PURPOSE: Dysregulation of the microbiota on different mucosal surfaces is associated with both immune-mediated and malignant diseases. Nevertheless, the involvement of different microbial communities is still poorly characterized. The aim of our study was to compare oral and gut microbiota composition between patients with uveitis, vitreoretinal lymphoma (VRL), and controls. METHODS: This study was designed as a prospective observational study. The inclusion criteria were treatment-naïve patients with immune-mediated uveitis or newly diagnosed VRL. The buccal swab and faecal samples were collected and bacterial 16S ribosomal RNA gene sequencing was used to identify the oral and gut microbiota. RESULTS: We enrolled 18 patients with uveitis, median age 39 years, 16 patients with VRL, median age 67.5 years, and 16 controls, median age 63 years. In the oral microbiota, the patients suffering from uveitis showed significant enrichment of genera Pseudomonas (p < 0.0001 and p < 0.0001), and Diaphorobacter (p = 0.007 and 0.013) and reduction of Streptococcus (p < 0.0001 and p < 0.0001) when compared to patients with VRL and control subjects, respectively. In addition, these patients had also significantly higher relative abundance of the genus Enhydrobacter (p = 0.029) and lower abundance of the genera Gemella (p = 0.002), Neisseria (p = 0.008), and Prevotella (p = 0.011) when compared to patients with VRL. We found only minor changes in the gut microbiota. CONCLUSION: Our study, as the first one, highlighted significant differences in the composition of oral microbiota among patients with uveitis, VRL, and control subjects.

• Keywords
• Microbiome, Microbiota, Sequencing, Uveitis, Vitreoretinal lymphoma,
• Publication type
• Journal Article MeSH

BACKGROUND: Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC. CONCLUSION/SIGNIFICANCE: In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.

• MeSH
• Biomarkers MeSH
• Crohn Disease * therapy   MeSH
• Tumor Necrosis Factor Inhibitors MeSH
• Humans MeSH
• Microbiota * MeSH
• Pilot Projects MeSH
• Ustekinumab therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Tumor Necrosis Factor Inhibitors MeSH
• Ustekinumab MeSH

The mycobiome is the fungal component of the human microbial ecosystem that represents only a small part of this environment but plays an essential role in maintaining homeostasis. Colonization by fungi begins immediately after birth. The initial mycobiome is influenced by the gestational age of a newborn, birth weight, delivery method and feeding method. During a human's life, the composition of the mycobiome is further influenced by a large number of endogenous and exogenous factors. The most important factors are diet, body weight, age, sex and antibiotic and antifungal therapy. The human mycobiome inhabits the oral cavity, gastrointestinal tract, respiratory tract, urogenital tract and skin. Its composition can influence the gut-brain axis through immune and non-immune mediated crosstalk systems. It also interacts with other commensals of the ecosystem through synergistic and antagonistic relationships. Moreover, colonization of the gut by opportunistic fungal pathogens in immunocompromised individuals can lead to clinically relevant disease states. Thus, the mycobiome represents an essential part of the microbiome associated with a variety of physiological and pathological processes. This review summarizes the current knowledge on the composition of the mycobiome in specific sites of the human body and its role in health and disease.

• Keywords
• colonization, composition, dysbiosis, fungi, genitourinary tract mycobiome, gut mycobiome, oral mycobiome, respiratory tract mycobiome, skin mycobiome,
• Publication type
• Journal Article MeSH
• Review MeSH

Crohn's disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where the role of gut but not skin dysbiosis is well recognized. Inhibitors of TNF have been successful in IBD treatment, but up to a quarter of patients suffer from unpredictable skin adverse events (SkAE). For this purpose, we analyzed temporal dynamics of skin microbiota and serum markers of inflammation and epithelial barrier integrity during anti-TNF therapy and SkAE manifestation in IBD patients. We observed that the skin microbiota signature of IBD patients differs markedly from healthy subjects. In particular, the skin microbiota of CD patients differs significantly from that of UC patients and healthy subjects, mainly in the retroauricular crease. In addition, we showed that anti-TNF-related SkAE are associated with specific shifts in skin microbiota profile and with a decrease in serum levels of L-FABP and I-FABP in IBD patients. For the first time, we showed that shifts in microbial composition in IBD patients are not limited to the gut and that skin microbiota and serum markers of the epithelium barrier may be suitable markers of SkAE during anti-TNF therapy.

• Keywords
• 16S RNA sequencing, IBD, TNF-alpha antagonist, serum biomarker, skin adverse events, skin microbiota,
• MeSH
• Biomarkers MeSH
• Crohn Disease * MeSH
• Inflammatory Bowel Diseases * drug therapy   MeSH
• Tumor Necrosis Factor Inhibitors MeSH
• Humans MeSH
• Microbiota * MeSH
• Colitis, Ulcerative * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Tumor Necrosis Factor Inhibitors MeSH

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn's disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).

• Keywords
• biological therapy, inflammatory bowel disease, microbiome, mycobiome, tumor necrosis factor-α,
• MeSH
• Biodiversity MeSH
• Adult MeSH
• Feces microbiology   MeSH
• Fungi genetics   MeSH
• Inflammatory Bowel Diseases blood   drug therapy   microbiology   surgery   MeSH
• Tumor Necrosis Factor Inhibitors therapeutic use   MeSH
• Interleukin-17 metabolism   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Humans MeSH
• Metagenomics MeSH
• Antibodies blood   MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Gastrointestinal Microbiome * genetics   MeSH
• Case-Control Studies MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Tumor Necrosis Factor Inhibitors MeSH
• Interleukin-17 MeSH
• Antibodies MeSH
• RNA, Ribosomal, 16S MeSH