5-Fluorouracil (5-FU) is a chemotherapeutic agent that disrupts pyrimidine metabolism, which can interact with gut microbiota, potentially causing dysbiosis and promoting antibiotic resistance. This study analyzed its antimicrobial and antibiofilm effects on Escherichia coli and Enterococcus spp. The Minimum Inhibitory Concentrations (MIC) and Minimum Biofilm Eradication Concentrations (MBEC) of 5-FU were determined against 17 clinical isolates, including resistant and susceptible strains. Biofilm formation and viability were assessed using crystal violet staining and resazurin assays, respectively. Growth curves were generated by exposing selected strains to increasing concentrations of 5-FU and monitoring Optical Density (OD) at 630 nm over 24 hours. Flow cytometry was used to evaluate membrane integrity, using Propidium Iodide (PI), and Reactive Oxygen Species (ROS) production, with DCFH-DA, while Scanning Electron Microscopy (SEM) was used to show the structural alterations in bacterial cells. 5-FU MIC values ranged from 128-512 μM against E. coli and 1-32 μM against Enterococcus spp., with higher MICs observed against resistant strains. MBEC values exceeded planktonic MICs by up to 16-fold for E. coli and 64-fold for Enterococcus spp., ranging from 128 to >2048 μM. At MIC concentrations, membrane damage was increased in both species, while at subinhibitory concentrations, ROS production was exclusively detected in Enterococcus faecalis strains. SEM revealed severe structural alterations, including pore formation, cell shrinkage, cytoplasmic leakage, and cell disintegration highlighting the impact of 5-FU on bacterial morphology. These findings highlight the antibacterial effect of 5-FU, underscoring its potential impact on gut microbial dynamics and the selective pressures it exerts during chemotherapy.

Gastric cancer is a common malignant tumor, and radical gastrectomy can markedly improve the prognosis of gastric cancer patients. However, some patients are diagnosed with advanced gastric cancer before receiving any antitumor therapy and need to receive neoadjuvant chemotherapy (NACT). Previous studies have shown that NACT may cause gut barrier dysfunction and intestinal dysbacteriosis which may further lead to infections. Probiotics have the potential to reduce postoperative infections and improve short-term outcomes after abdominal surgery; however, no large-sample, multicenter, randomized clinical trials have been conducted to explore the effectiveness of probiotics in gastric cancer patients receiving NACT. So we proposed a hypothesis that probiotics can improve short-term outcomes after minimally invasive radical gastrectomy in gastric cancer patients receiving NACT and designed this multicenter randomized controlled trial with the objective to verify this hypothesis.

The GISSG 2023-01 study will be a prospective, open-label, multicenter RCT to verify whether perioperatively probiotic supplementation (begin from the end of the last cycle of NACT to postoperative day 7 or the discharge day) can reduce postoperative infections and improve recovery of gastrointestinal function and other short-term outcomes after minimally invasive radical gastrectomy in gastric cancer patients receiving NACT. A total of 318 patients who meet the inclusion criteria will be enrolled in this study and randomly divided into two groups in a 1:1 ratio: the probiotic group (n = 159) and the control group (n = 159). The participants in the probiotic group will receive perioperative probiotic supplementation, and those in the control group will receive blank control management. The other perioperative management protocols will be the same between the two groups. The primary outcome is postoperative infection compared between the two groups, and the secondary outcomes are postoperative recovery of gastrointestinal function, quality of life, laboratory parameters of systemic inflammation and other short-term outcomes.

The results of this RCT should clarify whether perioperative probiotic supplementation would reduce postoperative infection, promote recovery of gastrointestinal function, reduce laboratory parameters of systemic inflammation and improve symptoms and quality of life after minimally invasive radical gastrectomy in gastric cancer patients receiving NACT. It is hoped that our data will provide evidence that probiotic supplementation improves short-term outcomes in gastric cancer patients receiving NACT.

This trial has been registered on https://clinicaltrials.gov/(NCT05901779 ).

With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.

Quinoa, rich in pharmacologically active ingredients, possesses the potential benefit in preventing cognitive impairments induced by hypoxia. In this study, the efficacy of quinoa ethanol extracts (QEE) consumption (200 and 500 mg/kg/d, respectively) against hypobaric hypoxia (HH)-induced cognitive deficits in mice was investigated. QEE significantly ameliorated hypoxic stress induced by HH, as evidenced by improvements in baseline indices and reductions in hypoxia-inducible factor 1α levels. Furthermore, QEE enhanced antioxidant defense mechanisms, alleviated neuroinflammation in brain regions associated with memory, and improved HH-induced cognitive impairments by modulating the cyclic adenosine monophosphate response element-binding protein/brain-derived neurotrophic factor signaling pathway. Higher doses generally yielded more effective outcomes than lower doses. QEE also significantly reshaped the gut microbiome structure of HH mice, inhibited gut barrier damage, and reduced lipopolysaccharide migration, thereby increasing short-chain fatty acids (SCFAs) levels. Our findings suggest that QEE may be a promising strategy for preventing hypoxia-induced cognitive impairments by maintaining gut microbiome stability and increasing SCFAs levels.

Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted. In our search for new intestinal mucositis therapies, we wanted to see how Lentinan (LT), derived from Lentinus edodes, would fare in mouse models of intestinal mucositis. To create the intestinal mucositis model in mice, we gave them intra-peritoneal doses of 5-fluorouracil (5-FU) (50 mg/kg) and then tested the effects of Lentinan on intestinal mucositis. This examination required constant monitoring of several factors, such as body weight fluctuations, food consumption, and diarrhea. In addition, we measured the levels of certain inflammatory cytokines (Tumour Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-10 (IL-10), looked at the expression of tight junction proteins (Zonula Occludens-1(ZO-1), Claudin-1), measured mucin-2 levels, and looked into changes in the gut flora. In the mouse model of intestinal mucositis, our findings showed that LT effectively reduced weight loss, increased food intake, and relieved diarrhea. Concurrently, we saw a decrease in the expression of inflammatory cytokines such as TNF-α, IL-1, and IL-6, as well as a considerable increase in the concentration of IL-10. Furthermore, LT reduced intestinal mucositis by increasing the length and structural integrity of the colon. Furthermore, increased expression of tight junction proteins (ZO-1, Claudin-1), mucin-2, and an increase in the number of goblet cells all confirmed our previous findings. Notably, the makeup of beneficial bacteria in the stomach increased as well. Finally, our findings suggest that LT can effectively prevent 5-fluorouracil-induced intestinal mucositis in mice by improving immune function, restoring intestinal barrier integrity, and rebalancing gut microbial flora.

The gut microbiota, a dynamic ecosystem of trillions of microorganisms, produces secondary metabolites that profoundly influence host health. Recent research has highlighted the significant role of these metabolites, particularly short-chain fatty acids, indoles, and bile acids, in modulating immune responses, impacting epigenetic mechanisms, and contributing to disease processes. In gastrointestinal (GI) cancers such as colorectal, liver, and gastric cancer, microbial metabolites can drive tumorigenesis by promoting inflammation, DNA damage, and immune evasion. Conversely, these same metabolites hold therapeutic promise, potentially enhancing responses to chemotherapy and immunotherapy and even directly suppressing tumor growth. In addition, gut microbial metabolites play crucial roles in infectious disease susceptibility and resilience, mediating immune pathways that impact pathogen resistance. By consolidating recent insights into the gut microbiota's role in shaping disease and health, this review underscores the therapeutic potential of targeting microbiome-derived metabolites for treating GI cancers and infectious diseases and calls for further research into microbiome-based interventions.

5-Fluorouracil (5-FU) is a common chemotherapeutic medication used to treat cancer. However, the intestinal tract may sustain oxidative damage as a result.

The purpose of this study was to clarify the underlying molecular mechanisms and examine the preventive benefits of cereal-based fermented drinks (CFBs) against intestinal injury in mice caused by 5-FU.

The mice were injected intraperitoneally with 5-FU to induce intestinal mucosal and treated with CFB. The factors for intestinal barrier integrity, oxidative stress and inflammation were measured.

The findings demonstrated that CFBs had high levels of polyphenol, flavonoids, and peptides and had in vitro high free radical scavenging capacity. Furthermore, CFBs effectively ameliorated 5-FU-induced intestinal epithelium damage, characterized by increasing intestinal tight junctions and reducing apoptosis in intestinal cells. These protective effects may attribute to the increased activity of antioxidant-related enzymes (SOD, CAT, and GSH) as well as decreased amounts of inflammatory and oxidative damage markers (IL-1β, TNF-α, and MDA) in the intestinal tract.

Overall, these results show that CFBs can mitigate intestinal damage caused by 5-FU by reducing oxidative stress, suggesting the potential utility of CFBs for therapeutic treatment against intestinal mucositis.

Colorectal cancer (CRC) is one of the most common cancers worldwide. The standard CRC chemo drug, 5-Fluorouracil (5-FU), has a poor response rate and chemoresistance, prompting the need for a more effective and affordable treatment. In this study, we aimed to evaluate whether Prohep, a novel probiotic mixture, would alleviate azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colorectal tumorigenesis and enhance 5-FU efficacy and its mechanism. Our results suggested that Prohep showed stronger anti-tumorigenesis effects than 5-FU alone or when combined in the AOM/DSS model. Prohep significantly reduced the total tumor count, total tumor size, caecum weight, colonic crypt depth, colonic inflammation, and collagen fibrosis. Prohep downregulated pro-inflammatory TNF-α and proliferative p-STAT3 and upregulated apoptotic p53. Metagenomics analysis indicated that Prohep-enriched Helicobacter ganmani, Desulfovibrio porci, Helicobacter hepaticus, and Candidatus Borkfalkia ceftriaxoniphila were inversely correlated to the total tumor count. In addition, Prohep-enriched Prevotella sp. PTAC and Desulfovibrio porci were negatively correlated to AOM/DSS enriched bacteria, while forming a co-existing community with other beneficial bacteria. From KEGG analysis, Prohep downregulated CRC-related pathways and enhanced pathways related to metabolites suppressing CRC like menaquinone, tetrapyrrole, aminolevulinic acid, and tetrahydrofolate. From Metacyc analysis, Prohep downregulated CRC-related peptidoglycan, LPS, and uric acid biosynthesis, and conversion. Prohep elevated the biosynthesis of the beneficial L-lysine, lipoic acid, pyrimidine, and palmitate. Prohep also elevated metabolic pathways related to energy utilization of lactic acid-producing bacteria (LAB) and acetate producers. Similarly, fecal acetate concentration was upregulated by Prohep. To sum up, Prohep demonstrated exceptional anti-tumorigenesis effects in the AOM/DSS model, which revealed its potential to develop into a novel CRC therapeutic in the future.

Despite ongoing breakthroughs in novel anticancer therapies, chemotherapy remains a mainstream therapeutic modality in different types of cancer. Unfortunately, chemotherapy-related toxicity (CRT) often leads to dose limitation, and even results in treatment termination. Over the past few years, accumulating evidence has indicated that the gut microbiota is extensively engaged in various toxicities initiated by chemotherapeutic drugs, either directly or indirectly. The gut microbiota can now be targeted to reduce the toxicity of chemotherapy. In the current review, we summarized the clinical relationship between the gut microbiota and CRT, as well as the critical role of the gut microbiota in the occurrence and development of CRT. We then summarized the key mechanisms by which the gut microbiota modulates CRT. Furthermore, currently available strategies to mitigate CRT by targeting the gut microbiota were summarized and discussed. This review offers a novel perspective for the mitigation of diverse chemotherapy-associated toxic reactions in cancer patients and the future development of innovative drugs or functional supplements to alleviate CRT via targeting the gut microbiota.

Depression is strongly associated with colorectal cancer (CRC). Few bibliometric analyses have systematically summarized the research focus and recent progress in this field.

To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression.

Articles on depression in CRC patients were collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were used to visualize bibliometric networks.

From 2001 to 2022, Supportive Care in Cancer, the United States, Tilburg University, and Mols were the most productive and influential journal, country, institution, and author name. Co-occurrence cluster analysis of keywords placed quality of life, anxiety, and psychological stress in the center of the visual network diagram. Further clustering was performed for the clusters with studies of the relevant mechanism of action, which showed that: (1) Cytokines have a role essential for the occurrence and development of depressive disorders in CRC; (2) MicroRNAs have a role essential for the development of depressive disorders in CRC; (3) Some anticancer drugs have pro-depressant activity; and (4) Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity.

Life quality and psychological nursing of the cancer population were key topics. The roles of cytokines and microRNAs, the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.

Chemotherapy-induced intestinal mucositis based on 5-fluorouracil (5-FU) slows down the progress of cancer treatment and causes significant suffering to patients. Pediococcus pentosaceus (P. pentosaceus), as a type of LAB, has a range of probiotic properties, including antioxidant, immune benefits, and cholesterol-lowering effects, which are attracting increasing attention. However, studies on the protective effect of P. pentosaceus against chemotherapeutic-induced intestinal mucositis caused by 5-FU remain unclear. Therefore, this study aimed to investigate the potential relieving effects of P. pentosaceus PP34 on 5-FU-induced intestinal mucositis and its mechanism. In the present study, a P. pentosaceus PP34 solution (2 × 109 CFU/mL) was administered daily by gavage followed by intraperitoneal injection of 5-FU to model intestinal mucositis. The body weight, serum biochemical indices, jejunal pathological organization, and expression levels of inflammatory cytokines in the jejunum were examined. The results indicated that the mice induced with 5-FU developed typical intestinal mucositis symptoms and histopathological changes with intense inflammatory and oxidative responses. Moreover, the gut microbiota was disturbed, while PP34 effectively decreased the oxidative reactions and the expression levels of inflammatory mediators and regulated the gut microbiota in 5-FU-exposed mice. Taken together, the study indicated that P. pentosaceus PP34 ameliorates 5-Fluorouracil-induced intestinal mucositis via inhibiting oxidative stress and restoring the gut microbiota.

The human gut microbiota is a complex ecosystem that plays a crucial role in promoting the interaction between the body and its environment. It has been increasingly recognized that the gut microbiota has diverse physiological functions. Recent studies have shown a close association between the gut microbiota and the development of certain tumors, including leukemia. Leukemia is a malignant clonal disease characterized by the uncontrolled growth of one or more types of blood cells, which is the most common cancer in children. The imbalance of gut microbiota is linked to the pathological mechanisms of leukemia. Probiotics, which are beneficial microorganisms that help maintain the balance of the host microbiome, play a role in regulating gut microbiota. Probiotics have the potential to assist in the treatment of leukemia and improve the clinical prognosis of leukemia patients. This study reviews the relationship between gut microbiota, probiotics, and the progression of leukemia based on current research. In addition, utilizing zebrafish leukemia models in future studies might reveal the specific mechanisms of their interactions, thereby providing new insights into the clinical treatment of leukemia. In conclusion, further investigation is still needed to fully understand the accurate role of microbes in leukemia.

5-Fluorouracil (5-FU) is commonly used as the primary chemotherapy for colorectal cancer (CRC). However, it can lead to unwanted chemoresistance. Resistant starch (RS), which functions similarly to fermentable dietary fiber, has the potential to reduce the risk of CRC. The effects of RS on improving CRC-associated cachectic symptoms and 5-FU chemotherapy-induced microbial dysbiosis remain unknown. Female BALB/cByJNarl mice were randomly divided into four groups: one tumor group (with CT26 colonic carcinoma but no treatment) and three CT26 colonic carcinoma-bearing groups that were administered 20 mg/kg 5-FU (T+5-FU group), a probiotic cocktail (4 × 108 CFUs) plus chemotherapy (T+5-FU+Pro), or resistant-starch-encapsulated probiotics plus chemotherapy (T+5-FU+RS-Pro). T+5-FU and T+5-FU+RS-Pro administration significantly suppressed tumor growth and activated apoptotic cell death in CT26-bearing mice. 5-FU-induced increases in inflammatory cytokines and NF-κB signaling were mitigated by the Pro or RS-Pro supplementation. A gut microbial composition comparison indicated that the abundance of intestinal bacteria in the T and T+5-FU groups decreased significantly, while the groups receiving Pro or RS-Pro maintained a greater abundance and healthy gut microbiota composition, suggesting that RS can reduce the microbial dysbiosis that occurs during 5-FU chemotherapy. The use of RS-Pro before chemotherapy should be considered for the regulation of chemotherapy-associated cachectic symptoms, inflammation, and chemotherapy-induced microbial dysbiosis.

Colorectal cancer (CRC) is a prevalent global health issue, with 5-fluorouracil (5-FU) being a commonly used chemotherapeutic agent for its treatment. However, the efficacy of 5-FU is often hindered by drug tolerance. Sodium butyrate (NaB), a derivative of intestinal flora, has demonstrated anti-cancer properties both in vitro and in vivo through pro-apoptotic effects and has shown promise in improving outcomes when used in conjunction with traditional chemotherapy agents. This study seeks to evaluate the impact and potential mechanisms of NaB in combination with 5-FU on CRC. We employed a comprehensive set of assays, including CCK-8, EdU staining, Hoechst 33258 staining, flow cytometry, ROS assay, MMP assay, immunofluorescence, and mitophagy assay, to detect the effect of NaB on the biological function of CRC cells in vitro. Western blotting and immunohistochemistry were used to verify the above experimental results. The xenograft tumor model was established to evaluate the in vivo anti-CRC activity of NaB. Subsequently, 16S rRNA gene sequencing was used to analyze the intestinal flora. The findings of our study demonstrate that sodium butyrate (NaB) exerts inhibitory effects on tumor cell proliferation and promotes tumor cell apoptosis in vitro, while also impeding tumor progression in vivo through the enhancement of the mitophagy pathway. Furthermore, the combined treatment of NaB and 5-fluorouracil (5-FU) yielded superior therapeutic outcomes compared to monotherapy with either agent. Moreover, this combination therapy resulted in the specific enrichment of Bacteroides, LigiLactobacillus, butyric acid-producing bacteria, and acetic acid-producing bacteria in the intestinal microbiota. The improvement in the intestinal microbiota contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Taken together, these findings indicate that NaB, a histone acetylation inhibitor synthesized through intestinal flora fermentation, has the potential to significantly enhance the therapeutic efficacy of 5-FU in CRC treatment and improve the prognosis of CRC patients.

This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU).

Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa.

These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

The current study investigated the potential effects of probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) and treated with 5-fluorouracil (5FU)-based chemotherapy in mice. Animals were randomly allocated in five different groups: Control: which not receive any treatment throughout the experimental course; Colitis model group (DMH): treated with DMH; DMH+ 5FU: animals received I.P. (intraperitoneal) dose of chemotherapy on a weekly basis; DMH+PROB: animals received daily administrations (via gavage) of probiotics (Lactobacillus: acidophilus and paracasei, Bifidobacterium lactis and bifidum); and DMH+ PROB+ 5FU: animals received the same treatment as the previous groups. After ten-week treatment, mice's large intestine was collected and subjected to colon length, histopathological, periodic acid-schiff (PAS) staining and immunohistochemistry (TLR2, MyD88, NF-κB, IL-6, TLR4, TRIF, IRF-3, IFN-γ, Ki-67, KRAS, p53, IL-10, and TGF-β) analyzes. Variance (ANOVA) and Kruskal-Wallis tests were used for statistical analysis, at significance level p 0.05. Probiotics' supplementation has increased the production of Ki-67 cell-proliferation marker, reduced body weight, and colon shortening, as well as modulated the chronic inflammatory process in colorectal carcinogenesis by inhibiting NF-κB expression and mitigating mucin depletion. Thus, these findings lay a basis for guide future studies focused on probiotics' action mechanisms in tumor microenvironment which might have implications in clinical practice.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis. This is due to the fact that most cases are only diagnosed at an advanced and palliative disease stage, and there is a high incidence of therapy resistance. Despite ongoing efforts, to date, the mechanisms underlying PDAC oncogenesis and its poor responses to treatment are still largely unclear. As the study of the microbiome in cancer progresses, growing evidence suggests that bacteria or fungi might be key players both in PDAC oncogenesis as well as in its resistance to chemo- and immunotherapy, for instance through modulation of the tumor microenvironment and reshaping of the host immune response. Here, we review how the microbiota exerts these effects directly or indirectly via microbial-derived metabolites. Finally, we further discuss the potential of modulating the microbiota composition as a therapy in PDAC.

The anaerobic cultivation of fecal microbiota is a promising approach to investigating how gut microbial communities respond to specific intestinal conditions and perturbations. Here, we describe a flexible protocol using 96-deepwell plates to cultivate stool-derived gut microbiota. Our protocol aims to address gaps in high-throughput culturing in an anaerobic chamber. We characterized the influence of the gas phase on the medium chemistry and microbial physiology and introduced a modular medium preparation process to enable the testing of several conditions simultaneously. Furthermore, we identified a medium formulation that maximized the compositional similarity of ex vivo cultures and donor microbiota while limiting the bloom of Enterobacteriaceae. Lastly, we validated the protocol by demonstrating that cultivated fecal microbiota responded similarly to dietary fibers (resistant dextrin, soluble starch) and drugs (ciprofloxacin, 5-fluorouracil) as reported in vivo. This high-throughput cultivation protocol has the potential to facilitate culture-dependent studies, accelerate the discovery of gut microbiota-diet-drug-host interactions, and pave the way to personalized microbiota-centered interventions.

Ongoing extensive research in the field of gut microbiota (GM) has highlighted the crucial role of gut-dwelling microbes in human health. These microbes possess 100 times more genes than the human genome and offer significant biochemical advantages to the host in nutrient and drug absorption, metabolism, and excretion. It is increasingly clear that GM modulates the efficacy and toxicity of drugs, especially those taken orally. In addition, intra-individual variability of GM has been shown to contribute to drug response biases for certain therapeutics. For instance, the efficacy of cyclophosphamide depends on the presence of Enterococcus hirae and Barnesiella intestinihominis in the host intestine. Conversely, the presence of inappropriate or unwanted gut bacteria can inactivate a drug. For example, dehydroxylase of Enterococcus faecalis and Eggerthella lenta A2 can metabolize L-dopa before it converts into the active form (dopamine) and crosses the blood-brain barrier to treat Parkinson's disease patients. Moreover, GM is emerging as a new player in personalized medicine, and various methods are being developed to treat diseases by remodeling patients' GM composition, such as prebiotic and probiotic interventions, microbiota transplants, and the introduction of synthetic GM. This review aims to highlight how the host's GM can improve drug efficacy and discuss how an unwanted bug can cause the inactivation of medicine.

The characteristics and management of ileitis induced by chemotherapy in cancer patients are poorly described in the literature.

This retrospective multicentre study enroled patients hospitalized in a digestive oncology unit for a symptomatic chemotherapy-induced ileitis.

Forty-three patients were included, with a regimen based on fluoropyrimidine and/or irinotecan in 95% of cases. Five patients were excluded due to the diagnosis of infectious ileitis (Clostridium difficile in 3 patients, Campylobacter jejuni in 1 patient and cytomegalovirus in 1 patient). The most frequently described symptoms were diarrhoea (77% including 54% of grade 3-4 diarrhoea), abdominal pain (58%), fever (51%) and vomiting (56%). An ileo-colonoscopy was performed in 35% of patients and did not show any specific results or severity criteria. The ileitis was complicated by bowel perforation and/or obstruction in 3 patients. Disease progression was favourable in 1-2 weeks in the vast majority of cases, on symptomatic treatment, allowing resumption of the chemotherapy regimen involved in 67% of patients.

Chemotherapy-induced ileitis is a rare complication that most often involves fluoropyri-midine- and/or irinotecan-based regimens. In most cases, endoscopic examinations were not contributory and do not seem useful in the event of non-severe symptomatology which most often develops favourably on symptomatic therapy, allowing resumption of the chemotherapy involved.

Antineoplastic treatment induces a type of gastrointestinal toxicity known as mucositis. Findings in animal models are usually easily reproducible, and standardized treatment regimens are often used, thus supporting translational science. Essential characteristics of mucositis, including intestinal permeability, inflammation, immune and oxidative responses, and tissue repair mechanisms, can be easily investigated in these models. Given the effects of mucositis on the quality of life of patients with cancer, and the importance of experimental models in the development of more effective new therapeutic alternatives, this review discusses progress and current challenges in using experimental models of mucositis in translational pharmacology research. Teaser Experimental models for studying gastrointestinal mucositis have provided a wealth of information improving the understanding of antineoplastic toxicity.

Fluoropyrimidines (FPs) are key drugs in many chemotherapy regimens; however, recipients are often prone to diarrhea due to gastrointestinal toxicity. Disruption of the intestinal epithelial barrier function by FPs leads to dysbiosis, which may exacerbate intestinal epithelial cell damage as a secondary effect and trigger diarrhea. However, despite studies on chemotherapy-induced changes in the intestinal microbiome of humans, the relationship between dysbiosis and diarrhea is unclear. In this study, we aimed to investigate the relationship between chemotherapy-induced diarrhea and the intestinal microbiome.

We conducted a single-center prospective observational study. Twenty-three patients who received chemotherapy, including FPs as first-line chemotherapy for colorectal cancer, were included. Stool samples were collected before the start of chemotherapy and after one cycle of treatment to analyze intestinal microbiome composition and perform PICRUSt predictive metagenomic analysis.

Gastrointestinal toxicity was observed in 7 of 23 patients (30.4%), diarrhea was observed in 4 (17.4%), and nausea and anorexia were observed in 3 (13.0%). In 19 patients treated with oral FPs, the α diversity of the microbial community decreased significantly following chemotherapy only in the diarrheal group. At the phylum level, the diarrheal group showed a significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Bacteroidetes with chemotherapy (p = 0.013 and 0.011, respectively). In the same groups, at the genus level, Bifidobacterium abundance was significantly decreased (p = 0.019). In contrast, in the non-diarrheal group, Actinobacteria abundance increased significantly with chemotherapy at the phylum level (p = 0.011). Further, Bifidobacterium, Fusicatenibacter, and Dorea abundance significantly increased at the genus level (p = 0.006, 0.019, and 0.011, respectively). The PICRUSt predictive metagenomic analysis revealed that chemotherapy caused significant differences in membrane transport in KEGG pathway level 2 and in 8 KEGG pathway level 3, including transporters and oxidative phosphorylation in the diarrhea group.

Organic-acid-producing bacteria seem to be involved in diarrhea associated with chemotherapy, including FPs.

Intestinal mucositis (IM) is a common side effect resulting from cancer treatment. However, the management so far has not been very effective. In the last years, the role of the gut microbiota in the development and severity of mucositis has been studied. Therefore, the use of probiotics and paraprobiotics could have a potential therapeutic effect on IM. The aim of our study was to investigate the impact of the administration of Lacticaseibacillus rhamnosus (L. rhamnosus) CGMCC1.3724 and the paraprobiotic on IM in mice. For 13 days, male Balb/c mice were divided into six groups: control (CTL) and mucositis (MUC)/0.1 mL of saline; CTL LrV and MUC LrV/0.1 mL of 10⁸ CFU of viable Lr; CTL LrI and MUC LrI/0.1 mL of 10⁸ CFU of inactivated Lr. On the 10th day, mice from the MUC, MUC LrV, and MUC LrI groups received an intraperitoneal injection (300 mg/kg) of 5-fluorouracil to induce mucositis. The results showed that the administration of the chemotherapeutic agent increased the weight loss and intestinal permeability of the animals in the MUC and MUC LrV groups. However, administration of paraprobiotic reduced weight loss and maintained PI at physiological levels. The paraprobiotic also preserved the villi and intestinal crypts, reduced the inflammatory infiltrate, and increased the mucus secretion, Muc2 gene expression, and Treg cells frequency.

Pancreatic cancer is an increasingly growing source of cancer-related deaths and is often diagnosed at advanced stages. Its treatment is difficult because of the poor results of conventional treatments, such as surgery, chemotherapy, and radiotherapy. Microbiota and their products can regulate the microenvironment of pancreatic tumors, the biological behavior of pancreatic cancer cells, and the functionality of the immune system. Promising results have been achieved in treating pancreatic cancer by regulating microbiota. However, intratumoral microbiota is still in its infancy as a new field of discovery for pancreatic cancer. This review summarizes the mechanisms by which intratumoral microbiota causes pancreatic cancer tumorigenesis, progression, and metastasis and demonstrates their significant potential in diagnosing and treating pancreatic cancer. Additionally, we present an outlook on the future of intratumoral microbiota in treating pancreatic cancer.

Background: Brucea javanica (L.) Merr, has a long history to be an anti-dysentery medicine for thousand of years, which is commonly called "Ya-Dan-Zi" in Chinese. The common liquid preparation of its seed, B. javanica oil (BJO) exerts anti-inflammatory action in gastrointestinal diseases and is popularly used as an antitumor adjuvant in Asia. However, there is no report that BJO has the potential to treat 5-Fluorouracil (5-FU)-induced chemotherapeutic intestinal mucosal injury (CIM). Aim of the study: To test the hypothesis that BJO has potential intestinal protection on intestinal mucosal injury caused by 5-FU in mice and to explore the mechanisms. Materials and methods: Kunming mice (half male and female), were randomly divided into six groups: normal group, 5-FU group (5-FU, 60 mg/kg), LO group (loperamide, 4.0 mg/kg), BJO group (0.125, 0.25, 0.50 g/kg). CIM was induced by intraperitoneal injection of 5-FU at a dose of 60 mg/kg/day for 5 days (from day 1 to day 5). BJO and LO were given orally 30 min prior to 5-FU administration for 7 days (from day 1 to day 7). The ameliorative effects of BJO were assessed by body weight, diarrhea assessment, and H&E staining of the intestine. Furthermore, the changes in oxidative stress level, inflammatory level, intestinal epithelial cell apoptosis, and proliferation, as well as the amount of intestinal tight junction proteins were evaluated. Finally, the involvements of the Nrf2/HO-1 pathway were tested by western blot. Results: BJO effectively alleviated 5-FU-induced CIM, as represented by the improvement of body weight, diarrhea syndrome, and histopathological changes in the ileum. BJO not only attenuated oxidative stress by upregulating SOD and downregulating MDA in the serum, but also reduced the intestinal level of COX-2 and inflammatory cytokines, and repressed CXCL1/2 and NLRP3 inflammasome activation. Moreover, BJO ameliorated 5-FU-induced epithelial apoptosis as evidenced by the downregulation of Bax and caspase-3 and the upregulation of Bcl-2, but enhanced mucosal epithelial cell proliferation as implied by the increase of crypt-localized proliferating cell nuclear antigen (PCNA) level. Furthermore, BJO contributed to the mucosal barrier by raising the level of tight junction proteins (ZO-1, occludin, and claudin-1). Mechanistically, these anti-intestinal mucositis pharmacological effects of BJO were relevant for the activation of Nrf2/HO-1 in the intestinal tissues. Conclusion: The present study provides new insights into the protective effects of BJO against CIM and suggests that BJO deserves to be applied as a potential therapeutic agent for the prevention of CIM.

Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.

Mucositis is a common and most debilitating complication associated with the cytotoxicity of chemotherapy. The condition affects the entire alimentary canal from the mouth to the anus and has a significant clinical and economic impact. Although oral and intestinal mucositis can occur concurrently in the same individual, these conditions are often studied independently using organ-specific models that do not mimic human disease. Hence, the purpose of this scoping review was to provide a comprehensive yet systematic overview of the animal models that are utilised in the study of chemotherapy-induced mucositis. A search of PubMed/MEDLINE and Scopus databases was conducted to identify all relevant studies. Multiple phases of filtering were conducted, including deduplication, title/abstract screening, full-text screening, and data extraction. Studies were reported according to the updated Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. An inter-rater reliability test was conducted using Cohen's Kappa score. After title, abstract, and full-text screening, 251 articles met the inclusion criteria. Seven articles investigated both chemotherapy-induced intestinal and oral mucositis, 198 articles investigated chemotherapy-induced intestinal mucositis, and 46 studies investigated chemotherapy-induced oral mucositis. Among a total of 205 articles on chemotherapy-induced intestinal mucositis, 103 utilised 5-fluorouracil, 34 irinotecan, 16 platinum-based drugs, 33 methotrexate, and 32 other chemotherapeutic agents. Thirteen articles reported the use of a combination of 5-fluorouracil, irinotecan, platinum-based drugs, or methotrexate to induce intestinal mucositis. Among a total of 53 articles on chemotherapy-induced oral mucositis, 50 utilised 5-fluorouracil, 2 irinotecan, 2 methotrexate, 1 topotecan and 1 with other chemotherapeutic drugs. Three articles used a combination of these drugs to induce oral mucositis. Various animal models such as mice, rats, hamsters, piglets, rabbits, and zebrafish were used. The chemotherapeutic agents were introduced at various dosages via three routes of administration. Animals were mainly mice and rats. Unlike intestinal mucositis, most oral mucositis models combined mechanical or chemical irritation with chemotherapy. In conclusion, this extensive assessment of the literature revealed that there was a large variation among studies that reproduce oral and intestinal mucositis in animals. To assist with the design of a suitable preclinical model of chemotherapy-induced alimentary tract mucositis, animal types, routes of administration, dosages, and types of drugs were reported in this study. Further research is required to define an optimal protocol that improves the translatability of findings to humans.

Chemotherapy-induced mucositis is characterized by diarrhoea and villous atrophy. However, it is not well-understood why diarrhoea arises, why it only occurs with some chemotherapeutics and how it is related to villus atrophy. The objectives in this study were to determine (i) the relationship between chemotherapy-induced diarrhoea and villus atrophy and to (ii) establish and validate a rat diarrhoea model with clinically relevant endpoints. Male Wistar Han IGS rats were treated with saline, doxorubicin, idarubicin, methotrexate, 5-fluorouracil, irinotecan or 5-fluorouracil+irinotecan. After 72 h, jejunal tissue was taken for morphological, apoptotic and proliferative analyses, and faecal water content and change in body weight were determined. All treatments except methotrexate caused a similar reduction (≈42%) in villus height, but none of them altered mucosal crypt cell proliferation or apoptosis. Doxorubicin, idarubicin, irinotecan and 5-fluorouracil+irinotecan caused body weight reduction, but only irinotecan and idarubicin caused diarrhoea. No direct correlation between diarrhoea and villus height or body weight loss was observed. Therefore, studies of the mechanisms for chemotherapy-induced diarrhoea should focus on functional factors. Finally, the irinotecan and idarubicin diarrhoea models established in this study will be useful in developing supportive treatments of this common and serious adverse effect in patients undergoing chemotherapy.

As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora.

Apc^Min/+ mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU.

The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in Apc^Min/+ mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in Apc^Min/+ mice being treated with 5-FU.

Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of Apc^Min/+ mice.

The protective effects of antibiotics against infection in cancer patients treated with chemotherapy remains unclear and related studies have been performed in healthy or pathogen-infected animal models. Here, we aimed to study the effects of antibiotic use on intestinal infection in tumor-bearing mice treated with chemotherapy and to determine the underlying mechanisms. Subcutaneous CT26 tumor-bearing mice were assigned to four groups: the control (Ctrl) group without any treatment, the antibiotic (ATB) group treated with a mixture of ampicillin, streptomycin, and colistin, the 5-fluorouracil (FU) group treated with four cycles of intraperitoneal injections of FU, and the ATB + FU group treated with the combination of ATB and FU. Gut microbial composition was determined and mesenteric lymph nodes (mLNs) were isolated for bacterial culturing. Intestinal permeability and integrity were assessed and the expression of cytokines was analyzed by quantitative PCR, ELISA, or flow cytometry (FCM). Monocytes in the colonic lamina propria (LP) were measured by FCM. Compared with the Ctrl and FU groups, the numbers of positive bacterial culturing results for mLNs were higher, and gut bacterial compositions were altered in the ATB and ATB + FU groups, with significantly decreased alpha diversity in the ATB + FU group. Intestinal integrity regarding the expression of tight junction proteins and intestinal permeability were not impaired significantly after treatments, but the colons were shorter in the ATB + FU group. The expression levels of intestinal IL-17A and IL-22, as well as the percentages of IL-17A⁺ cells in the colonic LP of the ATB + FU group, were lower than those in the FU group. The percentages of Ly6C^hi monocytes in the colonic LP were lower, but those in the spleen were higher in the ATB + FU group than in the FU group. The mRNA levels of colonic CCL8 were reduced in the ATB + FU group. Antibiotic use is associated with an increased incidence of intestinal infections in tumor-bearing mice treated with chemotherapy, which might in turn be associated with a dysregulated gut microbiota that inhibits colonic monocyte recruitment and IL-17A and IL-22 production.

This manuscript aims to explain the relationship between mucositis caused by 5-FU over gut bacterial species and susceptibility to opportunistic infection caused by P. aeruginosa.

BALB/c mice were intraperitoneally treated with PBS or 5-FU. Bodyweight and faecal consistency were checked daily. Mice faecal DNA was extracted, and bacterial phylogenetic groups were analysed using qPCR or high-throughput sequencing. Immunofluorescence was used to evaluate BMDM activation by mice-treated faecal content. Mice were challenged intratracheally with virulent P. aeruginosa, and the CFU and histology were analysed. Faecal microbiota were transplanted to evaluate the gut microbiota and resistance to pulmonary P. aeruginosa recovery.

The animals treated with 5-FU presented mucositis with great weight loss, altered faecal consistency, bacterial gut dysbiosis and histological changes in the intestinal mucosa. Mice under 5-FU treatment were more susceptible to lung infection by the bacteria P. aeruginosa and had more extensive tissue damage during their lung infection with greater pro-inflammatory gene expression. It was observed that the mucositis remained in the groups with 5-FU even with the FMT. The results caused by mucositis in animals that received allogeneic FMT were reversed, however, with a decrease in P. aeruginosa susceptibility in animals treated with 5-FU and allogeneic FMT compared to animals treated with 5-FU and autologous FMT.

Treatment with 5-FU in a murine model makes it more susceptible to pulmonary infection by the bacterium P. aeruginosa, FMT offers an opportunity to protect against this susceptibility to infection.

5-FU-induced intestinal mucositis (FUIIM) is a common gastrointestinal side effect of chemotherapy, leading to gastric pain in clinical cancer patients. In a previous study, we demonstrated that neutrophil elastase (NE) inhibitors could alleviate FUIIM and manipulate the homeostasis of the gut microbiota. The root of Melastoma malabathricum, also called Ye-Mu-Dan, has been used as a traditional Chinese medicine for gastrointestinal disease. Water extract of the roots of M. malabathricum exhibits an inhibitory effect on NE, with an IC₅₀ value of 9.13 μg/ml.

In this study, we aimed to isolate an anti-NE compound from the root of M. malabathricum and to determine the protective effect of the bioactive component on a mouse model of FUIIM with respect to tissue damage, inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis.

A water extract of the roots of M. malabathricum was prepared and its major bioactive compound, was identified using bioactivity-guided fractionation. The effects of samples on the inhibition of NE activity were evaluated using enzymatic assays. To evaluate the effects of the bioactive compound in an FUIIM animal model, male C57BL/6 mice treated with or without casuarinin (50 and 100 mg/kg/day, p.o.), and then received of 5-fluorouracil (50 mg/kg/day) intraperitoneally for 5 days to induce FUIIM. Histopathological staining was used to monitor the tissue damage, proliferation of intestinal crypts, and expression of tight junction proteins. The inflammation score was estimated by determining the levels of oxidative stress, neutrophil-related proteases, and proinflammatory cytokines in tissue and serum. The ecology of the gut microbiota was evaluated using 16S rRNA gene sequencing.

Casuarinin had the most potent and selective effect against NE, with an IC₅₀ value of 2.79 ± 0.07 μM. Casuarinin (100 mg/kg/day, p.o.) significantly improved 5-FU-induced body weight loss together with food intake reduction, and it also significantly reversed villus atrophy, restored the proliferative activity of the intestinal crypts, and suppressed inflammation and intestinal barrier dysfunction in the mouse model of FUIIM. Casuarinin also reversed 5-FU-induced gut microbiota dysbiosis, particularly the abundance of Actinobacteria, Candidatus Arthromitus, and Lactobacillus murinus, and the Firmicutes-to-Bacteroidetes ratio.

This study firstly showed that casuarinin isolated from the root part of M. malabathricum could be used as a NE inhibitor, whereas it could improve FUIIM by modulating inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis. In summary, exploring anti-NE natural product may provide a way to find candidate for improvement of FUIIM.

This study aimed to formulate Kappaphycus alvarezii compound powder containing Kappaphycus alvarezii powder (KP), cooked sorghum powder (SP), and longan powder (LP); which was evaluated for its therapeutic effects against chemotherapy-induced intestinal mucosal injury (CIMI). Based on rheological properties, sensory evaluation, and antioxidant activity and using single factor and response surface methodology, the optimal formula to develop the compound powder was determined to be 35% KP, 30% SP, 5% LP, and 30% xylitol. Thereafter, the efficacy of the compound powder was tested by feeding BALB/c mice with diets supplemented with the Kappaphycus alvarezii compound powder (3% and 5%) for 14 consecutive days. The chemotherapeutic drug 5-fluorouracil was intraperitoneally injected (50 mg/kg) in the mice to induce CIMI for the last three consecutive days. Compared to the CIMI mice, those fed 5% Kappaphycus alvarezii compound powder (HC) showed significantly improved the intestinal injury, increased mucin-2 secretion, and reduced TNF-α, IL-1β, IL-6, LT, and COX-2 levels. Furthermore, HC intake significantly reduced the Firmicutes-to-Bacteroidetes ratio, promoted the growth of beneficial bacteria, such as Alloprevotella, and inhibited the growth of harmful bacteria, such as Clostridium. In conclusion, HC has a protective effect against CIMI and provides a novel dietary strategy for patients undergoing chemotherapy.

Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be useful in treating either advanced or recurrent KRAS/NRAS/BRAF wild-type colorectal cancer. We herein report the case of a 60-year-old man with short bowel syndrome who developed hematochezia due to panitumumab-induced colitis with vitamin K deficiency during third-line chemotherapy. The cause of vitamin K deficiency was the lack of intravenous vitamin K supplementation following a change from central venous nutrition to peripheral venous nutrition. We advise clinicians to carefully check for colitis and manage the infusions of chemotherapy patients with short bowel syndrome.

Mucositis is severely painful and often reported as one of the most distressing adverse effects of cancer therapy; it is a significant threat to quality of life as well as life itself. Anti-inflammatory agents may modulate physiologic mechanisms that perpetuate mucositis and be useful in prevention efforts. Because systemic anti-inflammatory agents are not appropriate for many patients, locally acting agents (mouthwashes) may be more feasible for use. This review and meta-analysis evaluates the role that anti-inflammatory mouthwashes have in preventing or reducing oral mucositis associated with chemotherapy and radiation therapy.

A systematic literature review was conducted to identify studies evaluating the efficacy of anti-inflammatory mouthwashes to prevent therapy-associated mucositis. Meta-analysis was conducted to determine efficacy in preventing any mucositis and dose-limiting mucositis.

Eight peer-reviewed publications were identified; corticosteroid and nonsteroidal anti-inflammatory mouthwashes are effective in reducing overall incidence of mucositis and are associated with lower severity of mucositis. Meta-analysis reveals significant reduction in symptomatic mucositis incidence (OR 6.00, 95% CI 4.39-8.20, p < 0.0001) and reduction of dose-limiting mucositis (OR 2.12, 95% CI 1.07-4.28, p = 0.032).

Mouthwashes containing anti-inflammatory agents are a potential effective means to prevent or reduce mucositis associated with cancer therapy. There are limited adverse effects from these agents, and adherence is high, indicating safety and feasibility of use. Anti-inflammatory mouthwashes should be considered for supportive care in persons at risk for mucositis and must be further evaluated to investigate efficacy across multiple chemotherapy agents, adverse effects, and impacts on symptoms, pain, and quality of life.