PubMed

Adv Sci (Weinh). 2024 Feb 15:e2306659. doi: 10.1002/advs.202306659. Online ahead of print.ABSTRACTHigh-coverage mass spectrometry analysis of single-cell metabolomics remains challenging due to the extremely low abundance and wide polarity of metabolites and ultra-small volume in single cells. Herein, a novel concentric hybrid ionization source, nanoelectrospray ionization-atmospheric pressure chemical ionization (nanoESI-APCI), is ingeniously designed to detect polar and nonpolar metabolites simultaneously in single cells. The source is constructed by inserting a pulled glass capillary coaxially into a glass tube that acts as a dielectric barrier layer. Benefitting from the integrated advantages of nanoESI and APCI, its limit of detection is improved by one order of magnitude to 10 pg mL-1 . After the operational parameter optimization, 254 metabolites detected in nanoESI-APCI are tentatively identified from a single cell, and 82 more than those in nanoESI. The developed nanoESI-APCI is successively applied to study the metabolic heterogeneity of human hepatocellular carcinoma tissue microenvironment united with laser capture microdissection (LCM), the discrimination of cancer cell types and subtypes, the metabolic perturbations to glucose starvation in MCF7 cells and the metabolic regulation of cancer stem cells. These results demonstrated that the nanoESI-APCI not only opens a new avenue for high-coverage and high-sensitivity metabolomics analysis of single cell, but also facilitates spatially resolved metabolomics study coupled with LCM.PMID:38359005 | DOI:10.1002/advs.202306659

Exp Physiol. 2024 Feb 15. doi: 10.1113/EP091059. Online ahead of print.ABSTRACTThe field of exercise physiology has undergone significant technological advancements since the pioneering works of exercise physiologists in the early to mid-20th century. Historically, the ability to detect metabolites in biofluids from exercising participants was limited to single-metabolite analyses. However, the rise of metabolomics, a discipline focused on the comprehensive analysis of metabolites within a biological system, has facilitated a more intricate understanding of metabolic pathways and networks in exercise. This review explores some of the pivotal technological and bioinformatic advancements that have propelled metabolomics to the forefront of exercise physiology research. Metabolomics offers a unique 'fingerprint' of cellular activity, offering a broader spectrum than traditional single-metabolite assays. Techniques, including mass spectrometry and nuclear magnetic resonance spectroscopy, have significantly improved the speed and sensitivity of metabolite analysis. Nonetheless, challenges persist, including study design and data interpretation issues. This review aims to serve as a guide for exercise physiologists to facilitate better research design, data analysis and interpretation within metabolomics. The potential of metabolomics in bridging the gap between genotype and phenotype is emphasised, underscoring the critical importance of careful study design and the selection of appropriate metabolomics techniques. Furthermore, the paper highlights the need to deeply understand the broader scientific context to discern meaningful metabolic changes. The emerging field of fluxomics, which seeks to quantify metabolic reaction rates, is also introduced as a promising avenue for future research.PMID:38358958 | DOI:10.1113/EP091059

Elife. 2024 Feb 15;12:RP91407. doi: 10.7554/eLife.91407.ABSTRACTBACKGROUND: Primary angle closure glaucoma (PACG) is the leading cause of irreversible blindness in Asia, and no reliable, effective diagnostic, and predictive biomarkers are used in clinical routines. A growing body of evidence shows metabolic alterations in patients with glaucoma. We aimed to develop and validate potential metabolite biomarkers to diagnose and predict the visual field progression of PACG.METHODS: Here, we used a five-phase (discovery phase, validation phase 1, validation phase 2, supplementary phase, and cohort phase) multicenter (EENT hospital, Shanghai Xuhui Central Hospital), cross-sectional, prospective cohort study designed to perform widely targeted metabolomics and chemiluminescence immunoassay to determine candidate biomarkers. Five machine learning (random forest, support vector machine, lasso, K-nearest neighbor, and GaussianNaive Bayes [NB]) approaches were used to identify an optimal algorithm. The discrimination ability was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration was assessed by Hosmer-Lemeshow tests and calibration plots.RESULTS: Studied serum samples were collected from 616 participants, and 1464 metabolites were identified. Machine learning algorithm determines that androstenedione exhibited excellent discrimination and acceptable calibration in discriminating PACG across the discovery phase (discovery set 1, AUCs=1.0 [95% CI, 1.00-1.00]; discovery set 2, AUCs = 0.85 [95% CI, 0.80-0.90]) and validation phases (internal validation, AUCs = 0.86 [95% CI, 0.81-0.91]; external validation, AUCs = 0.87 [95% CI, 0.80-0.95]). Androstenedione also exhibited a higher AUC (0.92-0.98) to discriminate the severity of PACG. In the supplemental phase, serum androstenedione levels were consistent with those in aqueous humor (r=0.82, p=0.038) and significantly (p=0.021) decreased after treatment. Further, cohort phase demonstrates that higher baseline androstenedione levels (hazard ratio = 2.71 [95% CI: 1.199-6.104], p=0.017) were associated with faster visual field progression.CONCLUSIONS: Our study identifies serum androstenedione as a potential biomarker for diagnosing PACG and indicating visual field progression.FUNDING: This work was supported by Youth Medical Talents - Clinical Laboratory Practitioner Program (2022-65), the National Natural Science Foundation of China (82302582), Shanghai Municipal Health Commission Project (20224Y0317), and Higher Education Industry-Academic-Research Innovation Fund of China (2023JQ006).PMID:38358793 | DOI:10.7554/eLife.91407

Appl Microbiol Biotechnol. 2024 Feb 15;108(1):213. doi: 10.1007/s00253-024-13041-5.ABSTRACTType 2 diabetes mellitus (T2DM) was reported to be associated with impaired immune response and alterations in microbial composition and function. However, the underlying mechanism remains elusive. To investigate the association among retinoic acid-inducible gene-I-like receptors (RLRs) signaling pathway, intestinal bacterial microbiome, microbial tryptophan metabolites, inflammation, and a longer course of T2DM, 14 patients with T2DM and 7 healthy controls were enrolled. 16S rRNA amplicon sequencing and untargeted metabolomics were utilized to analyze the stool samples. RNA sequencing (RNA-seq) was carried out on the peripheral blood samples. Additionally, C57BL/6J specific pathogen-free (SPF) mice were used. It was found that the longer course of T2DM could lead to a decrease in the abundance of probiotics in the intestinal microbiome. In addition, the production of microbial tryptophan derivative skatole declined as a consequence of the reduced abundance of related intestinal microbes. Furthermore, low abundances of probiotics, such as Bacteroides and Faecalibacterium, could trigger the inflammatory response by activating the RLRs signaling pathway. The increased level of the member of TNF receptor-associated factors (TRAF) family, nuclear factor kappa-B (NF-κB) activator (TANK), in the animal colon activated nuclear factor kappa B subunit 2 (NFκB2), resulting in inflammatory damage. In summary, it was revealed that the low abundances of probiotics could activate the RLR signaling pathway, which could in turn activate its downstream signaling pathway, NF-κB, highlighting a relationship among gut microbes, inflammation, and a longer course of T2DM. KEY POINTS: Hyperglycemia may suppress tryptophanase activity. The low abundance of Bacteroides combined with the decrease of Dopa decarboxylase (DDC) activity may lead to the decrease of the production of tryptophan microbial derivative skatole, and the low abundance of Bacteroides or reduced skatole may further lead to the increase of blood glucose by downregulating the expression of glucagon-like peptide-1 (GLP1). A low abundance of anti-inflammatory bacteria may induce an inflammatory response by triggering the RLR signaling pathway and then activating its downstream NF-κB signaling pathway in prolonged T2DM.PMID:38358546 | DOI:10.1007/s00253-024-13041-5

Liver Int. 2024 Feb 15. doi: 10.1111/liv.15858. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed.METHODS: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry.RESULTS: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05).CONCLUSION: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients.PMID:38358068 | DOI:10.1111/liv.15858

J Clin Invest. 2024 Feb 15;134(4):e174824. doi: 10.1172/JCI174824.ABSTRACTNicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway - KYNU, HAAO, and NADSYN1 - have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation. Enzymatic assessment of variant deleteriousness in vitro revealed protein domain-specific perturbation, complemented by protein structure modeling in silico. We reproduced NADSYN1-dependent CNDD in mice and assessed various maternal NAD precursor supplementation strategies to prevent adverse pregnancy outcomes. While for Nadsyn1+/- mothers, any B3 vitamer was suitable to raise NAD, preventing embryo loss and malformation, Nadsyn1-/- mothers required supplementation with amidated NAD precursors (nicotinamide or nicotinamide mononucleotide) bypassing their metabolic block. The circulatory NAD metabolome in mice and humans before and after NAD precursor supplementation revealed a consistent metabolic signature with utility for patient identification. Our data collectively improve clinical diagnostics of NADSYN1-dependent CNDD, provide guidance for the therapeutic prevention of CNDD, and suggest an ongoing need to maintain NAD levels via amidated NAD precursor supplementation after birth.PMID:38357931 | DOI:10.1172/JCI174824

JPEN J Parenter Enteral Nutr. 2024 Feb 15. doi: 10.1002/jpen.2606. Online ahead of print.ABSTRACTDiet strongly shapes the gut microbiome and metabolome, which in turn influence intestinal inflammation in patients with inflammatory bowel disease (IBD). Separate from inflammation and malnutrition, diet's direct interactions with the gastrointestinal system can also provoke or attenuate a host of nonspecific gastrointestinal symptoms. Given these multifaceted effects of diet on inflammation and symptoms, nutrition has been investigated for its potential roles in the prevention and treatment of IBD. This review presents epidemiological, observational cohort, and clinical trial evidence that underlie our current understanding of nutrition for prevention and treatment of IBD.PMID:38357793 | DOI:10.1002/jpen.2606

iScience. 2024 Jan 20;27(2):108983. doi: 10.1016/j.isci.2024.108983. eCollection 2024 Feb 16.ABSTRACTRhizosphere dwelling microorganism such as Bacillus spp. are helpful for crop growth. However, these functions are adversely affected by long-term synthetic fertilizer application. We developed a modified CRISPR/Cas9 system using non-specific single-guide RNAs to disrupt the genome-wide cis-acting catabolite-responsive elements (cres) in a wild-type Bacillus pumilus strain, which conferred dual plant-benefit properties. Most of the mutations occurred around imperfectly matched cis-acting elements (cre-like sites) in genes that are mainly involved in carbon and secondary metabolism pathways. The comparative metabolomics and transcriptome results revealed that carbon is likely transferred to some pigments, such as riboflavin, carotenoid, and lycopene, or non-ribosomal peptides, such as siderophore, surfactin, myxochelin, and bacilysin, through the pentose phosphate and amino acid metabolism pathways. Collectively, these findings suggested that the mutation of global cre-like sequences in the genome might alter carbon flow, thereby allowing beneficial biological interactions between the rhizobacteria and plants.PMID:38357660 | PMC:PMC10864199 | DOI:10.1016/j.isci.2024.108983

Front Immunol. 2024 Jan 31;15:1335042. doi: 10.3389/fimmu.2024.1335042. eCollection 2024.ABSTRACTINTRODUCTION: Pregnancy outcomes of patients with systemic lupus erythematosus (SLE) have improved over the past four decades, leading to an increased desire for pregnancy among this cohort. However, the offspring of patients with SLE still face the risks of preterm birth, low birth weight, learning disabilities, and neurological disorders, while the causes underlying these risks remain unclear.METHODS: In this study, we analyzed the blood metabolic features of neonates born to 30 SLE patients and 52 healthy control mothers by employing tandem mass spectrometry with the dual aims of identifying the etiology of metabolic features specific to infants born from mothers with SLE and providing new insights into the clinical management of such infants.RESULTS: We found significant differences in serum metabolite levels between infants born from mothers with SLE and those born from mothers without SLE, including 15 metabolites with reduced serum levels. Further analysis revealed a disrupted tyrosine metabolism pathway in the offspring of mothers with SLE.DISCUSSION: By constructing a composite model incorporating various factors, such as serum tyrosine levels, gestational age, and birth weight, we were able to accurately differentiate between newborns of SLE and non-SLE pregnancies. Our data reveal significant differences in serum concentrations of amino acids and acylcarnitines in newborns born to mothers with SLE. We conclude that the reduction of blood L-tyrosine levels is a feature that is characteristic of adverse neurological outcomes in infants born from mothers with SLE.PMID:38357540 | PMC:PMC10864668 | DOI:10.3389/fimmu.2024.1335042

Front Nutr. 2024 Jan 12;10:1304540. doi: 10.3389/fnut.2023.1304540. eCollection 2023.ABSTRACTMOTIVATION: In the field of precision nutrition, predicting metabolic response to diet and identifying groups of differential responders are two highly desirable steps toward developing tailored dietary strategies. However, data analysis tools are currently lacking, especially for complex settings such as crossover studies with repeated measures.Current methods of analysis often rely on matrix or tensor decompositions, which are well suited for identifying differential responders but lacking in predictive power, or on dynamical systems modeling, which may be used for prediction but typically requires detailed mechanistic knowledge of the system under study. To remedy these shortcomings, we explored dynamic mode decomposition (DMD), which is a recent, data-driven method for deriving low-rank linear dynamical systems from high dimensional data.Combining the two recent developments "parametric DMD" (pDMD) and "DMD with control" (DMDc) enabled us to (i) integrate multiple dietary challenges, (ii) predict the dynamic response in all measured metabolites to new diets from only the metabolite baseline and dietary input, and (iii) identify inter-individual metabolic differences, i.e., metabotypes. To our knowledge, this is the first time DMD has been applied to analyze time-resolved metabolomics data.RESULTS: We demonstrate the potential of pDMDc in a crossover study setting. We could predict the metabolite response to unseen dietary exposures on both measured (R2 = 0.40) and simulated data of increasing size (Rmax2= 0.65), as well as recover clusters of dynamic metabolite responses. We conclude that this method has potential for applications in personalized nutrition and could be useful in guiding metabolite response to target levels.AVAILABILITY AND IMPLEMENTATION: The measured data analyzed in this study can be provided upon reasonable request. The simulated data along with a MATLAB implementation of pDMDc is available at https://github.com/FraunhoferChalmersCentre/pDMDc.PMID:38357465 | PMC:PMC10865386 | DOI:10.3389/fnut.2023.1304540

Food Chem X. 2024 Feb 6;21:101178. doi: 10.1016/j.fochx.2024.101178. eCollection 2024 Mar 30.ABSTRACTIn this study, okara was fermented with probiotic strains Lactobacillus gasseri LAC 343 and Limosilactobacillus fermentum PCC, respectively. Significant increases in cell count (by 2.22 log CFU/mL for LAC and 0.82 log CFU/mL for PCC) and significant decreases in pH (by 1.31 for LAC and 1.03 for PCC) were found in fermented okara slurry. In addition, strain LAC tended to produce amino acids, while strain PCC depleted most amino acids. An untargeted metabolomic-based approach using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to further understand the compositional changes and potential health benefits by identifying bioactive metabolites in fermented okara slurry. We successfully identified various beneficial bioactive compounds including γ-aminobutyric acid, indolelactic acid, d-phenyllactic acid, and p-hydroxyphenyllactic acid which had differences in fold-changes in okara slurry fermented with different strains. Our study indicated the feasibility of using probiotics to ferment okara for novel functional food development.PMID:38357377 | PMC:PMC10865209 | DOI:10.1016/j.fochx.2024.101178

Food Chem X. 2024 Feb 5;21:101189. doi: 10.1016/j.fochx.2024.101189. eCollection 2024 Mar 30.ABSTRACTFlavor profiles of various Pyrus spp. cultivars exhibit significant variations, yet the underlying flavor-contributing factors remain elusive. In this investigation, a comprehensive approach encompassing metabolomics analysis, volatile fingerprint analysis, and descriptive sensory analysis was employed to elucidate the flavor disparities among Nanguoli, Korla fragrant pear, and Qiuyueli cultivars and uncover potential flavor contributor. The study comprehensively characterized the categories and concentrations of nonvolatile and volatile metabolites, and 925 metabolites were identified. Flavonoids and esters dominated the highest cumulative response, respectively. Utilizing weighted correlation network analysis (WGCNA), seven highly correlated modules were identified, yielding 407 pivotal metabolites. Further correlation analysis of the differential substances provided potential flavor constituents strongly associated with various sensory attributes; taste factors had a certain association with olfactory characteristics. Our findings demonstrated the manifestation of flavor was a result of the synergistic effect of various compounds; evaluation olfactory flavor necessitated a comprehensive consideration of taste substances.PMID:38357376 | PMC:PMC10865235 | DOI:10.1016/j.fochx.2024.101189

Food Chem X. 2024 Feb 5;21:101197. doi: 10.1016/j.fochx.2024.101197. eCollection 2024 Mar 30.ABSTRACTIn this study, comprehensive and systematic nontargeted metabolomics analysis was performed with the metabolites of Zangju peel (Citrus reticulata cv. Manau Gan, CRZP, which has been cultivated for over 400 years in Derong County, China.) at four different mature stages. A total of 1878 metabolites were identified, among which flavonoids were the most abundant (62.04 %), and identified 62 key differential metabolites significantly affected by maturity. Based on biological activity measurements, CRZP showed better antioxidant activity, lipase inhibition ability, inhibition of adipogenic differentiation in 3TT-L1 cells and promotion of lipid metabolism, with the biological activity of CRZP at different maturity stages being associated with key differential metabolite. Thus, CRZP is natural antioxidants and possess anti-obesity potential, and industrial production needs to consider the Maturity stage of its collection.PMID:38357370 | PMC:PMC10865237 | DOI:10.1016/j.fochx.2024.101197

Food Chem X. 2024 Feb 5;21:101191. doi: 10.1016/j.fochx.2024.101191. eCollection 2024 Mar 30.ABSTRACTThe study aimed to investigate the impact of water-soluble extract from Semen Ziziphi Spinosae (SZSE) on yogurt quality and understand the underlying mechanism. The results demonstrated that adding 0.5% (w/v) SZSE had a significant effect on reducing yogurt syneresis and resulted in a more compact and uniform casein gel. Notably, the co-fermented yogurt with binary probiotics (Lacticaseibacillus casei CGMCC1.5956 and Levilactobacillus brevis CGMCC1.5954) along with SZSE led to increased viable probiotics and a higher odor score (23.23). This effect might be attributed to the increased amino acid utilization by binary probiotics through biosynthesis of valine, leucine and isoleucine, metabolic pathways, and amino acid biosynthesis to produce amino acid derivatives such as N5-(l-1-carboxyethyl)-l-ornithine and diaminopyrimidine acid. The yogurt contained 79 volatile flavor compounds, with hexanoic acid, 2-heptanone, and 2-nonanone potentially contributing to the high odor scores. These findings have strategic implications for developing yogurt with high gel characteristics and distinctive flavor.PMID:38357367 | PMC:PMC10864216 | DOI:10.1016/j.fochx.2024.101191

Front Microbiol. 2024 Jan 31;15:1292004. doi: 10.3389/fmicb.2024.1292004. eCollection 2024.ABSTRACTDepression is one of the most prevalent mental disorders today. Over the past decade, there has been considerable attention given to the field of gut microbiota associated with depression. A substantial body of research indicates a bidirectional communication pathway between gut microbiota and the brain. In this review, we extensively detail the correlation between gut microbiota, including Lactobacillus acidophilus and Bifidobacterium longum, and metabolites such as short-chain fatty acids (SCFAs) and 5-hydroxytryptamine (5-HT) concerning depression. Furthermore, we delve into the potential health benefits of microbiome-targeted therapies, encompassing probiotics, prebiotics, and synbiotics, in alleviating depression. Lastly, we underscore the importance of employing a constraint-based modeling framework in the era of systems medicine to contextualize metabolomic measurements and integrate multi-omics data. This approach can offer valuable insights into the complex metabolic host-microbiota interactions, enabling personalized recommendations for potential biomarkers, novel drugs, and treatments for depression.PMID:38357350 | PMC:PMC10864537 | DOI:10.3389/fmicb.2024.1292004

Front Cell Infect Microbiol. 2024 Jan 31;13:1322059. doi: 10.3389/fcimb.2023.1322059. eCollection 2023.ABSTRACTMigraine is a prevalent clinical disorder characterized by recurrent unilateral throbbing headache episodes accompanied by symptoms such as nausea, vomiting, photophobia, and phonophobia. Despite its common occurrence, the diagnosis, pathophysiology, and treatment of migraine remain controversial. Extensive research has implicated the gut microbiota in various central nervous system disorders, including anxiety disorders, depression, and Parkinson's disease. Some studies have also suggested that migraine may stem from disruptions to neurohormones and metabolism. This study aimed to investigate the disparities in gut microbiota and metabolites between migraine mice model and normal mice to shed light on the underlying mechanisms and potential therapeutic approaches. Distinct differences in gut microbial composition were observed between the migraine mouse model and normal mouse, indicating a potential correlation between these variations and the pathogenesis of migraine. This study provides evidence of differences in gut microbiota composition and metabolites between a migraine mouse model and normal mice, which showed that Akkermansiaceae constituted the most abundant taxon in the sham injection mouse group, while Lachnospiraceae constituted the most prevalent group in the migraine mouse model group. The associations between the abundances of Akkermansia muciniphila and Lachnospiraceae bacteria and metabolites suggested their potential roles in the pathogenesis of migraine. The altered abundance of Lachnospiraceae observed in migraine-afflicted mice and its correlations with changes in metabolites suggest that it may affect the host's health. Thus, probiotic therapy emerges as a possible treatment for migraine. Moreover, significant disparities in gut metabolites were observed between the migraine mouse model and normal mice. These alterations encompass multiple metabolic pathways, suggesting that metabolic disturbances may also contribute to the development of migraines.PMID:38357211 | PMC:PMC10864585 | DOI:10.3389/fcimb.2023.1322059

Front Cell Infect Microbiol. 2024 Jan 31;13:1343752. doi: 10.3389/fcimb.2023.1343752. eCollection 2023.ABSTRACTBACKGROUND: Ionizing radiation can cause intestinal microecological dysbiosis, resulting in changes in the composition and function of gut microbiota. Altered gut microbiota is closely related to the development and progression of radiation-induced intestinal damage. Although microbiota-oriented therapeutic options such as fecal microbiota transplantation (FMT) have shown some efficacy in treating radiation toxicity, safety concerns endure. Therefore, fecal bacteria-free filtrate transplantation (FFT), which has the potential to become a possible alternative therapy, is well worth investigating. Herein, we performed FFT in a mouse model of radiation exposure and monitored its effects on radiation damage phenotypes, gut microbiota, and metabolomic profiles to assess the effectiveness of FFT as an alternative therapy to FMT safety concerns.RESULTS: FFT treatment conferred radioprotection against radiation-induced toxicity, representing as better intestinal integrity, robust proinflammatory and anti-inflammatory cytokines homeostasis, and accompanied by significant shifts in gut microbiome. The bacterial compartment of recipients following FFT was characterized by an enrichment of radioprotective microorganisms (members of family Lachnospiraceae). Furthermore, metabolome data revealed increased levels of microbially generated short-chain fatty acids (SCFAs) in the feces of FFT mice.CONCLUSIONS: FFT improves radiation-induced intestinal microecological dysbiosis by reshaping intestinal mucosal barrier function, gut microbiota configurations, and host metabolic profiles, highlighting FFT regimen as a promising safe alternative therapy for FMT is effective in the treatment of radiation intestinal injury.PMID:38357210 | PMC:PMC10864540 | DOI:10.3389/fcimb.2023.1343752

Food Funct. 2024 Feb 15. doi: 10.1039/d3fo04980a. Online ahead of print.ABSTRACTKrill oil (KO) is rich in bioactive ingredients including phospholipids, omega-3 fatty acids, and astaxanthin. While health benefits and roles of KO in modulating lipid metabolism are well documented, its ability to alleviate symptoms related to infectious colitis and modulate gut microbial interactions is still largely unknown. Here we used a multi-omics approach, including transcriptome, microbiome, and metabolome analyses, to understand how KO mediates gut microbial interactions and promotes epithelial healing in an infectious colitis model. KO reversed the infection-induced intestinal hyperplasia to baseline. KO dampened intestinal inflammation via multiple targets, mediating several proinflammatory pathways, including IL17 signaling, and reducing luminal histamine levels. KO supplementation enriched butyrate-producing bacteria, including Roseburia and Clostridium, and strengthened beneficial microbial interactions in the gut microbial community. Supplementation with phospholipid-rich KO also increased microbial phylogenetic diversity. KO enhanced mucosal barrier function by increasing the production of Muc6 and the antimicrobial peptide, Leap2. KO played an active role during epithelial healing by inhibiting the expression of granzyme K while increasing the expression of a colitis protective factor, Dclk1. Together, our findings demonstrate that KO rich in omega-3 phospholipids can play a protective role in infectious colitis and should be considered a dietary option for promoting gut health.PMID:38356343 | DOI:10.1039/d3fo04980a

Adv Sci (Weinh). 2024 Feb 14:e2306000. doi: 10.1002/advs.202306000. Online ahead of print.ABSTRACTA key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in the modulation of the host immune response and are the cells responsible for persistent inflammatory reactions to implanted biomaterials. Two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophages in vitro are investigated. These also modulate in vivo foreign body responses (FBR) when implanted subcutaneously in mice. Immunofluorescent staining of tissue abutting the polymer reveals responses consistent with pro- or anti-inflammatory responses previously described for these polymers. Three Dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) analysis to spatially characterize the metabolites in the tissue surrounding the implant, providing molecular histology insight into the metabolite response in the host is applied. For the pro-inflammatory polymer, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti-inflammatory coating, the number of phospholipid species detected decreased, and pyridine and pyrimidine levels are elevated. Small molecule signatures from single-cell studies of M2 macrophages in vitro correlate with the in vivo observations, suggesting potential for prediction. Metabolite characterization by the 3D OrbiSIMS is shown to provide insight into the mechanism of bio-instructive materials as medical devices and to inform on the FBR to biomaterials.PMID:38356246 | DOI:10.1002/advs.202306000

Sci Rep. 2024 Feb 14;14(1):3691. doi: 10.1038/s41598-024-54195-6.ABSTRACTThe universe is a vast store of organic abiotic carbon that could potentially drive heterotrophy on habitable planets. Meteorites are one of the transporters of this carbon to planetary surfaces. Meteoritic material was accumulating on early Earth when life emerged and proliferated. Yet it is not known if this organic carbon from space was accessible to life. In this research, an anaerobic microbial community was grown with the CM2 carbonaceous chondrite Aguas Zarcas as the sole carbon, energy and nutrient source. Using a reversed 13C-stable isotope labelling experiment in combination with optical photothermal infrared (O-PTIR) spectroscopy of single cells, this paper demonstrates the direct transfer of carbon from meteorite into microbial biomass. This implies that meteoritic organics could have been used as a carbon source on early Earth and other habitable planets, and supports the potential for a heterotrophic metabolism in early living systems.PMID:38355968 | DOI:10.1038/s41598-024-54195-6