Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

Attributes of Physical Activity and Gut Microbiome in Adults: A Systematic Review.

Growing evidence shows the contribution of physical activity interventions to the gut microbiome. However, specific physical activity characteristics that can modify the gut microbiome are unknown. This review's aim was to explore the contribution of physical activity intervention characteristics on human gut microbiome composition, in terms of diversity, specific bacterial groups, and associated gut microbiome metabolites. A literature search in PubMed; Cochrane Library; CINAHL-EBSCO; SCOPUS; Web of Science; ClinicalTrials.gov; PROSPERO; and ProQuest. Five studies met the inclusion criteria of a physical activity intervention duration of at least five weeks, with any description of the type or dose used. All included studies reported an endurance training; two studies used endurance and an additional muscle-strengthening training regimen. All studies reported using a dietary intervention control. Reported gut microbiome α-diversity changes were non-significant, ß-diversity changes were mixed (three studies reported an increase, two reported non-significant changes). All studies reported significant changes in the abundances of specific bacterial/archaea groups and bacteria-related metabolites following interventions. In conclusion, physical activity (regardless of specific characteristics) has significant contribution to gut microbiome composition and associated metabolites. There are no current recommendations for physical activity to promote gut microbiome composition. Future studies should focus on the contribution of current recommended physical activity dose to gut microbiome composition.

Microbiota Metabolite Profiles and Dietary Intake in Older Individuals with Insomnia of Short vs. Normal Sleep Duration.

Recent evidence suggests that the gut microbiota plays a role in insomnia pathogenesis. This study compared the dietary habits and microbiota metabolites of older adults with insomnia of short vs. normal sleep duration (ISSD and INSD, respectively). Data collection included sleep assessment through actigraphy, dietary analysis using the Food Frequency Questionnaire, and metabolomic profiling of stool samples. The results show that ISSD individuals had higher body mass index and a greater prevalence of hypertension. Significant dietary differences were observed, with the normal sleep group consuming more kilocalories per day and specific aromatic amino acids (AAAs) phenylalanine and tyrosine and branch-chain amino acid (BCAA) valine per protein content than the short sleep group. Moreover, metabolomic analysis identified elevated levels of the eight microbiota metabolites, benzophenone, pyrogallol, 5-aminopental, butyl acrylate, kojic acid, deoxycholic acid (DCA), trans-anethole, and 5-carboxyvanillic acid, in the short compared to the normal sleep group. The study contributes to the understanding of the potential role of dietary and microbial factors in insomnia, particularly in the context of sleep duration, and opens avenues for targeted dietary interventions and gut microbiota modulation as potential therapeutic approaches for treating insomnia.

A personalized diet intervention improves depression symptoms and changes microbiota and metabolite profiles among community-dwelling older adults.

Introduction: The impact of diet on mental well-being and gut microorganisms in humans is well recognized. However, research on the connections between food nutrients, gut microbiota, and mental health remains limited. To address this, the present study aimed to assess the effects of a personalized diet, based on individual needs and aligned with the Mediterranean diet principles, on depression symptoms, quality of life, nutritional intake, and gut microbiota changes among older adults living in the community. Methods: The intervention involved regular visits from a registered dietitian, who provided tailored dietary recommendations. During the 6-month study, participants completed questionnaires to evaluate their depression levels, quality of life, and dietary habits. Additionally, they provided stool samples for analysis of gut microbiota and metabolites. Results: The results demonstrated that the personalized dietary intervention reduced depression symptoms and improved the quality of life among older adults. Furthermore, significant changes in the intake of certain nutrients, such as folate, lutein, zeaxanthin, EPA, and DHA, were observed following the intervention. Moreover, the intervention was associated with increased diversity in the gut microbiome and reduced total short-chain fatty acids, the main metabolites produced by gut microorganisms. The study also revealed correlations between food nutrients, gut microbiota, and mental health parameters. Discussion: In conclusion, this research highlights the potential advantages of personalized dietary interventions in managing depression and enhancing overall well-being among older populations. It also sheds light on the role of gut microbiota and its metabolites in these effects. The findings offer valuable insights into the significance of nutrition and gut health for mental well-being in older adults.

Variation in Gut Microbiota Composition is Associated with Sleep Quality and Cognitive Performance in Older Adults with Insomnia.

Purpose: Insomnia, a chronic condition affecting 50% of older adults, is often accompanied by cognitive decline. The mechanism underlying this comorbidity is not fully understood. A growing literature suggests the importance of gut microbiota for brain function. We tested associations between sleep quality and cognitive performance with gut microbiota in older adults with insomnia. Patients and Methods: Seventy-two older adults with insomnia (age 73.2 ± 5.73 years, 56 females) provided stool samples for gut microbial sequencing. Microbiota profile was determined using the DADA2 bioinformatics pipeline. Cognition was assessed with the Cambridge Neuropsychological Test Automated Battery. Objective sleep quality was monitored by a two-week actigraphic recording, and participants completed the Insomnia Severity Index (ISI). We used partial canonical correspondence analysis (pCCA) to examine the relative contribution of insomnia, based on actigraphic sleep efficiency (SE) and ISI, and of cognitive status, based on the Multitasking test of Median Reaction Latency (MTTLMD) and the Spatial Working Memory Between Errors (SWMBE), to variance in microbiota composition. We used Pearson correlations to correlate insomnia and cognitive status parameters with microbiota amplicon sequence variants, genera, and families. Results: The pCCA revealed that sleep quality and cognitive performance explained a variation of 7.5-7.9% in gut microbiota composition in older adults with insomnia. Correlation analysis demonstrated that Lachnoclostridium (genus) correlates positively with SE (r=0.42; P=0.05) and negatively with MTTLMD (r=-0.29; P=0.03), whereas Blautia (genus) correlates negatively with MTTLMD (r=-0.31; P=0.01). Conclusion: Findings demonstrate the associations of sleep quality and cognitive performance with variance in gut microbiota composition and with specific genus abundance in older adults with insomnia. Further studies should validate the findings, determine causal relationships, and evaluate potential interventions for the comorbidity of insomnia and cognitive impairment in older adults with insomnia.

Increased physical activity improves gut microbiota composition and reduces short-chain fatty acid concentrations in older adults with insomnia.

Physical activity (PA) can improve functional abilities, well-being, and independence in older adults with insomnia. Studies have shown that PA may be linked to changes in the gut microbiota composition and its metabolites' concentrations. This association among older adults with insomnia, however, is yet to be determined. We explored the relationships between physical activity (PA) levels, gut microbiota composition, and short-chain fatty acid (SCFA) levels in this population. Forty-nine community-dwelling adults with insomnia symptoms, aged 65 and older, participated in this study. Their average daily step-count and sleep continuity measures over a two-week period were calculated based on Actigraphic recordings. Each participant provided fecal samples for the microbiome and SCFA analyses, anthropometric measures, and information via questionnaires on medical history and food consumption. The gut microbiota composition and SCFA concentrations were determined by next-generation sequencing and Gas chromatography-mass spectrometry, respectively. Participants were divided into two groups (more and less active) according to their median step/day count. We compared the microbiota abundance and SCFA concentrations between groups and performed correlation analysis between gut microbiota abundances and study variables. Different microbiota taxa in each PA group and increased SCFAs in feces of less active individuals were found. Changes in step counts were positively or negatively associated with the relative abundance of 19 ASVs, 3 microorganisms at the family level, and 11 microorganisms at the genus level. Furthermore, significant associations were discovered among physical activity, gut microbiota, SCFAs, and sleep parameters. Our findings provide new insights on the relationship between PA, gut microbiota composition, and primary metabolites in older adults with insomnia.

Associations between fecal short-chain fatty acids and sleep continuity in older adults with insomnia symptoms.

Insomnia is a disorder characterized by difficulty falling asleep and poor sleep continuity and is associated with increased risks for physical and cognitive decline. Insomnia with short sleep duration is considered the most biologically severe phenotype of the disorder. Evidence suggests that short-chain fatty acids (SCFAs), the main byproducts of fiber fermentation in the gut, may affect sleep via gut-brain communications. This study explores associations between SCFAs and sleep continuity and compares SCFA concentrations in short vs. normal sleep insomnia phenotypes in older adults. Fifty-nine participants with insomnia symptoms (≥ 65 years), completed 2 weeks of objective sleep monitoring (actigraphy), and were divided into short and normal sleep duration phenotypes via cluster analysis. Sleep measures included total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO). Stool samples were collected and fecal SCFA concentrations were determined by gas-chromatography-mass-spectrometry (GCMS). Higher concentrations of acetate, butyrate, and propionate, and total SCFAs, were associated with lower SE and longer SOL after controlling for Body Mass Index (BMI). Concentrations were higher in the short sleep duration phenotype. Age, BMI, TST, and SOL explained 40.7% of the variance in total SCFAs. Findings contribute to understanding pathways along the gut-brain axis and may lead to the use of SCFAs as biomarkers of insomnia phenotypes.

Microbial signature in IgE-mediated food allergies.

BACKGROUND: Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. METHODS: To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). RESULTS: The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and ß-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. CONCLUSIONS: Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

In-vivo oxidized albumin- a pro-inflammatory agent in hypoalbuminemia.

Hypoalbuminemia of Hemodialysis (HD) patients is an independent cardiovascular risk factor, however, there is no mechanistic explanation between hypoalbuminemia and vascular injury. In the event of oxidative stress and inflammation to which HD patients are exposed, albumin is oxidized and undetected by common laboratory methods, rendering an apparent hypoalbuminemia. We wanted to show that these circulating modified oxidized albumin molecules cause direct vascular damage, mediating inflammation. Once these in-vivo albumin modifications were reduced in- vitro, the apparent hypoalbuminemia concomitantly with its inflammatory effects, were eliminated. Albumin modification profiles from 14 healthy controls (HC) and 14 HD patients were obtained by mass spectrometry (MS) analyses before and after reduction in- vitro, using redox agent 1,4 dithiothreitol (DTT). Their inflammatory effects were explored by exposing human umbilical endothelial cells (HUVEC) to all these forms of albumin. Albumin separated from hypoalbuminemic HD patients increased endothelial mRNA expression of cytokines and adhesion molecules, and augmented secretion of IL-6. This endothelial inflammatory state was almost fully reverted by exposing HUVEC to the in-vitro reduced HD albumin. MS profile of albumin modifications peaks was similar between HD and HC, but the intensities of the various peaks were significantly different. Abolishing the reversible oxidative modifications by DTT prevented endothelial injury and increased albumin levels. The irreversible modifications such as glycation and sulfonation show low intensities in HD albumin profiles and are nearly unobserved in HC. We showed, for the first time, a mechanistic link between hypoalbuminemia and the pro-inflammatory properties of in-vivo oxidized albumin, initiating vascular injury.

Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation.

SCOPE: Hyperglycemia is associated with oxidative stress, which accelerates cardiovascular complications. This study investigates the potential of glabridin to regulate paraoxonase 2 (PON2) levels, in vivo, and explores the glabridin protective effect on PON2 through tryptophan-fluorescence quenching and mass spectrometry. METHODS AND RESULTS: Adult mouse offspring of saturated fatty acids fed mothers, which developed hyperglycemia after exposure to a high fat diet in their adult life, had lower levels of heart PON2 mRNA and protein expression than did the control mice (64 and 26%, respectively). Glabridin supplementation significantly upregulated PON2 mRNA and protein expression in the liver (2.1-fold and 2.6-fold, respectively) and heart (2.5-fold and 1.6-fold, respectively) in these mice. In vitro studies demonstrated that the fluorescence quenching of PON2 by glabridin was a result of the formation of a glabridin-PON2 interaction. The binding constant (7.61 × 10(5) M(-1) ) and the ΔG (-33.55kJ/mol) indicated that this interaction was driven by a hydrophobic force, which confers protection against CuSO4 -induced PON2 oxidation. CONCLUSION: Such results indicate that glabridin preserves the anti-atherogenic abilities of PON2 by maintaining its levels, in vivo. The glabridin-PON2 interaction may be the mechanism by which glabridin protects PON2 from oxidation, thus contributing to the protection of PON2 activity in hyperglycemia.