The gut microbiota influences the reactivity of the immune system, and Parabacteroides distasonis has emerged as an anti-inflammatory commensal. Here, we investigated whether its lysate could prevent severe forms of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in mice and how this preventive strategy affects the gut microbiota and immune response. Lysate of anaerobically cultured P. distasonis (Pd lysate) was orally administered to C57BL/6 mice in four weekly doses. One week later, EAE was induced and disease severity was assessed three weeks after induction. Fecal microbiota changes in both vehicle- and Pd lysate-treated animals was analyzed by 16S V3-V4 amplicon sequencing and qPCR, antimicrobial peptide expression in the intestinal mucosa was measured by qPCR, and immune cell composition in the mesenteric and inguinal lymph nodes was measured by multicolor flow cytometry. Pd lysate significantly delayed the development of EAE and reduced its severity when administered prior to disease induction. EAE induction was the main factor in altering the gut microbiota, decreasing the abundance of lactobacilli and segmented filamentous bacteria. Pd lysate significantly increased the intestinal abundance of the genera Anaerostipes, Parabacteroides and Prevotella, and altered the expression of antimicrobial peptides in the intestinal mucosa. It significantly increased the frequency of regulatory T cells, induced an anti-inflammatory milieu in mesenteric lymph nodes, and reduced the activation of T cells at the priming site. Pd lysate prevents severe forms of EAE by triggering a T regulatory response and modulating T cell priming to autoantigens. Pd lysate could thus be a future modulator of neuroinflammation that increases the resistance to multiple sclerosis.

• MeSH
• Bacteroidetes imunologie   MeSH
• encefalomyelitida autoimunitní experimentální * imunologie   prevence a kontrola   MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• střevní mikroflóra * imunologie   MeSH
• střevní sliznice imunologie   mikrobiologie   metabolismus   MeSH
• T-lymfocyty imunologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The human intestine is a habitat for microorganisms and, recently, the composition of the intestinal microbiota has been correlated with the etiology of diseases such as inflammations, sores, and tumors. Although many studies have been conducted to understand the composition of that microbiota, expanding these studies to more samples and different backgrounds will improve our knowledge. In this work, we showed the colon microbiota composition and diversity of healthy subjects, patients with inflammatory bowel disease (IBD), and colon cancer by metagenomic sequencing. Our results indicated that the relative abundance of prokaryotic and eukaryotic microbes differs between the healthy vs. tumor biopsies, tumor vs. IBD biopsies, and fresh vs. paraffin-embedded tumor biopsies. Fusobacterium, Escherichia-Shigella, and Streptococcus genera were relatively abundant in fresh tumor biopsies, while Pseudomonas was significantly elevated in IBD biopsies. Additionally, another opportunist pathogen Malasseziales was revealed as the most abundant fungal clade in IBD biopsies, especially in ulcerative colitis. We also found that, while the Basidiomycota:Ascomycota ratio was slightly lower in tumor biopsies compared to biopsies from healthy subjects, there was a significant increase in IBD biopsies. Our work will contribute to the known diversity of prokaryotic and eukaryotic microbes in the colon biopsies in patients with IBD and colon cancer.

• MeSH
• Basidiomycota * MeSH
• Crohnova nemoc * mikrobiologie   MeSH
• idiopatické střevní záněty * mikrobiologie   MeSH
• lidé MeSH
• mikrobiota * MeSH
• nádory tračníku * MeSH
• střevní sliznice mikrobiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   terapeutické užití   MeSH
• buněčná stěna chemie   MeSH
• epitelové buňky mikrobiologie   fyziologie   MeSH
• gnotobiologické modely MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• Lactobacillaceae * fyziologie   MeSH
• myši MeSH
• podvýživa * patofyziologie   terapie   MeSH
• poruchy růstu patofyziologie   terapie   MeSH
• růst * účinky léků   fyziologie   MeSH
• signální adaptorový protein Nod2 * metabolismus   MeSH
• střeva * mikrobiologie   fyziologie   MeSH
• střevní mikroflóra * fyziologie   MeSH
• střevní sliznice mikrobiologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The aim of this study was to investigate the use of a standardized animal model subjected to antibiotic treatment, and the effects of this treatment on the course of dextran sodium sulphate (DSS)-induced colitis in mice. By decontamination with selective antibiotics and observation of pathogenesis of ulcerative colitis (UC) induced chemically by exposure of mice to various concentrations of DSS, we obtained an optimum animal PGF model of acute UC manifested by mucin depletion, epithelial degeneration and necrosis, leading to the disappearance of epithelial cells, infiltration of lamina propria and submucosa with neutrophils, cryptitis, and accompanied by decreased viability of intestinal microbiota, loss of body weight, dehydration, moderate rectal bleeding, and a decrease in the selected markers of cellular proliferation and apoptosis. The obtained PGF model did not exhibit changes that could contribute to inflammation by means of alteration of the metabolic status and the induced dysbiosis did not serve as a bearer of pathogenic microorganisms participating in development of ulcerative colitis. The inflammatory process was induced particularly by exposure to DSS and its toxic action on compactness and integrity of mucosal barrier in the large intestine. This offers new possibilities of the use of this animal model in studies with or without participation of pathogenic microbiota in IBD pathogenesis.

• MeSH
• antibakteriální látky farmakologie   MeSH
• apoptóza fyziologie   MeSH
• epitelové buňky patologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• proliferace buněk fyziologie   MeSH
• síran dextranu farmakologie   MeSH
• střevní mikroflóra účinky léků   fyziologie   MeSH
• střevní sliznice mikrobiologie   patologie   MeSH
• ulcerózní kolitida chemicky indukované   farmakoterapie   patologie   MeSH
• zánět farmakoterapie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Clostridioides difficile and Staphylococcus aureus are two well-known pathogens both causing hospital- and community-acquired infections. However, their intestinal coexistence was not well investigated in inflammatory bowel disease (IBD). Herein, we explored the prevalence of C. difficile, S. aureus and their coexistence in the gut of Iranian patients with IBD. Fecal and colon specimens were obtained from 70 outpatients with underlying IBD, and investigated for the presence of C. difficile and S. aureus. C. difficile isolates were characterised by CE-ribotyping. PCR was used for detection of toxin-encoding genes of C. difficile and S. aureus isolates. The antimicrobial susceptibility testing of C. difficile and S. aureus isolates were examined by agar dilution and Kirby-Bauer disk diffusion methods, respectively. Totally, C. difficile and S. aureus were detected in only 5.7% and 15.8% of IBD flares. Coexistence of C. difficile and S. aureus was detected in 5.7% of IBD flares. Two different C. difficile ribotypes including RT 126 and RT 017 were identified showing toxin profiles of tcdA+B+/cdtA+B+ and tcdA+B+, respectively. In S. aureus isolates, only positivity for the presence of sea enterotoxin was detected. C. difficile isolates were susceptible to metronidazole, ceftazidime and fidaxomicin. The highest resistance of S. aureus isolates was observed against penicillin (92.3%), following amoxicillin-clavulanate (38.5%) and amikacin (30.8%). Our findings demonstrated that patients with IBD flare are more sensitive to acquire coinfection of C. difficile and S. aureus than remission. However, more robust data is required to study the crosstalk between these enteric infections and their clinical relevance in patients with IBD flare.

• MeSH
• antibakteriální látky farmakologie   MeSH
• biopsie MeSH
• Clostridioides difficile * účinky léků   MeSH
• dítě MeSH
• dospělí MeSH
• feces mikrobiologie   MeSH
• idiopatické střevní záněty diagnóza   epidemiologie   etiologie   MeSH
• koinfekce komplikace   mikrobiologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mladiství MeSH
• mladý dospělý MeSH
• náchylnost k nemoci MeSH
• ochrana veřejného zdraví MeSH
• pacienti ambulantní * MeSH
• předškolní dítě MeSH
• prevalence MeSH
• senioři MeSH
• Staphylococcus aureus * účinky léků   MeSH
• střevní sliznice mikrobiologie   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Írán MeSH

The interplays between the metabolic products of intestinal microbiota and the host signaling through xenobiotic receptors, including pregnane X receptor (PXR), are of growing interest, in the context of intestinal health and disease. A distinct class of microbial catabolites is formed from dietary tryptophan, having the indole scaffold in their core structure, which is a biologically active entity. In the current study, we examined a series of ten tryptophan microbial catabolites for their interactions with PXR signaling. Utilizing a reporter gene assay, we identified indole (IND) and indole-3-acetamide (IAD) as PXR agonists. IND and IAD induced PXR-regulated genes CYP3A4 and MDR1 in human intestinal cancer cells. Using time-resolved fluorescence resonance energy transfer, we show that IND (IC50 292 μM) and IAD (IC50 10 μM) are orthosteric ligands of PXR. Binding of PXR in its DNA response elements was enhanced by IND and IAD, as revealed by chromatin immunoprecipitation assay. We demonstrate that tryptophan microbial intestinal metabolites IND and IAD are ligands and agonists of human PXR. These findings are of particular importance in understanding the roles of microbial catabolites in human physiology and pathophysiology. Furthermore, these results are seminal in expanding potential drug repertoire through microbial metabolic mimicry.

• MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• indoly metabolismus   MeSH
• kultivované buňky MeSH
• kyseliny indoloctové metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• P-glykoproteiny genetika   metabolismus   MeSH
• pregnanový X receptor agonisté   genetika   MeSH
• reportérové geny MeSH
• střevní mikroflóra * MeSH
• střevní sliznice * metabolismus   mikrobiologie   MeSH
• transfekce MeSH
• tryptofan metabolismus   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The ability to adhere via colonization factors to specific receptors located on the intestinal mucosa is a key virulence factor in enterotoxigenic Escherichia coli (ETEC) pathogenesis. Here, the potential glycosphingolipid receptors of the novel human ETEC colonization factor CS30 were examined by binding of CS30-expressing bacteria to glycosphingolipids on thin-layer chromatograms. We thereby found a highly specific binding of CS30-expressing bacteria to a fast-migrating acid glycosphingolipid of human and porcine small intestine, while no binding was obtained with a mutant ETEC strain unable to express CS30 fimbriae. The CS30 binding glycosphingolipid from human small intestine was isolated and characterized by mass spectrometry as sulfatide (SO3-3Galβ1Cer). Comparative binding studies using sulfatides with different ceramide compositions gave a preferential binding of CS30 to sulfatide with d18:1-h24:0 ceramide. This ceramide species of sulfatide was also isolated from human small intestine and characterized by mass spectrometry and antibody binding. These studies implicate sulfatide as candidate receptor for mediating attachment of CS30-fimbriated ETEC to human and porcine small intestinal cells. Our findings may be a basis for designing receptor saccharide analogues for inhibition of the intestinal adhesion of CS30-expressing E. coli.

• MeSH
• bakteriální adheze * MeSH
• ceramidy analýza   MeSH
• enterotoxigenní Escherichia coli metabolismus   MeSH
• faktory virulence metabolismus   MeSH
• glykosfingolipidy metabolismus   MeSH
• lidé MeSH
• prasata MeSH
• proteiny fimbrií genetika   metabolismus   MeSH
• proteiny z Escherichia coli metabolismus   MeSH
• střevní sliznice cytologie   mikrobiologie   MeSH
• sulfoglykosfingolipidy metabolismus   MeSH
• tenké střevo cytologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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.

• 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

Trans-resveratrol, a well-known plant phenolic compound, has been intensively investigated due to its association with the so-called French paradox. However, despite its high pharmacological potential, trans-resveratrol has shown relatively low bioavailability. Trans-resveratrol is intensively metabolized in the intestine and liver, yielding metabolites that may be responsible for its high bioactivity. The aim of this study was to investigate and compare the metabolism of trans-resveratrol (tRes), cis-resveratrol (cRes) and dihydroresveratrol (dhRes) in an in vitro epithelial model using Caco-2 cell lines. Obtained metabolites of tRes, cRes and dhRes were analyzed by LC/MS Q-TOF, and significant differences in the metabolism of each compound were observed. The majority of tRes was transported unchanged through the Caco-2 cells, while cRes was mostly metabolized. The main metabolite of both cis- and trans-resveratrol observed as a result of colon microbial metabolism, dhRes, was metabolized almost completely, with only traces of the unchanged molecule being found. A sulphate conjugate was identified as the main metabolite of tRes in our model, while a glucuronide conjugate was the major metabolite of cRes and dhRes. Since metabolism of simple phenolics and polyphenols plays a crucial role in their bioavailability, detailed knowledge of their transformation is of high scientific value.

• MeSH
• biologická dostupnost MeSH
• Caco-2 buňky MeSH
• lidé MeSH
• permeabilita MeSH
• resveratrol chemie   farmakokinetika   MeSH
• stereoizomerie MeSH
• stilbeny chemie   farmakokinetika   MeSH
• střevní sliznice cytologie   metabolismus   mikrobiologie   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• bronchiální astma * imunologie   krev   prevence a kontrola   MeSH
• globální zátěž nemocemi MeSH
• incidence MeSH
• lidé MeSH
• maternofetální výměna látek MeSH
• nedostatek vitaminu D dietoterapie   imunologie   komplikace   MeSH
• postnatální péče MeSH
• potravinová alergie * imunologie   krev   prevence a kontrola   MeSH
• prenatální péče MeSH
• střevní sliznice imunologie   metabolismus   mikrobiologie   MeSH
• vitamin D * aplikace a dávkování   krev   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH