INTRODUCTION: Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. METHODS: We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFAs) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. RESULTS: We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive versus impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal SCFAs in the entire dataset. CONCLUSIONS: Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain. INTRODUCTION: Impulsivity and aggression are often interlinked behavioral traits that have major implications for our society. Therefore, the study of this phenomenon and derivative interventions that could lead to better control of impulsive aggression are of interest. METHODS: We analyzed the composition and diversity of the gut bacterial microbiome of 33 impulsively violent female convicts with dissocial personality disorder and 20 non-impulsive age-matched women. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFAs) were analyzed in serum and stool samples. We also assessed all participants using a battery of psychological questionnaires and tested possible correlations between the collected clinical data and the composition and diversity of their microbiomes and metabolites. RESULTS: We identified four bacterial amplicon sequencing variants that were differentially abundant in non-impulsive versus impulsive women - the genera Bacteroides, Barnesiella, and the order Rhodospirillales were more abundant in impulsive women. In contrast, the genus Catenisphaera was more abundant in non-impulsive women. Fecal tryptophan levels were significantly higher in impulsive women. Association analysis revealed a strong positive intercorrelation between most fecal SCFAs in the entire dataset. CONCLUSIONS: Our study demonstrated possible associations between gut microbiomes and their metabolites and impulsive behavior in a unique cohort of prisoners convicted of violent assaults and a matched group of non-impulsive women from the same prison. Genus Bacteroides, which was differentially abundant in the two groups, encoded enzymes that affect serotonin pathways and could contribute to this maladaptive behavior. Similarly, increased fecal tryptophan levels in impulsive individuals could affect neuronal circuits in the brain.
- MeSH
- agrese fyziologie MeSH
- dospělí MeSH
- feces * mikrobiologie chemie MeSH
- impulzivní chování * fyziologie MeSH
- kyseliny mastné těkavé analýza metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- střevní mikroflóra * fyziologie MeSH
- tryptofan krev metabolismus MeSH
- zločinci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články 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
In recent years, there has been an increased interest in elucidating the influence of the gut microbiota on sleep physiology. The gut microbiota affects the central nervous system by modulating neuronal pathways through the neuroendocrine and immune system, the hypothalamus-pituitary-adrenal axis, and various metabolic pathways. The gut microbiota can also influence circadian rhythms. In this study, we observed the gut microbiota composition of patients suffering from narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. We did not observe any changes in the alpha diversity of the gut microbiota among patient groups and healthy controls. We observed changes in beta diversity in accordance with Jaccard dissimilarities between the control group and groups of patients suffering from narcolepsy type 1 and idiopathic hypersomnia. Our results indicate that both these patient groups differ from controls relative to the presence of rare bacterial taxa. However, after adjustment for various confounding factors such as BMI, age, and gender, there were no statistical differences among the groups. This indicates that the divergence in beta diversity in the narcolepsy type 1 and idiopathic hypersomnia groups did not arise due to sleep disturbances. This study implies that using metabolomics and proteomics approaches to study the role of microbiota in sleep disorders might prove beneficial.
- MeSH
- idiopatická hypersomnie * MeSH
- lidé MeSH
- narkolepsie * MeSH
- poruchy nadměrné spavosti * MeSH
- poruchy spánku a bdění * MeSH
- spánek MeSH
- střevní mikroflóra * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. METHODS: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). RESULTS: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. CONCLUSIONS: The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
BACKGROUND: Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC. CONCLUSION/SIGNIFICANCE: In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.
- MeSH
- biologické markery MeSH
- Crohnova nemoc * terapie MeSH
- inhibitory TNF MeSH
- lidé MeSH
- mikrobiota * MeSH
- pilotní projekty MeSH
- ustekinumab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.
- Publikační typ
- časopisecké články MeSH
Brain-gut microbiota interactions are intensively studied in connection with various neurological and psychiatric diseases. While anorexia nervosa (AN) pathophysiology is not entirely clear, it is presumably linked to microbiome dysbiosis. We aimed to elucidate the gut microbiota contribution in AN disease pathophysiology. We analyzed the composition and diversity of the gut microbiome of patients with AN (bacteriome and mycobiome) from stool samples before and after renourishment, and compared them to healthy controls. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in stool samples by MS and NMR, respectively. Biochemical, anthropometric, and psychometric profiles were assessed. The bacterial alpha-diversity parameter analyses revealed only increased Chao 1 index in patients with AN before the realimentation, reflecting their interindividual variation. Subsequently, core microbiota depletion signs were observed in patients with AN. Overrepresented OTUs (operation taxonomic units) in patients with AN taxonomically belonged to Alistipes, Clostridiales, Christensenellaceae, and Ruminococcaceae. Underrepresented OTUs in patients with AN were Faecalibacterium, Agathobacter, Bacteroides, Blautia, and Lachnospira. Patients exhibited greater interindividual variation in the gut bacteriome, as well as in metagenome content compared to controls, suggesting altered bacteriome functions. Patients had decreased levels of serotonin, GABA, dopamine, butyrate, and acetate in their stool samples compared to controls. Mycobiome analysis did not reveal significant differences in alpha diversity and fungal profile composition between patients with AN and healthy controls, nor any correlation of the fungal composition with the bacterial profile. Our results show the changed profile of the gut microbiome and its metabolites in patients with severe AN. Although therapeutic partial renourishment led to increased body mass index and improved psychometric parameters, SCFA, and neurotransmitter profiles, as well as microbial community compositions, did not change substantially during the hospitalization period, which can be potentially caused by only partial weight recovery.
- MeSH
- Archaea klasifikace růst a vývoj MeSH
- Bacteria klasifikace růst a vývoj metabolismus MeSH
- dospělí MeSH
- feces mikrobiologie MeSH
- houby klasifikace růst a vývoj metabolismus MeSH
- index tělesné hmotnosti MeSH
- kyseliny mastné těkavé metabolismus MeSH
- lidé MeSH
- longitudinální studie MeSH
- mentální anorexie metabolismus mikrobiologie MeSH
- metagenom MeSH
- mladý dospělý MeSH
- mykobiom MeSH
- neurotransmiterové látky metabolismus MeSH
- osa mozek-střevo MeSH
- střevní mikroflóra * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ag-inexperienced memory-like T (AIMT) cells are functionally unique T cells, representing one of the two largest subsets of murine CD8+ T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and an unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multiomics approaches, including analyses of gene expression, TCR repertoire, and microbial colonization. Our data showed that AIMT cells are steadily present in mice, independent of their genetic background and hygienic status. Despite differences in their gene expression profiles, young and aged AIMT cells originate from identical clones. We identified that CD122 discriminates two major subsets of AIMT cells in a strain-independent manner. Whereas thymic CD122LOW AIMT cells (innate memory) prevail only in young animals with high thymic IL-4 production, peripheral CD122HIGH AIMT cells (virtual memory) dominate in aged mice. Cohousing with feral mice changed the bacterial colonization of laboratory strains but had only minimal effects on the CD8+ T cell compartment, including AIMT cells.
- MeSH
- antigeny genetika imunologie MeSH
- fenotyp MeSH
- imunologická paměť genetika imunologie MeSH
- klonální evoluce MeSH
- myši inbrední BALB C MeSH
- myši inbrední C57BL MeSH
- myši transgenní MeSH
- myši MeSH
- nestabilita genomu MeSH
- stárnutí genetika imunologie MeSH
- T-lymfocyty imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
