Biology subjects

Taha, A. Y.

Publications and source records attributed to Taha, A. Y..

10 recordsLinked to original sources

bioRxiv2026

A pectin-based formulation protects milk fat globule membranes in stored human milk

During household storage, expressed human milk can develop odor and flavor changes that trigger infant refusal and lead caregivers to discard their saved milk supply. We show that typical refrigeration and freezing conditions disrupt the milk fat globule membrane (MFGM), exposing milk lipids to lipases that catalyze hydrolysis and oxidation. A pectin-based formulation (PBF) maintains MFGM integrity during storage and following lipase challenge, suppressing production of glycerol, free fatty acid, and oxylipin byproducts without broadly affecting milk macronutrients, the proteome, and culturable microbial burden. Across an independent cohort of lactating individuals, lipase activity varied but tracked with maternal milk lipase gene expression, implicating endogenous lipolysis in stored-milk deterioration. In a blinded olfactory panel, PBF-treated, lipase-challenged milk smelled more like fresh milk than untreated controls. Together, these findings show that stabilizing the MFGM can protect stored human milk from lipase-driven deterioration, preserve sensory quality, and support use for infant feeding.

biochemistry↗

bioRxiv2026

Discovering a new biocatalytic potential of milk fat globules: in situ conversion of exogenous docosahexaenoic acid to its oxylipins

Milk fat globules (MFG) are complex structures that emulsify the fat in milk and exhibit various biological activities. Using docosahexaenoic acid (DHA) as a model polyunsaturated fatty acid, we demonstrate for the first time that a MFG-enriched fraction (isolated from commercial raw and unhomogenized bovine milk) catalyzes the oxidation of exogenous polyunsaturated fatty acid to its oxylipins. Static incubation of the MFG-enriched fraction (at 20% w/v in phosphate buffer and 5% v/v ethanol) with 150 {micro}M of DHA for 1 h resulted in the production of [~]13 pmol/mg cream of DHA-derived oxylipins in free and esterified (i.e., bound) forms. High enrichment in free DHA-oxylipins was observed, wherein incubation with DHA resulted in >80% of all free oxylipins being derived from DHA, in contrast to control samples in which only <8% of all free oxylipins were DHA derivatives. The most abundant products generated were 17-hydroxydocosahexaenoic acid and 19(20)-epoxydocosapentaenoic acid. Oxylipin generation was dependent on the structural integrity of MFG, with mechanical disruption (vortexing) impairing oxylipin synthesis more severely than thermal treatment. These findings suggest that MFGs harbor multiple metabolically active enzymes, including cytochrome P450, lipoxygenases, acyl-CoA synthetases, and acyltransferases, that act cooperatively to synthesize and esterify DHA-derived oxylipins. In summary, this study highlights the dual potential of MFGs to serve both as a food-grade biocatalyst for the synthesis of DHA-derived oxylipins and as carriers for these bioactive lipids. Future studies should evaluate the bioavailability and physiological relevance of these metabolites when consumed in the diet.

biochemistry↗

bioRxiv2025

Whey Protein Phospholipid Concentrate Supplementation Prevents High-Fat Diet Induced Cognitive Impairment in Wistar Rats by Promoting Brain Neuronal Connectivity and Sphingolipid Clearance

Whey protein phospholipid concentrate (WPPC), a byproduct of whey protein processing, is high in phospholipids and glycoconjugates which serve as substrates for fatty acids and sugar monomers (e.g. sialic acid) critical to neuronal myelin synthesis in the brain. This led us to hypothesize that WPPC will improve cognitive impairment induced by a high fat (HF) diet by promoting myelin turnover and improving myelin-dependent processes associated with encoding and storing memory. Male Wistar rats were randomized to one of four diets starting at weaning to [~]6.5 months on age: a low-fat (LF) diet containing 10% fat by weight, a HF diet containing 45% fat by weight to induce cognitive impairment, and a HF diet containing either 1.6% or 10% WPPC by weight (n=12 per diet). Rats were subjected to cognitive testing after 2 and 4 months of dietary intervention and then implanted with chronic bipolar electrodes to measure axonal evoked responses within the entorhinal cortex-hippocampal circuitry. Phospholipid and sphingolipid components of myelin were quantified in the hippocampus. There were no significant differences in cognition measured by novel object recognition after 2 months of supplementation. At 4 months, rats on the HF diet performed significantly worse than rats on the LF, HF1.6 and HF10 diets. The beneficial effects of WPPC on cognition were due to a partial reversal in evoked response impairments in hippocampal memory storage. Additionally, hippocampus sphingolipids were higher in rats on the HF diet compared to the LF, HF1.6 and HF10 groups. These findings demonstrate that WPPC prevented cognitive impairment induced by a HF diet by regulating entorhinal cortex-hippocampal circuitries associated with memory storage, though modulating myelin turnover.

neuroscience↗

bioRxiv2025

A Milk Fat Globule Membrane-enriched dairy co-product modulates gut Faecalibaculum rodentium metabolism in association with the prevention of cognitive impairment in aging male Wistar rats

Consumption of the milk fat globule membrane (MFGM) by infants is linked to enhanced neurodevelopment and sustained cognitive improvements later in life. Aging, by contrast, is often marked by neurodegeneration and cognitive decline-a growing concern in the U.S. as 6.9 million Americans live with Alzheimers disease (AD). As such, identifying interventions to prevent cognitive impairment are imperative. The whey protein phospholipid concentrate (WPPC), a dairy co-product, is enriched in MFGM glycoconjugates. Given the cognitive health benefits conferred by MFGM consumption in early life, we previously found that high-fat (HF) diet induced cognitive impairment in aging male Wistar rats was prevented by supplementating with a 1.6% or 10% WPPC in the diet, compared to control rats fed a low-fat (LF) diet. We hypothesized that WPPC exerts protective effects against cognitive impairment through the gut-brain axis by modulating gut microbial composition and metabolism. To test this, we analyzed 16S rRNA sequencing data from fecal samples of aged male Wistar rat (4 months old) fed a LF, HF, HF + 1.6% WPPC, or HF + 10% WPPC diet (n=9-10/group). Compared to LF, the HF diet reduced the abundance of the Erysipelotrichaceae family, particularly the species Faecalibaculum rodentium, which increased numerically with the 10% WPPC diet. Interestingly, Erysipelotrichaceae relative abundance correlated with hippocampal memory storage (spearman correlation=0.4, p=0.034). In vitro growth assays confirmed that F. rodentium grew robustly in isolation on WPPC glycoconjugates and on constituent WPPC components (p<0.05). RNA sequencing of F. rodentium grown on the WPPC MFGM glycoconjugates versus glucose (n=3/group) revealed significant upregulation of genes involved in in amino acid metabolism and fatty acid oxidation (FDR<0.05). Collectively this data suggests a potential role for F. rodentium in preventing cognitive impairment through the gut-brain axis by metabolizing the WPPC that may act on the host.

microbiology↗

bioRxiv2024

Blood-based targeted metabolipidomics reveals altered omega fatty acid-derived lipid mediators in relapsing-remitting multiple sclerosis patients

Unresolved and uncontrolled inflammation is considered a hallmark of pathogenesis in chronic inflammatory diseases like multiple sclerosis (MS), suggesting a defective resolution process. Inflammatory resolution is an active process partially mediated by endogenous metabolites of dietary polyunsaturated fatty acids (PUFA), collectively termed specialized pro-resolving lipid mediators (SPMs). Altered levels of resolution mediators have been reported in several inflammatory diseases and may partly explain impaired inflammatory resolution. Performing LC-MS/MS-based targeted lipid mediator profiling, we observed distinct changes in fatty acid metabolites in serum from 30 relapsing-remitting MS (RRMS) patients relative to 30 matched healthy subjects (HS). Robust linear regression revealed 12 altered lipid mediators after adjusting for confounders (p <0.05). Of these, 15d-PGJ2, PGE3, and LTB5 were increased in MS while PGF2a, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 12-HEPE, 14-HDoHE, and DHEA were decreased in MS compared to HS. In addition, 12,13-DiHOME and 12,13-DiHODE were positively correlated with expanded disability status scale values (EDSS). Using Partial Least Squares, we identified several lipid mediators with high VIP scores (VIP > 1: 32% - 52%) of which POEA, PGE3, DHEA, LTB5, and 12-HETE were top predictors for distinguishing between RRMS and HS (AUC =0.75) based on the XGBoost Classifier algorithm. Collectively, these findings suggest an imbalance between inflammation and resolution. Altogether, lipid mediators appear to have potential as diagnostic and prognostic biomarkers for RRMS.

biochemistry↗

bioRxiv2022

Use of Ganoderma lucidum grown on agricultural waste to remove antibiotics from water

Antibiotic effluents from farming and medical applications into waterways pose serious risks for antibiotic drug resistance, promoting a need for effective strategies of removal from the environment. This experiment uses a novel mycoremediation approach to remove antibiotic contamination in synthetic wastewater. A white rot fungus, Ganoderma lucidum, was grown on biomass formed by agricultural waste from California (almond shells, fava bean stalks). Water containing or lacking Ganoderma lucidum was inoculated with twenty antibiotics from six different classes. The extent of antibiotic removal was measured at baseline and after 3 days with ultra-high pressure liquid chromatography coupled to tandem mass-spectrometry. In water containing Ganoderma lucidum mycelial biomass, we found a significant reduction compared to the baseline of the concentration in six (three quinolones and three sulfonamides) out of twenty tested antibiotics by Day 3, with normalized changes ranging from -24.4% to -82.4%. The mycelial biomass was particularly effective in reducing the presence of three quinolone antibiotics, a class of highly used antibiotics recalcitrant to processes in wastewater treatment plants. Our findings provide a novel approach to degrade certain antibiotics from water. This strategy could become a key component of removing antibiotic pollution using agricultural waste as part of the solution.

microbiology↗

bioRxiv2022

Pro-resolving lipid mediators within brain esterified lipid pools are reduced in female rats chronically exposed to traffic-related air pollution or genetically susceptible to Alzheimer's Disease phenotype

Traffic-related air pollution (TRAP) is a risk factor for Alzheimers disease (AD) where neuroinflammation underlies disease progression and pathogenesis. Unresolved inflammation in AD is known to be exacerbated by brain deficits in unesterified pro-resolving lipid mediators enzymatically synthesized from polyunsaturated fatty acids. Recently, we reported that in the brain, unesterified pro-resolving lipid mediators which are bioactive, can also be supplied from less bioactive esterified lipid pools such as neutral lipids (NLs) and phospholipids (PLs). It is not known whether esterified pro-resolving lipid mediators are affected by AD pathology and exacerbated by TRAP exposure. In the present study we addressed this data gap using TgF344-AD male and female rats that express human AD risk genes and their wildtype littermates exposed to filtered air (FA) or TRAP from 1 to 15 months of age. Esterified lipid mediators within NLs and PLs were quantified by mass-spectrometry. We observed a significant reduction in pro-resolving lipid mediators in both NLs and PLs of female TgF344-AD rats compared to wildtype controls. TRAP exposure also reduced pro-resolving lipids in the female brain, mainly in PL pools, but did not exacerbate changes observed in TgF344-AD rats. Minimal changes were observed in males. Our findings indicate that AD genotype and chronic TRAP exposure result in sex-specific deficits in brain esterified pro-resolving lipid mediators, the pool that supplies free and bioactive lipid mediators. These data provide new information on lipid-mediated mechanisms regulating impaired inflammation resolution in AD, and show for the first time that chronic TRAP exposure targets the same lipid network implicated in AD.

neuroscience↗

bioRxiv2021

Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. Ultimately, maternal obesity altered infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic biomarkers.

genomics↗

bioRxiv2021

Assessing the matrix effects of pigmented and non-pigmented salmon during multi-residue antibiotic analysis with liquid chromatography coupled to tandem mass spectrometry

Several validated methods exist for the quantitation of antibiotics in seafood with ultra-high pressure liquid chromatography coupled with tandem spectrometry (UPLC-MS/MS). To our knowledge, none have explored the effects of co-eluting matrix components on the accuracy of quantitation. Such matrix effects could disproportionally change the ionization of analytes and their respective surrogate/internal standards during UPLC-MS/MS analysis, resulting in over-or under-estimation of antibiotic values. In this study, we measured matrix effects, alongside extraction recoveries for 30 antibiotics and their respective class-specific surrogate standards in Sockeye, King and Ivory (non-pigmented) salmon extracted using the QUEChERS method. A modified QUEChERS method involving dispersive or hydrophilic-lipophilic balance (HLB) solid phase extraction (SPE) was also tested on Sockeye salmon. Despite acceptable extraction recoveries for most antibiotics extracted using the QUEChERS method, significant matrix effects were observed for most antibiotic standards. Dispersive or HLB SPE clean-up did not improve analyte recoveries from Sockeye salmon, and in some cases, increased matrix effects. Accuracy and sensitivity were reduced when matrix effects were high. Our results demonstrate that matrix components in salmon cause matrix effects on antibiotics during UPLC-MS/MS analysis which could impact the accuracy and sensitivity of the analysis.

biochemistry↗

bioRxiv2020

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification

Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy metabolism, including oxylipins, endocannabinoids, bile acids, and steroid hormones to identify metabolic biomarkers of mild cognitive impairment (MCI). Serum samples (n =210) were obtained from subjects with or without MCI opportunistically collected with incomplete fasting state information. To maximize power and stratify the analysis of metabolite associations with MCI by the fasting state, we developed an algorithm to predict subject fasting state when unknown (n =71). In non-fasted subjects, linoleic acid and palmitoleoyl ethanolamide levels were positively associated with perceptual speed. In fasted subjects, soluble epoxide hydrolase activity and tauro-alpha-muricholic acid levels were negatively associated with perceptual speed. Other cognitive domains showed associations with bile acid metabolism, but only in the non-fasted state. Importantly, this study shows unique associations between serum metabolites and cognitive function in the fasted and non-fasted states and provides a fasting state prediction algorithm based on measurable metabolites.

pathology↗