Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Expert consensus on the systemic treatment of atopic dermatitis in special populations.

With the increasing number of options for the treatment of moderate-to-severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein.

Position statement for a pragmatic approach to immunotherapeutics in patients with inflammatory skin diseases during the coronavirus disease 2019 pandemic and beyond.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, a novel RNA virus that was declared a global pandemic on 11 March 2020. The efficiency of infection with SARS-CoV-2 is reflected by its rapid global spread. The SARS-CoV-2 pandemic has implications for patients with inflammatory skin diseases on systemic immunotherapy who may be at increased risk of infection or more severe infection. This position paper is a focused examination of current evidence considering the mechanisms of action of immunotherapeutic drugs in relation to immune response to SARS-CoV-2. We aim to provide practical guidance for dermatologists managing patients with inflammatory skin conditions on systemic therapies during the current pandemic and beyond. Considering the limited and rapidly evolving evidence, mechanisms of action of therapies, and current knowledge of SARS-CoV-2 infection, we propose that systemic immunotherapy can be continued, with special considerations for at risk patients or those presenting with symptoms.

Genetic alterations in primary melanoma in Taiwan.

BACKGROUND: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. OBJECTIVES: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. METHODS: We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. RESULTS: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. CONCLUSIONS: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

Patients with psoriasis have different preferences for topical therapy, highlighting the importance of individualized treatment approaches: randomized phase IIIb PSO-INSIGHTFUL study.

BACKGROUND: Poor adherence to topical therapy in psoriasis remains an issue; it is associated with poor clinical outcomes, reduced quality of life and increased costs. Treatment-related factors leading to poor adherence include lack of efficacy, excessive time applying medication and poor cosmetic characteristics (e.g. slow absorption, greasiness). OBJECTIVE: To assess the topical treatment attributes that influence patient preference for fixed combination calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) foam vs. gel, as well as in comparison with the latest topical treatment (LTT) a patient received. METHODS: PSO-INSIGHTFUL was a Phase IIIb, prospective, multicentre (Canada/Germany), open-label, randomized, two-arm crossover study in patients aged ≥18 years with mild-to-severe psoriasis (NCT02310646). Following a washout period of up to 4 weeks, patients were randomized 1 : 1 to once-daily Cal/BD foam for 1 week, followed by Cal/BD gel for 1 week, or vice versa. Patients completed six questionnaires evaluating patient preferences. RESULTS: A total of 213 patients were randomized; 118 had received a topical treatment in the previous 3 months. Based on the Subject's Preference Assessment, 50% of patients preferred Cal/BD foam and 50% preferred Cal/BD gel. Based on the Topical Product Usability Questionnaire (TPUQ), overall mean scores were high for both Cal/BD foam and gel, and were often significantly in favour of both products compared with LTT. Greater differences between Cal/BD foam and gel vs. LTT occurred when the previous treatment was an ointment or cream. Cal/BD foam was generally preferred by younger patients (aged 18-39 years), whereas Cal/BD gel tended to be preferred by older patients (aged ≥40 years). Results from other questionnaires were aligned with the TPUQ. CONCLUSIONS: Patients with psoriasis have diverse needs and different preferences for topical treatment. This knowledge may help prescribers to choose the right formulation for the right patient, potentially leading to improved adherence and better treatment outcomes.

A Dermatologist's Guide to Infection Screening Prior to Initiating Immunosuppressive Therapy.

Dermatologists have within their armamentarium numerous immunosuppressant agents, both traditional and new, that are useful in the treatment of chronic cutaneous disorders such as autoimmune bullous diseases and psoriasis. It is imperative that users of these agents are aware of potential sequelae from therapy, particularly infections. In this review, we summarize the most common immunosuppressant medications currently used in dermatology, and provide recommendations for infection screening prior to initiating treatment.

An estimation of the incidence of tuberous sclerosis complex in a nationwide retrospective cohort study (1997-2010).

BACKGROUND: Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 and TSC2, leading to mammalian target of rapamycin hyperactivation. Patients with TSC develop hamartomas in brain, lungs, liver and skin. Two epidemiological studies, performed in Minnesota, U.S.A., have estimated the incidence of TSC to be 0·28-0·56 per 100 000 person-years (PY), based on < 12 patients. Furthermore, whether common comorbidities are associated with this rare disease is not known. OBJECTIVES: To estimate the incidence of TSC and investigate the associations of TSC with other comorbidities, including diabetes, peptic ulcers, stroke and myocardial infarction. METHODS: We estimated the incidence and prevalence of TSC and its comorbidities from 1997 to 2010, based on the Catastrophic Illness Certificate disease database and a beneficiary cohort of 1 million people. RESULTS: The incidence of TSC in Taiwan is 0·153 per 100 000 PY. The number of patients identified with TSC in Taiwan doubled from 206 in 2006 to 471 in 2010. In 2010, the prevalence of TSC in Taiwan was estimated to be 1·58 in 100 000. We confirmed that female patients with TSC are more likely to develop renal tumours than male patients. Surprisingly, patients with TSC have a significantly decreased risk of developing peptic ulcers compared with controls. CONCLUSIONS: This is the first large-scale and longitudinal incidence study of TSC. This study provides compelling evidence that TSC mutations in humans are associated with a decreased risk of peptic ulcers.

Presence of the Merkel cell polyomavirus in Merkel cell carcinoma combined with squamous cell carcinoma in a patient with chronic arsenism.

We present a case of Merkel cell carcinoma (MCC) coincident with squamous cell carcinoma (SCC) on the breast of a woman with chronic arsenism. This case demonstrates the distinct association of chronic arsenism with two different primary cutaneous carcinomas. Merkel cell polyomavirus (MCPyV) was identified in the lesional skin of the MCC but not in that of the SCC, suggesting there are different interactions of MCPyV in the pathogenesis of SCC and MCC related to arsenic. Physicians need to be vigilant in the occurrence of both SCC and MCC in patients with chronic arsenism. To our knowledge, this is the first study to show the presence of MCPyV in the MCC but not the SCC portion of an arsenic-induced tumour.

Electron beam irradiated ITO films as highly transparent p-type electrodes for GaN-based LEDs.

We have investigated the effect of electron beam irradiation on the electrical and optical properties of ITO film prepared by magnetron sputtering method at room temperature. Electron beam irradiation to the ITO films resulted in a significant decrease in sheet resistance from 1.28 x 10(-3) omega cm to 2.55 x 10(-4) omega cm and in a great increase in optical band gap from 3.72 eV to 4.16 eV, followed by improved crystallization and high transparency of 97.1% at a wavelength of 485 nm. The overall change in electrical, optical and structural properties of ITO films is related to annealing effect and energy transfer of electron by electron beam irradiation. We also fabricated GaN-based light-emitting diodes (LEDs) by using the ITO p-type electrode with/without electron beam irradiation. The results show that the LEDs having ITO p-electrode with electron beam irradiation produced higher output power due to the low absorption of light in the p-type electrode.

Mechanistic correlations between two itch biomarkers, cytokine interleukin-31 and neuropeptide ß-endorphin, via STAT3/calcium axis in atopic dermatitis.

BACKGROUND: Itch is the cardinal symptom of atopic dermatitis (AD). ß-Endorphin, a neuropeptide, is increased in both AD skin and sera. Interleukin (IL)-31, an itch-relevant cytokine, activates IL-31 receptors in keratinocytes. However, how IL-31 and ß-endorphin interact in AD skin remains elusive. OBJECTIVES: To investigate the mechanistic interaction of IL-31 and ß-endorphin in AD. METHODS: This was a prospective cross-sectional study. We recruited adult patients with AD and controls according to Hanifin's AD criteria. Serum levels of IL-31 and ß-endorphin were measured by enzyme-linked immunosorbent assay. Expressions of IL-31 receptor A (IL-31RA) and ß-endorphin in the skin were assessed by immunohistochemistry. Their expression in the skin and blood was compared and correlated in patients with AD and in controls. We also treated primary keratinocytes with IL-31 and measured calcium influx, ß-endorphin production and signalling pathways to define their mechanistic interactions. RESULTS: ß-Endorphin was increased in the supernatant from IL-31-treated keratinocytes. IL-31 receptor activation resulted in calcium influx and STAT3 activation; pretreatment with STAT3 inhibitor stopped the increase of ß-endorphin. Notably, either replacement of extracellular calcium or treatment with 2-aminoethoxydiphenyl borate, an inhibitor for the store-operated channel, blocked STAT3 activation. We found higher levels of blood ß-endorphin and IL-31, which were significantly correlated, in patients with AD. Moreover, IL-31RA and ß-endorphin were increased and colocalized both in AD human skin and TPA-painted mouse skin. CONCLUSIONS: IL-31 receptor activation in keratinocytes induces calcium influx and STAT3-dependent production of ß-endorphin. These results might contribute to an understanding of the regulatory mechanisms underlying peripheral itch.

Improved electrical and optical properties of ITO/Ag/ITO films by using electron beam irradiation and their application to ultraviolet light-emitting diode as highly transparent p-type electrodes.

We have investigated the effect of insertion of a Ag layer in ITO film as well as electron beam irradiation to the multilayer films on the electrical and optical properties of the ITO-based multilayer deposited by magnetron sputtering method at room temperature. Inserting a very thin Ag layer between ITO layers resulted in a significant decrease in sheet resistance and increased the optical band gap of the ITO/Ag/ITO multilayer to 4.35 eV, followed by a high transparency of approximately 80% at a wavelength of 375 nm. We have also fabricated ultraviolet light-emitting diodes (LED) by using the ITO/Ag/ITO p-type electrode with/without electron beam irradiation. The results show that the UV-LEDs having ITO/Ag/ITO p-electrode with electron beam irradiation produced 19% higher optical output power due to the low absorption of light in the p-type electrode.

Dental postoperative bleeding complications in patients with suspected and documented liver disease.

OBJECTIVES: The aims of this study were to determine the frequency of bleeding complications following dental procedures in patients with known or suspected chronic liver disease and whether international normalized ratio (INR) determination could aid in predicting bleeding complications in these patients. PATIENTS AND METHOD: We identified 90 patients (mean age: 51 ± 9 years) in this retrospective chart review. Sixty-nine patients had a known history of chronic liver disease and 21 had suspected chronic liver disease. Descriptive statistics were determined. Independent sample t-test and one-way variance test were utilized for continuous variables and chi-square test for dichotomous variables. RESULTS: The mean INR value for all patients was 1.2 ± 0.3. The INR value was significantly associated with the diagnosis of liver cirrhosis, the diagnoses of Hepatitis B and C together, the presence of ascites alone, and the number of clinical signs and symptoms (i.e. ascites, jaundice and encephalopathy) present. Nine patients with INR values between 1.5 and 2 underwent invasive dental procedures without postoperative bleeding complications. CONCLUSION: There were no episodes of postoperative bleeding in patients. The findings suggest that clinicians should not rely solely on an INR value to predict post-procedure bleeding in patients with liver disease.

Lifetime exposure to cigarette smoking and the development of adult-onset atopic dermatitis.

BACKGROUND: Adult-onset atopic dermatitis (AD) has recently been recognized as a distinct disease entity, but its risk factors have not yet been clearly defined. Although gestational and perinatal exposure to tobacco smoking may be associated with the development of classic AD, the association between active/passive smoking and adult-onset AD remains controversial. OBJECTIVES: To determine if exposure to smoking, including environmental tobacco smoke (ETS), is associated with the risk of adult-onset AD. METHODS: Tobacco smoking and exposure to ETS were measured in a case-control association analysis in 83 patients with physician-diagnosed adult-onset AD and 142 age- and sex-matched controls. RESULTS: Multiple logistic regression analyses showed that, among the potential environmental risk factors, both current and ever smoking were significant risk factors for adult-onset AD [odds ratio (OR) 4·994 and 3·619, respectively], compared with never smoking. Also, packs per year was significantly associated with adult-onset AD (OR 1·058, 95% confidence interval 1·028-1·089), suggesting a lifelong cumulative risk in current smokers. Moreover, nonsmokers with adult-onset AD reported significantly more exposure to ETS. CONCLUSIONS: Early and/or current exposure to cigarette smoking may contribute cumulatively to the development of adult-onset AD. Exposure to ETS in childhood is associated with the development of adult-onset AD. Adults should be discouraged from smoking to prevent adult-onset AD in themselves and their family members.

The effect of parenting styles on enforcement of oral health behaviours in children.

PURPOSE: To examine the relationship between parenting styles and parental attitudes towards oral health practices in children. METHODS: Parents of children aged 4-6 years presenting to four public dental clinics completed the Parenting Styles Dimensions Questionnaire (PSDQ) and a questionnaire on parental attitudes, child diet and oral hygiene practices. Child oral health was evaluated using Plaque Index (PI) and dmft-Index. RESULTS: Three hundred and eighty-nine children (mean age: 62.3 ± 9.8 months) were recruited. The median dmft was 4 (IQR = 9) and median PI was 1.5 (IQR = 0.8). An authoritative parenting style was observed in 95.1% of parents. Authoritative parents were more likely to monitor sweets/snacks intake (P = 0.004) and less inclined to offer sweets/snacks in exchange for good behaviour (P = 0.04) than permissive parents. However, actual between-meal snacking frequency did not differ between styles (P = 0.43). Permissive parents were less likely to ensure bedtime toothbrushing (P = 0.001) or brush thoroughly when busy or tired (P = 0.03) compared to authoritative parents; these attitudes were associated with higher frequencies of actual omission of bedtime toothbrushing (P = 0.006) in their children. A higher frequency of omitting bedtime toothbrushing significantly predicted a permissive parenting style (OR = 12.1, P = 0.009). Parenting styles were not associated with dmft (P = 0.72) and/or PI (P = 0.34). CONCLUSIONS: Authoritative parenting was associated with positive attitudes regarding both preventive dietary and oral hygiene practices. Actual oral hygiene practices were more ideal in children with authoritative parents, but parenting styles had no impact on actual dietary habits.

Rinsing with water for 1 min after milk formula increases plaque pH.

PURPOSE: Parents find it challenging to follow recommendations to brush young children after feeds at night despite the increase caries risk. This study compared three clinical recommendations (dilution, rinsing and wiping) on plaque pH after formula consumption. METHODS: Eighteen subjects were recruited. The five interventions with 2-week washout between visits included: Rinse with undiluted formula for 30 s (UF); rinse with 50% diluted formula for 30 s (DF); rinse with undiluted formula for 30 s, followed by rinsing with water for 1 minute (UF/R); rinse with undiluted formula for 30 s, followed by wiping (UF/W); rinse with 10% sucrose for 30 s as control (C). Plaque samples were collected at baseline, 2, 5, 10, 20 and 30 min after the intervention and pH measured using the plaque sampling method. RESULTS: UF/R resulted in significantly smaller pH drops at 5, 10 and 20 min compared to UF. It also resulted in higher minimum pH (UF/R: 6.34 ± 0.36 Vs UF: 6.06 ± 0.40, p = 0.02), smaller maximum pH drop (UF/R: 0.63 ± 0.35 Vs UF: 0.90 ± 0.49, p = 0.03), smaller sum of change of hydrogen ion concentration (UF/R: 9.22 × 10-7 ± 7.8 × 10-7 Vs UF: 2.30 × 10-6 ± 2.6 × 10-6, p = 0.04), and smaller area under the curve (UF/R: 7.70 ± 5.44 Vs UF: 13.44 ± 9.44, p = 0.02). DF and UF/W did not result in any significant pH change compared to UF. CONCLUSIONS: Of the three clinical recommendations, only rinsing with water for 1 min after undiluted formula reduced plaque acidogenicity. Teeth wiping with a moist cloth and 50% dilution of infant formula did not have an effect on plaque acidity.

Parental perspectives towards sugar-sweetened beverages and polices: a qualitative study.

PURPOSE: This qualitative study aimed to understand parental perception of (1) sugar-sweetened beverages (SSB) and implications of SSB on health; (2) their role in shaping their children's consumption of SSB; (3) the influences on SSB consumption of their children; and (4) potential government policies targeted at controlling SSB consumption. METHODS: English-speaking parents of pre-schoolers aged 2-6 years were recruited. Semi-structured interviews based on the knowledge, attitude, practice framework were conducted, and transcripts were subjected to thematic analysis based on inductive approaches. Recruitment continued until data saturation was reached. RESULTS: Twenty parents participated in the study and themes addressing the objectives identified. (1) There were misconceptions regarding the healthfulness of certain non-packaged SSB such as traditional remedies and juices. Some were unaware about the association between SSB and dental caries. (2) The need to reduce and restrict sugar consumption for overall and oral health reasons was well-recognised, but the extent of control varied. (3) Multiple stakeholders including pre-schools, grandparents and domestic helpers were involved in shaping children's diet. Children's sugar intake was also influenced by environmental factors, such as the ubiquitously available SSB, targeted marketing and high cost of healthy alternatives. (4) Participants were less accepting towards SSB taxation than the ban of SSB sales. CONCLUSION: Despite the awareness of the types of SSBs and the general/oral health implications of sugar consumption, misconceptions exist. Although most parents possessed the knowledge and attitude, this did not translate into the practice of reducing sugar consumption in their children. There was no SSB reduction policy that had overwhelming acceptability.

Transforming growth factor-ß enhances matrix metalloproteinase-2 expression and activity through AKT in fibroblasts derived from angiofibromas in patients with tuberous sclerosis complex.

BACKGROUND: Patients with tuberous sclerosis complex (TSC) develop fibrous tumours in the brain, skin, kidney, heart and lungs due to TSC1/2 mutations. In the skin, patients develop angiofibromas that have vascular and fibrotic components in which transforming growth factor (TGF)-ß and matrix metalloproteinase (MMP)-2 are important. OBJECTIVES: To investigate if the TGF-ß axis and MMP-2 play an important role in the pathogenesis of TSC angiofibromas. METHODS: Samples from TSC angiofibromas and normal skin were measured for expression of TGF-ß and MMP-2 by immunohistochemistry and real-time polymerase chain reaction. Fibroblasts grown from TSC angiofibromas (TSC fibroblasts) were incubated with TGF-ß. Expression of ERK, AKT and S6K was measured by Western blotting, and MMP-2 expression and activity were determined by enzyme-linked immunosorbent assay and gelatin zymography, respectively. RESULTS: There was an increase in the expression of TGF-ß and MMP-2 in TSC tumours compared with those in normal skin. The baseline expression of MMP-2 was increased in conditioned medium from TSC fibroblasts. In addition, TGF-ß enhanced MMP-2 production and activity, which could be abrogated by pretreatment with an AKT inhibitor (LY294002) but not with rapamycin. Finally, there was a significant colocalization of TGF-ß and MMP-2 in the TSC tumours. CONCLUSIONS: There is an increase of MMP-2 as a result of TGF-ß acting through AKT in TSC tumour cells. This regulation of the TGF-ß-AKT-MMP-2 axis is independent of mammalian target of rapamycin (mTOR) signalling. In addition to targeting the mTOR pathway, targeting TGF-ß simultaneously could block dysregulated tissue remodelling in TSC tumours.

Incidence of acute oral sequelae in pediatric patients undergoing chemotherapy.

PURPOSE: The purpose of this literature review was to assess the incidence of acute oral sequelae in children receiving cytotoxic therapy. METHODS: The dental literature was searched using 3 electronic databases--Cochrane, Medline, and Embase--from 1966 to 2006 and was limited to articles reporting acute oral sequelae in patients receiving chemotherapy with or without radiotherapy and to individuals younger than 20 years old. RESULTS: Nineteen articles fulfilled the inclusion criteria and were included in this review. The overall incidence of acute oral sequelae in children was 54%. The incidence of oral sequelae was higher in children who received myeloablative therapy prior to bone marrow transplantation compared to those who received only chemotherapy with or without radiotherapy. CONCLUSIONS: The lock of consensus on what constitutes acute oral sequelae and on universally accepted assessment tools complicates the determination of incidence. Acute oral sequelae are frequent in children and the incidence appears to be comparable to adults.

Role of oral flora in chemotherapy-induced oral mucositis in vivo.

OBJECTIVE: To determine if commensal oral microflora impacts the severity of chemotherapy-induced oral mucositis (OM). DESIGN: Specific-pathogen-free (SPF) and germ-free Swiss Webster mice in the experimental groups were dosed with 5-fluorouracil (5-FU) to induce OM. Mice in the control group received phosphate buffered saline. Comparative analyses of the epithelial thickness and cell proliferation/turnover rates, as well as the expression levels of metalloproteinases and pro-inflammatory mediators in the oral mucosa between the control and experimental groups were determined by histopathological and immunohistochemical analyses. RESULTS: 5-FU-treated SPF and germ-free mice showed characteristic features of OM with reduced oral epithelial thickness, presence of inflammatory cells in the connective tissues, and increased levels of expression of metalloproteinases and pro-inflammatory cytokines compared to the respective control groups. When 5-FU-treated SPF and germ-free mice were compared, 5-FU-treated germ-free mice exhibited less severe epithelial destruction with higher expression of the cell proliferation marker Ki67, coupled with lower expression levels of metalloproteinases and pro-inflammatory cytokine in the oral mucosa. CONCLUSION: This study provides the first histopathological evidence that oral flora has a detrimental effect on chemotherapy-induced OM in vivo.