Metabolomic Responses Research Articles

Effects of in situ experimental warming on metabolic expression in a soft sediment bivalve

Ocean surface temperatures and the frequency and intensity of marine heatwaves are increasing worldwide. Understanding how marine organisms respond and adapt to heat pulses and the rapidly changing climate is crucial for predicting responses of valued species and ecosystems to global warming. Here, we carried out an in situ experiment to investigate sublethal responses to heat spikes of a functionally important intertidal bivalve, the venerid clam Austrovenus stutchburyi. We describe changes in metabolic responses under two warming scenarios (five days and seven days) at two sites (muddy and sandy). Tidal flat warming during every low tide for five days affected the abundance of multiple functional metabolites within this species. The metabolic response was related to pathways such as metabolic energetics, amino acid and lipid metabolism, and accumulation of stress-related metabolites. There was some recovery after cooler weather during the final two days of the experiment. The degree of change was greater in muddy versus sandy sediments. Our findings provide new evidence of the metabolomic response of these important bivalve to heat stress, which could be used for resource managers when implementing strategies to mitigate the impacts of climate change on valuable marine resources.

Active biomonitoring of stream ecosystems: untargeted metabolomic and proteomic responses and free radical scavenging activities in mussels.

Many contaminants from scattered sources constantly endanger streams that flow through heavily inhabited areas, commercial districts, and industrial hubs. The responses of transplanted mussels in streams in active biomonitoring programs will reflect the dynamics of environmental stream conditions. This study evaluated the untargeted metabolomic and proteomic responses and free radical scavenging activities of transplanted mussels Sinanodonta woodiana in the Winongo Stream at three stations (S1, S2, S3) representing different pollution levels: low (S1), high (S2), and moderate (S3). The investigation examined untargeted metabolomic and proteomic responses in the gills and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) activities in the gills, mantle, and digestive glands. Metabolomic analysis revealed a clear separation between mussel responses from the three stations after 28 days of exposure, with specific metabolites responding to different pollution levels. Proteomic analysis identified β-Actin protein in all stations. The β-Actin protein sequence of unexposed mussels had coverage of 17%, and increased to 23% at S1 on day 28 and 34% at S2 and S3 on day 28. All tissues showed increased DPPH and ABTS activities from day 3 to day 28, mainly in stations S2 and S3. These findings underscore the impact of pollution levels on the metabolomic and proteomic responses of S. woodiana and the importance of these discoveries as early indicators (biomarkers) of long-term aquatic environmental problems. In the face of current environmental challenges, this research raises concerns about the health of water bodies. It underscores the importance of developing robust, standardized, and dependable analytical techniques for monitoring the health of aquatic environments.

Extraction potential of Trifolium repens and Medicago sativa for metals in landfill soil: Their metabolomic responses

Extraction potential of Trifolium repens and Medicago sativa for metals in landfill soil: Their metabolomic responses

Integrated analysis of biochemical, transcriptomic, and metabolomic response mechanisms in Ussuri catfish (Pseudobagrus ussuriensis) under acute heat stress.

Fish metabolism, growth, development, and physiological conditions are highly sensitive to fluctuations in water temperature. The Ussuri catfish (Pseudobagrus ussuriensis) is an important native economic species in China. However, research on heat stress in P. ussuriensis, particularly concerning gene expression and metabolites, remains limited. In this study, we conducted histological observations, biochemical measurements, transcriptomic analysis, and metabolomic analysis on liver tissue from a control group (22 ℃), an acute heat stress group (34 ℃, with samples taken at 0, 3, 6, 12, and 24 h), and a recovery group (sampled 24 h after recovery to 22 ℃). Histopathological analysis showed that liver damage worsened with the duration of heat stress. Biochemical results indicated that acute heat stress significantly impacted the activities of superoxide dismutase, catalase, and alanine aminotransferase, as well as the levels of glutathione, malondialdehyde, and total antioxidant capacity, with alterations remaining even after temperature recovery. Transcriptomic and metabolomic analyses revealed that compared to the control group, 3482, 800, 980, and 1479 differentially expressed genes (DEGs) were detected at 0, 6, and 24 h of acute heat stress and at 24 h post-recovery, respectively. Similarly, 114, 151, 365, and 326 differentially expressed metabolites (DEMs), respectively, were detected at the same time points. Furthermore, when comparing 24 h of heat stress with 24 h of recovery, 1279 DEGs and 157 DEMs were identified. Functional enrichment analysis revealed that these DEGs and DEMs were significantly enriched in key pathways, such as endoplasmic reticulum protein processing and glutathione metabolism, with significant changes continuing into the recovery phase. Additionally, substantial alterations in the expression levels of amino acids, sugars, and lipids were observed during heat stress. These findings provide valuable insights into the defense mechanisms of fish under high-temperature stress and lay a theoretical foundation for breeding heat-resistant P. ussuriensis strains, as well as improving sustainable aquaculture management.

Almond Consumption for 8 Weeks Differentially Modulates Metabolomic Responses to an Acute Glucose Challenge Compared to Crackers in Young Adults

Almond Consumption for 8 Weeks Differentially Modulates Metabolomic Responses to an Acute Glucose Challenge Compared to Crackers in Young Adults

Transcriptomic and metabolomic responses of maize under conventional and biodegradable microplastic stress

AbstractThe increasing accumulation of microplastics in agricultural soils potentially threatens crop safety and quality. However, studies regarding the molecular mechanisms underlying the effects of conventional and biodegradable microplastics on plant growth remain limited. Herein, we estimated the effects of biodegradable polybutylene adipate terephthalate, poly (butylene succinate), polylactic acid, and conventional non‐biodegradable polyethylene and polystyrene microplastics (at a concentration of 1% [w/w]) on the growth and physiological performance of maize (Zea mays L.). In addition, we studied the molecular mechanisms underlying the effects of these microplastics on maize. Exposure to microplastics induced the production of antioxidant enzymes and antioxidants at varying levels in the maize. While the maize antioxidant systems were induced against biodegradable microplastic exposure, maize photosynthesis was relatively more important for conventional microplastic treatments. Additionally, metabolomics and transcriptomic analyses revealed that the pathways of secondary metabolite biosynthesis, photosynthesis, energy metabolism, and carbohydrate metabolism were regulated by biodegradable and conventional microplastics. Specifically, microplastics induced the plant hormone signal transduction and mitogen‐activated protein kinase signaling pathways. Our results further indicated that microplastics could impact the plant through changing the soil environmental variables or altering the soil microbial communities. This study provides a molecular‐scale perspective on the responses of crops to microplastic contamination, and these findings will contribute to the ecological risk assessment of biodegradable and conventional microplastics.

Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase - 2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.

Metabolomic Response to Non-Steroidal Anti-Inflammatory Drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by side effects in the gastrointestinal and cardiovascular systems. We compared the effects of naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase -2 (Cox-2) inhibitor, in humans. Our findings showed a decrease in tryptophan and kynurenine levels in plasma of volunteers treated with naproxen. We further validated this result in mice. Additionally, we find that the depression of tryptophan was independent of both Cox-1 and Cox-2 inhibition, but rather was due to the displacement of bound tryptophan by naproxen. Supplementation of tryptophan in naproxen-treated mice rescued fecal blood loss and inflammatory gene expression driven by IL-1β in the heart.

1H NMR Milk Metabolomics Response from Goats Supplemented with Date (Phoenix Dactylifera L.) Pit Powder: Benefiting from Agricultural Waste Byproduct

Utilizing a systems biology approach through metabolomics is crucial for analyzing milk quality. Continual animal supplementing is crucial for enhancing milk quality to ensure high food quality and agricultural productivity. Date pits are agricultural waste byproducts that can be used as active components in cosmetics, as a coffee substitute, and as animal feed. The study investigated the impact of adding date pit powder (DPP) to dairy goats' diet on the milk metabolites to determine possible benefits. Saanen-Boer crossed dairy goats were divided into six groups: control (untreated), 10g and 20g of Ajwa DPP (high quality), 10 g and 20 g of Mariami DPP (agricultural waste byproduct), and 30g of Mariami DPP exclusively. DPP supplementation was administered daily for 12 weeks. The goat milk obtained was analyzed using 1H NMR and then subjected to chemometric studies, namely PCA and PLS. Metabolites were analyzed using tools such as BAYESIL, Chenomx profiler and HMDB. Principal Component Analysis (PCA) showed that milk metabolites changed over time (month), and that supplementing breastfeeding goats with DPP did not result in distinct clusters. However, BAYESIL identified L-Proline, L-Carnitine, and myoinositol as molecules with less than 30 % biological variance at months 1 and 3 of the research, indicating good conservation. Only the levels of L-Carnitine and acetoacetate in the milk showed significant differences between the treatments. Ultimately, the DPP dosages were insufficient to impact the goat's metabolism, resulting in no impacts on milk metabolites. An adaptive response to DPP cultivars and doses was indicated by the results. Overall, these findings might help dairy goat and other ruminant breeders in predicting milk quality by utilizing metabolites as markers for food security (production and quality).

M2ara: unraveling metabolomic drug responses in whole-cell MALDI mass spectrometry bioassays.

Fast computational evaluation and classification of concentration responses for hundreds of metabolites represented by their mass-to-charge (m/z) ratios is indispensable for unraveling complex metabolomic drug actions in label-free, whole-cell Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS) bioassays. In particular, the identification of novel pharmacodynamic biomarkers to determine target engagement, potency, and potential polypharmacology of drug-like compounds in high-throughput applications requires robust data interpretation pipelines. Given the large number of mass features in cell-based MALDI MS bioassays, reliable identification of true biological response patterns and their differentiation from any measurement artefacts that may be present is critical. To facilitate the exploration of metabolomic responses in complex MALDI MS datasets, we present a novel software tool, M2ara. Implemented as a user-friendly R-based shiny application, it enables rapid evaluation of Molecular High Content Screening (MHCS) assay data. Furthermore, we introduce the concept of Curve Response Score (CRS) and CRS fingerprints to enable rapid visual inspection and ranking of mass features. In addition, these CRS fingerprints allow direct comparison of cellular effects among different compounds. Beyond cellular assays, our computational framework can also be applied to MALDI MS-based (cell-free) biochemical assays in general. The software tool, code, and examples are available at https://github.com/CeMOS-Mannheim/M2ara and https://dx.doi.org/10.6084/m9.figshare.25736541.

Integrated physiological, transcriptomics and metabolomics analyses provide insights into thermal stress of razor clam, Sinonovacula constricta

Extreme high temperature is believed as a major inducer to summer mortality syndrome in molluscs, which frequently occurs and has caused serious economic losses. In this study, we elucidated the molecular differences of transcriptomic and metabolomics responses and investigated the mechanisms of response to heat stress in razor clam (Sinonovacula constricta) after exposure to 32 °C lasting for either 24 h or 15 d. Notably, protein processing in endoplasmic reticulum (ER) and glycerophospholipid pathway were obviously enriched, suggesting that maintaining ER and cell membrane homeostasis play an important role for razor clams to response to heat stress. After heat stress for 24 h, fatty acid synthesis-related genes, fasn, far1 and scd5, were repressed, and the contents of fumarate and citrate metabolites and the activities of SDH and CS enzymes in TCA cycle were significantly reduced. By contrast, T-SOD and CAT activities and MDA content were dramatically increased. After heat stress for 15 d, the lipid metabolism-related genes pparα and plb1 were downregulated, and the SDH activity was remarkably decreased. Conversely, the expression of pck1 and odh were upregulated, indicating that heat stress may limit the aerobic capacities of the razor clams. Additionally, T-SOD activity was still higher than that of the control group, while CAT activity and MDA content decreased. These findings suggested that heat stress may inhibit the lipid metabolism and TCA cycle, activate oxidative stress and cause misfolded proteins accumulation which leads to ER stress. This study contributes to understand the potential metabolism mechanisms of S.constricta in response to heat stress.

Boosted Meat Flavor by the Metabolomic Effects of Nile Tilapia Dietary Inclusion of Zophobas atratus Larval Meal.

Zophobas atratus larval meal (ZLM) is a high-quality feed supplement with potential activities that can improve fish growth performance and promote meat quality. However, there have been limited recent studies investigating the metabolic effects of ZLM. Therefore, this study aims to uncover the metabolomic mechanism through which ZLM improves tilapia meat flavor using metabolomic strategies. In this study, soybean meal in the basal diets was replaced with 15%, 30%, or 60% ZLM, where anti-nutrient factors were destroyed by high temperature treatment. After being fed these ZLM supplements for 30 days, dorsal muscles were collected from tilapia for meat sensory evaluation tests. Liver samples were also collected for metabolomic analysis using the gas chromatography-mass spectrometry (GC-MS) platform and combined with biochemical assays to verify metabolism-related enzyme activities and reveal crucial metabolic pathways and critical biomarkers associated with ZLM's ability to improve meat flavor. In tilapia livers, ZLM enhanced the activity of enzymes involved in energy metabolism including succinate dehydrogenase (SDH), pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (α-KGDH), NADP-malate dehydrogenase (NAD-MDH) and mitochondrial isocitrate dehydrogenase (ICDHm). This resulted in increased levels of reduced nicotinamide adenine dinucleotide (NADH), acetyl CoA and ATP which led to accumulation of flavor fatty acids such as arachidonic acid, linoleic acid (9,12-Octadecadienoic acid), linolenic acid (9,12,15-Octadecatrienoic acid) and oleic acid (9-Octadecenoic acid). Additionally, there was an increase in flavor nucleotides like guanosine adenosine-5'-monophosphate and uridine-5'-monophosphate while off-flavor metabolites like inosine and hypoxanthine decreased. Furthermore, beneficial metabolomic responses led to a decrease in off-flavor metabolites such as 2-methylisoborneol trimethylamine and geosmin while increasing umami metabolites like 2-methyl-3-furanthiol and nonanal. This metabolomic study demonstrates that inclusion of ZLM diets enhances the flavor profile of tilapia dorsal muscle. The accumulation of flavor compounds, coupled with a reduction in earthy taste and off-flavor metabolites, contributes to an improved meat flavor and freshness. Additionally, there is an increase in the levels of flavor-related amino acids and nucleotides. These previously unidentified metabolic effects highlight the potential significance of ZLM as a dietary supplement for enhancing the biosynthesis of flavor metabolites in tilapia.

Physiological, transcriptomic, and metabolomic analyses of the chilling stress response in two melon (Cucumis melo L.) genotypes

BackgroundChilling stress is a key abiotic stress that severely restricts the growth and quality of melon (Cucumis melo L.). Few studies have investigated the mechanism of response to chilling stress in melon.ResultsWe characterized the physiological, transcriptomic, and metabolomic response of melon to chilling stress using two genotypes with different chilling sensitivity (“162” and “13-5A”). “162” showed higher osmotic regulation ability and antioxidant capacity to withstand chilling stress. Transcriptome analysis identified 4395 and 4957 differentially expressed genes (DEGs) in “162” and “13-5A” under chilling stress, respectively. Metabolome analysis identified 615 and 489 differential enriched metabolites (DEMs) were identified in “162” and “13-5A” under chilling stress condition, respectively. Integrated transcriptomic and metabolomic analysis showed enrichment of glutathione metabolism, and arginine (Arg) and proline (Pro) metabolism, with differential expression patterns in the two genotypes. Under chilling stress, glutathione metabolism-related DEGs, 6-phosphogluconate dehydrogenase (G6PDH), glutathione peroxidase (GPX), and glutathione s-transferase (GST) were upregulated in “162,” and GSH conjugates (L-gamma-glutamyl-L-amino acid and L-glutamate) were accumulated. Additionally, “162” showed upregulation of DEGs encoding ornithine decarboxylase, Pro dehydrogenase, aspartate aminotransferase, pyrroline-5-carboxylate reductase, and spermidine synthase and increased Arg, ornithine, and Pro. Furthermore, the transcription factors (TFs), MYB, ERF, MADS-box, and bZIP were significantly upregulated, suggesting their crucial role in chilling tolerance of melon.ConclusionsThese findings elucidate the molecular response mechanism to chilling stress in melon and provide insights for breeding chilling-tolerant melon.

Variable glucagon metabolic actions in diverse mouse models of obesity and type 2 diabetes

ObjectiveThe study aimed to investigate the effects of glucagon on metabolic pathways in mouse models of obesity, fatty liver disease, and type 2 diabetes (T2D) to determine the extent and variability of hepatic glucagon resistance in these conditions. MethodsWe investigated glucagon's effects in mouse models of fatty liver disease, obesity, and type 2 diabetes (T2D), including male BKS-db/db, high-fat diet-fed, and western diet-fed C57Bl/6 mice. Glucagon tolerance tests were performed using the selective glucagon receptor agonist acyl-glucagon (IUB288). Blood glucose, serum and liver metabolites include lipids and amino acids were measured. Additionally, liver protein expression related to glucagon signalling and a comprehensive liver metabolomics were performed. ResultsWestern diet-fed mice displayed impaired glucagon response, with reduced blood glucose and PKA activation. In contrast, high-fat diet-fed and db/db mice maintained normal glucagon sensitivity, showing significant elevations in blood glucose and phospho-PKA motif protein expression. Acyl-glucagon treatment also lowered liver alanine and histidine levels in high-fat diet-fed mice, but not in western diet-fed mice. Additionally, some amino acids, such as methionine, were increased by acyl-glucagon only in chow diet control mice. Despite normal glucagon sensitivity in PKA signalling, db/db mice had a distinct metabolomic response, with acyl-glucagon significantly altering 90 metabolites in db/+ mice but only 42 in db/db mice, and classic glucagon-regulated metabolites, such as cyclic adenosine monophosphate (cAMP), being less responsive in db/db mice. ConclusionsThe study reveals that hepatic glucagon resistance in obesity and T2D is complex and not uniform across metabolic pathways, underscoring the complexity of glucagon action in these conditions.

The Effects of Anthropogenic Stressors on Above- and Belowground Phytochemical Diversity of the Wetland Grass, Phragmites australis.

Coastal wetlands face threats from climate change-induced flooding and biological invasions. Plants respond to these stressors through changes in their phytochemical metabolome, but it is unclear whether stressors affecting one tissue compartment (e.g., leaves) create vulnerabilities in others (e.g., roots) or elicit similar responses across tissues. Additionally, responses to multiple simultaneous stressors remain poorly understood due to the focus on individual metabolites in past studies. This study aims to elucidate how the phytochemical metabolome of three Phragmites australis (Cav.) lineages, common in the Mississippi River Delta, responds to flooding and infestation by the non-native scale insect Nipponaclerda biwakoensis (Kuwana). Among these lineages, one is non-native and poses a threat to North American wetlands. Results indicate that metabolomic responses are highly specific, varying with lineage, tissue type, stressor type, and the presence of multiple stressors. Notably, the non-native lineage displayed high chemical evenness, while the other two showed stressor-dependent responses. The 10 most informative features identified by a machine learning model showed less than 1% overlap with known metabolites linked to water and herbivory stress, underscoring gaps in our understanding of plant responses to environmental stressors. Our metabolomic approach offers a valuable tool for identifying candidate plant genotypes for wetland restoration.

Transcriptomic and metabolomic reveal OsCOI2 as the jasmonate-receptor master switch in rice root.

Jasmonate is an essential phytohormone involved in plant development and stress responses. Its perception occurs through the CORONATINE INSENSITIVE (COI) nuclear receptor allowing to target the Jasmonate-ZIM domain (JAZ) repressors for degradation by the 26S proteasome. Consequently, repressed transcription factors are released and expression of jasmonate responsive genes is induced. In rice, three OsCOI genes have been identified, OsCOI1a and the closely related OsCOI1b homolog, and OsCOI2. While the roles of OsCOI1a and OsCOI1b in plant defense and leaf senescence are well-established, the significance of OsCOI2 in plant development and jasmonate signaling has only emerged recently. To unravel the role of OsCOI2 in regulating jasmonate signaling, we examined the transcriptomic and metabolomic responses of jasmonate-treated rice lines mutated in both the OsCOI1a and OsCOI1b genes or OsCOI2. RNA-seq data highlight OsCOI2 as the primary driver of the extensive transcriptional reprogramming observed after a jasmonate challenge in rice roots. A series of transcription factors exhibiting an OsCOI2-dependent expression were identified, including those involved in root development or stress responses. OsCOI2-dependent expression was also observed for genes involved in specific processes or pathways such as cell-growth and secondary metabolite biosynthesis (phenylpropanoids and diterpene phytoalexins). Although functional redundancy exists between OsCOI1a/b and OsCOI2 in regulating some genes, oscoi2 plants generally exhibit a weaker response compared to oscoi1ab plants. Metabolic data revealed a shift from the primary metabolism to the secondary metabolism primarily governed by OsCOI2. Additionally, differential accumulation of oryzalexins was also observed in oscoi1ab and oscoi2 lines. These findings underscore the pivotal role of OsCOI2 in jasmonate signaling and suggest its involvement in the control of the growth-defense trade-off in rice.

A Comprehensive Multi-Omics Study of Serum Alterations in Red Deer Infected by the Liver Fluke Fascioloides magna.

Liver fluke infections are acknowledged as diseases with global prevalence and significant implications for both veterinary and public health. The large American liver fluke, Fascioloides magna, is a significant non-native parasite introduced to Europe, threatening the survival of local wildlife populations. The aim of this study was to analyze differences in the serum proteome and metabolome between F. magna-infected and control red deer. Serum samples from red deer were collected immediately following regular hunting operations, including 10 samples with confirmed F. magna infection and 10 samples from healthy red deer. A proteomics analysis of the serum samples was performed using a tandem mass tag (TMT)-based quantitative approach, and a metabolomics analysis of the serum was performed using an untargeted mass spectrometry-based metabolomics approach. A knowledge-driven approach was applied to integrate omics data. Our findings demonstrated that infection with liver fluke was associated with changes in amino acid metabolism, energy metabolism, lipid metabolism, inflammatory host response, and related biochemical pathways. This study offers a comprehensive overview of the serum proteome and metabolome in response to F. magna infection in red deer, unveiling new potential targets for future research. The identification of proteins, metabolites, and related biological pathways enhances our understanding of host-parasite interactions and may improve current tools for more effective liver fluke control.

Unravelling Different Water Management Strategies in Three Olive Cultivars: The Role of Osmoprotectants, Proteins, and Wood Properties

Understanding the responses of olive trees to drought stress is crucial for improving cultivation and developing drought-tolerant varieties. Water transport and storage within the plant is a key factor in drought-tolerance strategies. Water management can be based on a variety of factors such as stomatal control, osmoprotectant molecules, proteins and wood properties. The aim of the study was to evaluate the water management strategy under drought stress from an anatomical and biochemical point of view in three young Italian olive cultivars (Giarraffa, Leccino and Maurino) previously distinguished for their physiological and metabolomic responses. For each cultivar, 15 individuals in pots were exposed or not to 28 days of water withholding. Every 7 days, the content of sugars (including mannitol), proline, aquaporins, osmotins, and dehydrins, in leaves and stems, as well as the chemical and anatomical characteristics of the wood of the three cultivars, were analyzed. ‘Giarraffa’ reduced glucose levels and increased mannitol production, while ‘Leccino’ accumulated more proline. Both ‘Leccino’ and ‘Maurino’ increased sucrose and aquaporin levels, possibly due to their ability to remove embolisms. ‘Maurino’ and ‘Leccino’ accumulated more dehydrins and osmotins. While neither genotype nor stress affected wood chemistry, ‘Maurino’ had a higher vessel-to-xylem area ratio and a larger hydraulic diameter, which allows it to maintain a high transpiration rate but may make it more susceptible to cavitation. The results emphasized the need for an integrated approach, highlighting the importance of the relative timing and sequence of each parameter analyzed, allowing, overall, to define a “strategy” rather than a “response” to drought of each cultivar.

Propionate Decreases Microglial Activation but Impairs Phagocytic Capacity in Response to Aggregated Fibrillar Amyloid Beta Protein.

Microglia, the innate immune cell of the brain, are a principal player in Alzheimer's disease (AD) pathogenesis. Their surveillance of the brain leads to interaction with the protein aggregates that drive AD pathogenesis, most notably Amyloid Beta (Aβ). Microglia attempt to clear and degrade Aβ using phagocytic machinery, spurring damaging neuroinflammation in the process. Thus, modulation of the microglial response to Aβ is crucial in mitigating AD pathophysiology. SCFAs, microbial byproducts of dietary fiber fermentation, are blood-brain barrier permeable molecules that have recently been shown to modulate microglial function. It is unclear whether propionate, one representative SCFA, has beneficial or detrimental effects on microglia in AD. Thus, we investigated its impact on microglial Aβ response in vitro. Using a multiomics approach, we characterized the transcriptomic, metabolomic, and lipidomic responses of immortalized murine microglia following 1 h of Aβ stimulation, as well as characterizing Aβ phagocytosis and secretion of reactive nitrogen species. Propionate blunted the early inflammatory response driven by Aβ, downregulating the expression of many Aβ-stimulated immune genes, including those regulating inflammation, the immune complement system, and chemotaxis. Further, it reduced the expression of Apoe and inflammation-promoting Aβ-binding scavenger receptors such as Cd36 and Msr1 in favor of inflammation-dampening Lpl, although this led to impaired phagocytosis. Finally, propionate shifted microglial metabolism, altering phospholipid composition and diverting arginine metabolism, resulting in decreased nitric oxide production. Altogether, our data demonstrate a modulatory role of propionate on microglia that may dampen immune activation in response to Aβ, although at the expense of phagocytic capacity.

Effects of a potential host gut-derived probiotic, Bacillus amyloliquefaciens AV5, on the growth, biochemical and metabolic responses, and disease resistance of Nile tilapia (Oreochromis niloticus)

The influence of the dietary probiotic Bacillus amyloliquefaciens AV5 on the growth, biochemical and metabolic responses, and disease resistance of Nile tilapia (Oreochromis niloticus) was evaluated. The commercial diet (GC), a diet containing 106 and 108 CFU/g of B. amyloliquefaciens AV5, denoted as G1 and G2, respectively, was fed for 30 days. Fish were allocated to 9 plastic tanks, and each diet was randomly assigned to triplicate groups of 40 fish (22.4 ± 1.3 g).After 30 days of the feeding trial, the specific growth rate, weight gain rate, and final weight increased significantly in G2 compared to those in GC and G1. Feed conversion ratio was significantly higher in the fish-fed GC group than in the G2 group. However, the survival rate of the fish ranged from 99.13 % to 97.17 %, with no significant difference. Glucose levels did not differ significantly (P < 0.05). Total antioxidant capacity (T-AOC), (superoxide dismutase (SOD), and catalase (CAT), as well as digestive enzymes (trypsin, lipase, and protease), were significantly increased in the G2 group relative to the GC and G1 groups.Significantly lower ALT, AST, CHO, TG, and MDA activities were observed in the G2 group than in the GC group. To evaluate the metabolomic response, PCA, OPLS-DA, and volcano plots revealed a distinct difference between the G2 and GC diets, suggesting that the G2 diet impacted the hepatopancreas of fish. Furthermore, challenge experiments revealed that fish fed B. amyloliquefaciens AV5 exhibited substantially increased resistance (P < 0.05) to S. agalactiae at a concentration of 1x108CFU/g. Therefore, dietary supplementation with B. amyloliquefaciens AV5 enhanced the growth performance, metabolic activity, and disease resistance of O. niloticus.