Little is known about how zoonotic virus infections manifest in wildlife reservoirs. However, a common health consequence of enteric virus infections is gastrointestinal diseases following a shift in gut microbial composition. The sub-Saharan hipposiderid bat complex has recently emerged to host at least three coronaviruses (CoVs), with Hipposideros caffer D appearing particularly susceptible to Hibecovirus CoV-2B infection. In this study, we complement body condition and infection status data with information about the gut microbial community to understand the health impact of CoV infections in a wild bat population. Of the three CoVs, only infections with the distantly SARS-related Hibecovirus CoV-2B were associated with lower body condition and altered the gut microbial diversity and composition. The gut microbial community of infected bats became progressively less diverse and more dissimilar with infection intensity, arguing for dysbiosis as per the Anna Karenina principle. Putatively beneficial bacteria, such as Alistipes and Christensenella, decreased with infection intensity, while potentially pathogenic bacteria, namely Mycoplasma and Staphylococcus, increased. Infections with enterically replicating viruses may therefore cause changes in body condition and gut dysbiosis with potential negative health consequences even in virus reservoirs. We argue that high-resolution data on multiple health markers, ideally including microbiome information, will provide a more nuanced picture of bat disease ecology.

• Klíčová slova
• Anna Karenina principle, Chiroptera, Ghana, coronavirus, microbiome,
• Publikační typ
• časopisecké články 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

AIM: The metabolic performance of the gut microbiota contributes to the onset of type 2 diabetes. However, targeted dietary interventions are limited by the highly variable inter-individual response. We hypothesized (1) that the composition of the complex gut microbiome and metabolome (MIME) differ across metabolic spectra (lean-obese-diabetes); (2) that specific MIME patterns could explain the differential responses to dietary inulin; and (3) that the response can be predicted based on baseline MIME signature and clinical characteristics. METHOD: Forty-nine patients with newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 healthy lean (LH) volunteers were compared in a cross-sectional case-control study integrating clinical variables, dietary intake, gut microbiome, and fecal/serum metabolomes (16 S rRNA sequencing, metabolomics profiling). Subsequently, 27 DM were recruited for a predictive study: 3 months of dietary inulin (10 g/day) intervention. RESULTS: MIME composition was different between groups. While the DM and LH groups represented opposite poles of the abundance spectrum, OB was closer to DM. Inulin supplementation was associated with an overall improvement in glycemic indices, though the response was very variable, with a shift in microbiome composition toward a more favorable profile and increased serum butyric and propionic acid concentrations. The improved glycemic outcomes of inulin treatment were dependent on better baseline glycemic status and variables related to the gut microbiota, including the abundance of certain bacterial taxa (i.e., Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, or Phascolarctobacterium), serum concentrations of branched-chain amino acid derivatives and asparagine, and fecal concentrations of indole and several other volatile organic compounds. CONCLUSION: We demonstrated that obesity is a stronger determinant of different MIME patterns than impaired glucose metabolism. The large inter-individual variability in the metabolic effects of dietary inulin was explained by differences in baseline glycemic status and MIME signatures. These could be further validated to personalize nutritional interventions in patients with newly diagnosed diabetes.

• MeSH
• diabetes mellitus 2. typu * MeSH
• inulin * metabolismus   farmakologie   MeSH
• lidé MeSH
• multiomika MeSH
• nadváha metabolismus   MeSH
• obezita metabolismus   MeSH
• průřezové studie MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inulin * MeSH

The global incidence of numerous immune-mediated, metabolic, neurodegenerative, and psychiatric diseases is steadily increasing [...].

• Publikační typ
• úvodníky MeSH

BACKGROUND: The microbiome alterations are associated with cancer growth and may influence the immune system and response to therapy. Particularly, the gut microbiome has been recently shown to modulate response to melanoma immunotherapy. However, the role of the skin microbiome has not been well explored in the skin tumour microenvironment and the link between the gut microbiome and skin microbiome has not been investigated in melanoma progression. Therefore, the aim of the present study was to examine associations between dysbiosis in the skin and gut microbiome and the melanoma growth using MeLiM porcine model of melanoma progression and spontaneous regression. RESULTS: Parallel analysis of cutaneous microbiota and faecal microbiota of the same individuals was performed in 8 to 12 weeks old MeLiM piglets. The bacterial composition of samples was analysed by high throughput sequencing of the V4-V5 region of the 16S rRNA gene. A significant difference in microbiome diversity and richness between melanoma tissue and healthy skin and between the faecal microbiome of MeLiM piglets and control piglets were observed. Both Principal Coordinate Analysis and Non-metric multidimensional scaling revealed dissimilarities between different bacterial communities. Linear discriminant analysis effect size at the genus level determined different potential biomarkers in multiple bacterial communities. Lactobacillus, Clostridium sensu stricto 1 and Corynebacterium 1 were the most discriminately higher genera in the healthy skin microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus and Bacteroides were discriminately abundant in melanoma tissue microbiome. Bacteroides, Fusobacterium and Escherichia-Shigella were associated with the faecal microbiota of MeLiM piglets. Potential functional pathways analysis based on the KEGG database indicated significant differences in the predicted profile metabolisms between the healthy skin microbiome and melanoma tissue microbiome. The faecal microbiome of MeLiM piglets was enriched by genes related to membrane transports pathways allowing for the increase of intestinal permeability and alteration of the intestinal mucosal barrier. CONCLUSION: The associations between melanoma progression and dysbiosis in the skin microbiome as well as dysbiosis in the gut microbiome were identified. Results provide promising information for further studies on the local skin and gut microbiome involvement in melanoma progression and may support the development of new therapeutic approaches.

• Klíčová slova
• Dysbiosis, Gut microbiome, Gut-skin axis, MeLiM, Melanoma, Metagenomic analysis, NGS, Pig, Skin cancer, Skin microbiome, Tumour microenvironment,
• MeSH
• Bacteria genetika   MeSH
• dysbióza mikrobiologie   MeSH
• feces mikrobiologie   MeSH
• Fusobacterium MeSH
• melanom * MeSH
• mikrobiota * MeSH
• nádorové mikroprostředí MeSH
• prasata MeSH
• RNA ribozomální 16S genetika   MeSH
• střevní mikroflóra * genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• RNA ribozomální 16S MeSH

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its worldwide prevalence is rapidly increasing and is currently estimated at 24%. NAFLD is highly associated with many features of the metabolic syndrome, including obesity, insulin resistance, hyperlipidaemia, and hypertension. The pathogenesis of NAFLD is complex and not fully understood, but there is increasing evidence that the gut microbiota is strongly implicated in the development of NAFLD. In this review, we discuss the major factors that induce dysbiosis of the gut microbiota and disrupt intestinal permeability, as well as possible mechanisms leading to the development of NAFLD. We also discuss the most consistent NAFLD-associated gut microbiota signatures and immunological mechanisms involved in maintaining the gut barrier and liver tolerance to gut-derived factors. Gut-derived factors, including microbial, dietary, and host-derived factors involved in NAFLD pathogenesis, are discussed in detail. Finally, we review currently available diagnostic and prognostic methods, summarise latest knowledge on promising microbiota-based biomarkers, and discuss therapeutic strategies to manipulate the microbiota, including faecal microbiota transplantation, probiotics and prebiotics, deletions of individual strains with bacteriophages, and blocking the production of harmful metabolites.

• Klíčová slova
• cirrhosis, faecal microbiota transplantation, gut microbiota dysbiosis, hepatocellular carcinoma, intestinal permeability, liver steatosis, loss of diversity,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Redox status is a key determinant in the fate of β-cell. These cells are not primarily detoxifying and thus do not possess extensive antioxidant defense machinery. However, they show a wide range of redox regulating proteins, such as peroxiredoxins, thioredoxins or thioredoxin reductases, etc., being functionally compartmentalized within the cells. They keep fragile redox homeostasis and serve as messengers and amplifiers of redox signaling. β-cells require proper redox signaling already in cell ontogenesis during the development of mature β-cells from their progenitors. We bring details about redox-regulated signaling pathways and transcription factors being essential for proper differentiation and maturation of functional β-cells and their proliferation and insulin expression/maturation. We briefly highlight the targets of redox signaling in the insulin secretory pathway and focus more on possible targets of extracellular redox signaling through secreted thioredoxin1 and thioredoxin reductase1. Tuned redox homeostasis can switch upon chronic pathological insults towards the dysfunction of β-cells and to glucose intolerance. These are characteristics of type 2 diabetes, which is often linked to chronic nutritional overload being nowadays a pandemic feature of lifestyle. Overcharged β-cell metabolism causes pressure on proteostasis in the endoplasmic reticulum, mainly due to increased demand on insulin synthesis, which establishes unfolded protein response and insulin misfolding along with excessive hydrogen peroxide production. This together with redox dysbalance in cytoplasm and mitochondria due to enhanced nutritional pressure impact β-cell redox homeostasis and establish prooxidative metabolism. This can further affect β-cell communication in pancreatic islets through gap junctions. In parallel, peripheral tissues losing insulin sensitivity and overall impairment of glucose tolerance and gut microbiota establish local proinflammatory signaling and later systemic metainflammation, i.e., low chronic inflammation prooxidative properties, which target β-cells leading to their dedifferentiation, dysfunction and eventually cell death.

• Klíčová slova
• de/differentiation, inflammation, oxidative stress, pancreatic β-cells, redox homeostasis, redox signaling,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Characterization of metabolites and microbiota composition from human stool provides powerful insight into the molecular phenotypic difference between subjects with normal weight and those with overweight/obesity. The aim of this study was to identify potential metabolic and bacterial signatures from stool that distinguish the overweight/obesity state in children/adolescents. Using 1H NMR spectral analysis and 16S rRNA gene profiling, the fecal metabolic profile and bacterial composition from 52 children aged 7 to 16 was evaluated. The children were classified into three groups (16 with normal-weight, 17 with overweight, 19 with obesity). The metabolomic analysis identified four metabolites that were significantly different (p < 0.05) among the study groups based on one-way ANOVA testing: arabinose, butyrate, galactose, and trimethylamine. Significantly different (p < 0.01) genus-level taxa based on edgeR differential abundance tests were genus Escherichia and Tyzzerella subgroup 3. No significant difference in alpha-diversity was detected among the three study groups, and no significant correlations were found between the significant taxa and metabolites. The findings support the hypothesis of increased energy harvest in obesity by human gut bacteria through the growing observation of increased fecal butyrate in children with overweight/obesity, as well as an increase of certain monosaccharides in the stool. Also supported is the increase of trimethylamine as an indicator of an unhealthy state.

• MeSH
• Bacteria genetika   MeSH
• dítě MeSH
• feces mikrobiologie   MeSH
• lidé MeSH
• metabolom MeSH
• metabolomika MeSH
• mladiství MeSH
• obezita dětí a dospívajících metabolismus   mikrobiologie   MeSH
• obezita metabolismus   mikrobiologie   MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• RNA ribozomální 16S genetika   MeSH
• střevní mikroflóra genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• RNA ribozomální 16S MeSH

Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.

• Klíčová slova
• IBD, colitis, functional screening, holobiont, immune response, live biotherapeutic products (LBP), microbiota, probiotics,
• MeSH
• Bacteroidetes genetika   imunologie   izolace a purifikace   MeSH
• Caco-2 buňky MeSH
• DNA bakterií genetika   metabolismus   MeSH
• dospělí MeSH
• feces mikrobiologie   MeSH
• idiopatické střevní záněty imunologie   mikrobiologie   MeSH
• kolitida chemicky indukované   imunologie   mikrobiologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• kyselina trinitrobenzensulfonová škodlivé účinky   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• novorozenec MeSH
• regulační T-lymfocyty imunologie   MeSH
• střevní mikroflóra imunologie   MeSH
• střevní sliznice imunologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• myši MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA bakterií MeSH
• kyselina trinitrobenzensulfonová MeSH

Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies.

• MeSH
• cholin metabolismus   MeSH
• databáze genetické MeSH
• druhová specificita MeSH
• kohortové studie MeSH
• kolorektální nádory diagnóza   metabolismus   mikrobiologie   MeSH
• lidé MeSH
• lyasy genetika   metabolismus   MeSH
• metagenomika * MeSH
• nádorové biomarkery metabolismus   MeSH
• střevní mikroflóra MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• cholin MeSH
• lyasy MeSH
• nádorové biomarkery MeSH