the abundance of F. prausnitzii, and only minor differences in SCFA concentrations were observed. However, combining the results of the 50 and 100 mg/d groups showed a significant increase in butyrate production. While the gut bacterial diversity was not affected by riboflavin supplementation, the complexity and stability of the bacterial network were enhanced. Oral glucose tolerance tests showed a trend of increased plasma insulin concentration and GLP-1 after 100 mg/d supplementation. Innovation: Dietary supplements, such as vitamins, promote health by either directly targeting host physiology or indirectly via gut microbiota modulation. Here, we show for the first time that riboflavin intervention changes the activity of the microbiota. The butyrate production increased after intervention and although the composition did not change significantly, the network of microbial interactions was enforced. Conclusion: This RIBOGUT study suggests that oral riboflavin supplementation promotes butyrate production in the absence of major shifts in gut microbiota composition. ClinicalTrials.gov Identifier: NCT02929459.

5-Fluorouracil Induces an Acute Reduction in Neurogenesis and Persistent Neuroinflammation in a Mouse Model of the Neuropsychological Complications of Chemotherapy.

The neuropsychological symptoms associated with chemotherapy treatment remain a major challenge with their prevention hampered by insufficient understanding of pathophysiology. While long-term neuroimmune changes have been identified as a hallmark feature shared by neurological symptoms, the exact timeline of mechanistic events preceding neuroinflammation, and the relationship between the glial cells driving this neuroinflammatory response, remain unclear. We therefore aimed to longitudinally characterize the neuroimmunological changes following systemic 5-fluorouracil (5-FU) treatment to gain insight into the timeline of events preceding the well-documented chronic neuroinflammation seen following chemotherapy. Eighteen female C57Bl/6 mice received a single intraperitoneal dose of 5-FU and groups were killed at days 1 and 2 (acute timepoint), days 4 and 8 (subacute timepoint), and days 16 and 32 (chronic timepoint). A further six mice were administered with vehicle control with tissues collected from three mice on day 1 and day 32 of the study. The expression of key genes of interest, BCL2, BDNF, TIMP1, MMP-9, MMP-2, TNFα, IL-1ß, and IL-6R were assessed using real time polymerase chain reaction. Levels of neurogenesis were determined through immunofluorescent staining of doublecortin (DCX). The density of microglia and astrocytes were assessed using immunofluorescence staining of Iba1 and GFAP respectively. 5-FU treatment caused significant decreases to DCX staining at acute timepoints (p = 0.0030) which was positively correlated with BCL2 expression levels. An increase to microglial density was observed in the prefrontal cortex (p = 0.0256), CA3 region (p = 0.0283), and dentate gyrus (p = 0.0052) of the hippocampus at acute timepoints. 5-FU caused increases to astrocyte density, across multiple brains regions, at subacute and chronic timepoints which were positively correlated with TNFα, TIMP-1, MMP-2, and IL-6R expression. This study has identified acute objective neuroinflammatory changes suggesting that the role of early intervention should be explored to prevent the development of neuropsychological deficits in the longer-term following chemotherapy.

Gut Microbiota-Derived Short-Chain Fatty Acids: Impact on Cancer Treatment Response and Toxicities.

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.