AIMS: Ovarian hormone deficiency is one of the main risk factors for osteoporosis and bone fractures in women, and these risks can be mitigated by menopausal hormone therapy. Recent evidence suggests that gut microbiota may link changes in estrogen levels and bone metabolism. This study was conducted to investigate the potential relationship between hormonal and bone changes induced by oophorectomy and subsequent hormonal therapy and shifts in gut microbiota composition. METHODS: We collected 159 stool and blood samples in several intervals from 58 women, who underwent bilateral oophorectomy. Changes in fecal microbiota were assessed in paired samples collected from each woman before and after oophorectomy or the start of hormone therapy. Bacterial composition was determined by sequencing the 16S rRNA gene on Illumina MiSeq. Blood levels of estradiol, FSH, biomarkers of bone metabolism, and indices of low-grade inflammation were measured using laboratory analytical systems and commercial ELISA. Areal bone mineral density (BMD) of the lumbar spine, proximal femur, and femur neck was measured using dual-energy X-ray absorptiometry. RESULTS: We found no significant changes in gut microbiota composition 6 months after oophorectomy, despite major changes in hormone levels, BMD, and bone metabolism. A small decrease in bacterial diversity was apparent 18 months after surgery in taxonomy-aware metrics. Hormonal therapy after oophorectomy prevented bone loss but only marginally affected gut microbiota. There were no significant differences in β-diversity related to hormonal status, although several microbes (e.g., Lactococcus lactis) followed estrogen levels. Body mass index (BMI) was the most significantly associated with microbiota variance. Microbiota was not a suitable predictive factor for the state of bone metabolism. CONCLUSIONS: We conclude that neither the loss of estrogens due to oophorectomy nor their gain due to subsequent hormonal therapy is associated with a specific gut microbiota signature. Sources of variability in microbiota composition are more related to interindividual differences than hormonal status.
- MeSH
- estradiol * MeSH
- estrogeny MeSH
- krček femuru * MeSH
- lidé MeSH
- prospektivní studie MeSH
- RNA ribozomální 16S MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aims: Gestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development. Methods: We collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA). Results: We found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM. Conclusions: We conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.
- MeSH
- Bacteria genetika MeSH
- gestační diabetes * MeSH
- hydroxybutyráty MeSH
- krevní glukóza MeSH
- kyseliny mastné těkavé MeSH
- lidé MeSH
- mykobiom * MeSH
- obezita komplikace MeSH
- RNA ribozomální 16S genetika MeSH
- střevní mikroflóra * MeSH
- těhotenství MeSH
- valeráty MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference 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.
Diet is a strong modifier of microbiome and mucosal microenvironment in the gut. Recently, components of western-type diets have been associated with metabolic and immune diseases. Here, we studied how high-sugar diet (HSD) consumption influences gut mucosal barrier and immune response under steady state conditions and in a mouse model of acute colitis. We found that HSD significantly increased gut permeability, spleen weight, and neutrophil levels in spleens of healthy mice. Subsequent dextran sodium sulfate administration led to severe colitis. In colon, HSD significantly promoted neutrophil infiltration and increased the levels of IL-6, IL-1β, and TNF-α. Moreover, HSD-fed mice had significantly higher abundance of pathobionts, such as Escherichia coli and Candida, in fecal samples. Although germ-free mice colonized with microbiota of conventionally reared mice that consumed different diets had equally severe colitis, mice colonized with HSD microbiota showed markedly increased infiltration of neutrophils to the gut. The induction of colitis in Toll-like receptor 4 (TLR4)-deficient HSD-fed mice led to significantly milder colitis than in wild-type mice. In conclusion, our results suggested a significant role of HSD in disruption of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seemed to be highly influenced by resident potentially pathogenic microbiota or metabolites via the TLR4 signaling pathway.
- MeSH
- chronická nemoc MeSH
- dieta * MeSH
- DNA vazebné proteiny nedostatek metabolismus MeSH
- feces MeSH
- kolitida genetika imunologie patologie MeSH
- monosacharidy škodlivé účinky MeSH
- myši inbrední BALB C MeSH
- permeabilita MeSH
- regulace genové exprese MeSH
- signální transdukce * MeSH
- síran dextranu MeSH
- slizniční imunita MeSH
- střeva patologie MeSH
- střevní mikroflóra * MeSH
- stupeň závažnosti nemoci MeSH
- T-lymfocyty imunologie MeSH
- toll-like receptor 4 metabolismus MeSH
- zánět mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference 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 Mogibacteriumtimidum 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.
- Publikační typ
- časopisecké články MeSH
Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.
- MeSH
- biologické markery krev MeSH
- Crohnova nemoc komplikace diagnóza metabolismus MeSH
- dospělí MeSH
- dysbióza komplikace MeSH
- lidé středního věku MeSH
- lidé MeSH
- sklerozující cholangitida komplikace MeSH
- ulcerózní kolitida komplikace diagnóza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
