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.

• Klíčová slova
• Microbiome, Microbiota, Sequencing, Uveitis, Vitreoretinal lymphoma,
• Publikační typ
• časopisecké články MeSH

The association between bacterial as well as viral gut microbiota imbalance and carcinogenesis has been intensively analysed in many studies; nevertheless, the role of fungal gut microbiota (mycobiota) in colorectal, oral, and pancreatic cancer development is relatively new and undiscovered field due to low abundance of intestinal fungi as well as lack of well-characterized reference genomes. Several specific fungi amounts are increased in colorectal cancer patients; moreover, it was observed that the disease stage is strongly related to the fungal microbiota profile; thus, it may be used as a potential diagnostic biomarker for adenomas. Candida albicans, which is the major microbe contributing to oral cancer development, may promote carcinogenesis via several mechanisms, mainly triggering inflammation. Early detection of pancreatic cancer provides the opportunity to improve survival rate, therefore, there is a need to conduct further studies regarding the role of fungal microbiota as a potential prognostic tool to diagnose this cancer at early stage. Additionally, growing attention towards the characterization of mycobiota may contribute to improve the efficiency of therapeutic methods used to alter the composition and activity of gut microbiota. The administration of Saccharomyces boulardii in oncology, mainly in immunocompromised and/or critically ill patients, is still controversial.

• Klíčová slova
• Saccharomyces boulardii, colorectal cancer, gut microbiota, mycobiota, oral cancer, pancreatic cancer,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Oxidative stress with subsequent premutagenic oxidative DNA damage has been implicated in colorectal carcinogenesis. The repair of oxidative DNA damage is initiated by lesion-specific DNA glycosylases (hOGG1, NTH1, MUTYH). The direct evidence of the role of oxidative DNA damage and its repair is proven by hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome), where germline mutations cause loss-of-function in glycosylases of base excision repair, thus enabling the accumulation of oxidative DNA damage and leading to the adenoma-colorectal cancer transition. Unrepaired oxidative DNA damage often results in G:C>T:A mutations in tumor suppressor genes and proto-oncogenes and widespread occurrence of chromosomal copy-neutral loss of heterozygosity. However, the situation is more complicated in complex and heterogeneous disease, such as sporadic colorectal cancer. Here we summarized our current knowledge of the role of oxidative DNA damage and its repair on the onset, prognosis and treatment of sporadic colorectal cancer. Molecular and histological tumor heterogeneity was considered. Our study has also suggested an additional important source of oxidative DNA damage due to intestinal dysbiosis. The roles of base excision repair glycosylases (hOGG1, MUTYH) in tumor and adjacent mucosa tissues of colorectal cancer patients, particularly in the interplay with other factors (especially microenvironment), deserve further attention. Base excision repair characteristics determined in colorectal cancer tissues reflect, rather, a disease prognosis. Finally, we discuss the role of DNA repair in the treatment of colon cancer, since acquired or inherited defects in DNA repair pathways can be effectively used in therapy.

• Klíčová slova
• DNA repair, base excision repair (BER)glycosylases, colorectal cancer, oxidative DNA damage,
• MeSH
• buněčné mikroprostředí MeSH
• cílená molekulární terapie MeSH
• DNA-glykosylasy metabolismus   MeSH
• kolorektální nádory etiologie   metabolismus   patologie   terapie   MeSH
• lidé MeSH
• náchylnost k nemoci * MeSH
• nádorová transformace buněk genetika   metabolismus   MeSH
• oprava DNA MeSH
• oxidační stres * MeSH
• poškození DNA * MeSH
• střevní sliznice metabolismus   mikrobiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• DNA-glykosylasy MeSH

Recurrent aphthous stomatitis (RAS) is the most common disease of the oral mucosa, and it has been recently associated with bacterial and fungal dysbiosis. To study this link further, we investigated microbial shifts during RAS manifestation at an ulcer site, in its surroundings, and at an unaffected site, compared with healed mucosa in RAS patients and healthy controls. We sampled microbes from five distinct sites in the oral cavity. The one site with the most pronounced differences in microbial alpha and beta diversity between RAS patients and healthy controls was the lower labial mucosa. Detailed analysis of this particular oral site revealed strict association of the genus Selenomonas with healed mucosa of RAS patients, whereas the class Clostridia and genera Lachnoanaerobaculum, Cardiobacterium, Leptotrichia, and Fusobacterium were associated with the presence of an active ulcer. Furthermore, active ulcers were dominated by Malassezia, which were negatively correlated with Streptococcus and Haemophilus and positively correlated with Porphyromonas species. In addition, RAS patients showed increased serum levels of IgG against Mogibacterium timidum compared with healthy controls. Our study demonstrates that the composition of bacteria and fungi colonizing healthy oral mucosa is changed in active RAS ulcers, and that this alteration persists to some extent even after the ulcer is healed.

• Klíčová slova
• microbiome, mycobiome, oral mucosa,
• Publikační typ
• časopisecké články MeSH

Diet is a major factor determining gut microbiota composition and perturbances in this complex ecosystem are associated with the inflammatory bowel disease (IBD). Here, we used gnotobiotic approach to analyze, how interaction between diet rich in proteins and gut microbiota influences the sensitivity to intestinal inflammation in murine model of ulcerative colitis. We found that diet rich in animal protein (aHPD) exacerbates acute dextran sulfate sodium (DSS)-induced colitis while diet rich in plant protein (pHPD) does not. The deleterious effect of aHPD was also apparent in chronic DSS colitis and was associated with distinct changes in gut bacteria and fungi. Therefore, we induced acute DSS-colitis in germ-free mice and transferred gut microbiota from aCD or aHPD fed mice to find that this effect requires presence of microbes and aHPD at the same time. The aHPD did not change the number of regulatory T cells or Th17 cells and still worsened the colitis in immuno-deficient RAG2 knock-out mice suggesting that this effect was not dependent on adaptive immunity. The pro-inflammatory effect of aHPD was, however, abrogated when splenic macrophages were depleted with clodronate liposomes. This treatment prevented aHPD induced increase in colonic Ly-6Chigh pro-inflammatory monocytes, but the ratio of resident Ly-6C-/low macrophages was not changed. These data show that the interactions between dietary protein of animal origin and gut microbiota increase sensitivity to intestinal inflammation by promoting pro-inflammatory response of monocytes.

• Klíčová slova
• colitis, dietary protein, germ-free, macrophage, microbiota,
• MeSH
• adaptivní imunita imunologie   MeSH
• buňky Th17 imunologie   metabolismus   MeSH
• dieta škodlivé účinky   MeSH
• dietní proteiny aplikace a dávkování   škodlivé účinky   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• kolitida imunologie   metabolismus   patologie   MeSH
• kolon imunologie   metabolismus   patologie   MeSH
• makrofágy imunologie   metabolismus   patologie   MeSH
• modely nemocí na zvířatech MeSH
• monocyty imunologie   metabolismus   patologie   MeSH
• myši inbrední BALB C MeSH
• myši knockoutované MeSH
• myši MeSH
• regulační T-lymfocyty imunologie   metabolismus   MeSH
• střeva imunologie   patologie   MeSH
• střevní mikroflóra imunologie   fyziologie   MeSH
• zánět imunologie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dietní proteiny MeSH
• DNA vazebné proteiny MeSH