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 intestinal epithelium, a rapidly renewing tissue, is characterized by a continuous cell turnover that occurs through a well-coordinated process of cell proliferation and differentiation. This dynamic is crucial for the long-term function of the gastrointestinal tract. Disruption of this process can lead to colorectal carcinoma, a common malignancy worldwide. The first part of the review focuses on the cellular composition of the epithelium and the molecular mechanisms that control its functions, and describes the pathways that lead to epithelial transformation and tumor progression. This forms the basis for understanding the development and progression of advanced colorectal cancer. The second part deals with current therapeutic approaches and presents the latest treatment options, ongoing clinical trials and new drugs. In addition, the biological and medical perspectives of the adverse effects of therapies and models of regeneration of the intestinal epithelium are highlighted and, finally, future treatment options are discussed.
- MeSH
- kolorektální nádory * terapie patologie MeSH
- lidé MeSH
- nádorová transformace buněk MeSH
- onkologové MeSH
- střevní sliznice patologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- chronická pankreatitida metabolismus patofyziologie MeSH
- chuťová percepce MeSH
- Crohnova nemoc metabolismus patofyziologie MeSH
- cystická fibróza metabolismus patofyziologie MeSH
- enterocyty fyziologie MeSH
- gastrointestinální absorpce fyziologie MeSH
- gastrointestinální nemoci * metabolismus patofyziologie MeSH
- kyselina linolová metabolismus MeSH
- lidé MeSH
- mastné kyseliny * fyziologie metabolismus MeSH
- potravinová intolerance MeSH
- střeva metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Malabsorpční syndromy představují rozsáhlou skupinu onemocnění, pro která je typická porucha intraluminálního trávení či vstřebávání živin. Klinicky se manifestují jako průjem, steatorea, nadýmání anebo neprospívání. Některé jednotky mohou být doprovázeny i specifickými příznaky, jako jsou např. otoky, paličkovité prsty a perianální exantém. Článek má za cíl na základě recentních poznatků malabsorpční syndromy přehledně klasifikovat a shrnout jejich etiologii, etiopatogenezi a klinickou manifestaci. Nedílnou součástí textu je rovněž přiblížení aktuálních diagnostických a léčebných postupů. V souladu se zaměřením rubriky budou diskutovány zejména nozologické jednotky s častějším výskytem. Vzácnější choroby (např. malabsorpce při reakci štěpu proti hostiteli) budou zmíněny jen okrajově a čtenáři budou poskytnuty recentní zdroje s podrobnějšími informacemi.
Malabsorption syndromes represent a large group of diseases characterized by impaired intraluminal digestion or nutrient absorption and typically manifest as diarrhea, steatorrhea, bloating and/or failure to thrive. Some diseases may be accompanied by specific symptoms such as oedema, digital clubbing and perianal exanthema. This article aims to classify malabsorption syndromes based on recent findings and summarize their etiology, etiopathogenesis and clinical manifestation. We review current diagnostic and therapeutic approaches. In accordance with the section in which the text will be published, frequent nosological entities will be discussed. Rarer diseases (such as malabsorption due to graft versus host disease) will be mentioned briefly, we direct readers to relevant and detailed sources.
- MeSH
- celiakie diagnóza etiologie komplikace MeSH
- cholestáza diagnóza etiologie MeSH
- diferenciální diagnóza MeSH
- exsudativní enteropatie diagnóza etiologie komplikace MeSH
- lidé MeSH
- malabsorpční syndromy * diagnóza etiologie farmakoterapie klasifikace patofyziologie MeSH
- nemoci žaludku diagnóza klasifikace komplikace patofyziologie MeSH
- střevní sliznice patologie MeSH
- žaludeční sliznice patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy 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
- alkoholismus * imunologie komplikace patofyziologie MeSH
- enterocyty patologie MeSH
- lidé MeSH
- mikroglie patologie MeSH
- neurotransmiterové látky MeSH
- osa mozek-střevo * fyziologie imunologie MeSH
- poruchy nervového systému vyvolané alkoholem MeSH
- střevní mikroflóra imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- cystická fibróza * MeSH
- individualizovaná medicína MeSH
- kolforsin farmakologie MeSH
- lidé MeSH
- mutace MeSH
- protein CFTR genetika MeSH
- střevní sliznice MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
BACKGROUND: Mucosal healing (MH) has become a perspective treatment target in patients with Crohn's disease (CD). Data about the impact of MH on long-term outcome in pediatric patients are still scarce. METHODS: Seventy-six pediatric patients with CD were evaluated retrospectively (2000-2015) in a tertiary care center. Based on MH achievement, they were divided into two groups (MH, N.=17; and No MH, N.=59). The primary endpoint was to assess the association of MH and the need for CD-related hospitalizations or surgery in pediatric patients with CD. RESULTS: The number of hospitalized patients was 24% in the MH group and 42% in the No MH group (P=0.26). The total number of CD-related hospitalizations was not significant between the MH group and the No MH group (5 vs. 41, P=0.15). The time to the first hospitalization was 24 months in MH and 21 months in No MH (P>0.99). About 24% of the patients in the MH group and 39% patients in the No MH group underwent CD-related operation (P=0.39). Time to the first operation was 43 months for MH and 19 months for the No MH group (P=0.13). The follow-up period was 91 months in the MH group and 80 months in the No MH group (P=0.74). The use of infliximab was positively associated with MH (P=0.002). CONCLUSIONS: MH was not associated with fewer CD-related hospitalizations or operations in pediatric patients with CD during seven years of follow-up.
- MeSH
- časové faktory MeSH
- centra terciární péče MeSH
- Crohnova nemoc * terapie MeSH
- dítě MeSH
- hojení ran MeSH
- hospitalizace * statistika a číselné údaje MeSH
- infliximab terapeutické užití MeSH
- lidé MeSH
- mladiství MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- střevní sliznice * patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Inflammatory bowel diseases (IBD) frequently manifest in pediatric age, but may have atypical clinical, histological and laboratory features. Their underlying immune pathophysiology is incompletely understood, rendering quick diagnosis followed by tailored therapy difficult. The tumor necrosis factor superfamily receptor CD30 has been proposed as a potential marker of ulcerative colitis (UC) and has also been associated with elevated Th2 helper T cells. METHODS: A cohort of pediatric patients with UC and Crohn's disease (CD) was evaluated for serum soluble CD30 (sCD30) using ELISA and expression of CD30 and subpopulations of Th1/Th2/Th17 lymphocytes in the gastrointestinal mucosa using flow cytometry (FCM). The dataset is supported by endoscopic and microscopic activity of the disease and basic laboratory markers of inflammation. RESULTS: The cohort consisted of 102 observations from 94 patients. sCD30 levels did not differ between patients with CD or UC. However, sCD30 levels correlated with levels of CRP, ESR, fecal calprotectin and albumin and also with clinical activity of the disease in patients with both UC and CD. FCM was not helpful in evaluation of mucosal CD30, which was lowly expressed and not associated with the diagnosis or disease activity. We show augmented Th2 and Th1/17 response in terminal ileum and right-sided colon and decreased Th1/17 response in left-sided colon of UC patients. T lymphocyte subsets were also affected by anti-TNF treatment and patients' age. CONCLUSIONS: Neither sCD30 nor mucosal CD30 expression was helpful in differentiating between UC and CD. sCD30 seems to reflect a degree of systemic inflammation and clinical activity in IBD.
- MeSH
- biologické markery analýza MeSH
- Crohnova nemoc * diagnóza MeSH
- dítě MeSH
- idiopatické střevní záněty * komplikace MeSH
- inhibitory TNF MeSH
- lidé MeSH
- střevní sliznice patologie MeSH
- T-lymfocyty - podskupiny MeSH
- ulcerózní kolitida * diagnóza MeSH
- zánět patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
