Saengmaeksan, a traditional polyherbal formulation containing Panax ginseng, improves energy metabolism during exercise.

Saengmaeksan (SMS), a representative oriental medicine that contains Panax ginseng Meyer, Liriope muscari, and Schisandra chinensis (1:2:1), is used to improve body vitality and enhance physical activity. However, there is limited scientific evidence to validate the benefits of SMS. Here, we investigated the in vitro and in vivo regulatory effects of SMS and its constituents on energy metabolism and the underlying molecular mechanisms. For this, quantitative real-time polymerase chain reaction, 3D holotomographic microscopy, western blotting, and glucose uptake experiments using 18F-fluoro-2-deoxy-D-glucose (18F-FDG) were performed using L6 cells to investigate in vitro energy metabolism changes. In addition, 18F-fluorocholine (18F-FCH) and 18F-FDG positron emission tomography/computed tomography (PET/CT) analyses, immunohistochemistry, and respiratory gas analysis were performed in mice post-endurance exercise on a treadmill. In the energy metabolism of L6 cells, a significant reversal in glucose uptake was observed in the SMS-treated group, as opposed to an increase in uptake over time compared to the untreated control group. Furthermore, P. ginseng alone and SMS significantly decreased the volume of lipid droplets. SMS also regulated the phosphorylation of extracellular signal-regulated kinase (ERK), phosphorylation of p38, mitochondrial morphology, and the expression of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE/Ref-1) in H2O2-stimulated L6 cells. In addition, SMS treatment was found to regulate whole body and muscle energy metabolism in rats subjected to high-intensity exercise, as well as glucose and lipid metabolism in skeletal muscle. Therefore, SMS containing P. ginseng ameliorated imbalanced energy metabolism through oxidative stress-induced APE/Ref-1 expression. SMS may be a promising supplemental option for metabolic performance.

Genome-wide multi-omics analysis reveals the nutrient-dependent metabolic features of mucin-degrading gut bacteria.

The prevalence and occurrence of mucin-degrading (MD) bacteria, such as Akkermansia muciniphila and Ruminococcus gnavus, is highly associated with human health and disease states. However, MD bacterial physiology and metabolism remain elusive. Here, we assessed functional modules of mucin catabolism, through a comprehensive bioinformatics-aided functional annotation, to identify 54 A. muciniphila genes and 296 R. gnavus genes. The reconstructed core metabolic pathways coincided with the growth kinetics and fermentation profiles of A. muciniphila and R. gnavus grown in the presence of mucin and its constituents. Genome-wide multi-omics analyses validated the nutrient-dependent fermentation profiles of the MD bacteria and identified their distinct mucolytic enzymes. The distinct metabolic features of the two MD bacteria induced differences in the metabolite receptor levels and inflammatory signals of the host immune cells. In addition, in vivo experiments and community-scale metabolic modeling demonstrated that different dietary intakes influenced the abundance of MD bacteria, their metabolic fluxes, and gut barrier integrity. Thus, this study provides insights into how diet-induced metabolic differences in MD bacteria determine their distinct physiological roles in the host immune response and the gut ecosystem.

Groebke-Blackburn-Bienaymé Reaction for DNA-Encoded Library Technology.

This study presents a DNA-compatible synthesis of diverse 5-arylimidazo[1,2-a]pyridin-3-amine derivatives using the Suzuki-Miyaura reaction, followed by a Groebke-Blackburn-Bienaymé (GBB) reaction. The GBB reaction demonstrates a wide substrate scope, mild one-pot reaction conditions, and compatibility with subsequent enzymatic ligation, highlighting its potential in DNA-encoded library technology.

A rice seed-specific glycine-rich protein OsDOR1 interacts with GID1 to repress GA signaling and regulates seed dormancy.

Seed dormancy is an important agronomic trait under the control of complex genetic and environmental interactions, which have not been yet comprehensively understood. From the field screening of rice mutant library generated by a Ds transposable element, we identified a pre-harvest sprouting (PHS) mutant dor1. This mutant has a single insertion of Ds element at the second exon of OsDOR1 (LOC_Os03g20770), which encodes a novel seed-specific glycine-rich protein. This gene successfully complemented the PHS phenotype of dor1 mutant and its ectopic expression enhanced seed dormancy. Here, we demonstrated that OsDOR1 protein binds to the GA receptor protein, OsGID1 in rice protoplasts, and interrupts with the formation OsGID1-OsSLR1 complex in yeast cells. Co-expression of OsDOR1 with OsGID1 in rice protoplasts attenuated the GA-dependent degradation of OsSLR1, the key repressor of GA signaling. We showed the endogenous OsSLR1 protein level in the dor1 mutant seeds is significantly lower than that of wild type. The dor1 mutant featured a hypersensitive GA-response of α-amylase gene expression during seed germination. Based on these findings, we suggest that OsDOR1 is a novel negative player of GA signaling operated in the maintenance of seed dormancy. Our findings provide a novel source of PHS resistance.

Pathogen-induced autophagy regulates monolignol transport and lignin formation in plant immunity.

The evolutionary plant-pathogen arms race has equipped plants with the immune system that can defend against pathogens. Pattern-triggered immunity and effector-triggered immunity are two major branches of innate immunity that share immune responses, including oxidative bursts, transcriptional reprogramming, and cell wall modifications such as lignin deposition. In a previous study, we reported that lignin rapidly accumulates in pathogen-infected Arabidopsis leaves and acts as a mechanical barrier, spatially restricting pathogens and cell death. Lignin deposition into the cell wall is a three-step process: monolignol biosynthesis, transport, and polymerization. While monolignol biosynthesis and polymerization are relatively well understood, the mechanism of monolignol transport remains unclear. In this study, we show that macroautophagy/autophagy modulates pathogen-induced lignin formation. Lignification and other immune responses were impaired in autophagy-defective atg (autophagy-related) mutants. In microscopy analyses, monolignols formed punctate structures in response to pathogen infection and colocalized with autophagic vesicles. Furthermore, autophagic activity and lignin accumulation were both enhanced in dnd1 (defense, no death 1) mutant with elevated disease resistance but no cell death and crossing dnd1-1 with atg mutants resulted in a lignin deficit, further supporting that lignin formation requires autophagy. Collectively, these findings demonstrate that lignification, particularly monolignol transport, is achieved through autophagic membrane trafficking in plant immunity.Abbreviations: ABC transporter: ATP-binding cassette transporter; ACD2/AT4G37000: accelerated cell death 2; ATG: autophagy-related; C3'H/AT2G40890: p-coumaroyl shikimate 3-hydroxylase; C4H/AT2G30490: cinnamate 4-hydroxylase; CA: coniferyl alcohol; CaMV: cauliflower mosaic virus; CASP: Casparian strip membrane domain protein; CASPL: CASP-like protein; CBB: Coomassie Brilliant Blue; CCoAOMT1/AT4G34050: caffeoyl-CoA O-methyltransferase 1; CCR1/AT1G15950: cinnamoyl-CoA reductase 1; CFU: colony-forming unit; COMT1/AT5G54160: caffeic acid O-methyltransferase 1; Con A: concanamycin A; DMAC: dimethylaminocoumarin; DND1/AT5G15410: defense, no death 1; CNGC2: cyclic nucleotide-gated channel 2; ER: endoplasmic reticulum; ESB1/AT2G28670/DIR10: enhanced suberin 1; ETI: effector-triggered immunity; EV: extracellular vesicle; F5H/AT4G36220: ferulate-5-hydroxylase; Fluo-3 AM: Fluo-3 acetoxymethyl ester; GFP: green fluorescent protein; HCT/AT5G48930: p-hydroxycinnamoyl-CoA:quinate/shikimate p-hydroxycinnamoyltransferase; HR: hypersensitive response; LAC: laccase; LTG: LysoTracker Green; LSD1/AT4G200380: lesion stimulating disease 1; PAL1/AT2G37040: phenylalanine ammonia-lyase 1; PAMP: pathogen-associated molecular patterns; PCD: programmed cell death; PE: phosphatidylethanolamine; PRX: peroxidase; Pst DC3000: Pseudomonas syringe pv. tomato DC3000; PTI: pattern-triggered immunity; SA: salicylic acid; SD: standard deviation; SID2/AT1G7410: SA induction-deficient 2; UGT: UDP-glucosyltransferase; UPLC: ultraperformance liquid chromatography; UPS: unconventional protein secretion; V-ATPase: vacuolar-type H+-translocating ATPase.

Radotinib attenuates TGFß -mediated pulmonary fibrosis in vitro and in vivo: exploring the potential of drug repurposing.

BACKGROUND: Tyrosine kinase (TK) plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis. Here, we aimed to investigate whether radotinib (Rb) could inhibit pulmonary fibrosis by inhibiting TK in vitro and in vivo. METHODS: The antifibrotic effects of Rb in transforming growth factor-ß (TGF-ß)1-stimulated A549 cells were determined using real-time polymerase chain reaction, western blotting, and immunocytochemistry assays. Rb inhibition of bleomycin-induced lung fibrosis in Sprague Dawley (SD) rats was determined by histopathological and​ immunohistochemical analyses. Rb-interfering metabolites were analyzed using LC-MS/MS. RESULTS: Rb concentrations of up to 1000 nM did not affect the viability of A549 cells, but Rb (30 nM) significantly reduced expression of TGF-ß1 (10 ng/mL)-induced ECM factors, such as Snail, Twist, and F-actin. Rb also regulated TGF-ß1-overexpressed signal cascades, such as fibronectin and α-smooth muscle actin. Furthermore, Rb attenuated the phosphorylation of Smad2 and phosphorylation of kinases, such as, extracellular signal-regulated kinase, and protein kinase B. In the inhibitory test against bleomycin (5 mg/kg)-induced lung fibrosis, the Rb (30 mg/kg/daily)-treated group showed a half-pulmonary fibrosis region compared to the positive control group. In addition, Rb significantly reduced collagen type I and fibronectin expression in the bleomycin-induced fibrotic region of SD rats. Further, the identified metabolite pantothenic acid was not altered by Rb. CONCLUSION: Taken together, these results indicate that Rb inhibits TGF-ß1-induced pulmonary fibrosis both in vitro and in vivo. These findings suggest that Rb may be an effective treatment for pulmonary fibrosis-related disorders and idiopathic pulmonary fibrosis.

Bifidobacterial carbohydrate/nucleoside metabolism enhances oxidative phosphorylation in white adipose tissue to protect against diet-induced obesity.

BACKGROUND: Comparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population. RESULTS: Based on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice. CONCLUSIONS: Our findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity. Video Abstract.

Disordered development of gut microbiome interferes with the establishment of the gut ecosystem during early childhood with atopic dermatitis.

The gut microbiome influences the development of allergic diseases during early childhood. However, there is a lack of comprehensive understanding of microbiome-host crosstalk. Here, we analyzed the influence of gut microbiome dynamics in early childhood on atopic dermatitis (AD) and the potential interactions between host and microbiome that control this homeostasis. We analyzed the gut microbiome in 346 fecal samples (6-36 months; 112 non-AD, 110 mild AD, and 124 moderate to severe AD) from the Longitudinal Cohort for Childhood Origin of Asthma and Allergic Disease birth cohort. The microbiome-host interactions were analyzed in animal and in vitro cell assays. Although the gut microbiome maturated with age in both AD and non-AD groups, its development was disordered in the AD group. Disordered colonization of short-chain fatty acids (SCFA) producers along with age led to abnormal SCFA production and increased IgE levels. A butyrate deficiency and downregulation of GPR109A and PPAR-γ genes were detected in AD-induced mice. Insufficient butyrate decreases the oxygen consumption rate of host cells, which can release oxygen to the gut and perturb the gut microbiome. The disordered gut microbiome development could aggravate balanced microbiome-host interactions, including immune responses during early childhood with AD.

Ruminococcus gnavus ameliorates atopic dermatitis by enhancing Treg cell and metabolites in BALB/c mice.

BACKGROUND: Ruminococcus gnavus (R. gnavus) are mucin-degrading gut bacteria that play a key role in the early colonization of the gut by serving as endogenous sources of nutrients. They can also influence immune development. We had previously reported a lower abundance of R. gnavus in infants with atopic dermatitis (AD) compared with that in healthy subjects. However, the underlying mechanisms remain unclear. In this study, we investigated the effect of orally administered R. gnavus on antibiotic treatment-induced gut dysbiosis (and the underlying mechanism) in a mouse model of AD. METHODS: Four-week-old female BALB/C mice were administered antibiotic cocktails for 2 weeks. R. gnavus was orally administered throughout the study duration. At 6 weeks of age, AD was induced by epidermal sensitization with ovalbumin. AD phenotypes and systemic and gut immune responses were investigated. RESULTS: Orally administered R. gnavus significantly reduced AD-associated parameters (i.e., transepidermal water loss, clinical score, total serum immunoglobulin (Ig) E level, OVA-specific IgE level, and skin inflammation). R. gnavus treatment also resulted in significant downregulation of T helper 2-related cytokine mRNA and upregulation of interleukin (IL)-10 and Foxp3 in the skin. The population of CD4+ FOXP3+ T cells in mesenteric- and skin-draining lymph nodes and butyrate levels in the cecum increased in R. gnavus-administered AD mice. CONCLUSIONS: Immune modulation by orally administered R. gnavus may alleviate AD symptoms through the enhancement of regulatory T-cell counts and short-chain fatty acids production in AD mice.

Phytosphingosine induces systemic acquired resistance through activation of sphingosine kinase.

Phytosphingosine (PHS) is a naturally occurring bioactive sphingolipid molecule. Intermediates such as sphingolipid long-chain bases (LCBs) in sphingolipid biosynthesis have been shown to have important roles as signaling molecules. PHS treatment caused rapid cell damage and upregulated the generation of reactive oxygen species (ROS) and ethylene in tobacco plants. These events were followed by the induction of sphingosine kinase (SphK) in a biphasic manner, which metabolized PHS to phytosphingosine-1-phosphate (PHS-1-P). On the other hand, a PHS treatment with a virulent pathogen, Phytophthora parasitica var. nicotianae (Ppn), alleviated the pathogen-induced cell damage and reduced the growth of Ppn. A Ppn infection increased the PHS and PHS-1-P levels significantly in the upper part of the leaves at the infection site at the later stage. In addition, Ppn increased the transcription levels of serine palmitoyltransferase (LCB1 and LCB2) for sphingolipid biosynthesis at the later stage, which was enhanced further by PHS. Moreover, the PHS treatment increased the transcription and activity of SphK, which was accompanied by prominent increases in the transcription levels of ROS-detoxifying enzymes and PR proteins in the later phase of the pathogen infection. Overall, the PHS-induced resistant effects were prominent during the necrotic stage of this hemibiotrophic infection, indicating that it is more beneficial for inhibiting the pathogenicity on necrotic cell death. Phosphorylated LCBs reduced the pathogen-induced cell damage significantly in this stage. These results suggest that the selective channeling of sphingolipids into phosphorylated forms has a pro-survival effect on plant immunity.

Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice.

The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1-5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.

The Rice Abscisic Acid-Responsive RING Finger E3 Ligase OsRF1 Targets OsPP2C09 for Degradation and Confers Drought and Salinity Tolerance in Rice.

Drought and salinity are major important factors that restrain growth and productivity of rice. In plants, many really interesting new gene (RING) finger proteins have been reported to enhance drought and salt tolerance. However, their mode of action and interacting substrates are largely unknown. Here, we identified a new small RING-H2 type E3 ligase OsRF1, which is involved in the ABA and stress responses of rice. OsRF1 transcripts were highly induced by ABA, salt, or drought treatment. Upregulation of OsRF1 in transgenic rice conferred drought and salt tolerance and increased endogenous ABA levels. Consistent with this, faster transcriptional activation of key ABA biosynthetic genes, ZEP, NCED3, and ABA4, was observed in OsRF1-OE plants compared with wild type in response to drought stress. Yeast two-hybrid assay, BiFC, and co-immunoprecipitation analysis identified clade A PP2C proteins as direct interacting partners with OsRF1. In vitro ubiquitination assay indicated that OsRF1 exhibited E3 ligase activity, and that it targeted OsPP2C09 protein for ubiquitination and degradation. Cell-free degradation assay further showed that the OsPP2C09 protein is more rapidly degraded by ABA in the OsRF1-OE rice than in the wild type. The combined results suggested that OsRF1 is a positive player of stress responses by modulating protein stability of clade A PP2C proteins, negative regulators of ABA signaling.

Camphene Attenuates Skeletal Muscle Atrophy by Regulating Oxidative Stress and Lipid Metabolism in Rats.

Sarcopenia- or cachexia-related muscle atrophy is due to imbalanced energy metabolism and oxidative stress-induced muscle dysfunction. Monoterpenes play biological and pharmacological reactive oxygen species (ROS) scavenging roles. Hence, we explored the effects of camphene, a bicyclic monoterpene, on skeletal muscle atrophy in vitro and in vivo. We treated L6 myoblast cells with camphene and then examined the ROS-related oxidative stress using Mito TrackerTM Red FM and anti-8-oxoguanine antibody staining. To investigate lipid metabolism, we performed real-time polymerase chain reactions, holotomographic microscopy, and respiratory gas analysis. Rat muscle atrophy in in vivo models was observed using 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography and immunocytochemistry. Camphene reversed the aberrant cell size and muscle morphology of L6 myoblasts under starvation and in in vivo models. Camphene also attenuated E3 ubiquitin ligase muscle RING-finger protein-1, mitochondrial fission, and 8-oxoguanine nuclear expression in starved myotubes and hydrogen peroxide (H2O2)-treated cells. Moreover, camphene significantly regulated lipid metabolism in H2O2-treated cells and in vivo models. These findings suggest that camphene may potentially affect skeletal muscle atrophy by regulating oxidative stress and lipid metabolism.

UPLC-QTOF-MS/MS screening and identification of bioactive compounds in fresh, aged, and browned Magnolia denudata flower extracts.

The Magnolia denudata flower is used to prepare tea and is often fermented to improve its flavor. Herein, fresh, aged, and browned M. denudata flower extracts were characterized using ultra performance liquid chromatography coupled with a hybrid quadrupole orthogonal time-of-flight mass spectrometer (UPLC-Q-TOF/MS/MS). The 1223 and 458 mass ions of ESI+ and ESI- modes that were significantly changed by the fermentation process were selected using three criteria. Sixteen compounds including flavonoids, phenylethanoid glycoside derivatives (PhGs), caffeoylquinic acids (CQAs), and others were identified based on their accurate mass and MS/MS spectra and analyzed as the main chemical components. The levels of the main chemical components changed after fermentation. The comparative quantity and composition of the phytochemicals differed for the three extract types. For example, flavonols were affected by fermentation, resulting in an increase or decrease (fold change value of negative ion: rutin -0.47; keioside 1.00). The CQAs were low during fermentation (1-CQA, -1.62; chlorogenic acid, -1.48). However, the quinic acid content was significantly high (quinic acid, 1.36). Isomers of PhGs like isoverbasoside and isoacteoside were produced during fermentation (isoverbasoside, 5.42; isoacteoside, B 3.33). These observations may provide a basis for studying the physiological effects of non-fermented and fermented M. denudata flower.

Effect of probiotics on obesity-related markers per enterotype: a double-blind, placebo-controlled, randomized clinical trial.

BACKGROUND: Prevention and improvement of disease symptoms are important issues, and probiotics are suggested as a good treatment for controlling the obesity. Human gut microbiota has different community structures. Because gut microbial composition is assumed to be linked to probiotic function, this study evaluated the efficacy of probiotics on obesity-related clinical markers according to gut microbial enterotype. METHODS: Fifty subjects with body mass index over 25 kg/m2 were randomly assigned to either the probiotic or placebo group. Each group received either unlabeled placebo or probiotic capsules for 12 weeks. Body weight, waist circumference, and body composition were measured every 3 weeks. Using computed tomography, total abdominal fat area and visceral fat area were measured. Blood and fecal samples were collected before and after the intervention for biochemical parameters and gut microbial compositions analysis. RESULTS: Gut microbial compositions of all the subjects were classified into two enterotypes according to Prevotella/Bacteroides ratio. The fat percentage, blood glucose, and insulin significantly increased in the Prevotella-rich enterotype of the placebo group. The obesity-related markers, such as waist circumference, total fat area, visceral fat, and ratio of visceral to subcutaneous fat area, were significantly reduced in the probiotic group. The decrease of obesity-related markers was greater in the Prevotella-rich enterotype than in the Bacteroides-rich enterotype. CONCLUSION: Administration of probiotics improved obesity-related markers in obese people, and the efficacy of probiotics differed per gut microbial enterotype and greater responses were observed in the Prevotella-dominant enterotype.

CCOAOMT1, a candidate cargo secreted via VAMP721/722 secretory vesicles in Arabidopsis.

We previously found that VAMP721/722 SNARE proteins guide secretory vesicles to pathogen-attacking sites during immune responses in Arabidopsis, which suggests that these vesicles should deliver immune molecules. However, the lethality of vamp721 vamp722 double null mutant makes it difficult to understand the nature of cargo transported via VAMP721/722 vesicles. Since VAMP721/722-depleted (VAMP721+/-VAMP722-/- and VAMP721-/-VAMP722+/-) plants show compromised resistance to extracellular pathogens, we assume that an immune protein secreted through the VAMP721/722-engaged exocytosis would be remained more in VAMP721/722-depleted plants than WT. By comparing intracellular proteins between WT and VAMP721/722-depleted plants, we found caffeoyl-CoA O-methyltransferase 1 (CCOAOMT1) involved in the lignin biosynthesis was more abundantly detected in both VAMP721/722-depleted lines than WT. Plants are well-known to deposit secondary cell walls as physical barriers at pathogen-attempting sites. Therefore, extracellular detection of CCOAOMT1 and impaired resistance to Pseudomonas syringae DC3000 in ccoaomt1 plants suggest that plants secrete cell wall-modifying enzymes at least including CCOAOMT1 to reinforce the secondary cell walls for immunity.

Relationship Between the Gastrointestinal Side Effects of an Anti-Hypertensive Medication and Changes in the Serum Lipid Metabolome.

An earlier study using a rat model system indicated that the active ingredients contained in the anti-hypertensive medication amlodipine (AMD) appeared to induce various bowel problems, including constipation and inflammation. A probiotic blend was found to alleviate intestinal complications caused by the medicine. To gain more extensive insight into the beneficial effects of the probiotic blend, we investigated the changes in metabolite levels using a non-targeted metabolic approach with ultra-performance liquid chromatography-quadrupole/time-of-fligh (UPLC-q/TOF) mass spectrometry. Analysis of lipid metabolites revealed that rats that received AMD had a different metabolome profile compared with control rats and rats that received AMD plus the probiotic blend. In the AMD-administered group, serum levels of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, triglycerides with large numbers of double bonds, cholesterols, sterol derivatives, and cholesterol esters (all p < 0.05) were increased compared with those of the control group and the group that received AMD plus the probiotic blend. The AMD-administered group also exhibited significantly decreased levels of triglycerides with small numbers of double bonds (all p < 0.05). These results support our hypothesis that AMD-induced compositional changes in the gut microbiota are a causal factor in inflammation.