PubMed

Front Mol Biosci. 2023 May 15;10:1168782. doi: 10.3389/fmolb.2023.1168782. eCollection 2023.ABSTRACTBackground and Objective: Transjugular intrahepatic portal shunt (TIPS) insertion could promote weight gain and muscle and fat mass increase in patients with cirrhosis. However, few studies have focused on metabolic changes after TIPS. This study aims to explore metabolic changes after TIPS and potential biomarkers of adverse events. Methods: Peripheral and portal serum samples were collected before and after TIPS insertion. Untargeted metabolomics was performed using ultra-high-performance liquid chromatography-mass spectrometry. Spearman's correlation analysis was used to determine the relationship between metabolites and clinical parameters. Metabolite set enrichment analysis was performed to explore enriched pathways. The predictive value of the metabolites was calculated by receiver operating characteristic curve (ROC) analysis. Results: Metabolites in the peripheral and portal serum significantly changed early after TIPS. Some lipid metabolites were significantly correlated with liver function parameters. Both elevated and depleted metabolites were mainly enriched in amino acid metabolism. Nine and 12 portal metabolites have moderate predictive value in post-TIPS liver function decline and hepatic encephalopathy (HE), separately (area under curve >0.7). Conclusion: Metabolites in the peripheral and portal veins significantly changed after TIPS. Some metabolic changes might be ascribed to liver function decline early after TIPS. Nine and 12 portal metabolites might be potential biomarkers in prediction of liver function decline and HE, separately.PMID:37255539 | PMC:PMC10225654 | DOI:10.3389/fmolb.2023.1168782

Elife. 2023 May 31;12:e81289. doi: 10.7554/eLife.81289. Online ahead of print.ABSTRACTNutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels and how cancer cells cope with such nutrition is critical to understand the metabolism underpinning cancer cell biology. Previously, we performed quantitative metabolomics of the interstitial fluid (the local perfusate) of murine pancreatic ductal adenocarcinoma (PDAC) tumors to comprehensively characterize nutrient availability in the microenvironment of these tumors (M. R. Sullivan, Danai, et al., 2019). Here, we develop Tumor Interstitial Fluid Medium (TIFM), a cell culture medium that contains nutrient levels representative of the PDAC microenvironment, enabling us to study PDAC metabolism ex vivo under physiological nutrient conditions. We show that PDAC cells cultured in TIFM adopt a cellular state closer to that of PDAC cells present in tumors compared to standard culture models. Further, using the TIFM model, we found arginine biosynthesis is active in PDAC and allows PDAC cells to maintain levels of this amino acid despite microenvironmental arginine depletion. We also show that myeloid derived arginase activity is largely responsible for the low levels of arginine in PDAC tumors. Altogether, these data indicate that nutrient availability in tumors is an important determinant of cancer cell metabolism and behavior, and cell culture models that incorporate physiological nutrient availability have improved fidelity to in vivo systems and enable the discovery of novel cancer metabolic phenotypes.PMID:37254839 | DOI:10.7554/eLife.81289

Br Poult Sci. 2023 May 31. doi: 10.1080/00071668.2023.2214884. Online ahead of print.ABSTRACT1. A new assessment method for duck footpad dermatitis (FPD) evaluation was developed, combining visual and histological characters using the images and sections of 400 ducks' feet at 340 d of age. All ducks were graded as G0 (healthy), G1 (mild), G2 (moderate) and G3 (severe) according to the degree of FPD.2. To reveal the potential biomarkers in serum related to duck FPD, non-targeted metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore differential metabolites in each group.3. There were 57, 91 and 210 annotated differential metabolites in groups G1, G2 and G3 compared with G0, which meant that the severity of FPD increasedin line with the number of metabolites. Four metabolites, L-phenylalanine, L-arginine, L-leucine and L-lysine, were considered potential biomarkers related to FPD.4. KEGG enrichment analysis showed that the FPD was mainly involved in glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway and amino acid metabolism. These are related to production metabolism and can affect the physiological activities of ducks, which might explain the decrease in production performance.PMID:37254666 | DOI:10.1080/00071668.2023.2214884

Nutr Cancer. 2023 May 30:1-12. doi: 10.1080/01635581.2023.2217542. Online ahead of print.ABSTRACTDietary protein has been shown to impact physiology and pathophysiology, including inflammation and cancer, effects believed to occur through host and microbe-mediated mechanisms. However, the majority of studies investigating this concept have been conducted in animal models, with less information on the optimal approach, tolerability and biologic effects of modifying protein intake in humans. The current study presents a longitudinal controlled feeding trial carried out in healthy humans to acutely modulate protein intake using individualized diets. Adherence to study diets was monitored through subject-reported electronic picture-based assessments and global metabolomic analysis was performed on serum and stool, following each diet stage. Subjects exhibited strong adherence to study diets, with macronutrient intake meeting study goals during each stage. Metabolomic analysis revealed shifts in both serum and feces in association with modifying protein intake, including reciprocal changes in the abundance of amino acids and amino-acid related compounds, when comparing high to reduced protein stages. Additional fecal metabolite changes consisted of reduced microbial fermentation products following the reduced protein diet stage. Collectively, this study provides a robust method to precisely modify and monitor protein intake in humans, as well as assess corresponding metabolomic alterations.PMID:37254527 | DOI:10.1080/01635581.2023.2217542

Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231175768. doi: 10.1177/15330338231175768.ABSTRACTOBJECTIVES: PLU1 is upregulated in many cancers, including breast, mammary, colorectal, and hepatocellular carcinoma. However, little is known about the potential metabolic mechanisms of PLU1 in glioma progression. Therefore, we investigated the relationship between PLU1 and glioma development.METHODS: We analyzed the relationship between PLU1 expression and World Health Organization (WHO) grade using clinical databases and verified the role of PLU1 in glioma development using transcriptome sequencing, Western blotting, Cell Counting Kit 8, colony formation, and wound healing assays. The relationship between PLU1 and glioma glucose metabolism was also initially explored by changing the concentration of glucose in the culture medium and was validated by metabolomics and energy metabolism.RESULT: PLU1 expression was closely related to WHO grade and was significantly elevated in tumor tissues compared to nontumor tissues. Knockdown or inhibition of PLU1 inhibits proliferation and migration of glioma cells. In addition, we found that PLU1 expression was closely associated with glioma metabolism by transcriptomic, metabolomic, and energy-related molecular analyses and correlated with glucose metabolism. We also found that glucose concentration affects PLU1 expression, and that PLU1 expression affects intracellular glucose levels.CONCLUSION: PLU1 is a novel regulator of metabolic reprograming and a novel strategy for the treatment of glioma.PMID:37254514 | DOI:10.1177/15330338231175768

Food Res Int. 2023 Jul;169:112856. doi: 10.1016/j.foodres.2023.112856. Epub 2023 Apr 28.ABSTRACTChili pepper (Capsicum spp.) is one of the world's most popular vegetables and spices. Aroma is an important quality indicator of pepper, but the nature of the related volatiles is still not clear. In this study, we investigated the fruit of two pepper varieties, one with strong fruity aroma 'CC' Capsicum chinense and one without 'TJ' Capsicum annuum at four different developmental stages using transcriptomic and metabolomic analysis. The results showed that the content of green leaf volatiles (GLVs) was higher in TJ than in CC and was higher in the young fruit stage in both varieties. GLVs content was positively correlated with the expression of 13-LOX1, 2, 5 and HPL. But the levels of branched-chain (BC) esters and capsaicin were higher in CC, and were positively correlated with the expression of IMPS4 and DADH1. Our findings shed light on the molecular mechanism of aroma biosynthesis in pepper and provide a theoretical basis for the molecular breeding of high-quality pepper fruits.PMID:37254430 | DOI:10.1016/j.foodres.2023.112856

Food Res Int. 2023 Jul;169:112832. doi: 10.1016/j.foodres.2023.112832. Epub 2023 Apr 17.ABSTRACTHop is widely used in beer brewing and as a medicinal product. The present study comprehensively analyzed the main molecular determinants of the antibacterial activity of hop extracts. Minimum inhibitory concentrations (MIC) against Bacillus subtilis between 31.25 and 250 µg/mL were found in the ethanolic extracts of five hop varieties for beer brewing, but not in the tea hop sample. Activity-guided fractionation revealed the highest antibacterial activity for lupulone and adlupulone (MIC 0.98 µg/mL). Metabolome profiling and subsequent multistep statistical analysis detected 33 metabolites out of 1826 features to be associated with the antibacterial activity including humulone, adhumulone, colupulone, lupulone, and adlupulone. Xanthohumol, the three humulone- and three lupulone congeners were quantified in the hop extracts by a validated ultrahigh-performance liquid chromatography-mass spectrometry method. Considering concentrations and MICs, colupulone and lupulone were identified as major contributors to the antibacterial activity of hop extract with the highest antibacterial activity values (concentration/MIC) of 1.59 and 2.56.PMID:37254407 | DOI:10.1016/j.foodres.2023.112832

Food Res Int. 2023 Jul;169:112831. doi: 10.1016/j.foodres.2023.112831. Epub 2023 Apr 17.ABSTRACTSesame seeds contain several lipids and fragrances that offer health benefits. However, no studies have reported a relationship between the lipids or flavor compounds of sesame seeds and environmental factors. In this study, we aimed to identify this relationship by analyzing the contents of lipidic and flavor compounds in fifteen genotypes of sesame seeds grown in two cultivation regions (Jeonju and Miryang) and years (2018 and 2019). Herein, 17 lipids and 62 flavor compounds were detected. Multivariate statistical analyses revealed that the cultivation year had a larger influence on the contents of lipidic and flavor compounds than the cultivation region and genotype. Furthermore, heat stress due to high cultivation temperature in 2018 caused the accumulation of sugar and secondary metabolites, increased flavor-related substances, and inhibited the degradation of fatty acids. Our study is the first to demonstrate the metabolic changes in lipids and flavor components of sesame in response to environmental temperature changes affected by different cultivation years. Therefore, this study provides guidance for the cultivation of commercially advantageous sesame seeds in improving the quality of sesame seeds and their products.PMID:37254406 | DOI:10.1016/j.foodres.2023.112831

Food Res Int. 2023 Jul;169:112829. doi: 10.1016/j.foodres.2023.112829. Epub 2023 Apr 17.ABSTRACTIn this study, metabolomic analysis was employed to investigate the separation (fractionation) of active compounds into lemon juice (LJ) and lemon pomace (LP) during lemon juicing. A total of 968 metabolites were identified, and 438 differentially abundant metabolites (DAMs) were screened out between LJ and LP, suggesting significant metabolite fractionation during juicing. The "flavonoids", "phenolic acids", and "saccharides and alcohols" were mainly retained in the LP, while the fractionation of major "organic acids" was differentiated. Seven of the 12 potential bitter metabolites were more abundant in the LP and two were more abundant in the LJ, suggesting that LP would be more bitter. L-Ascorbic acid, thiamine, and acitretin were significantly lost during juicing, while riboflavin was newly dissolved during juicing. The antioxidant capacity of LP was significantly higher than that of LJ, which was closely related to the higher abundance of phenolic acid metabolites in LP. These findings suggtested that promoting the release of flavonoids and phenolic acids from LP is a potential strategy to improve the quality of LJ. Results also provides important information and reference for developing high-value products by using LP.PMID:37254405 | DOI:10.1016/j.foodres.2023.112829

Food Res Int. 2023 Jul;169:112761. doi: 10.1016/j.foodres.2023.112761. Epub 2023 Mar 31.ABSTRACTQuinoa is considered a "full nutritional food" owing to its high nutrition value. However, the whole grain form of quinoa is not always convenient direct consumption in everyday life. Extrusion is effective viable solution to this issue. In this study, the metabolic characterization of white quinoa (WQ) and extruded white quinoa (EWQ) was performed by investigating the characteristic amino acids, fatty acids, organic acids, and phenolic content of WQ after extrusion. A total of 24 amino acids, 25 organic acids, 32 fatty acids and 50 phenolics were identified in both WQ and EWQ, The results showed that extrusion and extrusion temperature significantly (p < 0.05) affect the content of amino acids, fatty acids, organic acids and phenolics in WQ. For example, the content of glutaconic acid (1231.9 μg/g of EWQ-180 to 1926.4 μg/g of WQ) and L-aspartic acid (115.47 μg/g of EWQ-140 to 643.70 μg/g of WQ) in WQ was significantly decreased, while L-serine (138.01 μg/g of WQ to 201.04 μg/g of EWQ-160) was increased respectively after extrusion. Among the EWQ samples, the highest content of glutaconic acid (1447.9 μg/g), L-aspartic acid (270.32 μg/g), and L-serine (201.04 μg/g) was observed in EWQ-160, EWQ-180 and EWQ-160, respectively. These results indicated extrusion affects the content of various amino acids differently and that the changes are dependent on the extrusion temperature. Similar result was also observed for fatty acids, organic acids, and phenolics. In conclusion, extrusion has potential in the processing of quinoas and the metabolic characterization of amino acids, fatty acids, organic acids, and phenolics in grains could be effectively analyzed using metabolomics.PMID:37254376 | DOI:10.1016/j.foodres.2023.112761

Food Res Int. 2023 Jul;169:112943. doi: 10.1016/j.foodres.2023.112943. Epub 2023 May 8.ABSTRACTThis study aimed to comprehensively elucidate the vital secondary metabolites of Wuchang Daohuaxiang (DHX) rice through widely targeted metabolomics analysis. Among the secondary metabolites detected, a total of 30 differential ones were screened out and categorized into 4 different classes, including 6 alkaloids (20%), 15 flavonoids (50%), 6 phenolic acids (20%), and 3 terpenoids (10%) between DHX and control groups. Of these, compounds as zarzissine, fagomine, arbutin, p-Hydroxypheny-β-D-allopyranoside, pimaric acid, kaurenoic acid, and isopimaric acid were more abundant in DHX than control group, with the possibility in serve as key secondary metabolites of DHX rice. Furthermore, arbutin, trigonelline and 6'-O-Feruloyl-D-sucrose were optimized as potential biomarkers for DHX rice discrimination. This study would supply data support for DHX rice authenticity and quality improvement.PMID:37254367 | DOI:10.1016/j.foodres.2023.112943

Food Res Int. 2023 Jul;169:112942. doi: 10.1016/j.foodres.2023.112942. Epub 2023 May 4.ABSTRACTLimited evidence suggests that the abundance of antioxidant polyphenols in dry red wine (DRW) may prevent cardiovascular diseases, a benefit likely attributed to abundant antioxidant polyphenols present in DRW. Here, we examined the anti-atherosclerotic effect of Cabernet Sauvignon DRW (CSDRW) in a mouse model of atherosclerosis (AS) using metabolomic profiling and molecular techniques. Oral administration of CSDRW reduced atherosclerotic lesion size in ApoE-/- mice, alleviated hyperlipidemia, ameliorated hepatic lipid accumulation mediated by AMPK activation, and promoted lipid metabolism via PPARγ-LXR-α-ABCA1 pathway regulation. CSDRW increased the relative abundance of beneficial gut microbiota, including Bacteroidetes, Verrucomicrobiota, and Akkermansiaceae. Metabolic analysis using liquid chromatography-tandem mass spectrometry revealed that CSDRW contained various polyphenols, including flavanol, phenolic acid, flavonol, and resveratrol, which possibly mediate the beneficial effects in AS by reducing inflammation, restoring normal endothelial function, regulating hepatic lipid metabolism, and modulating gut microbiota composition.PMID:37254366 | DOI:10.1016/j.foodres.2023.112942

Food Res Int. 2023 Jul;169:112908. doi: 10.1016/j.foodres.2023.112908. Epub 2023 Apr 29.ABSTRACTBlack soybeans are extensively planted and consumed in China due to their high nutritional value and numerous health benefits. However, very few is known about the characteristic metabolites of black soybeans from different geographical origins in China. In the present study, 31 black soybean samples were collected from 11 main producing provinces in China. A combined metabolomics approach using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatography coupled to an Orbitrap mass analyzer (GC-orbitrap-MS) was performed for the first time to comprehensively investigate the metabolite variability among the black soybeans from different geographical origins. A total of 48 differential non-volatile metabolites and 14 differential volatile metabolites were identified based on orthogonal partial least squares discriminant analysis (OPLS-DA) coupled with analysis of variance (ANOVA). Higher procyanidin B1, procyanidin B2, epicatechin, malonylated isoflavones, and β-pinene were observed in Gansu black soybeans. Guangxi black soybeans had higher amounts of linoleic acid and its oxidation products of hexanal and pentane. The black soybeans from Xinjiang and Yunnan were found to have higher delphinidin-derived anthocyanins, gamma-glutamyl peptides, and aromatic hydrocarbons. The characteristic metabolites of black soybeans from other geographical origins were also clarified. This study indicated that the integrated untargeted metabolomic approach can be a powerful tool to provide knowledge for developing specialty black soybeans.PMID:37254343 | DOI:10.1016/j.foodres.2023.112908

Food Res Int. 2023 Jul;169:112865. doi: 10.1016/j.foodres.2023.112865. Epub 2023 Apr 22.ABSTRACTFermentation plays a key role in taste formation in traditional fermented golden pompano and involves a series of complex metabolic reactions. Indeed, the taste profile of fermented golden pompano exhibits remarkable variation during early fermentation. Herein, nutritional fingerprinting (proteins, amino acids, lipids, etc.) was applied to discriminate the various biomolecular changes involved in golden pompano fermentation. Among the differential metabolites, amino acids, small peptides, lipids, and nucleotides were considered taste-related compounds. An increase in the amino acid content was observed during fermentation, while the peptide content decreased. Glutamic acid, alanine, and lysine had the highest taste activity values and were the main contributors to taste formation. Metabolic pathway enrichment analysis revealed that taste formation was primarily associated with alanine, aspartate, and glutamate metabolism. These findings provide a deeper understanding of taste mechanisms and establish a basis for the targeted regulation of taste formation in the fermented fish industry.PMID:37254315 | DOI:10.1016/j.foodres.2023.112865

Environ Microbiome. 2023 May 30;18(1):44. doi: 10.1186/s40793-023-00496-8.ABSTRACTBACKGROUND: Understanding the functional diversity, composition, and dynamics of microbiome is critical for quality in composting. Denitrifying microbiota, possessing multiple metabolic pathways simultaneously. Denitrification-based biodegradation of aromatic metabolites has been widely applied in the bioremediation of sediments. However, role in biodegradation of denitrifying microbiota in kitchen waste composting remain unclear. In this study, microbiome and metabolome were used to comprehensively decipher the relationship of denitrifying microbiota and aromatic metabolites, and its implication in kitchen waste (KW) composting.RESULTS: This study was investigated by adjusting moisture content 60% as control test (CK), 70% as denitrification test (DE). In addition, one tests referred as DE + C, which received 10% of biochar to amend denitrification. Results indicated the quantities of denitrification genes narG were 1.22 × 108 copies/g in DE at the 55th day, which were significantly higher than that in CK and DE + C (P < 0.05). Similarly, the abundance of nirK gene also significantly increased in DE (P < 0.05). The relative abundance of denitrification-related microbes in DE was higher than that in CK, DE + C could weaken their abundance. Metabolomics results demonstrated that metabolites were downgraded in aromatic amino acid and catechin metabolic pathways in DE, which were identified as precursors to synthesis key product fulvic acid. The concentrations of fulvic acid dramatically decreased 21.05 mg/g in DE comparison with CK. Biochar addition alleviated the biodegradation of aromatic metabolites and reduced the utilization of fulvic acid. Integrative analyses of metabolomics and microbiome suggested that the microbiota involved in nitrite reduction pathway was vital for the biodegradation aromatic metabolites. Mantel test verified that NO3--N, moisture content, eta, environmental factors were important drivers behind the changes in the denitrifying microbiota biodegradation function.CONCLUSION: The data confirm the biodegradation function of denitrifying microbiota led to the loss of core product fulvic acid in KW composting, which highlighted the adverse role and implication of denitrification for composting humification. Control of denitrification with biochar was recommended to improve composting quality.PMID:37254173 | DOI:10.1186/s40793-023-00496-8

BMC Plant Biol. 2023 May 30;23(1):288. doi: 10.1186/s12870-023-04295-8.ABSTRACTBACKGROUND: Plants in the genus Artemisia are rich in active ingredients and specialized metabolites. Many of these compounds, especially flavonoids, have potential medicinal and nutritional applications, and are of growing interest to scientists due to their wide range of pharmacological and biological activities. Artemisia cultivars are commonly used as raw materials for medicine, food, and moxibustion in China. However, most of the metabolites produced by Artemisia species have not been identified, and few studies have addressed differences in active compounds between species and cultivars.RESULTS: We here investigated two Artemisia cultivars, 'Nanyangshiyong' (NYSY) and 'Nanyangyaoyong' (NYYY), which are commonly used in foods and moxibustion, respectively. NYSY and NYYY were confirmed to be Artemisia argyi cultivars. Total flavonoids contents and antioxidant activities were higher in NYYY than in NYSY. A total of 882 metabolites were identified in the samples; most of the potentially medicinally active compounds, especially flavonoids (e.g., flavone, flavonol, isoflavone, and anthocyanin), were up-regulated in NYYY compared to NYSY. Furthermore, most of the genes related to flavonoids biosynthesis were up-regulated in NYYY. Correlation analysis was used to identify putative members of transcription factor families that may regulate genes encoding key flavonoids biosynthesis enzymes.CONCLUSIONS: We found that the antioxidant activities and flavonoids contents significantly varied between two Artemisia cultivars of the same species. We also uncovered metabolomic and transcriptomic evidence of the molecular phenomena underlying those differences in flavonoids contents between the two Artemisia cultivars. This study provides a wealth of data for future utilization and improvements of Artemisia cultivars, and highlights a need to study the specific metabolite profiles of plants that are used in foods and medicines.PMID:37254042 | DOI:10.1186/s12870-023-04295-8

Nat Aging. 2022 Jul;2(7):680. doi: 10.1038/s43587-022-00258-0.NO ABSTRACTPMID:37253873 | DOI:10.1038/s43587-022-00258-0

Nat Commun. 2023 May 30;14(1):3120. doi: 10.1038/s41467-023-38710-3.ABSTRACTMarginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.PMID:37253729 | DOI:10.1038/s41467-023-38710-3

Nat Commun. 2023 May 30;14(1):3111. doi: 10.1038/s41467-023-38800-2.ABSTRACTCirculating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.PMID:37253714 | DOI:10.1038/s41467-023-38800-2

BMJ Open Diabetes Res Care. 2023 May;11(3):e003282. doi: 10.1136/bmjdrc-2022-003282.ABSTRACTINTRODUCTION: Gut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized that FMT may be a potential therapeutic method for T2DM, but its precise mechanisms in T2DM remains to be elucidated.RESEARCH DESIGN AND METHODS: Eight db/m mice were FMT donors and control mice, and 16 genetically diabetic db/db mice were equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The db/db+FMT group was administered fresh fecal suspension (0.2 mL/mice) daily for 4 weeks. Analysis of the GM and serum metabolome was carried out by 16S ribosomal RNA sequencing and liquid chromatogram-mass spectrometry, respectively. Effects of FMT on the gut barrier and pancreas were assessed using protein assays, messenger RNA, immunohistology and clinical indicators testing.RESULTS: Our results showed that FMT treatment of db/db mice relieves a series of clinical indicators, including fasting plasma glucose, serum insulin and oral glucose tolerance test among others. Compared with non-diabetic control mice, db/db+PBS mice exhibited decreased abundance of Ruminococaceae, Porphyromonadaceae and increased abundance of Rikenellaceae and Lactobacillaceae. FMT treatment reversed this effect on the microbiome. Eleven metabolites were changed between the db/db+PBS and db/db+FMT groups. Correlation analysis showed that the structural changes of the GM were correlated with host metabolite levels. We further showed that FMT treatment of db/db mice improved intestinal barrier function, reduced inflammation and caused an alteration in the number of circulating immune cells.CONCLUSIONS: FMT-mediated changes in the GM, serum metabolites, intestinal epithelial barrier, inflammation and circulating immune cells play an important role in the efficacy of FMT on T2DM disease progression.PMID:37253485 | DOI:10.1136/bmjdrc-2022-003282