PubMed

Biomed Pharmacother. 2023 Mar 10;161:114495. doi: 10.1016/j.biopha.2023.114495. Online ahead of print.ABSTRACTConstipation arising from the poor bowel movement is a rife enteric health problem. Shouhui Tongbian Capsule (SHTB) is a traditional Chinese medicine (TCM) which effectively improve the symptoms of constipation. However, the mechanism has not been fully evaluated. The purpose of this study was to evaluate the effect of SHTB on the symptoms and intestinal barrier of mice with constipation. Our data showed that SHTB effectively improved the constipation induced by diphenoxylate, which was confirmed by shorter first defecation time, higher internal propulsion rate and fecal water content. Additionally, SHTB improved the intestinal barrier function, which was manifested by inhibiting the leakage of Evans blue in intestinal tissues and increasing the expression of occludin and ZO-1. SHTB inhibited NLRP3 inflammasome signaling pathway and TLR4/NF-κB signaling pathway, reduced the number of proinflammatory cell subsets and increased the number of immunosuppressive cell subsets to relieve inflammation. The photochemically induced reaction coupling system combined with cellular thermal shift assay and central carbon metabolomics technology confirmed that SHTB activated AMPKα through targeted binding to Prkaa1 to regulate Glycolysis/Gluconeogenesis and Pentose Phosphate Pathway, and finally inhibited intestinal inflammation. Finally, no obvious toxicity related to SHTB was found in a repeated drug administration toxicity test for consecutive 13 weeks. Collectively, we reported SHTB as a TCM targeting Prkaa1 for anti-inflammation to improve intestinal barrier in mice with constipation. These findings broaden our knowledge of Prkaa1 as a druggable target protein for inflammation inhibition, and open a new avenue to novel therapy strategy for constipation injury.PMID:36906969 | DOI:10.1016/j.biopha.2023.114495

Mol Nutr Food Res. 2023 Mar 12:e2200289. doi: 10.1002/mnfr.202200289. Online ahead of print.ABSTRACTSCOPE: Pre-diabetes and diabetes are major public health problems worldwide without specific cure currently. Gut microbes have been recognized as one of the vital therapeutic targets for diabetes. The exploration that nobiletin (NOB) whether affect gut microbes provided a scientific basis for its application.METHODS AND RESULTS: A hyperglycemia animal model was established using high-fat-fed ApoE-/- mice. After 24 weeks of NOB intervention, the level of fasting blood glucose (FBG), glucose tolerance, insulin resistance, and glycosylated serum protein (GSP) were measured. Pancreas integrity was observed by HE staining and transmission electron microscopy. 16s RNA sequencing and untargeted metabolomics were to determine the changes of intestinal microbial composition and metabolic pathways. The levels of FBG and GSP in hyperglycemic mice were effectively reduced. The secretory function of pancreas was improved. Meanwhile, NOB treatment restored the gut microbial composition and affected metabolic function. Furthermore, NOB treatment regulated the metabolic disorder mainly through lipid metabolism, amino acid metabolism and Secondary bile acid metabolism, etc. In addition, it was possibly existed mutual promotion between microbe and metabolites.CONCLUSION: NOB probably played a vital role in the hypoglycemic effect and pancreatic islets protection by improving microbiota composition and gut metabolism. This article is protected by copyright. All rights reserved.PMID:36906890 | DOI:10.1002/mnfr.202200289

Sci Rep. 2023 Mar 11;13(1):4063. doi: 10.1038/s41598-023-31287-3.ABSTRACTMethods for collection of placental tissue at room temperature for metabolic profiling are described. Specimens were excised from the maternal side of the placenta and immediately flash frozen or fixed and stored for 1, 6, 12, 24, or 48 h in 80% methanol. Untargeted metabolic profiling was performed on both the methanol-fixed tissue and the methanol extract. Data were analyzed using Gaussian generalized estimating equations, two sample t-tests with false discovery rate (FDR) corrections, and principal components analysis. Methanol-fixed tissue samples and methanol extracts had a similar number of metabolites (p = 0.45, p = 0.21 in positive vs. negative ion mode). In positive ion mode, when compared to flash frozen tissue, both the methanol extract and methanol-fixed tissue (6 h) had a higher number of metabolites detected (146 additional metabolites, pFDR = 0.020; 149 additional metabolites, pFDR = 0.017; respectively), but these associations were not found in negative ion mode (all pFDR ≥ 0.05). Principle components analysis demonstrated separation of the metabolite features in the methanol extract, but similarity between methanol-fixed tissue and flash frozen tissue. These results show that placental tissue samples collected in 80% methanol at room temperature can yield similar metabolic data to flash frozen specimens.PMID:36906704 | DOI:10.1038/s41598-023-31287-3

Oncogene. 2023 Mar 11. doi: 10.1038/s41388-023-02631-8. Online ahead of print.ABSTRACTCellular heterogeneity in cancer is linked to disease progression and therapy response, although mechanisms regulating distinct cellular states within tumors are not well understood. We identified melanin pigment content as a major source of cellular heterogeneity in melanoma and compared RNAseq data from high-pigmented (HPCs) and low-pigmented melanoma cells (LPCs), suggesting EZH2 as a master regulator of these states. EZH2 protein was found to be upregulated in LPCs and inversely correlated with melanin deposition in pigmented patient melanomas. Surprisingly, conventional EZH2 methyltransferase inhibitors, GSK126 and EPZ6438, had no effect on LPC survival, clonogenicity and pigmentation, despite fully inhibiting methyltransferase activity. In contrast, EZH2 silencing by siRNA or degradation by DZNep or MS1943 inhibited growth of LPCs and induced HPCs. As the proteasomal inhibitor MG132 induced EZH2 protein in HPCs, we evaluated ubiquitin pathway proteins in HPC vs LPCs. Biochemical assays and animal studies demonstrated that in LPCs, the E2-conjugating enzyme UBE2L6 depletes EZH2 protein in cooperation with UBR4, an E3 ligase, via ubiquitination at EZH2's K381 residue, and is downregulated in LPCs by UHRF1-mediated CpG methylation. Targeting UHRF1/UBE2L6/UBR4-mediated regulation of EZH2 offers potential for modulating the activity of this oncoprotein in contexts in which conventional EZH2 methyltransferase inhibitors are ineffective.PMID:36906655 | DOI:10.1038/s41388-023-02631-8

Nat Commun. 2023 Mar 11;14(1):1348. doi: 10.1038/s41467-023-37055-1.ABSTRACTCommensal bacteria are major contributors to mammalian metabolism. We used liquid chromatography mass spectrometry to study the metabolomes of germ-free, gnotobiotic, and specific-pathogen-free mice, while also evaluating the influence of age and sex on metabolite profiles. Microbiota modified the metabolome of all body sites and accounted for the highest proportion of variation within the gastrointestinal tract. Microbiota and age explained similar amounts of variation the metabolome of urine, serum, and peritoneal fluid, while age was the primary driver of variation in the liver and spleen. Although sex explained the least amount of variation at all sites, it had a significant impact on all sites except the ileum. Collectively, these data illustrate the interplay between microbiota, age, and sex in the metabolic phenotypes of diverse body sites. This provides a framework for interpreting complex metabolic phenotypes and will help guide future studies into the role that the microbiome plays in disease.PMID:36906623 | DOI:10.1038/s41467-023-37055-1

FEMS Microbiol Rev. 2023 Mar 11:fuad011. doi: 10.1093/femsre/fuad011. Online ahead of print.ABSTRACTGalleria mellonella (greater wax moth) larvae are used widely as surrogate infectious disease models, due to ease of use and the presence of an innate immune system functionally similar to that of vertebrates. Here we review G. mellonella-human intracellular bacteria pathogen infection models from the genera Burkholderia, Coxiella, Francisella, Listeria, and Mycobacterium. For all genera, G. mellonella use has increased understanding of host-bacterial interactive biology, particularly through studies comparing the virulence of closely related species and/or wild-type versus mutant pairs. In many cases, virulence in G. mellonella mirrors that found in mammalian infection models, although it is unclear whether the pathogenic mechanisms are the same. The use of G. mellonella larvae has speeded up in vivo efficacy and toxicity testing of novel antimicrobials to treat infections caused by intracellular bacteria: an area that will expand since the FDA no longer requires animal testing for licensure. Further use of G. mellonella-intracellular bacteria infection models will be driven by advances in G. mellonella genetics, imaging, metabolomics, proteomics, and transcriptomic methodologies, alongside the development and accessibility of reagents to quantify immune markers, all of which will be underpinned by a fully annotated genome.PMID:36906279 | DOI:10.1093/femsre/fuad011

J Ethnopharmacol. 2023 Mar 9:116357. doi: 10.1016/j.jep.2023.116357. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Adverse reactions to traditional Chinese medicine injections involve pseudo-allergic reactions (PARs). However, in clinical practice, "immediate allergic reactions" and PARs in response to these injections are not often differentiated.AIM OF THE STUDY: This study aimed to clarify the type of reactions produced by Shengmai injections (SMI) and elucidate the possible mechanism.MATERIALS AND METHODS: A mouse model was used to evaluate vascular permeability. Metabolomic and arachidonic acid metabolite (AAM) analyses were performed using UPLC-MS/MS, and the p38 MAPK/cPLA2 pathway was detected by western blotting.RESULTS: The first exposure to intravenous SMI rapidly and dose-dependently induced edema and exudative reactions in the ears and lungs. These reactions were not IgE-dependent and were likely to be PARs. Metabolomic analysis showed that endogenous substances were perturbed in SMI-treated mice, in which the arachidonic acid (AA) metabolic pathway was the most affected. SMI substantially increased the levels of AAMs in lung, including prostaglandins (PGs), leukotrienes (LTs), and hydroxy-eicosatetraenoic acids (HETEs). The p38 MAPK/cPLA2 signaling pathway was activated after a single SMI dose. Inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes reduced exudation and inflammation in the ears and lungs of mice.CONCLUSION: Production of inflammatory factors that increase vascular permeability may result in SMI-induced PARs, and p38 MAPK/cPLA2 signaling pathway and downstream AA metabolic pathway are involved in the reactions.PMID:36906156 | DOI:10.1016/j.jep.2023.116357

Sci Total Environ. 2023 Mar 9:162778. doi: 10.1016/j.scitotenv.2023.162778. Online ahead of print.ABSTRACTOcean warming and marine heatwaves significantly alter environmental conditions in marine and estuarine environments. Despite their potential global importance for nutrient security and human health, it is not well understood how thermal impacts could alter the nutritional quality of harvested marine resources. We tested whether short-term experimental exposure to seasonal temperatures, projected ocean-warming temperatures, and marine heatwaves affected the nutritional quality of the eastern school prawn (Metapenaeus macleayi). In addition, we tested whether nutritional quality was affected by the duration of exposure to warm temperatures. We show the nutritional quality of M. macleayi is likely to be resilient to short- (28 d), but not longer-term (56 d) exposure to warming temperatures. The proximate, fatty acid and metabolite compositions of M. macleayi were unchanged after 28 d exposure to simulated ocean warming and marine heatwaves. The ocean-warming scenario did, however, show potential for elevated sulphur, iron and silver levels after 28d. Decreasing saturation of fatty acids in M. macleayi after 28 d exposure to cooler temperatures indicates homeoviscous adaptation to seasonal changes. We found that 11 % of measured response variables were significantly different between 28 and 56 d when exposed to the same treatment, indicating the duration of exposure time and time of sampling are critical when measuring this species' nutritional response. Further, we found that future acute warming events could reduce harvestable biomass, despite survivors retaining their nutritional quality. Developing a combined knowledge of the variability in seafood nutrient content with shifts in the availability of harvested seafood is crucial for understanding seafood-derived nutrient security in a changing climate.PMID:36906039 | DOI:10.1016/j.scitotenv.2023.162778

Int J Pharm. 2023 Mar 9:122813. doi: 10.1016/j.ijpharm.2023.122813. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with serious mucosal inflammation mainly in the colon and rectum. Currently, there is no effective therapeutics for UC. Indoximod (IND) is a water-insoluble inhibitor for indolamine 2, 3-dioxygenase (IDO) and has been mainly reported in cancer therapy. Here, we prepared orally administrated IND nanoparticles (IND-NPs) for UC treatment and investigated their functions and mechanisms in cellular and animal inflammatory models. Confocal imaging demonstrated that IND-NPs maintained the expression level of ZO-1, Occludin and E-cadherin, thereby stabilizing of intercellular junction in Caco-2 cells. It was found that IND-NPs could lower the ROS level and increase mitochondrial membrane potential as well as ATP level, indicating that IND-NPs could restore DSS-induced mitochondrial dysfunction. In the mice model with DSS-induced colitis, IND-NPs were found to alleviate UC-associated symptoms, inhibit inflammatory response, and improve the integrity of epithelial barrier. The untargeted metabolomics analysis validated that IND-NPs also contributed to regulate the metabolite levels to normal. As an agonist of aryl hydrocarbon receptor (AhR), IND-NPs might repair mucosa via the AhR pathway. These findings demonstrated that IND-NPs prominently ameliorated DSS-induced colonic injury and inflammation and preserved intestinal barrier integrity, showing a promising potential in UC treatment.PMID:36905975 | DOI:10.1016/j.ijpharm.2023.122813

J Hazard Mater. 2023 Mar 4;451:131140. doi: 10.1016/j.jhazmat.2023.131140. Online ahead of print.ABSTRACTNanoparticles have been found in large-scale environmental media in recent years, causing toxic effects in various organisms and even humans through food chain transmission. The ecotoxicological impact of microplastics on specific organisms is currently receiving much attention. However, relatively little research to date has examined the mechanisms through which nanoplastic residue may exert an interference effect on floating macrophytes in constructed wetlands. In our study, the aquatic plant Eichhornia crassipes was subjected to 100 nm polystyrene nanoplastics at concentrations of 0.1, 1 and 10 mg L-1 after 28 days of exposure. E. crassipes can decrease the concentration of nanoplastics in water by 61.42∼90.81% through phytostabilization. The abiotic stress of nanoplastics on the phenotypic plasticity (morphological and photosynthetic properties and antioxidant systems as well as molecular metabolism) of E. crassipes was assessed. The presence of nanoplastics reduced the biomass (10.66%∼22.05%), and the functional organ (petiole) diameters of E. crassipes decreased by 7.38%. The photosynthetic efficiency was determined, showing that the photosynthetic systems of E. crassipes are very sensitive to stress by nanoplastics at a concentration of 10 mg L-1. Oxidative stress and imbalance of antioxidant systems in functional organs are associated with multiple pressure modes from nanoplastic concentrations. The catalase contents of roots increased by 151.19% in the 10 mg L-1 treatment groups compared with the control group. Moreover, 10 mg L-1 concentrations of the nanoplastic pollutant interfere with purine and lysine metabolism in the root system. The hypoxanthine content was reduced by 6.58∼8.32% under exposure to different concentrations of nanoplastics. In the pentose phosphate pathway, the phosphoric acid content was decreased by 32.70% at 10 mg L-1 PS-NPs. In the pentose phosphate pathway, the phosphoric acid content was decreased by 32.70% at 10 mg L-1 PS-NPs. Nanoplastics disturb the efficiency of water purification by floating macrophytes, which reduces the chemical oxygen demand (COD) removal efficiency (from 73% to 31.33%) due to various abiotic stresses. This study provided important information for further clarifying the impact of nanoplastics on the stress response of floating macrophytes.PMID:36905907 | DOI:10.1016/j.jhazmat.2023.131140

Phytomedicine. 2023 Mar 2;113:154737. doi: 10.1016/j.phymed.2023.154737. Online ahead of print.ABSTRACTBACKGROUND: Antibiotic-associated diarrhea (AAD) has had a significant increase in the last years, with limited available effective therapies. Shengjiang Xiexin Decoction (SXD), a classic traditional Chinese medicine formula for treating diarrhea, is a promising alternative for reducing the incidence of AAD.PURPOSE: This study aimed to explore the therapeutic effect of SXD on AAD and to investigate its potential therapeutic mechanism by integrated analysis of the gut microbiome and intestinal metabolic profile.METHODS: 16S rRNA sequencing analysis of the gut microbiota and untargeted-metabolomics analysis of feces were performed. The mechanism was further explored by fecal microbiota transplantation (FMT).RESULTS: SXD could effectively ameliorate AAD symptoms and restore intestinal barrier function. In addition, SXD could significantly improve the diversity of the gut microbiota and accelerate the recovery of the gut microbiota. At the genus level, SXD significantly increased the relative abundance of Bacteroides spp (p < 0.01) and decreased the relative abundance of Escherichia_Shigela spp (p < 0.001). Untargeted metabolomics showed that SXD significantly improved gut microbiota and host metabolic function, particularly bile acid metabolism and amino acid metabolism.CONCLUSION: This study demonstrated that SXD could extensively modulate the gut microbiota and intestinal metabolic homeostasis to treat AAD.PMID:36905867 | DOI:10.1016/j.phymed.2023.154737

Ecotoxicol Environ Saf. 2023 Mar 9;254:114736. doi: 10.1016/j.ecoenv.2023.114736. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.PMID:36905847 | DOI:10.1016/j.ecoenv.2023.114736

Food Chem. 2023 Mar 6;417:135817. doi: 10.1016/j.foodchem.2023.135817. Online ahead of print.ABSTRACTThe edible values of P. cocos from different origins vary significantly, therefore, it is important to investigate the traceability of geographical regions and identify the geographical biomarkers of P. cocos. The metabolites of P. cocos of the different geographical origins were assessed using liquid chromatography tandem-mass spectrometry, principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA). The OPLS-DA could clearly discriminate the metabolites of P. cocos from the three cultivation regions (YN, Yunnan; AH, Anhui; JZ, Hunan). Finally, three carbohydrates, four amino acids, and four triterpenoids were selected as biomarkers for P. cocos origin tracing. Correlation matrix analysis revealed that the contents of biomarkers were closely related to geographical origin. Altitude, temperature, and soil fertility were the main factors responsible for the differences in biomarker profiles in P. cocos. The metabolomics approach provides an effective strategy for tracing and identifying the biomarkers of P. cocos from different geographical origins.PMID:36905692 | DOI:10.1016/j.foodchem.2023.135817

Ecotoxicology. 2023 Mar 11. doi: 10.1007/s10646-023-02638-7. Online ahead of print.ABSTRACTCarabids (Coleoptera: Carabidae) are abundant predators in ecosystems and serve as pest biocontrol in agroecosystems and forestry. Here we test the impact of thiamethoxam, among the most used neonicotinoids on the consumption rate, locomotion, metabolomics, and oxidative stress level measuring superoxide dismutase (SOD) activity in a predatory carabid, Abax parallelus (Duftschmid, 1812), after acute exposure in the laboratory trials, to get additional data that might link the use of pesticides and predation efficiency. Beetles were exposed to increasing concentrations of thiamethoxam by dipping method, and left to feed overnight prior to the assays. The results showed that individuals treated with higher concentrations of thiamethoxam (20 and 40 mg/L) consumed significantly less food per body weight and had a higher share of intoxicated and moribund individuals. The mass of consumed food per beetle body weight and observed locomotion did not differ significantly between control and groups treated with lower concentrations of thiamethoxam. There are significant differences in concentrations of some metabolites between treated and control individuals, primary in succinate and d-glucose, indicating a disruption in energy production. On the other hand, there is no statistically significant differences in SOD activity among the groups. To conclude, acute exposure to thiamethoxam can result in negative sub-lethal effects in predatory activity and energy budget, while the effects of long-term exposure to lower doses require further research, as well as field assessment on the predation efficiency after pesticide application.PMID:36905482 | DOI:10.1007/s10646-023-02638-7

Brief Funct Genomics. 2023 Mar 10:elad003. doi: 10.1093/bfgp/elad003. Online ahead of print.ABSTRACTA standard model that is able to generalize data on myriad involvement of the immune system in organismal physio-pathology and to provide a unified evolutionary teleology for immune functions in multicellular organisms remains elusive. A number of such 'general theories of immunity' have been proposed based on contemporaneously available data, starting with the usual description of self-nonself discrimination, followed by the 'danger model' and the more recent 'discontinuity theory.' More recent data deluge on involvement of immune mechanisms in a wide variety of clinical contexts, a number of which fail to get readily accommodated into the available teleologic standard models, makes deriving a standard model of immunity more challenging. But technological advances enabling multi-omics investigations into an ongoing immune response, covering genome, epigenome, coding and regulatory transcriptome, proteome, metabolome and tissue-resident microbiome, bring newer opportunities for developing a more integrative insight into immunocellular mechanisms within different clinical contexts. The new ability to map the heterogeneity of composition, trajectory and endpoints of immune responses, in both health and disease, also necessitates incorporation into the potential standard model of immune functions, which again can only be achieved through multi-omics probing of immune responses and integrated analyses of the multi-dimensional data.PMID:36905355 | DOI:10.1093/bfgp/elad003

Nutrients. 2023 Feb 28;15(5):1208. doi: 10.3390/nu15051208.ABSTRACTAnthocyanins (ACNs) are (poly)phenols associated with reduced cardiometabolic risk. Associations between dietary intake, microbial metabolism, and cardiometabolic health benefits of ACNs have not been fully characterized. Our aims were to study the association between ACN intake, considering its dietary sources, and plasma metabolites, and to relate them with cardiometabolic risk factors in an observational study. A total of 1351 samples from 624 participants (55% female, mean age: 45 ± 12 years old) enrolled in the DCH-NG MAX study were studied using a targeted metabolomic analysis. Twenty-four-hour dietary recalls were used to collect dietary data at baseline, six, and twelve months. ACN content of foods was calculated using Phenol Explorer and foods were categorized into food groups. The median intake of total ACNs was 1.6mg/day. Using mixed graphical models, ACNs from different foods showed specific associations with plasma metabolome biomarkers. Combining these results with censored regression analysis, metabolites associated with ACNs intake were: salsolinol sulfate, 4-methylcatechol sulfate, linoleoyl carnitine, 3,4-dihydroxyphenylacetic acid, and one valerolactone. Salsolinol sulfate and 4-methylcatechol sulfate, both related to the intake of ACNs mainly from berries, were inversely associated with visceral adipose tissue. In conclusion, plasma metabolome biomarkers of dietary ACNs depended on the dietary source and some of them, such as salsolinol sulfate and 4-methylcatechol sulfate may link berry intake with cardiometabolic health benefits.PMID:36904207 | DOI:10.3390/nu15051208

Nutrients. 2023 Feb 27;15(5):1185. doi: 10.3390/nu15051185.ABSTRACTRoux-en-Y Gastric bypass (RYGB) promotes improvement in type 2 diabetes (T2D) shortly after surgery, with metabolic mechanisms yet to be elucidated. This study aimed to investigate the relationship between food intake, tryptophan metabolism, and gut microbiota on the glycemic control of obese T2D women after RYGB surgery. Twenty T2D women who underwent RYGB were evaluated before and three months after surgery. Food intake data were obtained by a seven-day food record and a food frequency questionnaire. Tryptophan metabolites were determined by untargeted metabolomic analysis, and the gut microbiota was determined by 16S rRNA sequencing. The glycemic outcomes were fasting blood glucose, HbA1C, HOMA-IR, and HOMA-beta. Linear regression models were applied to assess the associations between the changes in food intake, tryptophan metabolism, and gut microbiota on glycemic control after RYGB. All variables changed after RYGB (p < 0.05), except for tryptophan intake. Jointly, the variation in red meat intake, plasma indole-3-acetate, and Dorea longicatena was associated with postoperative HOMA-IR {R2 0.80, R2 adj 0.74; p < 0.01}. Red meat intake decreased three months after bariatric surgery while indole-3-acetate and Dorea longicatena increased in the same period. These combined variables were associated with better insulin resistance in T2D women after RYGB.PMID:36904185 | DOI:10.3390/nu15051185

Nutrients. 2023 Feb 24;15(5):1149. doi: 10.3390/nu15051149.ABSTRACTAcute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.PMID:36904149 | DOI:10.3390/nu15051149

Nutrients. 2023 Feb 24;15(5):1143. doi: 10.3390/nu15051143.ABSTRACTProtein-energy malnutrition still impacts children's growth and development. We investigated the prolonged effects of egg supplementation on growth and microbiota in primary school children. For this study, 8-14-year-old students (51.5% F) in six rural schools in Thailand were randomly assigned into three groups: (1) whole egg (WE), consuming 10 additional eggs/week (n = 238) (n = 238); (2) protein substitute (PS), consuming yolk-free egg substitutes equivalent to 10 eggs/week (n = 200); and (3) control group (C, (n = 197)). The outcomes were measured at week 0, 14, and 35. At the baseline, 17% of the students were underweight, 18% were stunted, and 13% were wasted. At week 35, compared to the C group the weight and height difference increased significantly in the WE group (3.6 ± 23.5 kg, p < 0.001; 5.1 ± 23.2 cm, p < 0.001). No significant differences in weight or height were observed between the PS and C groups. Significant decreases in atherogenic lipoproteins were observed in the WE, but not in PS group. HDL-cholesterol tended to increase in the WE group (0.02 ± 0.59 mmol/L, ns). The bacterial diversity was similar among the groups. The relative abundance of Bifidobacterium increased by 1.28-fold in the WE group compared to the baseline and differential abundance analysis which indicated that Lachnospira increased and Varibaculum decreased significantly. In conclusion, prolonged whole egg supplementation is an effective intervention to improve growth, nutritional biomarkers, and gut microbiota with unaltered adverse effects on blood lipoproteins.PMID:36904143 | DOI:10.3390/nu15051143

Nutrients. 2023 Feb 22;15(5):1100. doi: 10.3390/nu15051100.ABSTRACTHuman milk (HM) is a complex biofluid containing a wide cell variety including epithelial cells and leukocytes. However, the cellular compositions and their phenotypic properties over the course of lactation are poorly understood. The aim of this preliminary study was to characterize the cellular metabolome of HM over the course of lactation. Cells were isolated via centrifugation and the cellular fraction was characterized via cytomorphology and immunocytochemical staining. Cell metabolites were extracted and analyzed using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QqTOF-MS) in the positive and negative electrospray ionization modes. Immunocytochemical analysis revealed a high variability of the number of detected cells with relative median abundances of 98% of glandular epithelial cells, 1% of leukocytes, and 1% of keratinocytes. Significant correlations between the milk postnatal age with percentage of epithelial cells and leukocytes, and with total cell count were observed. Results from the Hierarchical Cluster Analysis of immunocytochemical profiles were very similar to those observed in the analysis of the metabolomic profiles. In addition, metabolic pathway analysis showed alterations in seven metabolic pathways correlating with postnatal age. This work paves the way for future investigations on changes in the metabolomic fraction of the cellular compartment of HM.PMID:36904100 | DOI:10.3390/nu15051100