Effect of experimental gingivitis induction and erythritol on the salivary metabolome and functional biochemistry of systemically healthy young adults

Introduction

Understanding the changes occurring in the oral ecosystem during development of gingivitis could help improve prevention and treatment strategies for oral health. Erythritol is a non-caloric polyol proposed to have beneficial effects on oral health.

Objectives

To examine the effect of experimental gingivitis and the effect of erythritol on the salivary metabolome and salivary functional biochemistry.

Methods

In a two-week experimental gingivitis challenge intervention study, non-targeted, mass spectrometry-based metabolomic profiling was performed on saliva samples from 61 healthy adults, collected at five time-points. The effect of erythritol was studied in a randomized, controlled trial setting. Fourteen salivary biochemistry variables were measured with antibody- or enzymatic activity-based assays.

Results

Bacterial amino acid catabolites (cadaverine, N-acetylcadaverine, and α-hydroxyisovalerate) and end-products of bacterial alkali-producing pathways (N-α-acetylornithine and γ-aminobutyrate) increased significantly during the experimental gingivitis. Significant changes were found in a set of 13 salivary metabolite ratios composed of host cell membrane lipids involved in cell signaling, host responses to bacteria, and defense against free radicals. An increase in mevalonate was also observed. There were no significant effects of erythritol. No significant changes were found in functional salivary biochemistry.

Conclusions

The findings underline a dynamic interaction between the host and the oral microbial biofilm during an experimental induction of gingivitis.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Estrogen Receptor-α Correlates with Higher Fungal Cell Number in Oral Paracoccidioidomycosis in Women

Background

Paracoccidioidomycosis is a neglected tropical fungal infection with great predilection for adult men, indicating the participation of female hormone estrogen in preventing paracoccidioidomycosis development in women. Estrogen has an immunologic effect leading to polarization toward the Th2 immune response, which favors the disease evolution.

Objectives

To evaluate estrogen and progesterone receptors in oral paracoccidioidomycosis lesions and to verify any association with tissue fungi counting in women and men.

Methods

Thirty-two cases of chronic oral paracoccidioidomycosis were included. Immunohistochemical analyses for anti-estrogen receptor-α, anti-progesterone receptor and anti-Paracoccidioides brasiliensis antibodies were performed. The differences between women and men and the relations among the immunomarkers for each gender were also evaluated.

Results

A significant positive correlation was observed between estrogen receptor-α and the amount of fungi in women. In addition, estrogen receptor-α was mildly expressed in the inflammatory cells of female patients, while progesterone receptor was expressed in both genders, with similar expression between women and men. Moreover, fungi counting revealed no differences between genders.

Conclusions

Estrogen receptor-α was expressed only in women and showed a positive correlation with the amount of fungi in oral paracoccidioidomycosis, while progesterone receptor was observed in both genders and exhibited no correlation with estrogen receptor-α or fungi counting.

     

Relationship between cognitive appraisals of symptoms and negative mood for subtypes of irritable bowel syndrome

Background

The onset and course of irritable bowel syndrome (IBS) are strongly influenced by psychological factors, and treatment often includes cognitive-behavioral therapy. We conducted a study of the relationships between cognitive appraisal of IBS symptoms and negative mood for the subtypes of IBS.

Method

The participants were 1087 college students who completed a set of questionnaires that included the Rome II Modular Questionnaire, Self-reported IBS Questionnaire, Cognitive Appraisal Rating Scale, and the Hospital Anxiety and Depression Scale.

Results

The participants included 206 individuals with IBS; 61 had diarrhea-predominant IBS (IBSD) and 45 had constipation-predominant IBS (IBSC). The overall IBS group scored higher on anxiety and depression than the control group. The IBSD and IBSC groups each had significantly higher scores for anxiety but did not significantly differ from the control group in scores for depression. There were no significant differences between the IBSD and IBSC groups in their cognitive appraisal of IBS symptoms. For the IBSD group, anxiety was significantly, positively correlated with commitment, effect, and threat, and depression was significantly, negatively correlated with controllability. In contrast, there were no significant correlations between mood and cognitive appraisal for the IBSC group. Multiple regression analyses with abdominal symptoms as dependent variables and cognitive appraisals as independent variables showed that for the IBSD group, abdominal pain was significantly, positively correlated with commitment, and abdominal discomfort was significantly, positively correlated with appraisal of effect and threat. For the IBSC group, abdominal pain and hard stool were significantly, positively correlated with commitment, and abdominal discomfort was significantly, positively correlated with appraisal of effect and threat.

Conclusion

IBS patients as a general group report high levels of anxiety and depression. However, IBSD and IBSC were both associated only with high anxiety, but not depression, when compared to the non-IBS control group. For the IBSD group, anxiety was associated with cognitive appraisals, but this association was not found for the IBSC group. These groups did not differ in their associated cognitive appraisals, and are similar in terms of the positive relationship between abdominal pain and discomfort and the cognitive appraisals of coping.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Genetic variation in the TAS2R38 taste receptor contributes to the oral microbiota in North and South European locations: a pilot study

Background

Microbial communities are influenced by environmental factors including host genetics. We investigated the relationship between host bitter taste receptor genotype hTAS2R38 and oral microbiota, together with the influence of geographical location.

Methods

hTAS2R38 polymorphisms and 16S bacterial gene sequencing from oral samples were analyzed from a total of 45 healthy volunteers from different geographical locations.

Results

Genetic variation in the bitter taste receptor TAS2R38 reflected in the microbial composition of oral mucosa in Finnish and Spanish subjects. Multivariate analysis showed significant differences in the microbial composition between country and also dependent on taste genotype. Oral microbiota was shown to be more stable to the geographical location impact among AVI-homozygotes than PAV-homozygotes or heterozygotes (PAV/AVI).

Conclusion

Geographical location and genetic variation in the hTAS2R38 taste receptor impact oral mucosa microbial composition. These findings provide an advance in the knowledge regarding the interactions between taste receptor genes and oral microbiota. This study suggests the role of host-microbiota interactions on the food taste perception in food choices, nutrition, and eating behavior.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

Extraction of natural products from bark of <Emphasis Type="Italic">Betula pendula</Emphasis> using ionic liquids

Introduction

Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.

Objectives

To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.

Methods

The extracted compounds were analyzed by LC/MS and GC/MS.

Results

The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.

Conclusion

From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.

     

Monitoring of pre-frontal oxygen status in helicopter pilots using near-infrared spectrophotometers

Background

There are few in-flight studies of cognition-related cerebral oxygen status in helicopter pilots.

Methods

Four male helicopter pilots volunteered for nine sorties during visual flight in a BK117 and UH-60J. The pilots' pre-frontal oxy-hemoglobin (O₂Hb) and deoxy-hemoglobin (HHb) concentration were continuously monitored from the right/left sections of the forehead using near-infrared spectrophotometers with a consideration of motion artifacts.

Results

The concentration of O₂Hb progressively increased (13.98 μmol?L^-1 as a maximum increased concentration) in both the right/left sections of the forehead from the basal level during the heightened cognitive demand of helicopter flight. There was comparatively little change (4.32 μmol?L^-1 as a maximum increased concentration) in HHb concentration during measurement of helicopter flight. HHb changes were apparently not affected by a heightened cognitive demand of helicopter pilots.

Conclusion

These results demonstrate that near-infrared spectroscopy, especially O₂Hb measurements, provides a sensitive method for the monitoring of cognitive demand (maneuvers) in helicopter pilots.

     

Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure

Background

Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging.

Methods

Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations.

Results

Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race.

Conclusion

The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

Metabolic response of porcine colon explants to in vitro infection by <Emphasis Type="Italic">Brachyspira hyodysenteriae</Emphasis>: a leap into disease pathophysiology

Introduction

Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.

Objective

The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.

Methods

Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.

Results

Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.

Conclusions

The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.

     

<Emphasis Type="Italic">massPix</Emphasis>: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.

     

Iridoid and phenylethanoid/phenylpropanoid metabolite profiles of <Emphasis Type="Italic">Scrophularia</Emphasis> and <Emphasis Type="Italic">Verbascum</Emphasis> species used medicinally in North America

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.

     

Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.