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

Obesity is a complex disease that increases the risk of other pathologies. Its prevention and long-term weight loss maintenance are problematic. Gut microbiome is considered a potential obesity modulator. The objective of the present study was to summarize recent findings regarding the relationships between obesity, gut microbiota, and diet (vegetable/animal proteins, high-fat diets, restriction of carbohydrates), with an emphasis on dietary fiber and resistant starch. The composition of the human gut microbiome and the methods of its quantification are described. Products of the gut microbiome metabolism, such as short-chain fatty acids and secondary bile acids, and their effects on the gut microbiota, intestinal barrier function and immune homeostasis are discussed in the context of obesity. The importance of dietary fiber and resistant starch is emphasized as far as effects of the host diet on the composition and function of the gut microbiome are concerned. The complex relationships between human gut microbiome and obesity are finally summarized.

• Klíčová slova
• butyrate, dietary fiber, immune homeostasis, intestinal barrier function, resistant starch, secondary bile acids, short-chain fatty acids,
• MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• dieta * MeSH
• kyseliny mastné těkavé metabolismus   MeSH
• lidé MeSH
• obezita * mikrobiologie   MeSH
• potravní vláknina * aplikace a dávkování   MeSH
• střevní mikroflóra * fyziologie   MeSH
• žlučové kyseliny a soli metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kyseliny mastné těkavé MeSH
• potravní vláknina * MeSH
• žlučové kyseliny a soli MeSH

The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.

• Klíčová slova
• Fecal microbiota transplantation, Gut microbiota, Hallmarks of cancer, Tumor microenvironment,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer's patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut-eye axis.

• Klíčová slova
• Escherichia coli Nissle 1917, experimental autoimmune uveitis, macrophages, mucosal immune system, probiotics,
• MeSH
• autoimunitní nemoci terapie   MeSH
• Escherichia coli * MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• probiotika * aplikace a dávkování   farmakologie   MeSH
• střevní sliznice patologie   MeSH
• uveitida terapie   MeSH
• zánět terapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Psoriatic patients have altered microbiota, both in the intestine and on the skin. It is not clear, however, whether this is a cause or consequence of the disease. In this study, using an experimental mouse model of psoriasis induced by imiquimod (IMQ), we show that oral treatment with a broad spectrum of antibiotics (MIX) or metronidazole (MET) alone mitigates the severity of skin inflammation through downregulation of Th17 immune response in conventional mice. Since some antibiotics, including MET, can influence immune system reactivity, we also evaluated the effect of MIX in the same model under germ-free (GF) conditions. GF mice treated with MET did not show milder signs of imiquimod-induced skin inflammation (IISI) which supports the conclusion that the therapeutic effect is mediated by changes in microbiota composition. Moreover, compared to controls, mice treated with MIX had a significantly higher abundance of the genus Lactobacillus in the intestine and on the skin. Mice treated with MET had a significantly higher abundance of the genera Bifidobacterium and Enterococcus both on the skin and in the intestine and of Parabacteroides distasonis in the intestine. Additionally, GF mice and mice monocolonized with either Lactobacillus plantarum or segmented filamentous bacteria (SFB) were more resistant to IISI than conventional mice. Interestingly, compared to GF mice, IMQ induced a higher degree of systemic Th17 activation in mice monocolonized with SFB but not with L. plantarum. The present findings provide evidence that intestinal and skin microbiota directly regulates IISI and emphasizes the importance of microbiota in the pathogenesis of psoriasis.

• Klíčová slova
• animal model, antibiotics, germ-free, imiquimod, intestine, microbiota, psoriasis, skin,
• Publikační typ
• časopisecké články MeSH

The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γ and IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.

• MeSH
• adaptivní imunita MeSH
• aktivace lymfocytů MeSH
• antibakteriální látky farmakologie   MeSH
• autoantigeny imunologie   MeSH
• autoimunitní nemoci chemicky indukované   imunologie   mikrobiologie   MeSH
• bakteriální nálož účinky léků   MeSH
• gnotobiologické modely MeSH
• interferon gama biosyntéza   MeSH
• interleukin-17 biosyntéza   MeSH
• makrofágy imunologie   MeSH
• mikrobiota * imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oči imunologie   patologie   MeSH
• oční proteiny imunologie   MeSH
• proteiny vázající retinol imunologie   MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• retina imunologie   MeSH
• retinitida chemicky indukované   etiologie   imunologie   mikrobiologie   MeSH
• uveitida chemicky indukované   imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• autoantigeny MeSH
• interferon gama MeSH
• interleukin-17 MeSH
• interstitial retinol-binding protein MeSH Prohlížeč
• oční proteiny MeSH
• proteiny vázající retinol MeSH