Nejvíce citovaný článek - PubMed ID 21278760
The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases
PURPOSE OF THE REVIEW: The purpose of this Review was to summarize the evidence on the associations among estrogen status, cellular senescence, the gut microbiome and osteoporosis. RECENT FINDINGS: Indicate that osteoporosis is a global public health problem that impacts individuals and society. In postmenopausal women, a decrease in estrogen levels is associated with a decrease in gut microbial diversity and richness, as well as increased permeability of the gut barrier, which allows for low-grade inflammation. The direct effects of estrogen status on the association between bone and the gut microbiome were observed in untreated and treated ovariectomized women. In addition to the direct effects of estrogens on bone remodeling, estrogen therapy could reduce the risk of postmenopausal osteoporosis by preventing increased gut epithelial permeability, bacterial translocation and inflammaging. However, in studies comparing the gut microbiota of older women, there were no changes at the phylum level, suggesting that age-related comorbidities may have a greater impact on changes in the gut microbiota than menopausal status does. Estrogens modify bone health not only by directly influencing bone remodeling, but also indirectly by influencing the gut microbiota, gut barrier function and the resulting changes in immune system reactivity.
- Klíčová slova
- Aging, Estrogen, Inflammation, Leaky gut, Microbiota, Osteoporosis, Ovariectomy,
- MeSH
- estrogeny * MeSH
- lidé MeSH
- osteoporóza MeSH
- postmenopauzální osteoporóza * MeSH
- remodelace kosti * MeSH
- stárnutí buněk MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- estrogeny * MeSH
Psoriasis is a chronic, immune-mediated, inflammatory disease primarily affecting the skin. It is currently coming to light that patients with psoriasis have disrupted intestinal barrier and often suffer from comorbidities associated with the gastrointestinal tract. Moreover, there is growing evidence of both cutaneous and intestinal paradoxical reactions during biologic treatment in patients with psoriasis. This review focuses on barrier defects and changes in immune responses in patients with psoriasis, which play an important role in the development of the disease but are also influenced by modern biological treatments targeting IL-17 and TNFα cytokines. Here, we highlight the relationship between the gut-skin axis, microbiota, psoriasis treatment, and the incidence of paradoxical reactions, such as inflammatory bowel disease in patients with psoriasis. A better understanding of the interconnection of these mechanisms could lead to a more personalized therapy and lower the incidence of treatment side effects, thereby improving the quality of life of the affected patients.
- Klíčová slova
- Biologics, Gut microbiota, Gut–skin axis, IBD, IL-17, Psoriasis, Skin adverse events, Skin microbiota, TNFα,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- Bifidobacterium, Lactobacillus, exopolysaccharides, peptidoglycan, post-biotics, probiotics, vesicles,
- Publikační typ
- úvodníky MeSH
Growing evidence suggests that diabetes mellitus is associated with impairment of the intestinal barrier. However, it is not clear so far if the impairment of the intestinal barrier is a consequence of prolonged hyperglycemia or the consequence of external factors influencing the gut microbiota and intestinal mucosa integrity. Aim of the study was to perform an estimation of relationship between serological markers of impairment of the intestinal barrier: intestinal fatty acid-binding protein (I-FABP), cytokeratin 18 caspase-cleaved fragment (cCK-18), and soluble CD14 (sCD14) and markers of prolonged hyperglycemia, such as the duration of diabetes mellitus and glycated hemoglobin (HbA1c) via a correlation analysis in patients with diabetes mellitus. In 40 adult patients with type 1 diabetes mellitus and 30 adult patients with type 2 diabetes mellitus the estimation has been performed. Statistically significant positive correlation was found between cCK-18 and HbA1c (r=0.5047, p=0.0275) in patients with type 1 diabetes mellitus with fading insulitis (T1D). In patients with type 1 diabetes mellitus with ongoing insulitis (T1D/INS) and in patients with type 2 diabetes mellitus (T2D), no statistically significant positive correlations were found between serological markers of intestinal barrier impairment (I-FABP, cCK-18, sCD14) and duration of diabetes or levels of HbA1c. Similarly, in cumulative cohort of patients with T1D/INS and patients with T1D we revealed statistically positive correlation only between HbA1c and cCK-18 (r=0.3414, p=0.0311). Surprisingly, we found statistically significant negative correlation between the duration of diabetes mellitus and cCK-18 (r=-0.3050, p=0.0313) only in cumulative group of diabetic patients (T1D, T1D/INS, and T2D). Based on our results, we hypothesize that the actual condition of the intestinal barrier in diabetic patients is much more dependent on variable interactions between host genetic factors, gut microbiota, and environmental factors rather than effects of long-standing hyperglycemia (assessed by duration of diabetes mellitus or HbA1c).
- MeSH
- biologické markery MeSH
- diabetes mellitus 1. typu * diagnóza metabolismus MeSH
- diabetes mellitus 2. typu * diagnóza MeSH
- dospělí MeSH
- glykovaný hemoglobin analýza MeSH
- hyperglykemie * MeSH
- lidé MeSH
- lipopolysacharidové receptory MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- glykovaný hemoglobin MeSH
- lipopolysacharidové receptory MeSH
Early postnatal events are important for the development of the neonatal immune system. Harboring the pioneering microorganisms forming the microbiota of the neonatal gastrointestinal tract is important for priming the immune system, as well as inducing appropriate tolerance to the relatively innocuous environmental antigens and compounds of normal healthy microbiota. Early postnatal supplementation of suitable, safe probiotics could accelerate this process. In the current study, the immunomodulatory capacity of the probiotic strain of Escherichia coli O83:K24:H31 (EcO83) was characterized in vitro and in vivo. We compared the capacity of EcO83 with and without hemolytic activity on selected immune characteristics in vitro as determined by flow cytometry and quantitative real-time PCR. Both strains with and without hemolytic activity exerted comparable capacity on the maturation of dendritic cells while preserving the induction of interleukin 10 (Il10) expression in dendritic cells and T cells cocultured with EcO83 primed dendritic cells. Early postnatal supplementation with EcO83 led to massive but transient colonization of the neonatal gastrointestinal tract, as detected by in vivo bioimaging. Early postnatal EcO83 administration promoted gut barrier function by increasing the expression of claudin and occludin and the expression of Il10. Early postnatal EcO83 application promotes maturation of the neonatal immune system and promotes immunoregulatory and gut barrier functions.
- Klíčová slova
- E. coli O83:K24:H31, IL-10, dendritic cell, early postnatal probiotic administration, indol amine 2,3 dioxygenase, luciferase, probiotic,
- MeSH
- dendritické buňky MeSH
- Escherichia coli MeSH
- interleukin-10 MeSH
- lidé MeSH
- mikrobiota * MeSH
- novorozenec MeSH
- probiotika * farmakologie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interleukin-10 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.
- Klíčová slova
- 16S RNA sequencing, IBD, TNF-alpha antagonist, serum biomarker, skin adverse events, skin microbiota,
- MeSH
- biologické markery MeSH
- Crohnova nemoc * MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- inhibitory TNF MeSH
- lidé MeSH
- mikrobiota * MeSH
- ulcerózní kolitida * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- inhibitory TNF MeSH
- Klíčová slova
- germ-free, gnotobiology, host-bacteria interactions, immune system, microbiota,
- MeSH
- Bacteria růst a vývoj imunologie metabolismus MeSH
- bakteriální nálož MeSH
- bydlení zvířat MeSH
- chov zvířat MeSH
- druhová specificita MeSH
- gnotobiologické modely * MeSH
- interakce hostitele a patogenu MeSH
- lidé MeSH
- mikrobiota * MeSH
- modely nemocí na zvířatech MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodní články MeSH
- úvodníky MeSH
Continuous activation of the immune system inside a tissue can lead to remodelling of the tissue structure and creation of a specific microenvironment, such as during the tumour development. Chronic inflammation is a central player in stimulating changes that alter the tissue stroma and can lead to fibrotic evolution. In the colon mucosa, regulatory mechanisms, including TGF-β1, avoid damaging inflammation in front of the continuous challenge by the intestinal microbiome. Inducing either DSS colitis or AOM colorectal carcinogenesis in AVN-Wistar rats, we evaluated at one month after the end of each treatment whether immunological changes and remodelling of the collagen scaffold were already in development. At this time point, we found in both models a general downregulation of pro-inflammatory cytokines and even of TGF-β1, but not of IL-6. Moreover, we demonstrated by multi-photon microscopy the simultaneously presence of pro-fibrotic remodelling of the collagen scaffold, with measurable changes in comparison to the control mucosa. The scaffold was significantly modified depending on the type of induced stimulation. These results suggest that at one month after the end of the DSS or AOM inductions, a smouldering inflammation is present in both induced conditions, since the pro-inflammatory cytokines still exceed, in proportion, the local homeostatic regulation of which TGF-β1 is a part (inflammatory threshold). Such an inflammation appears sufficient to sustain remodelling of the collagen scaffold that may be taken as a possible pathological marker for revealing pre-neoplastic inflammation.
- Klíčová slova
- AOM, DSS-induced colitis, IL-6, chronic inflammation, collagen, colorectal cancer, tissue scaffold, tumour niche,
- Publikační typ
- časopisecké články MeSH
The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.
- Klíčová slova
- alpha-MSH, anorexia nervosa and bulimia, autoantibody, caseinolytic peptidase B, fecal microbial transplantation, ghrelin, gut and blood-brain barrier permeability, microbiome,
- MeSH
- autoprotilátky * MeSH
- ghrelin imunologie MeSH
- inzulin imunologie MeSH
- leptin imunologie MeSH
- lidé MeSH
- melanocyty stimulující hormony imunologie MeSH
- neuropeptid Y imunologie MeSH
- poruchy příjmu potravy imunologie mikrobiologie MeSH
- střevní mikroflóra imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- autoprotilátky * MeSH
- ghrelin MeSH
- inzulin MeSH
- leptin MeSH
- melanocyty stimulující hormony MeSH
- neuropeptid Y MeSH
Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and β-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer.
- Klíčová slova
- GPR81, SCFA, colorectal cancer, functional food, intestinal metabolome, microbiome,
- MeSH
- beta-glukany farmakologie MeSH
- butyráty farmakologie MeSH
- kyselina mléčná farmakologie MeSH
- kyseliny mastné těkavé metabolismus farmakologie MeSH
- lidé MeSH
- metabolom MeSH
- nádory dietoterapie metabolismus MeSH
- potravní doplňky mikrobiologie MeSH
- prebiotika mikrobiologie MeSH
- probiotika metabolismus farmakologie MeSH
- střevní mikroflóra účinky léků MeSH
- sulfan farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- beta-glukany MeSH
- butyráty MeSH
- kyselina mléčná MeSH
- kyseliny mastné těkavé MeSH
- prebiotika MeSH
- sulfan MeSH