Serum zonulin measured by enzyme-linked immunosorbent assay may not be a reliable marker of small intestinal permeability in healthy adults

The association between intestinal permeability (IP) and body composition remains unclear. The gold standard differential sugar-absorption test is arduous to complete, with zonulin being increasingly used as an independent biomarker of IP. This pilot study aimed to explore the association between small IP, zonulin concentrations and body composition in healthy adults. The urinary lactulose-rhamnose ratio was used to measure small IP. Serum zonulin, lipopolysaccharide (LPS) and high-sensitivity C-reactive protein (hs-CRP) were analyzed in serum. Body composition was measured using dual-energy X-ray absorptiometry and anthropometric measurements were collected. In total, 34 participants were included (12 males, median age 28 years, body mass index 24kg/m2, waist circumference 77cm). No correlation was observed between the lactulose-rhamnose ratio and zonulin (r -0.016, p 0.929). The lactulose-rhamnose ratio displayed a strong positive correlation with LPS (n 22, r 0.536, p 0.018) but did not correlate with body composition measures. Conversely, zonulin displayed a moderate positive correlation with waist circumference (r 0.437, p 0.042) in female participants and hs-CRP (r 0.485, p 0.004) in all participants. These findings raise important considerations for the measurement of small IP, warranting exploration in larger powered studies that address the limitations of the present study

Current and future perspectives on the structural identification of small molecules in biological systems

Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as "statistically significant" in the study. Such metabolic "dark matter" means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function

Current and future perspectives on the structural identification of small molecules in biological systems

Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as "statistically significant" in the study. Such metabolic "dark matter" means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function

Use of a sensitive multisugar test for measuring segmental intestinal permeability in critically ill, mechanically ventilated adults: A pilot study

BACKGROUND: Increased intestinal permeability (IP) is associated with sepsis in the intensive care unit (ICU). This study aimed to pilot a sensitive multisugar test to measure IP in the nonfasted state. METHODS: Critically ill, mechanically ventilated adults were recruited from 2 ICUs in Australia. Measurements were completed within 3 days of admission using a multisugar test measuring gastroduodenal (sucrose recovery), small-bowel (lactulose-rhamnose [L-R] and lactulose-mannitol [L-M] ratios), and whole-gut permeability (sucralose-erythritol ratio) in 24-hour urine samples. Urinary sugar concentrations were compared at baseline and after sugar ingestion, and IP sugar recoveries and ratios were explored in relation to known confounders, including renal function. RESULTS: Twenty-one critically ill patients (12 males; median, 57 years) participated. Group median concentrations of all sugars were higher following sugar administration; however, sucrose and mannitol increases were not statistically significant. Within individual patients, sucrose and mannitol concentrations were higher in baseline than after sugar ingestion in 9 (43%) and 4 (19%) patients, respectively. Patients with impaired (n = 9) vs normal (n = 12) renal function had a higher L-R ratio (median, 0.130 vs 0.047; P = .003), lower rhamnose recovery (median, 15% vs 24%; P = .007), and no difference in lactulose recovery. CONCLUSION: Small-bowel and whole-gut permeability measurements are possible to complete in the nonfasted state, whereas gastroduodenal permeability could not be measured reliably. For small-bowel IP measurements, the L-R ratio is preferred over the L-M ratio. Alterations in renal function may reduce the reliability of the multisugar IP test, warranting further exploration

Current and future perspectives on the structural identification of small molecules in biological systems

Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as “statistically significant” in the study. Such metabolic “dark matter” means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function

Identifying and responding to depression in adolescents in primary care: A quality improvement response

The American Academy of Pediatrics (AAP) recommends adolescent depression screening and subsequent follow-up for those scoring at-risk. The current study assessed the outcomes of a Quality Improvement (QI) project that implemented these guidelines during annual well-child visits in a network of pediatric practices. This project used a two-stage screening process. First, adolescents were screened with the Pediatric Symptom Checklist (PSC-17). Second, adolescents who screened at-risk on the PSC-17 were asked to complete the Patient Health Questionnaire (PHQ-9). QI-participating providers received training on how to categorize the severity of their patient’s depression based on PHQ-9 cut-off scores and clinical interview, and to implement and document appropriate options for follow-up. Patients in the QI group were significantly more likely to be screened with both the PSC-17 (93.8% vs. 89.1%, p &lt; .001) and the PHQ-9 (54.8% vs. 16.4%, p &lt; .001) compared to those in the non-QI group. Of the 80 adolescents in the QI group at-risk on the PSC-17 and with a completed PHQ-9, 65 (81.3%) received at least one type of referral for mental health, ranging from behavioral health services to lifestyle interventions. Findings support the feasibility of adolescent depression screening and referrals within pediatric primary care. </jats:p