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1.
Neurosci Biobehav Rev ; 162: 105722, 2024 Jul.
Article En | MEDLINE | ID: mdl-38754717

FRILEUX, M., BOLTRI M. and al. Cognition and Gut microbiota in schizophrenia spectrum and mood disorders: a Systematic Review. NEUROSCI BIOBEHAV REV (1) 2024 Schizophrenia spectrum disorders and major mood disorders are associated with cognitive impairments. Recent studies suggest a link between gut microbiota composition and cognitive functioning. Here, we review the relationship between gut microbiota and cognition in these disorders. To do this, we conducted a systematic review, searching Cochrane Central Register of Controlled Trials, EBSCOhost, Embase, Pubmed, Scopus, and Web of Science. Studies were included if they investigated the relationship between gut microbiota composition and cognitive function through neuropsychological assessments in patients with bipolar, depressive, schizophrenia spectrum, and other psychotic disorders. Ten studies were identified. Findings underscore a link between gut dysbiosis and cognitive impairment. This relationship identified specific taxa (Haemophilus, Bacteroides, and Alistipes) as potential contributors to bolstered cognitive performance. Conversely, Candida albicans, Toxoplasma gondii, Streptococcus and Deinococcus were associated with diminished performance on cognitive assessments. Prebiotics and probiotics interventions were associated with cognitive enhancements, particularly executive functions. These results emphasize the role of gut microbiota in cognition, prompting further exploration of the underlying mechanisms paving the way toward precision psychiatry.


Gastrointestinal Microbiome , Mood Disorders , Schizophrenia , Humans , Gastrointestinal Microbiome/physiology , Schizophrenia/microbiology , Schizophrenia/physiopathology , Mood Disorders/microbiology , Mood Disorders/etiology , Cognition/physiology , Cognitive Dysfunction/microbiology , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Dysbiosis/microbiology
2.
Benef Microbes ; 13(3): 253-264, 2022 Aug 03.
Article En | MEDLINE | ID: mdl-35786408

The microbiota-gut-brain axis is important in anxiety-depressive disorders. These conditions are associated with dysbiosis of the intestinal microbiota, intestinal hyperpermeability and an increase in circulating markers of inflammation and oxidative stress. They are also associated with a deregulation of the glutamine-glutamate-γ-aminobutyric acid cycle, with impairment of the excitatory/inhibitory balance in the brain. Our aim was to examine the impact of chronic treatment with the probiotic organism Lacticaseibacillus rhamnosus GG, alone or in combination with glutamine and curcumin, in a validated model of anxiety-depressive disorder in mice. Six-month-old mice (n=144) were exposed to chronic unpredictable mild stress (CUMS) stimulation for 3 weeks and emotional disturbances were assessed using two tests assessing anxiety (elevated plus maze test) and depressive-like behaviour (tail suspension test). After discontinuation of CUMS, mice were force-fed once-daily with curcumin, glutamine and probiotic alone or in combination for 21 consecutive days. Emotional reactivity was assessed in two separate behavioural tests: open field test and forced swim test. The outcomes of the interventions were compared with those induced by acute intraperitoneal administration of clomipramine, one of the major tricyclic antidepressants used in humans. Two independent sets of experiment were performed in this study, in order to evaluate the effects of two different formulations based on the utilisation of the probiotic L. rhamnosus GG in its live or inactivated form. CUMS led to an impairment of the emotional state of 6-month-old mice. However, chronic treatment with a combination of glutamine, curcumin and L. rhamnosus GG rescued the anxiety and depressive-like phenotype with an efficiency similar to clomipramine. A synergistic effect of the three compounds was observed, suggesting that simultaneous action on different targets is a relevant approach for the management of anxiety-depressive disorders.


Curcumin , Depressive Disorder , Lacticaseibacillus rhamnosus , Probiotics , Animals , Clomipramine , Curcumin/pharmacology , Depression/drug therapy , Disease Models, Animal , Glutamine , Humans , Infant , Mice , Stress, Psychological/drug therapy , Stress, Psychological/psychology
3.
J Eur Acad Dermatol Venereol ; 33 Suppl 2: 57-62, 2019 Mar.
Article En | MEDLINE | ID: mdl-30811691

The International Agency for Research on Cancer classified, in July 2009, exposure to artificial tanning devices (sunbeds) as carcinogenic to humans. This classification was based on evidence from epidemiological and experimental animal studies. The present chapter will review these epidemiological evidences. The summary risk estimates from 27 epidemiological studies obtained through a meta-analysis showed an increased risk of melanoma: summary relative risk (SRR) = 1.20 [95% confidence interval (CI) 1.08-1.34]. The risk was higher when exposure took place at younger age (SRR = 1.59; 95% CI 1.36-1.85). The risk was independent of skin sensitivity or population and a dose response was evident. A meta-analysis of 12 studies was conducted for non-melanoma skin cancers and showed a significantly increased risk for basal cell carcinoma (SRR = 1.29; 95% CI 1.08-1.53) and for squamous cell carcinoma (SRR = 1.67; 95% CI 1.29-2.17). As for melanoma, the risk for other skin cancers increased for first exposures at young age. Epidemiological studies have gradually strengthened the evidence for a causal relationship between indoor tanning and skin cancer and they fit with prior knowledge on relationship between UV exposure and skin cancer. Additionally, several case-control studies provided consistent evidence of a positive association between use of sunbed and ocular melanoma, also with greater risk for first exposures at younger age. Preventive measures based on information on risk or by requiring parental authorization for young users proved to be inefficient in several studies. The significant impact of strong actions or total ban, such as performed in Iceland, or a total ban of sunbed use, as in Brazil or Australian states, needs to be further assessed.


Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Melanoma/epidemiology , Skin Neoplasms/epidemiology , Sunbathing/statistics & numerical data , Ultraviolet Rays/adverse effects , Carcinogenesis , Carcinoma, Basal Cell/etiology , Carcinoma, Squamous Cell/etiology , Health Education , Humans , Melanoma/etiology , Melanoma/prevention & control , Meta-Analysis as Topic , Skin Neoplasms/etiology , Skin Neoplasms/prevention & control , Uveal Neoplasms/epidemiology
4.
Sci Rep ; 8(1): 74, 2018 01 08.
Article En | MEDLINE | ID: mdl-29311617

Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models. The effect was predominantly attributable to the histone deacetylase inhibitory activity of SCFA and minor, but significant contributions of FFA2 (GPR43). Consistent with the SCFA-dependent elevation of PYY gene expression, we also observed increased basal and stimulated PYY hormone secretion. Interestingly, the transcriptional stimulation of PYY was specific to human-derived cell models and not reproduced in murine primary cultures. This is likely due to substantial differences in PYY gene structure between mouse and human. In summary, this study revealed a strong regulation of PYY production by SCFA that was evident in humans but not mice, and suggests that high fibre diets elevate plasma concentrations of the anorexigenic hormone PYY, both by targeting gene expression and hormone secretion.


Enteroendocrine Cells/metabolism , Fatty Acids, Volatile/metabolism , Peptide YY/metabolism , Cell Line , Cells, Cultured , Enteroendocrine Cells/drug effects , Fatty Acids, Volatile/pharmacology , Gene Expression , Glucagon-Like Peptide 1/genetics , Glucagon-Like Peptide 1/metabolism , Humans , Peptide YY/genetics
5.
Food Res Int ; 97: 123-132, 2017 07.
Article En | MEDLINE | ID: mdl-28578032

Wheat flour doughs were processed with soluble dietary fibres (DF) added up to 40% (w/w flour). DF were made of a ternary mixture of maltodextrins (MT, 3/5), pectins (PE, 1/5) and inulin (IN, 1/5). The addition of DF decreased the specific mechanical energy developed by the mixer, mainly because of water addition. It increased the ratio of storage moduli and the elongational viscosity of the dough, but decreased the strain hardening index. Energy input and rheological changes at mixing largely explained the decreases of porosity characteristic time and stability time during fermentation. It was possible to add up to 30% DF with a moderate increase of bread density, and 20%, with little change of crumb cellular structure. Hence, the changes of bread crumb texture were not mainly due to bread density, but rather likely to the changes of properties of the intrinsic material. Results obtained by addition of single fibre source, especially inulin, deviated from the main trends observed for texture and rheological properties. These results provide a good basis to design breads with increased dietary fibre content.


Bread/analysis , Dietary Fiber/analysis , Flour/analysis , Triticum/chemistry , Fermentation , Rheology , Viscosity
6.
Gut ; 65(6): 954-62, 2016 06.
Article En | MEDLINE | ID: mdl-26628508

OBJECTIVES: Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial. DESIGN: Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis. RESULTS: ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/ß Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence. CONCLUSIONS: ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.


Colon/surgery , Crohn Disease/microbiology , Crohn Disease/surgery , Gastrointestinal Microbiome , Ileum/surgery , Lactobacillus johnsonii/metabolism , Biopsy , Colon/pathology , Crohn Disease/pathology , Double-Blind Method , Dysbiosis/prevention & control , Follow-Up Studies , Humans , Ileum/pathology , Intestinal Mucosa/microbiology , Recurrence , Remission Induction
7.
Benef Microbes ; 5(1): 67-77, 2014 Mar.
Article En | MEDLINE | ID: mdl-24322881

The gut microbiota is increasingly recognised as a key-player in defining the health status of the gastrointestinal tract. Recently, we demonstrated that colonisation of healthy germfree mice with a conventional microbiota (conventionalisation) elicits temporal and region specific host-microbe communication responses that lead to the establishment of a microbiota-accommodating homeostatic state within 30 days. Here, the microbiota composition profiles, mucosal transcriptomes and plasma-analytes in germ-free and conventionalised C57/BL 6 J mice were assessed to decipher the features of the distinctive and pivotal events occurring four days after initiation of the conventionalisation process. The dominance of the microbial genera Helicobacter, Sphingomonas and Mucispirillum in the gut microbiota coincided with the transient mounting of proinflammatory responses in the mucosa and the transiently elevated levels of specific (inflammatory) cytokines and amines in plasma. The overrepresented microbes have previously been associated with the potential to cause disease under certain conditions, illustrating that conventionalisation proceeds through a transient state that resembles situations associated with dysbiosis. However, no overt mucosal inflammation was observed, suggesting a pivotal role of the overrepresented bacterial groups in priming and maturation of the immune system during the process of conventionalisation. These findings imply that the transiently elevated relative overgrowth of particular microbial genera functions as pivotal adjuvants to elicit the corresponding proinflammatory cascades, which precede the full maturation of the different arms of the immune system following these events and is required to achieve a microbiota-accommodating homeostasis in healthy animals.


Helicobacter/growth & development , Inflammation/microbiology , Intestinal Mucosa/microbiology , Microbiota/immunology , Sphingomonas/growth & development , Amines/blood , Animals , Cytokines/blood , Dysbiosis/immunology , Dysbiosis/microbiology , Gene Expression Profiling , Germ-Free Life , Homeostasis/immunology , Inflammation/immunology , Intestinal Mucosa/immunology , Mice , Mice, Inbred C57BL
8.
J Phys Condens Matter ; 25(45): 454203, 2013 Nov 13.
Article En | MEDLINE | ID: mdl-24140935

The disordered structure of commercially available CXV activated carbon produced from finely powdered wood-based carbon has been studied using the wide-angle x-ray scattering technique, molecular dynamics and density functional theory simulations. The x-ray scattering data has been converted to the real space representation in the form of the pair correlation function via the Fourier transform. Geometry optimizations using classical molecular dynamics based on the reactive empirical bond order potential and density functional theory at the B3LYP/6-31g* level have been performed to generate nanoscale models of CXV carbon consistent with the experimental data. The final model of the structure comprises four chain-like and buckled graphitic layers containing a small percentage of four-fold coordinated atoms (sp(3) defects) in each layer. The presence of non-hexagonal rings in the atomic arrangement has been also considered.

9.
Neurogastroenterol Motil ; 25(1): 4-15, 2013 Jan.
Article En | MEDLINE | ID: mdl-23279728

BACKGROUND: The microbial community of the human gut - the enteric microbiota - plays a critical role in functions that sustain health and is a positive asset in host defenses. In recent years, our understanding of this so-called human 'super organism' has advanced, following characterization of fecal metagenomes which identified three core bacterial enterotypes, and based on basic and clinical research into the impact and consequences of microbiota biodiversity and change on gastrointestinal disorders and diseases. PURPOSE: This article considers current knowledge and future perspectives on the make-up and function of human gut microbiota, with a particular focus on altered microbiota and gastrointestinal disorders, nutritional influences on the gut microbiota, and the consequences for gastrointestinal health, as well as improved understanding of gut-microbiota-brain communication.


Gastrointestinal Diseases/microbiology , Gastrointestinal Tract/microbiology , Humans , Metagenome
10.
Diabetologia ; 54(12): 3055-61, 2011 Dec.
Article En | MEDLINE | ID: mdl-21976140

AIMS/HYPOTHESIS: Evidence suggests that bacterial components in blood could play an early role in events leading to diabetes. To test this hypothesis, we studied the capacity of a broadly specific bacterial marker (16S rDNA) to predict the onset of diabetes and obesity in a general population. METHODS: Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) is a longitudinal study with the primary aim of describing the history of the metabolic syndrome. The 16S rDNA concentration was measured in blood at baseline and its relationship with incident diabetes and obesity over 9 years of follow-up was assessed. In addition, in a nested case-control study in which participants later developed diabetes, bacterial phylotypes present in blood were identified by pyrosequencing of the overall 16S rDNA gene content. RESULTS: We analysed 3,280 participants without diabetes or obesity at baseline. The 16S rDNA concentration was higher in those destined to have diabetes. No difference was observed regarding obesity. However, the 16S rDNA concentration was higher in those who had abdominal adiposity at the end of follow-up. The adjusted OR (95% CIs) for incident diabetes and for abdominal adiposity were 1.35 (1.11, 1.60), p = 0.002 and 1.18 (1.03, 1.34), p = 0.01, respectively. Moreover, pyrosequencing analyses showed that participants destined to have diabetes and the controls shared a core blood microbiota, mostly composed of the Proteobacteria phylum (85-90%). CONCLUSIONS/INTERPRETATION: 16S rDNA was shown to be an independent marker of the risk of diabetes. These findings are evidence for the concept that tissue bacteria are involved in the onset of diabetes in humans.


Biomarkers/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/microbiology , Metabolic Syndrome/blood , Metagenome , RNA, Ribosomal, 16S/blood , Adult , Aged , Bacteria/classification , Bacteria/isolation & purification , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Female , France , Humans , Longitudinal Studies , Male , Middle Aged , Obesity/blood , Obesity, Abdominal/blood , Obesity, Abdominal/epidemiology
11.
J Chem Phys ; 134(6): 064509, 2011 Feb 14.
Article En | MEDLINE | ID: mdl-21322707

Water confined in a sol-gel network has been characterized by x-ray and neutron diffraction for two samples of mesoporous silica: one with a hydrophilic character (a nonmodified one) and another with a hydrophobic character (a modified one with a methylated internal pore surface). The pore size has been previously characterized [J. Jelassi et al., Phys. Chem. Chem. Phys. 134, 1039 (2010)] to have a mean pore diameter of approximately 55 Å. The diffraction measurements presented in this paper have been made at room temperature [293 K] for a filling factor of 0.45, giving a mean thickness of 8-9 Å for the water layer. The results show that the local order of the confined water molecules in the intermediate region of 3-6 Å is significantly different from that of the bulk water and also for the two different environments. For the hydrophilic sample, the siloxyl groups at the surface modify the water structure through the effects of interfacial hydrogen-bonding, which influences the orientational configuration of local water molecules and creates a modified spatial arrangement in the pore. In the case of the hydrophobic sample, there is no specific interaction with the pore wall, which is primarily van der Waals type, and the water molecules at the interface are differently oriented to create a hydrogen-bonded network linked more directly to the rest of the water volume. In the present circumstances, the thickness of the water layer has a relatively small dimension so that the interpretation of the measured diffraction pattern is not as straightforward as for the bulk liquids, and it is necessary to consider the effects of diffraction-broadening from a distributed sample volume and also the contribution from cross-terms that remain after conducting a "wet-minus-dry" analysis procedure. These analytic difficulties are discussed in the context of the present measurements and compared with the work of other groups engaged in the study of water confined in different environments. The present results, again, emphasize the complexity influencing the properties of water in a confined geometry and the strong influence of surface interactions on its behavior.


Silicon Dioxide/chemistry , Temperature , Water/chemistry , Hydrophobic and Hydrophilic Interactions , Molecular Structure , Neutron Diffraction , Porosity , Surface Properties , Wettability , X-Rays
12.
Ann Oncol ; 22(8): 1726-35, 2011 Aug.
Article En | MEDLINE | ID: mdl-21252058

BACKGROUND: Breast cancer mortality is declining in many Western countries. If mammography screening contributed to decreases in mortality, then decreases in advanced breast cancer incidence should also be noticeable. PATIENTS AND METHODS: We assessed incidence trends of advanced breast cancer in areas where mammography screening is practiced for at least 7 years with 60% minimum participation and where population-based registration of advanced breast cancer existed. Through a systematic Medline search, we identified relevant published data for Australia, Italy, Norway, Switzerland, The Netherlands, U.K. and the U.S.A. Data from cancer registries in Northern Ireland, Scotland, the U.S.A. (Surveillance, Epidemiology and End Results (SEER), and Connecticut), and Tasmania (Australia) were available for the study. Criterion for advanced cancer was the tumour size, and if not available, spread to regional/distant sites. RESULTS: Age-adjusted annual percent changes (APCs) were stable or increasing in ten areas (APCs of -0.5% to 1.7%). In four areas (Firenze, the Netherlands, SEER and Connecticut) there were transient downward trends followed by increases back to pre-screening rates. CONCLUSIONS: In areas with widespread sustained mammographic screening, trends in advanced breast cancer incidence do not support a substantial role for screening in the decrease in mortality.


Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Early Detection of Cancer/methods , Mammography/methods , Adult , Aged , Female , Humans , Incidence , Middle Aged , Neoplasm Staging
13.
Inflamm Bowel Dis ; 17(1): 185-92, 2011 Jan.
Article En | MEDLINE | ID: mdl-20722058

BACKGROUND: Recent studies suggest that gastrointestinal (GI) microbes play a part in the pathogenesis of Crohn's disease (CD). METHODS: Fecal samples were collected from 16 healthy individuals and 16 CD patients (age- and sex-matched). The DNA extracted from these samples were subjected to two different methods of microbiome analysis. Specific bacterial groups were quantified by real-time polymerase chain reaction (PCR) methods using primers designed using a high-throughput in-house bioinformatics pipeline. The same DNA extracts were also used to produce fluorescently labeled cRNA amplicons to interrogate a custom-designed phylogenetic microarray for intestinal bacteria. RESULTS: Even though the intersubject variability was high, differences in the fecal microbiomes of healthy and CD patients were detected. Faecalibacterium prausnitzii and Escherichia coli were more represented in healthy and ileal CD patients, respectively. Additionally, probes specific for Ruminococcus bromii, Oscillibacter valericigenes, Bifidobacterium bifidum, and Eubacterium rectale produced stronger hybridization signals with the DNA samples from healthy subjects. Conversely, species overrepresented in CD patients were E. coli, Enterococcus faecium, and species from the Proteobacteria not normally found in the healthy human GI tract. Furthermore, we detected "healthy specific" molecular species or operational taxonomic units (OTUs) that are not closely related to any known species (Faecalibacterium, Subdoligranulum, and Oscillospora species), indicating that the phylogenetic dysbiosis is broader than at strain or species level. CONCLUSIONS: These two techniques of microbiome analysis provided a statistically robust new picture of the dysbiosis in fecal microbiota from ileal CD patients. Specifically, we identified a set of six species discriminant for CD, which provides a preliminary diagnostic tool.


Crohn Disease/genetics , Crohn Disease/microbiology , Gastrointestinal Tract/microbiology , Metagenome/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Crohn Disease/diagnosis , Female , Gastrointestinal Tract/pathology , Humans , Male , Middle Aged , Phylogeny , Prognosis , Young Adult
15.
Gastroenterol Clin Biol ; 34 Suppl 1: S7-15, 2010 Sep.
Article Fr | MEDLINE | ID: mdl-20889008

The human intestinal microbiota constitutes a complex ecosystem which is now well recognized for its impact on human health and well-being. It contributes to maturation of the immune system and provides a direct barrier against colonization by pathogens. Its possible implication in diseases of modern societies, currently increasing in prevalence, has been reported. These include allergies, inflammatory bowel diseases and possibly metabolic and degenerative disorders. The analysis of the molecular composition of the human intestinal microbiota indicates marked inter-individual variations which may seem paradoxical considering the high degree of conservation of major functions of the intestinal microbiota such as anaerobic digestion of alimentary fibres. We have characterized a phylogenetic core within the human intestinal microbiota, in terms of composition, i.e., a set of conserved species that could be responsible for major conserved functions. Based on culture-independent molecular assessments, current knowledge enables a definition of criteria qualifying the normal state of the human intestinal microbiota that we call normobiosis. This further enables the identification of specific deviations from normobiosis, i.e., dysbiosis in immune, metabolic or degenerative diseases. Notably, Crohn's disease, an inflammatory bowel disease of yet unknown aetiology, is associated with intestinal dysbiosis with a lower representation of the Clostridium leptum group among the Firmicutes phylum. We further showed that the bacterial species Faecalibacterium prausnitzii exerts anti-inflammatory properties in vitro and in animal models; this could explain its ability, when detected in the mucosa-associated microbiota of patients in vivo, to protect patients from post-operative recurrence of endoscopic signs of inflammation 6 months after surgical resection of the ileocecal region of the gut. By confirming the major role of the microbiota in bowel-related disorders, which are especially associated with a disruption of homeostasis, we are currently applying high throughput functional metagenomic screens in order to identify signal molecules and mechanisms of bacteria-host cross-talk. Together with the high resolution description of the human intestinal metagenome, as well as explorations of environmental proteins and metabolites, these observations will further our understanding of the functional roles bacteria play in the maintenance of health and well-being in humans. It will open new perspectives for the monitoring and design of strategies for modulating the microbiota for health.


Intestine, Large/microbiology , Intestine, Small/microbiology , Metagenome , Gram-Positive Bacteria/isolation & purification , Humans , Hypersensitivity/microbiology , Hypersensitivity/prevention & control , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/prevention & control , Intestinal Mucosa/microbiology , Metabolic Diseases/microbiology , Metabolic Diseases/prevention & control , Metabolic Syndrome/microbiology , Metabolic Syndrome/prevention & control , Neurodegenerative Diseases/microbiology , Neurodegenerative Diseases/prevention & control
16.
Br J Cancer ; 101(7): 1107-13, 2009 Oct 06.
Article En | MEDLINE | ID: mdl-19707197

BACKGROUND: The human kallikrein-related peptidase family consists of 15 genes. Twelve of these genes are overexpressed in ovarian cancer and may represent potential markers for diagnosis, prognosis, and/or response to treatment. The aim of this study was to determine the prognostic significance of kallikrein-related peptidase 6 (KLK6) and kallikrein-related peptidase 13 (KLK13) in epithelial ovarian cancer by quantifying gene expression levels with tumour pathology and patient survival data. METHODS: Total RNA was isolated from 106 patients diagnosed with primary ovarian cancer, as well as 8 normal ovary controls. Samples were analysed by quantitative real-time PCR for KLK6 and KLK13 expression. Correlation between kallikrein gene expression and clinical characteristics was evaluated with the chi(2)-test. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression models. RESULTS: Expression levels of both KLK6 and KLK13 mRNA were significantly increased in invasive cancers relative to normal ovaries (P=0.002 and 0.039 respectively). High KLK6 and KLK13 expression was an indicator of poor prognosis, with patients having a shorter recurrence-free survival (P=0.002 and 0.027 respectively). High KLK6 expression was also significantly associated with lower overall survival (P=0.011). When subjected to multivariate analysis, patients with either high KLK6 or KLK13 were 3- and 2.2-fold, respectively, more likely to have a recurrence than patients with low kallikrein expression. CONCLUSION: These data show increased mRNA expression of KLK6 and KLK13 in ovarian cancer compared to normal ovarian tissues. High KLK6 or KLK13 expression in primary ovarian tumours can significantly predict prognosis in terms of recurrence-free survival and overall survival. In all, this study shows KLK6 and KLK13 as potential biomarkers and may be therapeutic targets for treatment of ovarian cancer.


Kallikreins/genetics , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/mortality , Female , Humans , Immunohistochemistry , Kallikreins/analysis , Neoplasm Recurrence, Local , Neoplasms, Glandular and Epithelial/chemistry , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/metabolism , Prognosis , RNA, Messenger/analysis , Regression Analysis
17.
BMC Microbiol ; 9: 123, 2009 Jun 09.
Article En | MEDLINE | ID: mdl-19508720

BACKGROUND: In humans, the intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Applying current molecular methods is necessary to surmount the limitations of classical culturing techniques in order to obtain an accurate description of the microbiota composition. RESULTS: Here we report on the comparative assessment of human fecal microbiota from three age-groups: infants, adults and the elderly. We demonstrate that the human intestinal microbiota undergoes maturation from birth to adulthood and is further altered with ageing. The counts of major bacterial groups Clostridium leptum, Clostridium coccoides, Bacteroidetes, Bifidobacterium, Lactobacillus and Escherichia coli were assessed by quantitative PCR (qPCR). By comparing species diversity profiles, we observed age-related changes in the human fecal microbiota. The microbiota of infants was generally characterized by low levels of total bacteria. C. leptum and C. coccoides species were highly represented in the microbiota of infants, while elderly subjects exhibited high levels of E. coli and Bacteroidetes. We observed that the ratio of Firmicutes to Bacteroidetes evolves during different life stages. For infants, adults and elderly individuals we measured ratios of 0.4, 10.9 and 0.6, respectively. CONCLUSION: In this work we have confirmed that qPCR is a powerful technique in studying the diverse and complex fecal microbiota. Our work demonstrates that the fecal microbiota composition evolves throughout life, from early childhood to old age.


Aging , Bacteroidetes/isolation & purification , Bifidobacterium/isolation & purification , Clostridium/isolation & purification , Escherichia coli/isolation & purification , Intestines/microbiology , Adult , Aged , Aged, 80 and over , Bacteroidetes/classification , Bacteroidetes/genetics , Bifidobacterium/classification , Bifidobacterium/genetics , Clostridium/classification , Clostridium/genetics , Colony Count, Microbial , DNA, Bacterial/genetics , Escherichia coli/classification , Escherichia coli/genetics , Feces/microbiology , Humans , Infant , Infant, Newborn , Lactobacillus/classification , Lactobacillus/genetics , Lactobacillus/isolation & purification , Middle Aged
19.
Inflamm Bowel Dis ; 15(8): 1183-9, 2009 Aug.
Article En | MEDLINE | ID: mdl-19235886

BACKGROUND: The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS). METHODS: fecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log(10) CFU) for statistical analysis. RESULTS: Bacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01). CONCLUSIONS: The fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa.


Colitis, Ulcerative/microbiology , Crohn Disease/microbiology , Feces/microbiology , Gram-Positive Bacterial Infections/microbiology , Ruminococcus/isolation & purification , Adult , Case-Control Studies , Colitis, Ulcerative/pathology , Colon/microbiology , Colon/pathology , Colony Count, Microbial , Crohn Disease/pathology , DNA, Bacterial/genetics , Feces/chemistry , Female , Gram-Positive Bacterial Infections/pathology , Humans , Male , Remission Induction , Ruminococcus/genetics
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