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
BACKGROUND: Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate. METHODS: Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions. RESULTS: Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%. CONCLUSION: Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.
- MeSH
- Bacteria izolace a purifikace MeSH
- feces * mikrobiologie MeSH
- fekální transplantace * metody MeSH
- lidé MeSH
- mikrobiální viabilita * MeSH
- myši MeSH
- průtoková cytometrie * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Faecal microbiota transplantation (FMT) is an established treatment for Clostridioides difficile infection and is under investigation for other conditions. The availability of suitable donors and the logistics of fresh stool preparation present challenges, making frozen, biobanked stools an attractive alternative. AIMS: This study aimed to evaluate the long-term viability of bacterial populations in faecal samples stored at -80°C for up to 12 months, supporting the feasibility of using frozen grafts for FMT. METHODS: Fifteen faecal samples from nine healthy donors were processed, mixed with cryoprotectants and stored at -80°C. Samples were assessed at baseline and after 3, 6 and 12 months using quantitative culturing methods to determine the concentration of live bacteria. RESULTS: Quantitative analysis showed no significant decrease in bacterial viability over the 12-month period for both aerobic and anaerobic cultures (p = 0.09). At all timepoints, the coefficients of variability in colony-forming unit (CFU) counts were greater between samples (102 ± 21% and 100 ± 13% for aerobic and anaerobic cultures, respectively) than the variability between measurements of the same sample (30 ± 22% and 30 ± 19%). CONCLUSIONS: The study confirmed that faecal microbiota can be preserved with high viability in deep-freeze storage for up to a year, making allogenic FMT from biobanked samples a viable and safer option for patients. However, a multidonor approach may be beneficial to mitigate the risk of viability loss in any single donor sample.
- MeSH
- feces * mikrobiologie MeSH
- fekální transplantace * metody MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- mikrobiální viabilita * MeSH
- zmrazování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Endoluminal radiofrequency ablation (RFA) has been promoted as palliative treatment for patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) in order to improve biliary drainage and eventually prolong survival. No high level evidence is, however, available on this technique. DESIGN: In this randomised controlled study, we compared endoluminal RFA plus stenting with stenting alone (control group) in patients with malignant biliary obstruction; metal stents were primarily placed. Primary outcome was overall survival; secondary outcomes were stent patency, quality of life and adverse events. In a superiority design, survival was assumed to be doubled by RFA as compared with 6.4 months in the control group (n=280). RESULTS: A total of 161 patients (male:female 90:71, mean age 71±9 years) were randomised before recruitment was terminated for futility after an interim analysis. Eighty-five patients had CCA (73 hilar, 12 distal) and 76 had pancreatic cancer. There was no difference in survival in both subgroups: for patients with CCA, median survival was 10.5 months (95% CI 6.7 to 18.3) in the RFA group vs 10.6 months (95% CI 9.0 to 24.8), p=0.58)) in the control group. In the subgroup with pancreatic cancer, median survival was 6.4 months (95% CI 4.3 to 9.7) for the RFA vs 7.7 months (95% CI 5.6 to 11.3), p=0.73) for the control group. No benefit was seen in the RFA group with regard to stent patency (at 12 months 40% vs 36% in CCA and 66% vs 65% in PDAC), and quality of life was unchanged by either treatment and comparable between the groups. Adverse events occurred in seven patients in each groups. CONCLUSION: A combination of endoluminal RFA and stenting was not superior to stenting alone in prolonging survival or improving stent patency in patients with malignant biliary obstruction. TRIAL REGISTRATION NUMBER: NCT03166436.
- MeSH
- cholangiokarcinom * MeSH
- cholestáza * etiologie chirurgie MeSH
- katetrizační ablace * škodlivé účinky metody MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory slinivky břišní * komplikace chirurgie MeSH
- nádory žlučových cest * komplikace chirurgie MeSH
- radiofrekvenční ablace * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stenty škodlivé účinky MeSH
- výsledek terapie MeSH
- žlučové cesty intrahepatální chirurgie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Fecal microbiota transfer may serve as a therapeutic tool for treating obesity and related disorders but currently, there is no consensus regarding the optimal donor characteristics. We studied how microbiota from vegan donors, who exhibit a low incidence of non-communicable diseases, impact on metabolic effects of an obesogenic diet and the potential role of dietary inulin in mediating these effects. Ex-germ-free animals were colonized with human vegan microbiota and fed a standard or Western-type diet (WD) with or without inulin supplementation. Despite the colonization with vegan microbiota, WD induced excessive weight gain, impaired glucose metabolism, insulin resistance, and liver steatosis. However, supplementation with inulin reversed steatosis and improved glucose homeostasis. In contrast, inulin did not affect WD-induced metabolic changes in non-humanized conventional mice. In vegan microbiota-colonized mice, inulin supplementation resulted in a significant change in gut microbiota composition and its metabolic performance, inducing the shift from proteolytic towards saccharolytic fermentation (decrease of sulfur-containing compounds, increase of SCFA). We found that (i) vegan microbiota alone does not protect against adverse effects of WD; and (ii) supplementation with inulin reversed steatosis and normalized glucose metabolism. This phenomenon is associated with the shift in microbiota composition and accentuation of saccharolytic fermentation at the expense of proteolytic fermentation.
- MeSH
- fekální transplantace MeSH
- glukosa farmakologie MeSH
- inulin farmakologie MeSH
- lidé MeSH
- myši MeSH
- potravní vláknina farmakologie MeSH
- střevní mikroflóra * MeSH
- vegani MeSH
- západní dieta MeSH
- ztučnělá játra * prevence a kontrola farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
V následující kazuistice prezentujeme případ 31letého pacienta vyšetřovaného pro podezření na nádor tenkého střeva. Nádory tenkého střeva jsou samy o sobě relativně vzácné a k definitivní diagnóze mnohdy dochází až po chirurgické resekci. Stejně tomu bylo i u našeho pacienta vyšetřovaného pro nález měkkotkáňového útvaru v oblasti tenkého střeva dle zobrazovacích vyšetření. Po vyloučení hormonální aktivity byla provedena diagnostická laparotomie. Histopatologicky byl zjištěn vzácný nádor mezenteria – desmoidní fibromatóza. Jedná se o nádor bez metastatického potenciálu se středně maligním potenciálem pro agresivní růst do okolních struktur a orgánů a velké procento lokálních recidiv.
In the following report, we present the case of a 31-year-old patient examined for a suspected small bowel tumour. Small bowel tumours are relatively rare and definitive diagnosis is often preceded by surgical resection. The same was true for our patient examined for a soft tissue lesion found with imaging techniques in close proximity to the small intestine. After ruling out hormonal activity, diagnostic laparotomy was performed. Desmoid fibromatosis, a rare tumour of the mesentery, was confirmed histopathologically. Although without metastatic potential, desmoid fibromatosis is a tumour with moderately malignant potential for aggressive growth into surrounding structures and organs and a large percentage of local recurrences.
- MeSH
- agresivní fibromatóza * chirurgie diagnostické zobrazování MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- lidé MeSH
- mezenterium chirurgie diagnostické zobrazování patologie MeSH
- střevní nádory * chirurgie diagnostické zobrazování MeSH
- tenké střevo chirurgie patologie MeSH
- vzácné nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Lidská střevní mikrobiota je složena z bakterií, archeí, hub a virů a její složení, které je pro každého jedince specifické, je formováno mnoha faktory. Patologická nerovnováha ve složení a/nebo rozmanitosti mikroorganismů (dysbióza) je asociována s celou řadou onemocnění. Složení střevního mikrobiomu je výsledkem komplikované souhry mezi hostitelem a střevní mikroflórou. Kriticky nemocní pacienti mají snížené množství symbiotických bakterií (zejména z kmene Firmicutes a Bacteroidetes) a naopak relativní zvýšení patogenních střevních bakterií (zejména z kmene Proteobacteria). Míra střevní dysbiózy je u těchto pacientů přímo úměrná závažnosti kritického stavu. Střevní mikrobiota má vliv na permeabilitu intestinální bariéry, imunitní regulace, systémový zánět, a tím na průběh stonání kriticky nemocných. Ovlivnění složení střevních bakterií pomocí probiotik, prebiotik nebo antibiotik je dlouhodobě používanou metodou na jednotkách intenzivní péče. Extrémním zásahem do střevní mikrobioty je fekální mikrobiální transplantace (FMT) od zdravých dárců. U kriticky nemocných je FMT popsána v kazuistikách a sériích kazuistik jako účinná a bezpečná metoda v léčbě dysmikrobie u závažné a fulminantní klostridiové kolitidy, neklostridiových postantibiotických průjmů, těžkých forem idiopatických střevních zánětů či jako záchranná terapie sepse. Přes nepochybnou biologickou plauzibilitu a pozitivní efekt pozorovaný u jednotlivých pacientů nelze FMT u této vysoce rizikové populace stále doporučit jako rutinní postup, neboť kvalitní prospektivní kontrolované klinické studie úplně chybí. V článku jsou shrnuty směry možného dalšího výzkumu, indikací a provedení metody FMT v rámci prospektivních randomizovaných studií u kriticky nemocných.
Human gut microbiota consists of bacteria, archaea, fungi and viruses, and its composition, specific to each individual, is shaped by many factors. Pathological imbalance in the composition and/or diversity of microorganisms (dysbiosis), is associated with a wide range of diseases. The intestinal microbiome is the result of a complicated interplay between the host and the intestinal microflora. Critically ill patients have a reduced number of symbiotic bacteria ( particularly Firmicutes and Bacteroidetes) and, conversely, a relative increase in pathogenic intestinal bacteria (particularly Proteobacteria), and the rate of dysbiosis is directly proportional to the severity of their condition. On the other hand, the intestinal microbiota affects the permeability of the intestinal barrier, immune regulation, systemic inflammation, and, in turn, influences the clinical condition of critically ill patients. Altering the composition of intestinal bacteria by probiotics, prebiotics or antibiotics has long been used in intensive care. Ultimate intervention to affect the intestinal microbiota is fecal microbial transplantation (FMT) from healthy donors. In critically ill patients, FMT is described in case reports and case series as effective and safe method in the treatment of dysmicrobia in severe and fulminant C. difficile colitis, antibiotic-associated diarrhea, severe forms of inflammatory bowel disease or as a rescue therapy of sepsis. Despite the undisputable biological plausibility and positive effect observed in individual patients, FMT cannot be recommended as a routine procedure in this high-risk population, as high-quality prospective controlled clinical studies are completely absent. The article summarizes directions of future research and the method of implementation of FMT in critically ill patients.
- Klíčová slova
- postantibiotický průjem,
- MeSH
- fekální transplantace metody MeSH
- kritický stav * MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed "dysbiosis", is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischemia, exposure to antibiotics, and/or the underlying disease, critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria that alter metabolic, immune, and even neurocognitive functions and that turn the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of fecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Nonetheless, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials have generated hypotheses that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for the determination of patient-centered outcomes.
- MeSH
- dysbióza epidemiologie mikrobiologie terapie MeSH
- feces mikrobiologie MeSH
- fekální transplantace metody MeSH
- idiopatické střevní záněty epidemiologie mikrobiologie terapie MeSH
- kritický stav epidemiologie MeSH
- lidé MeSH
- průjem epidemiologie mikrobiologie terapie MeSH
- střevní mikroflóra genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Klíčová slova
- Biliární ileus,
- MeSH
- cholecystolitiáza komplikace MeSH
- dospělí MeSH
- gastrointestinální nemoci diagnostické zobrazování terapie MeSH
- ileus * diagnostické zobrazování etiologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- střevní píštěle etiologie komplikace MeSH
- žlučové kameny * komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH