Myristoleic acid

Metabolomic profiles in Jamaican children with and without autism spectrum disorder.[Pubmed:38560734]

ArXiv [Preprint]. 2024 Mar 11:arXiv:2403.07147v1.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a wide range of behavioral and cognitive impairments. While genetic and environmental factors are known to contribute to its etiology, the underlying metabolic perturbations associated with ASD which can potentially connect genetic and environmental factors, remain poorly understood. Therefore, we conducted a metabolomic case-control study and performed a comprehensive analysis to identify significant alterations in metabolite profiles between children with ASD and typically developing (TD) controls. OBJECTIVE: To elucidate potential metabolomic signatures associated with ASD in children and identify specific metabolites that may serve as biomarkers for the disorder. METHODS: We conducted metabolomic profiling on plasma samples from participants in the second phase of Epidemiological Research on Autism in Jamaica (ERAJ-2), which was a 1:1 age (+/-6 months)-and sex-matched cohort of 200 children with ASD and 200 TD controls (2-8 years old). Using high-throughput liquid chromatography-mass spectrometry techniques, we performed a targeted metabolite analysis, encompassing amino acids, lipids, carbohydrates, and other key metabolic compounds. After quality control and imputation of missing values, we performed univariable and multivariable analysis using normalized metabolites while adjusting for covariates, age, sex, socioeconomic status, and child's parish of birth. RESULTS: Our findings revealed unique metabolic patterns in children with ASD for four metabolites compared to TD controls. Notably, three of these metabolites were fatty acids, including Myristoleic acid, eicosatetraenoic acid, and octadecenoic acid. Additionally, the amino acid sarcosine exhibited a significant association with ASD. CONCLUSIONS: These findings highlight the role of metabolites in the etiology of ASD and suggest opportunities for the development of targeted interventions.

Application of benzothiadiazole to Cabernet Gernischt grapes (Vitis vinifera L.) for quality improvement: Effects on aroma metabolism precursors and related genes expression.[Pubmed:38513517]

Plant Physiol Biochem. 2024 Mar;208:108537.

Pre-harvest spraying of benzothiadiazole (BTH) can improve the winemaking properties of grapes, especially their aroma compounds and phenolics. Limited research has explored the molecular mechanisms by which BTH influences the accumulation of grape aroma precursors during early grape development. This study investigated the effects and putative molecular mechanisms of applying 0.37 mM BTH through whole-plant spraying on the accumulation of aroma metabolism precursors and gene expression in Cabernet Gernischt grapes during ripening. The results showed that BTH treatment increased the levels of fructose, alanine, aspartate, threonine, myristic acid, Myristoleic acid, palmitic acid, beta-cryptoxanthin, norisoprenoids and methoxypyrazines. Contrarily, it decreased the levels of glucose, sucrose, phenylalanine, tyrosine, leucine, valine, glycine, arginine, histidine, total unsaturated fatty acids (particularly linoleic acid), zeaxanthin, lutein, and organic acids. Additionally, BTH upregulated the expression of genes associated with the production and degradation of amino acids, fatty acids, and carotenoids while decreasing the expression of genes involved in the synthesis and degradation of soluble sugars and organic acids. Ten different metabolites, including fumaric acid, were identified as potential biological markers for distinguishing BTH-treated grapes from control grapes. The study demonstrates that BTH treatment had a substantial impact on the concentration and developmental patterns of aroma metabolism precursors. Furthermore, it altered the winemaking characteristics of Cabernet Gernischt grapes by modulating genes associated with the production and breakdown of metabolites.

Metabolomic profiling of pediatric post-tonsillectomy pain: A proof-of-concept study.[Pubmed:38466029]

Paediatr Anaesth. 2024 Mar 11.

INTRODUCTION: Tonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate-to-severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post-tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post-tonsillectomy pain. METHODS: Venous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy +/- adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain. RESULTS: Pain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post-tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and Myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post-tonsillectomy pain, with AUC values ranging from 0.85 to 0.95. CONCLUSION: This study identified novel candidate biomarker panels that effectively differentiated varying severity of post-tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries.

Identification of four genes responsible for antimicrobial resistance of MEL-B against S. aureus.[Pubmed:38290176]

Biochem Biophys Res Commun. 2024 Mar 5;699:149566.

There is increasing interest in the antimicrobial activity of mannosylerythritol lipids-B (MEL-B) against Gram-positive bacteria such as Staphylococcus aureus (S. aureus). However, the specific molecules involved in MEL-B's antimicrobial action against S. aureus have not been identified. This study utilized the Nebraska transposon mutant library (NTML), which contains 1920 mutants, each lacking three-quarters of the genes found in S. aureus. The NTML was screened to identify mutants resistant to MEL-B. Four mutants (Accession Number: SAUSA300_0904, SAUSA300_0752, SAUSA300_0387, and SAUSA300_2311) largely unaffected by incubation with MEL-B, indicating MEL-B resistance. Despite the strong binding of MEL-B to these mutants, the four molecules encoded by the deleted genes (yjbI, clpP, pbuX, or brpS) in each mutant were not directly recognized by MEL-B. Given that these molecules are not localized on the outer surface of S. aureus and that the antibacterial activity of MEL-B against S. aureus is facilitated by the effective transfer of two antibacterial fatty acids (caprylic acid and Myristoleic acid) to S. aureus via ME, the deletion of each of the four molecules may alter the peptidoglycan structure, potentially inhibiting the effective transfer of these antimicrobial fatty acids into S. aureus.

The Specificities of Lysophosphatidic Acid Acyltransferase and Fatty Acid Desaturase Determine the High Content of Myristic and Myristoleic Acids in Cyanobacterium sp. IPPAS B-1200.[Pubmed:38255848]

Int J Mol Sci. 2024 Jan 7;25(2):774.

The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes for lysophosphatidic acid acyltransferase (LPAAT; EC 2.3.1.51) and Delta9 fatty acid desaturase (FAD; EC 1.14.19.1) from Cyanobacterium sp. IPPAS B-1200 in Synechococcus elongatus PCC 7942, which synthesizes myristic and Myristoleic acids at the level of 0.5-1% and produces mainly palmitic (~60%) and palmitoleic (35%) acids. S. elongatus cells that expressed foreign LPAAT synthesized myristic acid at 26%, but did not produce Myristoleic acid, suggesting that Delta9-FAD of S. elongatus cannot desaturate FAs with chain lengths less than C16. Synechococcus cells that co-expressed LPAAT and Delta9-FAD of Cyanobacterium synthesized up to 45% palmitoleic and 9% Myristoleic acid, suggesting that Delta9-FAD of Cyanobacterium is capable of desaturating saturated acyl chains of any length.

Enhancement of antimicrobial and antibiofilm activities of liposomal fatty acids.[Pubmed:38070368]

Colloids Surf B Biointerfaces. 2024 Feb;234:113698.

Microbial biofilms are protected surface-attached communities of bacteria or fungi with high drug tolerance that typically cause persistent infections. Smart drug carriers are being explored as a promising platform of antimicrobials to address their recalcitrance to antibiotic agents and minimize the side effects of current therapies. In this study, soy lecithin liposomes loaded with lauric acid (LA) and Myristoleic acid (MA) were formulated using an emulsification method, and their antibiofilm properties were evaluated. The physio-chemical properties of the most potent liposome were characterized using a zeta sizer, transmission electron microscopy (TEM), fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. TEM and zeta sizer analysis of the liposome revealed a homogeneous spherical structure with an average size of 159.2 nm and zeta potential of - 5.4 mV. The unilamellar liposomes loaded with LA at 0.1-0.5 microg/mL achieved obvious antibiofilm efficiency against Staphylococcus aureus and Candida albicans and their dual biofilms. Also, LA-loaded liposome formulation efficiently disrupted preformed biofilms of S. aureus and C. albicans. Furthermore, formulated liposomal LA (0.1 microg/mL) exhibited 100-fold increased dual biofilm inhibition compared to LA alone. The single biofilms and dual biofilm formation on polystyrene were reduced as determined by 3D-bright field and scanning electron microscopy. Zeta potential measurements exhibited neutralized surface charge of S. aureus, and the liposomes inhibited hyphae formation in C. albicans. These findings demonstrated that the LA-incorporated liposomes have great potential to become a new, effective, and good antibiofilm agent for treating S. aureus and C. albicans infections.

Effects of Supplementing Growing-Finishing Crossbred Pigs with Glycerin, Vitamin C and Niacinamide on Carcass Characteristics and Meat Quality.[Pubmed:38066986]

Animals (Basel). 2023 Nov 24;13(23):3635.

The objective of this study was to determine the influence of supplementing the diet of growing-finishing pigs with glycerin and/or a mixture of vitamin C and niacinamide on carcass traits and pork quality. Eighty-four weaned piglets with an initial average body weight of 20.35 +/- 2.14 kg were assigned, at random, to four groups for a 103-day feeding experiment: control; glycerin-supplemented group; vitamin C and niacinamide-supplemented group; and glycerin, vitamin C and niacinamide-supplemented group. At the end of the experiment, three pigs/group were randomly selected and slaughtered, and samples were collected for analysis. The results indicated that supplementing crossbred pigs with glycerin, vitamin C and niacinamide simultaneously increased the redness (a*) value (p < 0.05), glycerol content (p < 0.01) and Myristoleic acid content (p < 0.01) in the longissimus dorsi and tended to increase the level of flavor amino acids, linoleic acid, linolenic acid and erucic acid, as well as the percentage and density of type I myofibers in the longissimus dorsi and the semimembranosus muscle. Glycerin had an influence (p < 0.01) on the erucic acid content in the longissimus dorsi and the semimembranosus muscle, and vitamin C and niacinamide had an interaction effect (p < 0.05) on the redness (a*) value of the longissimus dorsi. Glycerin, vitamin C and niacinamide supplementation in the diet of crossbred pigs improved the color, flavor and nutritional value of pork, which contributed to an increased intent to purchase this product.

A Metabolomics Analysis of a Novel Phenotype of Older Adults at Higher Risk of Dementia.[Pubmed:37781807]

J Alzheimers Dis. 2023 Sep 28.

BACKGROUND: Older adults presenting with dual-decline in cognition and walking speed face a 6-fold higher risk for dementia compared with those showing no decline. We hypothesized that the metabolomics profile of dual-decliners would be unique even before they show signs of decline in cognition and gait speed. OBJECTIVE: The objective of this study was to determine if plasma metabolomics signatures can discriminate dual-decliners from no decliners, purely cognitive decliners, and purely motor decliners prior to decline. METHODS: A retrospective cross-sectional study using baseline plasma for untargeted metabolomics analyses to investigate early signals of later dual-decline status in study participants (n = 76) with convenient sampling. Dual-decline was operationalized as decline in gait speed (>10 cm/s) and cognition (>2 points decline in Montreal Cognitive Assessment score) on at least two consecutive 6-monthly assessments. The participants' decliner status was evaluated 3 years after the blood sample was collected. Pair-wise comparison of detected compounds was completed using principal components and hierarchical clustering analyses. RESULTS: Analyses did not detect any cluster separation in untargeted metabolomes across baseline groups. However, follow-up analyses of specific molecules detected 4 compounds (17-Hydroxy-12-(hydroxymethyl)-10-oxo-8 oxapentacyclomethyl hexopyranoside, Fleroxacin, Oleic acid, and 5xi-11,12-Dihydroxyabieta-8(14),9(11),12-trien-20-oic acid) were at significantly higher concentration among the dual-decliners compared to non-decliners. The pure cognitive decliner group had significantly lower concentration of six compounds (1,3-nonanediol acetate, 4-(2-carboxyethyl)-2-methoxyphenyl beta-D-glucopyranosiduronic acid, oleic acid, 2E-3-[4-(sulfo-oxy)phenyl] acrylic acid, palmitelaidic acid, and Myristoleic acid) compared to the non-decliner group. CONCLUSIONS: The unique metabolomics profile of dual-decliners warrants follow-up metabolomics analysis. Results may point to modifiable pathways.

Glutamine supplementation alleviated aortic atherosclerosis in mice model and in vitro.[Pubmed:37679095]

Proteomics. 2024 Mar;24(5):e2300179.

This study aimed to clarify the role of glutamine in atherosclerosis and its participating mechanism. Forty C57BL/6J mice were divided into wild control (wild Con), ApoE(-) /(-) control (ApoE(-) /(-) Con), glutamine + ApoE(-) /(-) control (Glut + ApoE(-) /(-) Con), ApoE(-) /(-) high fat diet (ApoE(-) /(-) HFD), and glutamine + ApoE(-) /(-) HFD (Glut + ApoE(-) /(-) HFD) groups. The degree of atherosclerosis, western blotting, and multiomics were detected at 18 weeks. An in vitro study was also performed. Glutamine treatment significantly decreased the degree of aortic atherosclerosis (p = 0.03). O-GlcNAcylation (O-GlcNAc), IL-1beta, IL-1alpha, and pyruvate kinase M2 (PKM2) in the ApoE(-) /(-) HFD group were significantly higher than those in the ApoE(-) /(-) Con group (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05), and aggravated by O-GlcNA transferase (OGT) overexpression in the in vitro study (p < 0.05). Multiomics showed that the ApoE(-) /(-) HFD group had higher levels of oxidative stress regulatory molecules (guanine deaminase [GUAD], xanthine dehydrogenase [XDH]), proinflammatory regulatory molecules (myristic acid and Myristoleic acid), and stress granules regulatory molecules (caprin-1 and deoxyribose-phosphate aldolase [DERA]) (p < 0.05). These differences were attenuated by glutamine treatment (p < 0.05). We conclude that glutamine supplementation might alleviate atherosclerosis through downregulation of O-GlcNAc, glycolysis, oxidative stress, and proinflammatory pathway.

Metabolomics analysis of serum metabolites during endometrial transformation: association with recurrent implantation failure in hormonal replacement therapy-frozen embryo transfers cycles.[Pubmed:37568040]

J Assist Reprod Genet. 2023 Oct;40(10):2473-2483.

PURPOSE: The purpose of this study was to investigate alterations in serum metabolites during endometrial transformation and possible associations with recurrent implantation failure (RIF) in hormonal replacement therapy (HRT)-frozen embryo transfer (FET) cycles. METHODS: We performed a prospective study involving 100 patients scheduled for HRT-FET cycles during January 2022 to April 2022. Blood serum samples were collected on the day of progesterone administration (dPA) and on the third day of progesterone administration (d3PA). Gas chromatography-mass spectrometry (GC-MS) analysis was performed to identify and quantify serum metabolites. A nested case-control study including 19 RIF patients and 19 matching controls was conducted to explore the predictive value of serum metabolites for RIF. Partial least squares discriminant analysis (PLS-DA) and receiver operating characteristic (ROC) curve analysis were performed to establish prediction models. MAIN RESULTS: We identified 105 serum metabolites, with 76 of them exhibiting significant alterations during the initial 3 days of endometrial transformation. Metabolites involved in amino acid metabolism and tricarboxylic acid (TCA) cycle showed lower levels during endometrial transformation. In the nested case-control study, the prediction model based on the ratio of serum metabolites between d3PA and dPA showed the highest area under the ROC curve (AUC), accuracy, and R(2) and Q(2) values. Eight metabolites, including indol-3-propionic acid, beta-alanine, Myristoleic acid, malic acid, indole, DL-isocitric acid, proline, and itaconic acid, exhibited high predictive values for RIF. CONCLUSION: This study demonstrates alterations in serum metabolites during endometrial transformation, particularly in amino acid metabolism and TCA cycle. The identified metabolites, especially indol-3-propionic acid and malic acid, show potential as predictive markers for RIF. These findings contribute to a better understanding of the metabolic changes associated with endometrial receptivity and provide insights for the development of personalized approaches to improve implantation outcomes in FET cycles.

Phytochemical Composition, In Vitro Antimicrobial, Antioxidant, and Enzyme Inhibition Activities, and In Silico Molecular Docking and Dynamics Simulations of Centaurea lycaonica: A Computational and Experimental Approach.[Pubmed:37396208]

ACS Omega. 2023 Jun 13;8(25):22854-22865.

Centaurea lycaonica is a local endemic species from the Centaurea L. genus. The Centaurea species has a wide range of usage in treating diseases in folk medicine. There are limited biological activity studies on this species in the literature. This study investigated enzyme inhibition and antimicrobial activity, antioxidant effect, and chemical content of extract and fractions of C. lycaonica. Enzyme inhibition activity was tested by alpha-amylase, alpha-glucosidase, and tyrosinase enzyme inhibition methods and antimicrobial activity by the microdilution method. The antioxidant activity was investigated using DPPH(*), ABTS(*+), and FRAP tests. The chemical content was determined by LC-MS/MS. The methanol extract showed the highest activity for alpha-glucosidase and alpha-amylase, even surpassing the positive control acarbose, with IC(50) values of 56.333 +/- 0.986 and 172.800 +/- 0.816 mug/mL, respectively. Additionally, the ethyl acetate fraction also exhibited high activity for alpha-amylase with an IC(50) value of 204.067 +/- 1.739 mug/mL and tyrosinase with an IC(50) value of 213.900 +/- 1.553 mug/mL. Moreover, this extract and fraction were found to have the highest total phenolic and flavonoid contents and antioxidant activity. Additionally, LC-MS/MS analyses of active extract and fraction revealed mainly the presence of phenolic compounds and flavonoids. In silico molecular docking and molecular dynamics simulation studies of determining compounds apigenin and Myristoleic acid, common in CLM and CLE extracts and active against alpha-glucosidase and alpha-amylase, were performed. In conclusion, methanol extract and ethyl acetate fraction showed potential enzyme inhibition and antioxidant activity as a natural agent. Molecular modeling studies corroborate the findings of in vitro activity analyses.

Earth Worming-An Evaluation of Earthworm (Eisenia andrei) as an Alternative Food Source.[Pubmed:37238766]

Foods. 2023 May 10;12(10):1948.

Aside from their bioremediation roles, little is known about the food and feed value of earthworms. In this study, a comprehensive evaluation of the nutritional composition (proximate analysis and profiles of fatty acids and minerals) and techno-functional properties (foaming and emulsion stability and capacity) of earthworm (Eisenia andrei, sourced in New Zealand) powder (EAP) were investigated. Lipid nutritional indices, omega6/omega3, atherogenicity index, thrombogenicity index, hypocholesterolemic/hypercholesterolemic acid ratio, and health-promoting index of EAP lipids are also reported. The protein, fat, and carbohydrate contents of EAP were found to be 53.75%, 19.30%, and 23.26% DW, respectively. The mineral profile obtained for the EAP consisted of 11 essential minerals, 23 non-essential minerals, and 4 heavy metals. The most abundant essential minerals were potassium (8220 mg.kg(-1) DW), phosphorus (8220 mg.kg(-1) DW), magnesium (744.7 mg.kg(-1) DW), calcium (2396.7 mg.kg(-1) DW), iron (244.7 mg.kg(-1) DW), and manganese (25.6 mg.kg(-1) DW). Toxic metals such as vanadium (0.2 mg.kg(-1) DW), lead (0.2 mg.kg(-1) DW), cadmium (2.2 mg.kg(-1) DW), and arsenic (2.3 mg.kg(-1) DW) were found in EAP, which pose safety considerations. Lauric acid (20.3% FA), Myristoleic acid (11.20% FA), and linoleic acid (7.96% FA) were the most abundant saturated, monounsaturated, and polyunsaturated fatty acids, respectively. The lipid nutritional indices, such as IT and omega-6/omega-3, of E. andrei were within limits considered to enhance human health. A protein extract derived from EAP (EAPPE), obtained by alkaline solubilisation and pH precipitation, exhibited an isoelectric pH of ~5. The total essential amino acid content and essential amino acid index of EAPPE were 373.3 mg.g(-1) and 1.36 mg.g(-1) protein, respectively. Techno-functional analysis of EAPPE indicated a high foaming capacity (83.3%) and emulsion stability (88.8% after 60 min). Heat coagulation of EAPPE was greater at pH 7.0 (12.6%) compared with pH 5.0 (4.83%), corroborating the pH-solubility profile and relatively high surface hydrophobicity (1061.0). These findings demonstrate the potential of EAP and EAPPE as nutrient-rich and functional ingredients suitable as alternative food and feed material. The presence of heavy metals, however, should be carefully considered.

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study.[Pubmed:37168086]

Front Psychiatry. 2023 Apr 24;14:1169787.

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained >/=5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and Myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (>/=5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.

Nobiletin Ameliorates Nonalcoholic Fatty Liver Disease by Regulating Gut Microbiota and Myristoleic Acid Metabolism.[Pubmed:37139957]

J Agric Food Chem. 2023 May 17;71(19):7312-7323.

Disturbance of the gut microbiota plays a critical role in the development of nonalcoholic fatty liver disease (NAFLD). Increasing evidence supports that natural products may serve as prebiotics to regulate the gut microbiota in the treatment of NAFLD. In the present study, the effect of nobiletin, a naturally occurring polymethoxyflavone, on NAFLD was evaluated, and metabolomics, 16S rRNA gene sequencing, and transcriptomics analysis were performed to determine the underlying mechanism of nobiletin, and the key bacteria and metabolites screened were confirmed by in vivo experiment. Nobiletin treatment could significantly reduce lipid accumulation in high-fat/high-sucrose diet-fed mice. 16S rRNA analysis demonstrated that nobiletin could reverse the dysbiosis of gut microbiota in NAFLD mice and nobiletin could regulate Myristoleic acid metabolism, as revealed by untargeted metabolomics analysis. Treatment with the bacteria Allobaculum stercoricanis, Lactobacillus casei, or the metabolite Myristoleic acid displayed a protective effect on liver lipid accumulation under metabolic stress. These results indicated that nobiletin might target gut microbiota and Myristoleic acid metabolism to ameliorate NAFLD.