Genome-wide identification of copy neutral loss of heterozygosity reveals its possible association with spatial positioning of chromosomes.

Loss of heterozygosity (LOH) is a genetic alteration that results from the loss of one allele at a heterozygous locus. In particular, copy neutral LOH (CN-LOH) events are generated, for example, by mitotic homologous recombination after monoallelic defection or gene conversion, resulting in novel homozygous locus having two copies of the normal counterpart allele. This phenomenon can serve as a source of genome diversity and is associated with various diseases. To clarify the nature of the CN-LOH such as the frequency, genomic distribution and inheritance pattern, we made use of whole-genome sequencing data of the three-generation CEPH/Utah family cohort, with the pedigree consisting of grandparents, parents and offspring. We identified an average of 40.7 CN-LOH events per individual taking advantage of 285 healthy individuals from 33 families in the cohort. On average 65% of them were classified as gonosomal-mosaicism-associated CN-LOH, which exists in both germline and somatic cells. We also confirmed that the incidence of the CN-LOH has little to do with the parents' age and sex. Furthermore, through the analysis of the genomic region including the CN-LOH, we found that the chance of the occurrence of the CN-LOH tends to increase at the GC-rich locus and/or on the chromosome having a relatively close inter-homolog distance. We expect that these results provide significant insights into the association between genetic alteration and spatial position of chromosomes as well as the intrinsic genetic property of the CN-LOH.

Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues.

A concise synthesis of pareitropone by oxidative cyclization of a phenolic nitronate is delineated. The use of TMSOTf as an additive to promote the facile formation of a strained norcaradiene intermediate provides convenient access to highly condensed multicyclic tropones in high yields. This synthesis is modular, efficient, and scalable, highlighting the synthetic utility of radical anion coupling reactions in annulation reactions. This work is discussed in the context of total syntheses of the tropoloisoquinoline alkaloids. Also included are the preparation of several congeners and a brief description of their biological activities.

Clinical Features and Risk Factors of Adrenal Insufficiency in Patients With Cancer Admitted to the Hospitalist-Managed Medical Unit.

BACKGROUND: The symptoms of adrenal insufficiency (AI) overlap with the common effects of advanced cancer and chemotherapy. Considering that AI may negatively affect the overall prognosis of cancer patients if not diagnosed in a timely manner, we analyzed the incidence, risk factors, and predictive methods of AI in cancer patients. METHODS: We retrospectively analyzed the medical records of 184 adult patients with malignancy who underwent a rapid adrenocorticotrophic hormone stimulation test in the medical hospitalist units of a tertiary hospital. Their baseline characteristics and clinical features were evaluated, and the risk factors for AI were identified using logistic regression analysis. RESULTS: Of the study patients, 65 (35%) were diagnosed with AI, in whom general weakness (63%) was the most common symptom. Multivariate logistic regression showed that eosinophilia (adjusted odds ratio [aOR], 4.28; 95% confidence interval [CI], 1.10-16.63; P = 0.036), history of steroid use (aOR, 2.37; 95% CI, 1.10-5.15; P = 0.028), and history of megestrol acetate use (aOR, 2.71; 95% CI, 1.38-5.33; P = 0.004) were associated with AI. Baseline cortisol levels of 6.2 µg/dL and 12.85 µg/dL showed a specificity of 95.0% and 95.4% for AI diagnosis, respectively. CONCLUSION: AI was found in about one-third of patients with cancer who showed general symptoms that may be easily masked by cancer or chemotherapy, suggesting that clinical suspicion of AI is important while treating cancer patients. History of corticosteroids or megestrol acetate were risk factors for AI and eosinophilia was a pre-test predictor of AI. Baseline cortisol level appears to be a useful adjunct marker for AI.

Comparative genomic analysis of inbred rat strains reveals the existence of ancestral polymorphisms.

In an alignment of closely related genomic sequences, the existence of discordant mutation sites, which do not reflect the phylogenetic relationship of the genomes, is often observed. Although these discordant mutation sites are thought to have emerged by ancestral polymorphism or gene flow, their frequency and distribution in the genome have not yet been analyzed in detail. Using the genome sequences of all protein coding genes of 25 inbred rat strains, we analyzed the frequency and genome-wide distribution of the discordant mutation sites. From the comparison of different substrains, it was found that these loci are not substrain specific, but are common among different groups of substrains, suggesting that the discordant sites might have mainly emerged through ancestral polymorphism. It was also revealed that the discordant sites are not uniformly distributed along chromosomes, but are concentrated at certain genomic loci, such as RT1, major histocompatibility complex of rats, and olfactory receptors, indicating that genes known to be highly polymorphic tend to have more discordant sites. Our results also showed that loci with a high density of discordant sites are also rich in heterozygous variants, even though these are inbred strains.

Probing the speciation of quaternary ammonium polybromides by voltammetric tribromide titration.

The speciation of quaternary ammonium polybromides (QBr2n+1) was quantitatively determined by voltammetric tribromide titration on a Pt ultramicroelectrode (UME). The concentration of Br3- in a QBr2n+1-water mixed solution (QBr2n+1-WMS) was electrochemically estimated by measuring the steady state current associated with the electro-reduction of Br3- in a linear sweep voltammogram (LSV). The pBr3- titration curves of QBr2n+1-WMSs show 2-4 plateaus, each of which relates to the formation of QBr2n+1 from Br3- and Br2. The values of pBr3- at these plateaus can be regarded as corrected equilibrium constants of QBr2n+1, K'eq(n), which is Keq(n)/γ±, where γ± is a mean activity coefficient in QBr2n+1-WMS. Based on the estimated K'eq(n), fractional diagrams of QBr2n+1 were obtained, which gave information on QBr2n+1 speciation.

Exposure to cigarette smoke disturbs adipokines secretion causing intercellular damage and insulin resistance in high fructose diet-induced metabolic disorder mice.

A large amount of fructose intake along with smoking is associated with increased incidence of diseases linked to metabolic syndrome. More research is necessary to understand the complex mechanism that ultimately results in metabolic syndrome and the effect, if any, of high fructose dietary intake and smoking on individual health. In this study, we investigated changes in ER-Golgi network and disturbance to secretion of adipokines induced by cigarette smoking (CS) and excess fructose intake and their contribution to the disruption of metabolic homeostasis. We used high fructose-induced metabolic disorder mice model by feeding them with high fructose diet for 8 weeks. For CS exposure experiment, these mice were exposed to CS for 28 days according to OECD guideline 412. Our results clearly showed that the immune system was suppressed and ER stress was induced in mice with exposure to CS and fed with high fructose. Furthermore, their concentrations of adipokines including leptin and adiponectin were aberrant. Such alteration in secretion of adipokines could cause insulin resistance which may lead to the development of type 2 diabetes.

Cigarette Smoking Condensate Disrupts Endoplasmic Reticulum-Golgi Network Homeostasis Through GOLPH3 Expression in Normal Lung Epithelial Cells.

INTRODUCTION: Cigarette smoke (CS) is associated with a broad range of diseases including lung cancer. Many researchers have suggested that cigarette smoke condensate (CSC) may be more toxic compared to cigarette smoke extract (CSE) because CSC contains the lipid-soluble faction of smoke while CSE contains the hydrophilic or gas phase. The aim of this research is to investigate the effects of CSC on the disruption of endoplasmic reticulum (ER)-Golgi homeostasis in normal lung epithelial cells. METHODS: CS was generated according to the ISO 3308 method. To ascertain the mechanistic effects of CSC on lung toxicity, normal lung epithelial cells of the cell line 16HBE14o- were treated with CSC (0.1mg/mL) for 48 hours. The toxic effects of CSC on ER-Golgi homeostasis and GOLPH3 expression were observed through diverse molecular tools including transmission electron microscope analysis. RESULTS: Our results demonstrated that CSC treatment increased reactive oxygen species generation in lung cells and led to the alteration of ER-Golgi homeostasis in conjunction with increased autophagy. In particular, GOLPH3, known as an oncogene and a marker protein for the trans-Golgi network, was upregulated in CSC-treated cells. GOLPH3 protein overexpression was also confirmed in the lungs of human lung cancer patients as well as NNK-treated mice. CONCLUSION: Our study revealed that CSC caused lung damage through the disruption of ER-Golgi homeostasis and autophagy induction. The expression level of the trans-Golgi marker protein GOLPH3 could serve as a reliable bio-indicator for CS-related lung cancer. IMPLICATIONS: CS is a harmful factor in the development of many diseases including cancer. In this research, we demonstrated that CSC treatment led to malfunction of the ER-Golgi network, with the disrupted ER and Golgi causing GOLPH3 overexpression and abnormal autophagy accumulation. In addition, although the value of GOLPH3 as a predictor remains to be fully elucidated, our data suggest that GOLPH3 levels may be a novel prognostic biomarker of tobacco related lung disease.

The impact of positive peritoneal cytology on prognosis in patients with cervical cancer: a meta-analysis.

BACKGROUND: The impact of positive peritoneal cytology on the prognosis of cervical cancer is controversial. Thus, we performed a meta-analysis to determine its impact on recurrence, and to investigate correlations between abnormal cytology and/or lymph node metastasis in cervical cancer. METHODS: A systematic literature review was conducted through July 2014. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques with the fixed-effects models, if there was no significant statistical heterogeneity across studies by using I(2). RESULTS: Of 303 studies retrieved, 6 were included in the meta-analysis. These six case-control observational studies included 1360 cervical cancer patients who showed negative peritoneal cytology and 64 who showed positive peritoneal cytology. Over the combined study period, 20 of 45 in the positive peritoneal cytology group experienced recurrence, whereas 88 of 539 controls did. The meta-analysis based on the fixed-effects model indicated a significant increase in the risk of recurrence in the positive peritoneal cytology group relative to the control group (OR: 4.47; 95% CI: 2.33-8.58, P<0.001, I(2)=0.0%). Moreover, the results of our meta-analysis suggested that the positive peritoneal cytology group displayed more lymph node metastasis than the negative peritoneal cytology group (OR: 3.73; 95% CI: 2.13-6.53, P<0.001, I(2)=0.0%). CONCLUSIONS: Although based mainly on retrospective observational studies, our meta-analysis indicates that abnormal peritoneal cytology may be strongly associated with poor prognosis in patients with cervical cancer. Future research should verify this relationship through prospective observational studies over a longer term.

Bactericidal effect of extracts and metabolites of Robinia pseudoacacia L. on Streptococcus mutans and Porphyromonas gingivalis causing dental plaque and periodontal inflammatory diseases.

The mouth cavity hosts many types of anaerobic bacteria, including Streptococcus mutans and Porphyromonas gingivalis, which cause periodontal inflammatory diseases and dental caries. The present study was conducted to evaluate the antibacterial potential of extracts of Robinia pseudoacacia and its different fractions, as well as some of its natural compounds against oral pathogens and a nonpathogenic reference bacteria, Escherichia coli. The antibacterial activity of the crude extract and the solvent fractions (hexane, chloroform, ethyl acetate and butanol) of R. pseudoacacia were evaluated against S. mutans, P. gingivalis and E. coli DH5α by standard micro-assay procedure using conventional sterile polystyrene microplates. The results showed that the crude extract was more active against P. gingivalis (100% growth inhibition) than against S. mutans (73% growth inhibition) at 1.8 mg/mL. The chloroform and hexane fractions were active against P. gingivalis, with 91 and 97% growth inhibition, respectively, at 0.2 mg/mL. None of seven natural compounds found in R. pseudoacacia exerted an antibacterial effect on P. gingivalis; however, fisetin and myricetin at 8 µg/mL inhibited the growth of S. mutans by 81% and 86%, respectively. The crude extract of R. pseudoacacia possesses bioactive compounds that could completely control the growth of P. gingivalis. The antibiotic activities of the hexane and chloroform fractions suggest that the active compounds are hydrophobic in nature. The results indicate the effectiveness of the plant in clinical applications for the treatment of dental plaque and periodontal inflammatory diseases and its potential use as disinfectant for various surgical and orthodontic appliances.

Antibacterial effect of crude extract and metabolites of Phytolacca americana on pathogens responsible for periodontal inflammatory diseases and dental caries.

BACKGROUND: The oral cavity is the store house of different species of microorganisms that are continuously engaged in causing diseases in the mouth. The present study was conducted to evaluate the antibacterial potential of crude extracts of the aerial parts of Phytolacca americana and its natural compounds against two oral pathogens, Porphyromonas gingivalis and Streptococcus mutans, which are primarily responsible for periodontal inflammatory diseases and dental caries, as well as a nonpathogenic Escherichia coli. METHODS: Crude extract and fractions from the aerial parts of P. americana (0.008-1.8 mg/mL) were evaluated for their potential antibacterial activity against two oral disease causing microorganisms by micro-assays. The standard natural compounds present in P. americana, kaempferol, quercetin, quercetin 3-glucoside, isoqueritrin and ferulic acid, were also tested for their antibacterial activity against the pathogens at 1-8 µg/mL. RESULTS: The crude extract was highly active against P. gingivalis (100% growth inhibition) and moderately active against S. mutans (44% growth inhibition) at 1.8 mg/mL. The chloroform and hexane fraction controlled the growth of P. gingivalis with 91% and 92% growth inhibition at a concentration of 0.2 mg/mL, respectively. Kaempferol exerted antibacterial activity against both the pathogens, whereas quercetin showed potent growth inhibition activity against only S. mutans in a concentration dependent manner. CONCLUSION: The crude extract, chloroform fraction, and hexane fraction of P. americana possesses active natural compounds that can inhibit the growth of oral disease causing bacteria. Thus, these extracts have the potential for use in the preparation of toothpaste and other drugs related to various oral diseases.

CopA3 peptide prevents ultraviolet-induced inhibition of type-I procollagen and induction of matrix metalloproteinase-1 in human skin fibroblasts.

Ultraviolet (UV) exposure is well-known to induce premature aging, which is mediated by matrix metalloproteinase-1 (MMP-1) activity. A 9-mer peptide, CopA3 (CopA3) was synthesized from a natural peptide, coprisin, which is isolated from the dung beetle Copris tripartitus. As part of our continuing search for novel bioactive natural products, CopA3 was investigated for its in vitro anti-skin photoaging activity. UV-induced inhibition of type-I procollagen and induction of MMP-1 were partially prevented in human skin fibroblasts by CopA3 peptide in a dose-dependent manner. At a concentration of 25 µM, CopA3 nearly completely inhibited MMP-1 expression. These results suggest that CopA3, an insect peptide, is a potential candidate for the prevention and treatment of skin aging.

Native Pig and Chicken Breed Database: NPCDB.

Indigenous (native) breeds of livestock have higher disease resistance and adaptation to the environment due to high genetic diversity. Even though their extinction rate is accelerated due to the increase of commercial breeds, natural disaster, and civil war, there is a lack of well-established databases for the native breeds. Thus, we constructed the native pig and chicken breed database (NPCDB) which integrates available information on the breeds from around the world. It is a nonprofit public database aimed to provide information on the genetic resources of indigenous pig and chicken breeds for their conservation. The NPCDB (http://npcdb.snu.ac.kr/) provides the phenotypic information and population size of each breed as well as its specific habitat. In addition, it provides information on the distribution of genetic resources across the country. The database will contribute to understanding of the breed's characteristics such as disease resistance and adaptation to environmental changes as well as the conservation of indigenous genetic resources.

Phosphorylation of chloramphenicol by a recombinant protein Yhr2 from Streptomyces avermitilis MA4680.

Although phosphorylation of chloramphenicol has been shown to occur in the chloramphenicol producer, Streptomyces venezuelae, there are no reports on the existence of chloramphenicol phosphorylase in other Streptomyces species. In the present study, we report the modification of chloramphenicol by a recombinant protein, designated as Yhr2 (encoded by SAV_877), from Streptomyces avermitilis MA4680. Recombinant Yhr2 was expressed in Escherichia coli BL21 (DE3) and the cells expressing this recombinant protein were shown to phosphorylate chloramphenicol to a 3'-O-phosphoryl ester derivative, resulting in an inactivated form of the antibiotic. Expression of yhr2 conferred chloramphenicol resistance to E. coli cells up to 25 µg/mL and in an in vitro reaction, adenosine triphosphate (ATP), guanosine triphosphate (GTP), adenosine diphosphate (ADP) and guanosine diphosphate (GDP) were shown to be the phosphate donors for phosphorylation of chloramphenicol. This study highlights that antibiotic resistance conferring genes could be easily expressed and functionalized in other organisms that do not produce the respective antibiotic.

Factors Affecting the Length of Stay in the Emergency Department in Psychiatric Emergency Patients in the COVID-19 Pandemic Context.

To reduce overcrowding in emergency departments (ED), which is a serious international problem, it is important to reduce the length of ED stay (ED LOS) of emergency patients. In particular, due to the COVID 19 pandemic, psychiatric emergency patients spent much longer in ED. This study was conducted to identify the characteristics of psychiatric emergency patients who visited the ED during the COVID-19 pandemic and to identify factors affecting ED LOS. This retrospective study was conducted on adult patients aged 19 years or older who visited a psychiatric emergency center operated by an ED from 1 May 2020 to 31 April 2021 because of the COVID-19 pandemic. In this study, the average ED LOS of psychiatric emergency patients was 7.8 h. Factors affecting ED LOS for over 12 h were isolation (OR = 2.39, CI = 1.409-4.052), unaccompanied police officers (OR = 2.106, CI = 1.338-3.316), night-time visits (OR = 2.127, CI = 1.357-3.332), use of sedatives (OR = 1.671, CI = 1.030-2.713), and restraints (OR = 1.968, CI = 1.172-4.895). The ED LOS of psychiatric emergency patients is longer than that of general emergency patients, and a long ED LOS causes ED overcrowding. To reduce the ED LOS of psychiatric emergency patients, they must be accompanied by a police officer when visiting the ED, and the treatment process should be reorganized so that a psychiatrist can promptly intervene. Furthermore, it is necessary to reorganize the isolation guidelines and admission criteria for mental emergency patients.

Antibiotics use patterns in end-of-life cancer patients and medical staff's perception of antimicrobial stewardship programs.

BACKGROUND/AIMS: While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff. METHODS: Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff's perceptions of antibiotics in cancer patients with EOL. RESULTS: Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST. CONCLUSION: Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient's right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.

Enhanced catalytic oxidation of naproxen via activation of peroxymonosulfate by Fe-based metal-organic framework aerogels functionalized with Ag nanoparticles.

In this study, Ag3PO4 and Fe-based metal-organic frameworks (MOFs)-functionalized three-dimensional (3D) porous gelatin aerogels (Ag/Fe@GMA) were fabricated and used as adsorbents and catalysts for the activation of peroxymonosulfate (PMS) for naproxen (NPX) removal from water. The morphology, crystallinity, surface functional groups, and surface chemical element compositions of the fabricated Ag/Fe@GMA was evaluated using various analytical techniques. Our results showed that as an adsorbent, Ag/Fe@GMA showed a 18.0 % higher NPX adsorption capacity compared with the pristine aerogels. This can be attributed to the well-embedded Ag3PO4 and MOFs, indicating a stronger interaction between functionalized aerogels and NPX. After adsorption, 99.9 % of total NPX removal was achieved within 15 min by activating PMS and effectively generating •OH and •SO4- in water. The PMS/Ag/Fe@GMA aerogel system also showed high removal performance for rhodamine B (99.5 %) and tetracycline (93.7 %). Moreover, the Ag/Fe@GMA aerogels showed excellent reusability to achieve 95.7 % NPX removal efficiency after six times of recycling. This study revealed that the Ag/Fe@GMA aerogels had good potential for PMS activation and NPX removal. In particular, as an alternative to powdery materials, 3D shape of Ag/Fe@GMA with excellent reusability facilitates its application in the treatment of water contaminated with organic contaminants.

Uric acid regulates α-synuclein transmission in Parkinsonian models.

Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson's disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model. In a cellular model, UA treatment decreased internalized cytosolic α-syn levels and neuron-to-neuron transmission of α-syn in donor-acceptor cell models by modulating dynamin-mediated and clathrin-mediated endocytosis. Moreover, UA elevation in α-syn-inoculated mice inhibited propagation of extracellular α-syn which decreased expression of phosphorylated α-syn in the dopaminergic neurons of the substantia nigra leading to their increased survival. UA treatment did not lead to change in markers related with autophagolysosomal and microglial activity under the same experimental conditions. These findings suggest UA may control the pathological conditions of PD via additive mechanisms which modulate the propagation of α-syn.

Different response of body weight change according to ketonuria after fasting in the healthy obese.

The relationship between obesity and ketonuria is not well-established. We conducted a retrospective observational study to evaluate whether their body weight reduction response differed by the presence of ketonuria after fasting in the healthy obese. We used the data of 42 subjects, who had medical records of initial urinalysis at routine health check-up and follow-up urinalysis in the out-patient clinic, one week later. All subjects in the initial urinalysis showed no ketonuria. However, according to the follow-up urinalysis after three subsequent meals fasts, the patients were divided into a non-ketonuria group and ketonuria group. We compared the data of conventional low-calorie diet programs for 3 months for both groups. Significantly greater reduction of body weight (-8.6 ± 3.6 kg vs -1.1 ± 2.2 kg, P < 0.001), body mass index (-3.16 ± 1.25 kg/m(2) vs -0.43 ± 0.86 kg/m(2), P < 0.001) and waist circumference (-6.92 ± 1.22 vs -2.32 ± 1.01, P < 0.001) was observed in the ketonuria group compared to the non-ketonuria group. Fat mass and lean body mass were also more reduced in the ketonuria group. In addition, serum free fatty acid concentration after intervention in the ketonuria group showed significant more increment than in the non-ketonuria group. The presence of ketonuria after fasting may be a predicting factor of further body weight reduction.

Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites.

Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (ß = -189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = -0.0938 and -0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (ß = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.

Differences in dietary patterns related to metabolic health by gut microbial enterotypes of Korean adults.

Diet has a profound impact on the progression of metabolic syndrome (MetS) into various diseases. The gut microbiota could modulate the effect of diet on metabolic health. We examined whether dietary patterns related to MetS differed according to gut microbial enterotypes among 348 Korean adults aged 18-60 years recruited between 2018∼2021 in a cross-sectional study. The enterotype of each participant was identified based on 16S rRNA gut microbiota data. The main dietary pattern predicting MetS (MetS-DP) of each enterotype was derived using reduced-rank regression (RRR) models. In the RRR models, 27 food group intakes assessed by a semi-quantitative food frequency questionnaire and MetS prediction markers including triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) were used as predictor and response variables, respectively. The MetS-DP extracted in Bacteroides enterotype (B-type) was characterized by high consumption of refined white rice and low consumption of eggs, vegetables, and mushrooms. The MetS-DP derived among Prevotella enterotype (P-type) was characterized by a high intake of sugary food and low intakes of bread, fermented legumes, and fermented vegetables. The MetS-DP of B-type was positively associated with metabolic unhealthy status (OR T3 vs. T1 = 3.5; 95% CI = 1.5-8.2), comparing the highest tertile to the lowest tertile. Although it was not significantly associated with overall metabolic unhealthy status, the MetS-DP of P-type was positively associated with hyperglycemia risk (OR T3 vs. T1 = 6.2; 95% CI = 1.6-24.3). These results suggest that MetS-DP may differ according to the gut microbial enterotype of each individual. If such associations are found to be causal, personalized nutrition guidelines based on the enterotypes could be recommended to prevent MetS.