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Nizam, R.

Publications and source records attributed to Nizam, R..

3 recordsLinked to original sources

Comparative Machine Learning Analysis of Saliva and Plaque Microbiomes in Children with Type 1 Diabetes

BackgroundType 1 diabetes (T1D) is associated with microbial dysbiosis. While most research has focused on the gut microbiome, limited data address the role of the oral microbiome in T1D. The oral and gut microbiomes overlap substantially, and the oral cavity may influence the gut microbial composition. Saliva and dental plaque represent two distinct oral niches with unique microbial communities, but it remains unclear which better reflects systemic disease states such as T1D. This study compared the performance of salivary and plaque microbiomes in classifying pediatric T1D status. MethodsPaired saliva and plaque samples were collected from 46 children (23 with T1D and 23 healthy controls). Microbial DNA was extracted and sequenced to target the 16S rRNA gene. The data were processed via QIIME 2 for taxonomic classification and centered log-ratio transformation. Alpha diversity, microbial abundance, and clustering analyses were performed to compare the oral microbiome between the T1D and control groups. Random forest classifiers were used to evaluate and compare the predictive accuracy of saliva- and plaque-based models, both with and without clinical metadata. ResultsSaliva samples presented lower alpha diversity than plaque samples did but presented significantly greater bacterial loads and total microbial abundances. Saliva-based models outperformed plaque-based models, achieving a classification accuracy of 94.2% with or without clinical metadata, compared with 73.3% accuracy for plaque-based models. ROC curve analysis further supported this difference, with saliva models reaching an AUC of approximately 0.94 versus 0.75 for plaque, indicating superior discriminative performance. UMAP clustering revealed more distinct separation of the T1D and control groups in terms of the salivary profiles than in the plaque profiles. Feature importance analysis revealed both unique and shared taxa predictive of T1D in each niche. The incorporation of clinical and demographic metadata did not enhance model performance, underscoring the robustness and predictive strength of microbiome data alone. ConclusionThe salivary microbiome is a more effective biospecimen than dental plaque for detecting T1D-associated microbial profiles in children. It offers superior classification accuracy and greater sensitivity in distinguishing T1D status, supporting salivas potential as a noninvasive, scalable medium for future microbiome-based monitoring.

microbiology↗

Glucose intolerance induces anxiety-like behaviors independent of obesity and insulin resistance in a novel model of nutritional metabolic stress

Type 2 diabetes (T2D) and its comorbidities are a major public health concern. In addition to peripheral tissues, T2D also impacts the central nervous system leading to neurocognitive impairments, including memory deficits, anxiety, and depression. The metabolic determinants of these neurocognitive impairments remain unidentified. Here, we used a novel proprietary high-fat diet, in which glucose intolerance precedes weight gain, to decipher the metabolic determinants of neurocognitive affects. We show that this model exhibits anxiety-like behaviors, without eliciting depression nor recognition memory deficits. Long-term feeding leads to weight gain, brain glucose hypometabolism and impaired recognition memory alongside the early onset anxiety-like behavior. Using an established genetic model of T2D (db/db) and of diet-induced obesity we show that additional insulin resistance and obesity are associated with depressive-like behaviors and recognition memory deficits. Our findings indicate that glucose intolerance alone can elicit anxiety-like behaviors. Through this study we also provide a novel nutritional model to characterize the discrete effects of glucose intolerance on cognition, behavior, and the physiology of metabolic disease.

animal behavior and cognition↗

A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine

The severity of the new COVID-19 pandemic caused by the SARS-CoV-2 virus is strikingly variable in different global populations. SARS-CoV-2 uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences of individuals from the Middle Eastern populations (Kuwait, Qatar, and Iran) to explore natural variations in the ACE2, TMPRSS2, and FURIN genes. We identified two activating variants (K26R and N720D) in the ACE2 gene that are more common in Europeans than in the Middle Eastern, East Asian, and African populations. We postulate that K26R can activate ACE2 and facilitate binding to S-protein RBD while N720D enhances TMPRSS2 cutting and, ultimately, viral entry. We also detected deleterious variants in FURIN that are frequent in the Middle Eastern but not in the European populations. This study highlights specific genetic variations in the ACE2 and FURIN genes that may explain SARS-CoV-2 clinical disparity. We showed structural evidence of the functionality of these activating variants that increase the SARS-CoV-2 aggressiveness. Finally, our data illustrate a significant correlation between ACE2 variants identified in people from Middle Eastern origins that can be further explored to explain the variation in COVID-19 infection and mortality rates globally.

genetics↗