A data browsing application for accessing gene and module-level blood transcriptome profiles of healthy pregnant women from high- and low-resource settings.

Transcriptome profiling data, generated via RNA sequencing, are commonly deposited in public repositories. However, these data may not be easily accessible or usable by many researchers. To enhance data reuse, we present well-annotated, partially analyzed data via a user-friendly web application. This project involved transcriptome profiling of blood samples from 15 healthy pregnant women in a low-resource setting, taken at 6 consecutive time points beginning from the first trimester. Additional blood transcriptome profiles were retrieved from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) public repository, representing a cohort of healthy pregnant women from a high-resource setting. We analyzed these datasets using the fixed BloodGen3 module repertoire. We deployed a web application, accessible at https://thejacksonlaboratory.shinyapps.io/BloodGen3_Pregnancy/which displays the module-level analysis results from both original and public pregnancy blood transcriptome datasets. Users can create custom fingerprint grid and heatmap representations via various navigation options, useful for reports and manuscript preparation. The web application serves as a standalone resource for exploring blood transcript abundance changes during pregnancy. Alternatively, users can integrate it with similar applications developed for earlier publications to analyze transcript abundance changes of a given BloodGen3 signature across a range of disease cohorts. Database URL: https://thejacksonlaboratory.shinyapps.io/BloodGen3_Pregnancy/.

Design of a targeted blood transcriptional panel for monitoring immunological changes accompanying pregnancy.

Background: Immunomodulatory processes exert steering functions throughout pregnancy. Detecting diversions from this physiologic immune clock may help identify pregnant women at risk for pregnancy-associated complications. We present results from a data-driven selection process to develop a targeted panel of mRNAs that may prove effective in detecting pregnancies diverting from the norm. Methods: Based on a de novo dataset from a resource-constrained setting and a dataset from a resource-rich area readily available in the public domain, whole blood gene expression profiles of uneventful pregnancies were captured at multiple time points during pregnancy. BloodGen3, a fixed blood transcriptional module repertoire, was employed to analyze and visualize gene expression patterns in the two datasets. Differentially expressed genes were identified by comparing their abundance to non-pregnant postpartum controls. The selection process for a targeted gene panel considered (i) transcript abundance in whole blood; (ii) degree of correlation with the BloodGen3 module; and (iii) pregnancy biology. Results: We identified 176 transcripts that were complemented with eight housekeeping genes. Changes in transcript abundance were seen in the early stages of pregnancy and similar patterns were observed in both datasets. Functional gene annotation suggested significant changes in the lymphoid, prostaglandin and inflammation-associated compartments, when compared to the postpartum controls. Conclusion: The gene panel presented here holds promise for the development of predictive, targeted, transcriptional profiling assays. Such assays might become useful for monitoring of pregnant women, specifically to detect potential adverse events early. Prospective validation of this targeted assay, in-depth investigation of functional annotations of differentially expressed genes, and assessment of common pregnancy-associated complications with the aim to identify these early in pregnancy to improve pregnancy outcomes are the next steps.

Unveiling the dynamics of the breast milk microbiome: impact of lactation stage and gestational age.

BACKGROUND: Breast milk (BM) provides complete nutrition for infants for the first six months of life and is essential for the development of the newborn's immature immune and digestive systems. While BM was conventionally believed to be sterile, recent advanced high throughput technologies have unveiled the presence of diverse microbial communities in BM. These insights into the BM microbiota have mainly originated from uncomplicated pregnancies, possibly not reflecting the circumstances of mothers with pregnancy complications like preterm birth (PTB). METHODS: In this article, we investigated the BM microbial communities in mothers with preterm deliveries (before 37 weeks of gestation). We compared these samples with BM samples from healthy term pregnancies across different lactation stages (colostrum, transitional and mature milk) using 16S rRNA gene sequencing. RESULTS: Our analysis revealed that the microbial communities became increasingly diverse and compositionally distinct as the BM matured. Specifically, mature BM samples were significantly enriched in Veillonella and lactobacillus (Kruskal Wallis; p < 0.001) compared to colostrum. The comparison of term and preterm BM samples showed that the community structure was significantly different between the two groups (Bray Curtis and unweighted unifrac dissimilarity; p < 0.001). Preterm BM samples exhibited increased species richness with significantly higher abundance of Staphylococcus haemolyticus, Propionibacterium acnes, unclassified Corynebacterium species. Whereas term samples were enriched in Staphylococcus epidermidis, unclassified OD1, and unclassified Veillonella among others. CONCLUSION: Our study underscores the significant influence of pregnancy-related complications, such as preterm birth (before 37 weeks of gestation), on the composition and diversity of BM microbiota. Given the established significance of the maternal microbiome in shaping child health outcomes, this investigation paves the way for identifying modifiable factors that could optimize the composition of BM microbiota, thereby promoting maternal and infant health.

The Era of Precision Nutrition in the Field of Reproductive Health and Pregnancy.

When it comes to reproductive health, various lifestyle habits can act as major contributors to either an optimized or worsened scenario of female and male fertility [...].

The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease.

Acute graft-versus-host disease (aGVHD) is a severe side effect of allogeneic hematopoietic stem cell transplantation (aHSCT) that has complex phenotypes and often unpredictable outcomes. The current management is not always able to prevent aGVHD. A neglected actor in the management of aGVHD is the gut microbiota. Gut microbiota dysbiosis after aHSCT is caused by many factors and may contribute to the development of aGVHD. Diet and nutritional status modify the gut microbiota and a wide range of products are now available to manipulate the gut microbiota (pro-, pre-, and postbiotics). New investigations are testing the effect of probiotics and nutritional supplements in both animal models and human studies, with encouraging results. In this review, we summarize the most recent literature about the probiotics and nutritional factors able to modulate the gut microbiota and we discuss the future perspective in developing new integrative therapeutic approaches to reducing the risk of graft-versus-host disease in patients undergoing aHSCT.

Modulation of gut microbiota: The effects of a fruits and vegetables supplement.

The consumption of an optimal amount of fruits and vegetables is known to improve physical fitness and physiological body functions. Healthy eating habits, including intake of fruits and vegetables, can modify gut microbiota. This study aimed to demonstrate the effectiveness of a formulated fruit and vegetable supplement (FVS) in modulating the antioxidant capacity and the gut microbiota composition. We enrolled 30 healthy volunteer subjects, matched for age, gender, BMI, and smoking habits, and randomized them into the FVS and the placebo (PLA) groups. Among the serum vitamins, the folic acid level was significantly higher (p = 0.001) in the FVS group than in the PLA group, whereas the vitamin B2 level was significantly higher in the PLA group than in the FVS group (p = 0.028). The antioxidant capacity, measured by using the oxygen radical absorbance capacity (ORAC) method, was also slightly higher in the FVS group than in the PLA group but did not reach statistical significance. The dietary intake, assessed by 24-h recalls, did not show any significant changes after the supplementation in both the groups. The gut microbiome composition, measured by 16S rDNA sequencing, showed no difference in both alpha and beta diversities, whereas the LEfse analysis revealed a microbial shift after the treatment, with a decreased abundance of the genus Ruminococcus from the Lachnospiraceae family (p = 0.009), and the unclassified genus from the family Erysipelotrichaceae (UC36, p = 0.003) in the FVS group compared with the PLA group (confirmed by SIAMCAT analysis, AUC = 74.1%). With a minor effect, the genus Faecalibacterium and unclassified genus and family from the order Lactobacillales (UC31) were also increased in the FVS group compared with the PLA group (p = 0.0474, p = 0.0352, respectively). SCFA measurement by gas chromatography-mass spectrometry showed an increased level of 2-methylbutyrate in the FVS group compared with the PLA group (p = 0.0385). Finally, the Spearman correlation analysis showed that in the FVS group, the genus Faecalibacterium positively correlated with 2-methyl butyrate (p = 0.040). In the PLA group, none of the significant bacteria correlated with either SCFA or serum biomarkers. The network analysis confirmed the positive correlation between genus Faecalibacterium and 2-methyl butyrate. We can conclude that the FVS in healthy individuals modified the gut microbiota composition and metabolites, and it can potentially contribute to reduce the pro-inflammatory response along with the antioxidant capacity.

The potential impact of a probiotic: Akkermansia muciniphila in the regulation of blood pressure-the current facts and evidence.

Akkermansia muciniphila (A. muciniphila) is present in the human gut microbiota from infancy and gradually increases in adulthood. The potential impact of the abundance of A. muciniphila has been studied in major cardiovascular diseases including elevated blood pressure or hypertension (HTN). HTN is a major factor in premature death worldwide, and approximately 1.28 billion adults aged 30-79 years have hypertension. A. muciniphila is being considered a next-generation probiotic and though numerous studies had highlighted the positive role of A. muciniphila in lowering/controlling the HTN, however, few studies had highlighted the negative impact of increased abundance of A. muciniphila in the management of HTN. Thus, in the review, we aimed to discuss the current facts, evidence, and controversy about the role of A. muciniphila in the pathophysiology of HTN and its potential effect on HTN management/regulation, which could be beneficial in identifying the drug target for the management of HTN.

Female infertility and diet, is there a role for a personalized nutritional approach in assisted reproductive technologies? A Narrative Review.

Female infertility is a major public health concern and a global challenge. It is a disorder of the reproductive system, defined as the inability to achieve a clinical pregnancy. Nutrition and other environmental factors are found to impact reproductive health in women as well as the outcome of assisted reproductive technologies (ART). Dietary factors, such as polyunsaturated fatty acids (PUFA), fiber as well as the intake of Mediterranean diet appear to exert beneficial effects on female reproductive outcomes. The exact mechanisms associating diet to female fertility are yet to be identified, although genomic, epigenomic, and microbial pathways may be implicated. This review aims to summarize the current knowledge on the impact of dietary components on female reproduction and ART outcomes, and to discuss the relevant interplay of diet with genome, epigenome and microbial composition.

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.

Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement.

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two established markers of skin- and gut aGvHD. The discovery cohort (n = 39) revealed that at the time of diagnosis, plasma KRT20 showed a progressive decrease from unaffected individuals to patients with single-, and patients with multi-organ aGvHD. KRT20 was affected by cutaneous (p = 0.0263) and gastrointestinal aGvHD (p = 0.0242) independently and in an additive manner. Sensitivity and specificity of KRT20 for aGvHD involving both target organs (AUC = 0.852) were comparable to that of PI3 for skin-aGvHD (AUC = 0.708) or that of REG3A for gut-aGvHD (AUC = 0.855). Patient follow-up in the validation cohort (n = 67) corroborated these observations (p < 0.001), and linked low KRT20 to grade 2+ disease (p < 0.001), but failed to confirm low KRT20 as an independent risk factor. These data established a link between low plasma KRT20 levels and moderate to severe aGvHD involving multiple target organs.

Microbiota medicine: towards clinical revolution.

The human gastrointestinal tract is inhabited by the largest microbial community within the human body consisting of trillions of microbes called gut microbiota. The normal flora is the site of many physiological functions such as enhancing the host immunity, participating in the nutrient absorption and protecting the body against pathogenic microorganisms. Numerous investigations showed a bidirectional interplay between gut microbiota and many organs within the human body such as the intestines, the lungs, the brain, and the skin. Large body of evidence demonstrated, more than a decade ago, that the gut microbial alteration is a key factor in the pathogenesis of many local and systemic disorders. In this regard, a deep understanding of the mechanisms involved in the gut microbial symbiosis/dysbiosis is crucial for the clinical and health field. We review the most recent studies on the involvement of gut microbiota in the pathogenesis of many diseases. We also elaborate the different strategies used to manipulate the gut microbiota in the prevention and treatment of disorders. The future of medicine is strongly related to the quality of our microbiota. Targeting microbiota dysbiosis will be a huge challenge.

Risk factor-based screening compared to universal screening for gestational diabetes mellitus in marginalized Burman and Karen populations on the Thailand-Myanmar border: An observational cohort.

Background: Gestational diabetes mellitus (GDM) contributes to maternal and neonatal morbidity. As data from marginalized populations remains scarce, this study compares risk-factor-based to universal GDM screening in a low resource setting. Methods: This is a secondary analysis of data from a prospective preterm birth cohort. Pregnant women were enrolled in the first trimester and completed a 75g oral glucose tolerance test (OGTT) at 24-32 weeks' gestation. To define GDM cases, Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO trial) criteria were used. All GDM positive cases were treated. Sensitivity and specificity of risk-factor-based selection for screening (criteria: age ≥30y, obesity (Body mass index (BMI) ≥27.5kg/m 2), previous GDM, 1 st degree relative with diabetes, previous macrosomia (≥4kg), previous stillbirth, or symphysis-fundal height ≥90th percentile) was compared to universal screening using the OGTT as the gold standard. Adverse maternal and neonatal outcomes were compared by GDM status. Results: GDM prevalence was 13.4% (50/374) (95% CI: 10.3-17.2). Three quarters of women had at least one risk factor (n=271 women), with 37/50 OGTT positive cases correctly identified: sensitivity 74.0% (59.7-85.4) and specificity 27.8% (3.0-33.0). Burman women (self-identified) accounted for 29.1% of the cohort population, but 38.0% of GDM cases. Percentiles for birthweight (p=0.004), head circumference (p=0.002), and weight-length ratio (p=0.030) were higher in newborns of GDM positive compared with non-GDM mothers. 21.7% (75/346) of newborns in the cohort were small-for-gestational age (≤10 th percentile). In Burman women, overweight/obese BMI was associated with a significantly increased adjusted odds ratio 5.03 (95% CI: 1.43-17.64) for GDM compared with normal weight, whereas in Karen women, the trend in association was similar but not significant (OR 2.36; 95% CI 0.95-5.89). Conclusions: Risk-factor-based screening missed one in four GDM positive women. Considering the benefits of early detection of GDM and the limited additional cost of universal screening, a two-step screening program was implemented.

Can the Salivary Microbiome Predict Cardiovascular Diseases? Lessons Learned From the Qatari Population.

Background: Many studies have linked dysbiosis of the gut microbiome to the development of cardiovascular diseases (CVD). However, studies assessing the association between the salivary microbiome and CVD risk on a large cohort remain sparse. This study aims to identify whether a predictive salivary microbiome signature is associated with a high risk of developing CVD in the Qatari population. Methods: Saliva samples from 2,974 Qatar Genome Project (QGP) participants were collected from Qatar Biobank (QBB). Based on the CVD score, subjects were classified into low-risk (LR < 10) (n = 2491), moderate-risk (MR = 10-20) (n = 320) and high-risk (HR > 30) (n = 163). To assess the salivary microbiome (SM) composition, 16S-rDNA libraries were sequenced and analyzed using QIIME-pipeline. Machine Learning (ML) strategies were used to identify SM-based predictors of CVD risk. Results: Firmicutes and Bacteroidetes were the predominant phyla among all the subjects included. Linear Discriminant Analysis Effect Size (LEfSe) analysis revealed that Clostridiaceae and Capnocytophaga were the most significantly abundant genera in the LR group, while Lactobacillus and Rothia were significantly abundant in the HR group. ML based prediction models revealed that Desulfobulbus, Prevotella, and Tissierellaceae were the common predictors of increased risk to CVD. Conclusion: This study identified significant differences in the SM composition in HR and LR CVD subjects. This is the first study to apply ML-based prediction modeling using the SM to predict CVD in an Arab population. More studies are required to better understand the mechanisms of how those microbes contribute to CVD.

Omouma: a prospective mother and child cohort aiming to identify early biomarkers of pregnancy complications in women living in Qatar.

BACKGROUND: Pregnancy is governed by multiple molecular and cellular processes, which might influence pregnancy health and outcomes. Failure to predict and understand the cause of pregnancy complications, adverse pregnancy outcomes, infant's morbidity and mortality, have limited effective interventions. Integrative multi-omics technologies provide an unbiased platform to explore the complex molecular interactions with an unprecedented depth. The objective of the present protocol is to build a longitudinal mother-baby cohort and use multi-omics technologies to help identify predictive biomarkers of adverse pregnancy outcomes, early life determinants and their effect on child health. METHODS/DESIGN: One thousand pregnant women with a viable pregnancy in the first trimester (6-14 weeks of gestation) will be recruited from Sidra Medicine hospital. All the study participants will be monitored every trimester, at delivery, and one-year post-partum. Serial high-frequency sampling, including blood, stool, urine, saliva, skin, and vaginal swabs (mother only) from the pregnant women and their babies, will be collected. Maternal and neonatal health, including mental health and perinatal growth, will be recorded using a combination of questionnaires, interviews, and medical records. Downstream sample processing including microbial profiling, vaginal immune response, blood transcriptomics, epigenomics, and metabolomics will be performed. DISCUSSION: It is expected that the present study will provide valuable insights into predicting pregnancy complications and neonatal health outcomes. Those include whether specific microbial and/or epigenomics signatures, immune profiles are associated with a healthy pregnancy and/or complicated pregnancy and poor neonatal health outcome. Moreover, this non-interventional cohort will also serve as a baseline dataset to understand how familial, socioeconomic, environmental and lifestyle factors interact with genetic determinants to influence health outcomes later in life. These findings will hold promise for the diagnosis and precision-medicine interventions.

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.