BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea. METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota. DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).

• MeSH
• antibakteriální látky * škodlivé účinky   terapeutické užití   MeSH
• dysbióza terapie   mikrobiologie   MeSH
• feces mikrobiologie   MeSH
• fekální transplantace * metody   škodlivé účinky   MeSH
• klinické zkoušky, fáze II jako téma MeSH
• kritický stav * MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• prospektivní studie MeSH
• průjem * terapie   mikrobiologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• střevní mikroflóra * účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

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

Diabetes mellitus is a chronic disease affecting glucose metabolism. The pathophysiological reactions underpinning the disease can lead to the development of late diabetes complications. The gut microbiota plays important roles in weight regulation and the maintenance of a healthy digestive system. Obesity, diabetes mellitus, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy are all associated with a microbial imbalance in the gut. Modern technical equipment and advanced diagnostic procedures, including xmolecular methods, are commonly used to detect both quantitative and qualitative changes in the gut microbiota. This review summarises collective knowledge on the role of the gut microbiota in both types of diabetes mellitus and their late complications, with a particular focus on diabetic foot syndrome.

• MeSH
• diabetes mellitus * MeSH
• diabetická noha * MeSH
• diabetická retinopatie * MeSH
• diabetické nefropatie * etiologie   MeSH
• lidé MeSH
• obezita MeSH
• střevní mikroflóra * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. METHODS: Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. RESULTS: Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. CONCLUSIONS: This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

• MeSH
• Crohnova nemoc * terapie   mikrobiologie   imunologie   MeSH
• dítě MeSH
• enterální výživa * metody   MeSH
• feces * mikrobiologie   chemie   MeSH
• leukocytární L1-antigenní komplex * analýza   MeSH
• leukocyty mononukleární imunologie   metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• střevní mikroflóra * MeSH
• TNF-alfa * metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

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.

• 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

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.

• 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

Heterogeneous cancers that lack strong driver mutations with high penetrance, such as head and neck squamous cell carcinoma (HNSCC), present unique challenges to understanding their aetiology due to the complex interactions between genetics and environmental factors. The interplay between lifestyle factors (such as poor oral hygiene, smoking, or alcohol consumption), the oral and gut microbiome, and host genetics appears particularly important in the context of HNSCC. The complex interplay between the gut microbiota and cancer treatment outcomes has also received increasing attention in recent years. This review article describes the bidirectional communication between the host and the oral/gut microbiome, focusing on microbiome-derived metabolites and their impact on systemic immune responses and the modulation of the tumour microenvironment. In addition, we review the role of host lifestyle factors in shaping the composition of the oral/gut microbiota and its impact on cancer progression and therapy. Overall, this review highlights the rationality of considering the oral/gut microbiota as a critical determinant of cancer therapy outcomes and points to therapeutic opportunities offered by targeting the oral/gut microbiota in the management of HNSCC.

• MeSH
• dlaždicobuněčné karcinomy hlavy a krku * mikrobiologie   patologie   imunologie   terapie   MeSH
• lidé MeSH
• nádorové mikroprostředí * imunologie   MeSH
• nádory hlavy a krku * imunologie   mikrobiologie   patologie   terapie   MeSH
• střevní mikroflóra * imunologie   MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In the first days of life, the newborns' intestinal microbiota develops simultaneously with the intestinal gut barrier and follows intestinal immunity. The mode of delivery shows significant impact on microbial development and, thus, the initiation of the tryptophan catabolism pathway. Further antibiotics (ATB) treatment of mothers before or during delivery affects the microbial and tryptophan metabolite composition of stool of the caesarean- and vaginal-delivered newborns. The determination of microbiome and levels of tryptophan microbial metabolites in meconium and stool can characterize intestinal colonization of a newborn. From 134 samples from the Central European Longitudinal Studies of Parents and Children: The Next Generation (CELSPAC: TNG) cohort study, 16S rRNA gene sequencing was performed, and microbial tryptophan metabolites were quantified using ultra-high-performance liquid chromatography with triple-quadrupole mass spectrometry. Microbial diversity and concentrations of tryptophan metabolites were significantly higher in stool compared to meconium. Treatment of mothers with ATB before or during delivery affects metabolite composition and microbial diversity in stool of vaginal- and caesarean-delivered newborns. Correlation of microbial and metabolite composition shows significant positive correlations of indol-3-lactic acid, N-acetyl-tryptophan and indol-3-acetic acid with Bifidobacterium, Bacteroides and Peptoclostridium. The positive effect of vaginal delivery on newborns' microbiome development is degraded when mother is treated with ATB before or during delivery. KEY POINTS: • Antibiotic treatment diminishes the positive effects of vaginal delivery. • Antibiotic treatment affects metabolite and microbial composition in newborns. • Bifidobacterium and Peptoclostridium could be the producer of indole-lactic acid.

• MeSH
• antibakteriální látky * MeSH
• Bifidobacterium metabolismus   růst a vývoj   MeSH
• feces * mikrobiologie   chemie   MeSH
• indoly metabolismus   MeSH
• kyseliny indoloctové metabolismus   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mekonium * mikrobiologie   chemie   MeSH
• novorozenec MeSH
• RNA ribozomální 16S * genetika   MeSH
• střevní mikroflóra * účinky léků   MeSH
• tryptofan * metabolismus   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII. MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing. RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK. CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.

• MeSH
• katechin * analogy a deriváty   farmakologie   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádory pánve * radioterapie   MeSH
• proteinkinasy aktivované AMP metabolismus   MeSH
• radiační poranění * prevence a kontrola   MeSH
• radioprotektivní látky farmakologie   terapeutické užití   MeSH
• střeva účinky záření   účinky léků   mikrobiologie   MeSH
• střevní mikroflóra * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

SCOPE: This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects. METHODS AND RESULTS: An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques, namely proton nuclear magnetic resonance (1H NMR), next-generation sequencing (NGS), and liquid chromatography-mass spectrometry (LC-MS) was used to determine silymarin microbial metabolites over 24 h, overall metabolome, and microbiota composition. Silymarin at a low diet-relevant dose of 50 μg mL-1 significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study reveals age-related differences in silymarin catabolism. Healthy elderly donors (70-80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12-45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which is associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003. CONCLUSION: This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies, and advancing our understanding of dietary (poly)phenol metabolism.

• MeSH
• dítě MeSH
• dospělí MeSH
• feces mikrobiologie   MeSH
• fermentace MeSH
• kolon * mikrobiologie   metabolismus   účinky léků   MeSH
• kyseliny mastné těkavé metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• silymarin * farmakologie   MeSH
• střevní mikroflóra * účinky léků   fyziologie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH