The Effect of a Planetary Health Diet on the Human Gut Microbiome : A Descriptive Analysis

In 2019, researchers from the EAT-Lancet Commission developed the ‘Planetary Health (PH) diet’. Specifically, they provided recommendations pertaining to healthy diets derived from sustainable food systems. Thus far, it has not been analysed how such a diet affects the human intestinal microbiome, which is important for health and disease development. Here, we present longitudinal genome-wide metagenomic sequencing and mass spectrometry data on the gut microbiome of healthy volunteers adhering to the PH diet, as opposed to vegetarian or vegan (VV) and omnivorous (OV) diets. We obtained basic epidemiological information from 41 healthy volunteers and collected stool samples at inclusion and after 2, 4, and 12 weeks. Individuals opting to follow the PH diet received detailed instructions and recipes, whereas individuals in the control groups followed their habitual dietary pattern. Whole-genome DNA was extracted from stool specimens and subjected to shotgun metagenomic sequencing (~3 GB per patient). Conventional bacterial stool cultures were performed in parallel and bacterial species were identified with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. We analysed samples from 16 PH, 16 OV, and 9 VV diet patterns. The α-diversity remained relatively stable for all dietary groups. In the PH group, we observed a constant increase from 3.79% at inclusion to 4.9% after 12 weeks in relative abundance of Bifidobacterium adolescentis. Differential PH abundance analysis highlighted a non-significant increase in possible probiotics such as Paraprevotella xylaniphila and Bacteroides clarus. The highest abundance of these bacteria was observed in the VV group. Dietary modifications are associated with rapid alterations to the human gut microbiome, and the PH diet led to a slight increase in probiotic-associated bacteria at ≥4 weeks. Additional research is required to confirm these findings

Characteristics of the Skin Microbiome in Selected Dermatological Conditions : A Narrative Review

The skin is the largest and outermost organ of the human body. The microbial diversity of the skin can be influenced by several variable factors such as physiological state, lifestyle, and geographical locations. Recent years have seen increased interest in research aiming at an improved understanding of the relationship between the human microbiota and several diseases. Albeit understudied, interesting correlations between the skin microbiota and several dermatological conditions have been observed. Studies have shown that a decrease or increase in the abundance of certain microbial communities can be implicated in several dermatological pathologies. This narrative review (i) examines the role of the skin microbiota in the maintenance of skin homeostasis and health, (ii) provides examples on how some common skin diseases (acne inversa, candidiasis, psoriasis) are associated with the dysbiosis of microbial communities, and (iii) describes how recent research approaches used in skin microbiome studies may lead to improved, more sensitive diagnostics and individual therapeutics in the foreseeable future

Evaluating Different Storage Media for Identification of Taenia saginata Proglottids Using MALDI-TOF Mass Spectrometry

Taenia saginata is a helminth that can cause taeniasis in humans and cysticercosis in cattle. A species-specific diagnosis and differentiation from related species (e.g., Taenia solium) is crucial for individual patient management and disease control programs. Diagnostic stool microscopy is limited by low sensitivity and does not allow discrimination between T. saginata and T. solium. Molecular diagnostic approaches are not routinely available outside research laboratories. Recently, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was proposed as a potentially suitable technique for species-specific helminth diagnosis. However, standardized protocols and commercial databases for parasite identification are currently unavailable, and pre-analytical factors have not yet been assessed. The purpose of this study was to employ MALDI-TOF MS for the identification of T. saginata proglottids obtained from a human patient, and to assess the effects of different sample storage media on the technique’s diagnostic accuracy. We generated T. saginata-specific main spectral profiles and added them to an in-house database for MALDI-TOF MS-based diagnosis of different helminths. Based on protein spectra, T. saginata proglottids could be successfully differentiated from other helminths, as well as bacteria and fungi. Additionally, we analyzed T. saginata proglottids stored in (i) LC–MS grade water; (ii) 0.45% sodium chloride; (iii) 70% ethanol; and (iv) 37% formalin after 2, 4, 6, 8, 12, and 24 weeks of storage. MALDITOF MS correctly identified 97.2–99.7% of samples stored in water, sodium chloride, and ethanol, with log-score values ≥2.5, thus indicating reliable species identification. In contrast, no protein spectra were obtained for samples stored in formalin. We conclude that MALDI-TOF-MS can be successfully employed for the identification of T. saginata, and that water, sodium chloride, and ethanol are equally effective storage solutions for prolonged periods of at least 24 weeks

Identification of Adult Fasciola spp. Using Matrix-Assisted Laser/Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry

Fascioliasis is a neglected trematode infection caused by Fasciola gigantica and Fasciola hepatica. Routine diagnosis of fascioliasis relies on macroscopic identification of adult worms in liver tissue of slaughtered animals, and microscopic detection of eggs in fecal samples of animals and humans. However, the diagnostic accuracy of morphological techniques and stool microscopy is low. Molecular diagnostics (e.g., polymerase chain reaction (PCR)) are more reliable, but these techniques are not routinely available in clinical microbiology laboratories. Matrix-assisted laser/desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) is a widely-used technique for identification of bacteria and fungi; yet, standardized protocols and databases for parasite detection need to be developed. The purpose of this study was to develop and validate an in-house database for Fasciola species-specific identification. To achieve this goal, the posterior parts of seven adult F. gigantica and one adult F. hepatica were processed and subjected to MALDI-TOF MS to create main spectra profiles (MSPs). Repeatability and reproducibility tests were performed to develop the database. A principal component analysis revealed significant differences between the spectra of F. gigantica and F. hepatica. Subsequently, 78 Fasciola samples were analyzed by MALDI-TOF MS using the previously developed database, out of which 98.7% (n = 74) and 100% (n = 3) were correctly identified as F. gigantica and F. hepatica, respectively. Log score values ranged between 1.73 and 2.23, thus indicating a reliable identification. We conclude that MALDI-TOF MS can provide species-specific identification of medically relevant liver flukes

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis

BACKGROUND We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research

Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE)

OBJECTIVES Comprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist. DESIGN Repeated cross sectional study. SETTING Swiss, German and Canadian research ethics committees (RECs). PARTICIPANTS RCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292). PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reported RESULTS: The median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%-79%) in 2012 to 77% (IQR, 68%-82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%-72%) in 2012 to 76% (IQR, 64%-83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%-80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship. CONCLUSIONS In 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of industry-sponsored protocols, which did not improve

The Effect of a Planetary Health Diet on the Human Gut Microbiome: A Descriptive Analysis

In 2019, researchers from the EAT-Lancet Commission developed the ‘Planetary Health (PH) diet’. Specifically, they provided recommendations pertaining to healthy diets derived from sustainable food systems. Thus far, it has not been analysed how such a diet affects the human intestinal microbiome, which is important for health and disease development. Here, we present longitudinal genome-wide metagenomic sequencing and mass spectrometry data on the gut microbiome of healthy volunteers adhering to the PH diet, as opposed to vegetarian or vegan (VV) and omnivorous (OV) diets. We obtained basic epidemiological information from 41 healthy volunteers and collected stool samples at inclusion and after 2, 4, and 12 weeks. Individuals opting to follow the PH diet received detailed instructions and recipes, whereas individuals in the control groups followed their habitual dietary pattern. Whole-genome DNA was extracted from stool specimens and subjected to shotgun metagenomic sequencing (~3 GB per patient). Conventional bacterial stool cultures were performed in parallel and bacterial species were identified with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. We analysed samples from 16 PH, 16 OV, and 9 VV diet patterns. The α-diversity remained relatively stable for all dietary groups. In the PH group, we observed a constant increase from 3.79% at inclusion to 4.9% after 12 weeks in relative abundance of Bifidobacterium adolescentis. Differential PH abundance analysis highlighted a non-significant increase in possible probiotics such as Paraprevotella xylaniphila and Bacteroides clarus. The highest abundance of these bacteria was observed in the VV group. Dietary modifications are associated with rapid alterations to the human gut microbiome, and the PH diet led to a slight increase in probiotic-associated bacteria at ≥4 weeks. Additional research is required to confirm these findings

Characteristics of the Skin Microbiome in Selected Dermatological Conditions: A Narrative Review

The skin is the largest and outermost organ of the human body. The microbial diversity of the skin can be influenced by several variable factors such as physiological state, lifestyle, and geographical locations. Recent years have seen increased interest in research aiming at an improved understanding of the relationship between the human microbiota and several diseases. Albeit understudied, interesting correlations between the skin microbiota and several dermatological conditions have been observed. Studies have shown that a decrease or increase in the abundance of certain microbial communities can be implicated in several dermatological pathologies. This narrative review (i) examines the role of the skin microbiota in the maintenance of skin homeostasis and health, (ii) provides examples on how some common skin diseases (acne inversa, candidiasis, psoriasis) are associated with the dysbiosis of microbial communities, and (iii) describes how recent research approaches used in skin microbiome studies may lead to improved, more sensitive diagnostics and individual therapeutics in the foreseeable future

Identification of Adult Fasciola spp. Using Matrix-Assisted Laser/Desorption Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry

Fascioliasis is a neglected trematode infection caused by Fasciola gigantica and Fasciola hepatica. Routine diagnosis of fascioliasis relies on macroscopic identification of adult worms in liver tissue of slaughtered animals, and microscopic detection of eggs in fecal samples of animals and humans. However, the diagnostic accuracy of morphological techniques and stool microscopy is low. Molecular diagnostics (e.g., polymerase chain reaction (PCR)) are more reliable, but these techniques are not routinely available in clinical microbiology laboratories. Matrix-assisted laser/desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) is a widely-used technique for identification of bacteria and fungi; yet, standardized protocols and databases for parasite detection need to be developed. The purpose of this study was to develop and validate an in-house database for Fasciola species-specific identification. To achieve this goal, the posterior parts of seven adult F. gigantica and one adult F. hepatica were processed and subjected to MALDI-TOF MS to create main spectra profiles (MSPs). Repeatability and reproducibility tests were performed to develop the database. A principal component analysis revealed significant differences between the spectra of F. gigantica and F. hepatica. Subsequently, 78 Fasciola samples were analyzed by MALDI-TOF MS using the previously developed database, out of which 98.7% (n = 74) and 100% (n = 3) were correctly identified as F. gigantica and F. hepatica, respectively. Log score values ranged between 1.73 and 2.23, thus indicating a reliable identification. We conclude that MALDI-TOF MS can provide species-specific identification of medically relevant liver flukes

Occurrence, resistance patterns, and management of carbapenemase-producing bacteria in war-wounded refugees from Ukraine

We analyzed consecutive clinical cases of infections due to carbapenemase-producing gram-negative bacteria detected in war-wounded patients from Ukraine who were treated at one university medical center in southwest Germany between June and December 2022. The isolates of multiresistant gram-negative bacteria were subjected to a thorough microbiological characterization and whole genome sequencing (WGS). We identified five war-wounded Ukrainian patients who developed infections with New Delhi metallo-β-lactamase 1-positive Klebsiella pneumoniae. Two isolates also carried OXA-48 carbapenemases. The bacteria were resistant to novel antibiotics, such as ceftazidime/avibactam and cefiderocol. The used treatment strategies included combinations of ceftazidime/avibactam + aztreonam, colistin, or tigecycline. WGS suggested transmission during primary care in Ukraine. We conclude that there is an urgent need for thorough surveillance of multiresistant pathogens in patients from war zones