Oxidative Stress Biomarkers in Predictive Multi-Class Modeling of Depression Severity with Diabetes Mellitus, Cardiovascular Disease and Hypertension Comorbidity.

In this study, depression severity was defined by the Patient Health Questionnaire (PHQ-9) and five machine learning algorithms were applied to classify depression severity in the presence of diabetes mellitus (DM), cardiovascular disease (CVD), and hypertension (HT) utilizing oxidative stress (OS) biomarkers (8-isoprostane, 8-hydroxydeoxyguanosine, reduced glutathione and oxidized glutathione), demographic details, and medication for eight hundred and thirty participants. The results show that the Random Forest (RF) outperformed other classifiers with the highest accuracy of 92% in a 4-class depression classification when considering all OS biomarkers along with DM, CVD and HT. RF also achieved the highest accuracy of 91% in 3-class classification when studying depression in presence of DM only and an accuracy of 88% and 87% in 5-class classification when investigating depression with CVD and HT, respectively. Moreover, RF performed best in the 3-class depression model with an accuracy of 85% when examining depression severity in the presence of OS biomarkers only. Our findings suggest that depression severity can be accurately identified with RF as a base classifier and that OS is a major contributor to depression severity in the presence of comorbidities. Biomarker analysis can supplement DSM-5-based diagnostics as part of personalized medicine and especially as point of care testing has become available for many of the given OS biomarkers.Clinical Relevance- Depression is the most common form of psychiatric disorder that has an oxidative stress etiology. Current diagnosis relies primarily on the Diagnostic and Statistical Manual for Mental Disorders (DSM-5), which may be too general and not informative for optimal multi-comorbidity diagnostics and treatment. Understanding the role of oxidative stress associated with depression can provide additional information for timely detection, comprehensive assessment, and appropriate intervention of depression illness.

Increased Relative Abundance of Ruminoccocus Is Associated With Reduced Cardiovascular Risk in an Obese Population.

Background: Obesity is a complex disease with underlying genetic, environmental, psychological, physiological, medical, and epigenetic factors. Obesity can cause various disorders, including cardiovascular diseases (CVDs), that are among the most prevalent chronic conditions in Qatar. Recent studies have highlighted the significant roles of the gut microbiome in improving the pathology of various diseases, including obesity. Thus, in this study, we aimed to investigate the effects of dietary intake and gut microbial composition in modulating the risk of CVD development in obese Qatari adults. Methods: We enrolled 46 adult subjects (18-65 years of age) who were classified based on their CVD risk scores, calculated using the Framingham formula, into a CVD no-risk group (score of <10%, n = 36) and CVD risk group (score of ≥10%, n = 10). For each study subject, we measured the gut microbial composition with a 16s rDNA sequencing method that targeted the v3-v4 region using Illumina Miseq, and their nutritional status was recorded based on 24-h dietary recall. Dietary intake, bacterial taxa summary, diversity index, microbial markers, pathway analysis, and network correlation were determined for the study subjects. Results: The CVD risk group showed a lower intake of vitamin D, reduced relative abundance of genera Ruminococcus and Bifidobacterium, no change in bacterial diversity, and higher levels of taurine, hypotaurine, and lipoic acid metabolism than the CVD no-risk group. Besides, the relative abundance of genus Ruminococcus was positively correlated with the intake of protein, monounsaturated fat, vitamin A, and vitamin D. Conclusion: Taken together, our results suggest that the genus Ruminococcus could be used as a microbial marker, and its reduced relative abundance could mediate the risk of CVDs in the Obese Qatari population.

Personalized Nutrition Approach in Pregnancy and Early Life to Tackle Childhood and Adult Non-Communicable Diseases.

The development of childhood and adult non-communicable diseases (NCD) is associated with environmental factors, starting from intrauterine life. A new theory finds the roots of epigenetic programming in parental gametogenesis, continuing during embryo development, fetal life, and finally in post-natal life. Maternal health status and poor nutrition are widely recognized as implications in the onset of childhood and adult diseases. Early nutrition, particularly breastfeeding, also plays a primary role in affecting the health status of an individual later in life. A poor maternal diet during pregnancy and lack of breastfeeding can cause a nutrient deficiency that affects the gut microbiota, and acts as a cofactor for many pathways, impacting the epigenetic controls and transcription of genes involved in the metabolism, angiogenesis, and other pathways, leading to NCDs in adult life. Both maternal and fetal genetic backgrounds also affect nutrient adsorption and functioning at the cellular level. This review discusses the most recent evidence on maternal nutrition and breastfeeding in the development of NCD, the potentiality of the omics technologies in uncovering the molecular mechanisms underlying it, with the future prospective of applying a personalized nutrition approach to prevent and treat NCD from the beginning of fetal life.

Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus.

Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe.

Nutri-epigenetics: the effect of maternal diet and early nutrition on the pathogenesis of autoimmune diseases.

Autoimmune diseases comprise a wide group of diseases involving a self-response of the immune system against the host. The etiopathogenesis is very complex involving disease-specific factors but also environmental factors, among which the diet. Maternal diet during pregnancy as well as early nutrition recently attracted the interest of the scientists as contributing to the immune programming. In this paper, we reviewed the most recent literature on the effect of maternal diet and early nutrition in modulating the immune system in a selected subset of autoimmune diseases: type 1 diabetes, celiac disease, inflammatory bowel disease, juvenile idiopathic arthritis and rheumatoid arthritis. Particularly, we focused our narrative on the role of maternal and perinatal nutrition in the epigenetic mechanisms underlying the auto-immune response. Maternal diet during pregnancy as well as breastfeeding and early nutrition play a big role in many epigenetic mechanisms. Most of the nutrients consumed by the mother and the infant are known exerting epigenetic functions, such as folate, methionine, zinc, vitamins B12 and D, fibers, casein and gliadin, and they were linked to gene expression changes in the immune pathways. Despite the common role of maternal diet, breastfeeding and early nutrition in almost all the autoimmune diseases, each disease seems to have specific diet-driver epigenetic mechanisms that require further investigations. The research in this field is opening new routes to establishing a precision nutrition approach to the auto-immune diseases.

Akkermansia, a Possible Microbial Marker for Poor Glycemic Control in Qataris Children Consuming Arabic Diet-A Pilot Study on Pediatric T1DM in Qatar.

In Qatar, Type 1 Diabetes mellitus (T1DM) is one of the most prevalent disorders. This study aimed to explore the gut microbiome's relation to the continuous subcutaneous insulin infusion (CSII) therapy, dietary habits, and the HbA1c level in the pediatric T1DM subjects in Qatar. We recruited 28 T1DM subjects with an average age of 10.5 ± 3.53 years. The stool sample was used to measure microbial composition by 16s rDNA sequencing method. The results have revealed that the subjects who had undergone CSII therapy had increased microbial diversity and genus Akkermansia was significantly enriched in the subjects without CSII therapy. Moreover, genus Akkermansia was higher in the subjects with poor glycemic control (HbA1c > 7.5%). When we classified the subjects based on dietary patterns and nationality, Akkermansia was significantly enriched in Qataris subjects without the CSII therapy consuming Arabic diet than expatriates living in Qatar and eating a Western/mixed diet. Thus, this pilot study showed that abundance of Akkermansia is dependent on the Arabic diet only in poorly controlled Qataris T1DM patients, opening new routes to personalized treatment for T1DM in Qataris pediatric subjects. Further comprehensive studies on the relation between the Arabic diet, ethnicity, and Akkermansia are warranted to confirm this preliminary finding.