Ethanol Metabolism Research Articles

Enhanced bacterial cellulose production in Komagataeibacter sucrofermentans: impact of different PQQ-dependent dehydrogenase knockouts and ethanol supplementation

BackgroundBacterial cellulose (BC) is a biocompatible material with unique mechanical properties, thus holding a significant industrial potential. Despite many acetic acid bacteria (AAB) being BC overproducers, cost-effective production remains a challenge. The role of pyrroloquinoline quinone (PQQ)-dependent membrane dehydrogenases (mDH) is crucial in the metabolism of AAB since it links substrate incomplete oxidation in the periplasm to energy generation. Specifically, glucose oxidation to gluconic acid substantially lowers environmental pH and hinders BC production. Conversely, ethanol supplementation is known to enhance BC yields in Komagataeibacter spp. by promoting efficient glucose utilization.ResultsK. sucrofermentans ATCC 700178 was engineered, knocking out the four PQQ-mDHs, to assess their impact on BC production. The strain KS003, lacking PQQ-dependent glucose dehydrogenase (PQQ-GDH), did not produce gluconic acid and exhibited a 5.77-fold increase in BC production with glucose as the sole carbon source, and a 2.26-fold increase under optimal ethanol supplementation conditions. In contrast, the strain KS004, deficient in the PQQ-dependent alcohol dehydrogenase (PQQ-ADH), showed no significant change in BC yield in the single carbon source experiment but showed a restrained benefit from ethanol supplementation.ConclusionsThe results underscore the critical influence of PQQ-GDH and PQQ-ADH and clarify the effect of ethanol supplementation on BC production in K. sucrofermentans ATCC 700178. This study provides a foundation for further metabolic pathway optimization, emphasizing the importance of diauxic ethanol metabolism for high BC production.

Preparation, Structural Identification, and Screening of Egg-Derived Peptides with Facilitating Alcohol Metabolism Activity.

The aim of this study was to obtain egg-derived peptides with facilitating alcohol metabolism (EPs) by enzymolysis, to identify their structures, and screen small polypeptides with higher activity by molecular docking. The optimum conditions for preparing EPs with facilitating alcohol metabolism were obtained by a single factor experiment, adding 2% Protamex and performing enzymolysis for 3 h with a liquid-material ratio of 35:1. The dose-response relationship experiment showed that 800 mg/kg·bw EPs played a better role in facilitating alcohol metabolism. EPs contained 40% hydrophobic amino acids (HAA), including 9.24% Leu. Eighty-four peptides were identified by HPLC-MS/MS and four peptides with potential activation of alcohol dehydrogenase were further selected by molecular docking. The tetrapeptide Trp-Ile-Val-Asp (WIVD) with the highest binding energy reached -7.16 kcal/mol. These findings suggest that egg is a good source for the preparation of peptides with facilitating alcohol metabolism activity.

Beneficial Effects of Probiotics on Liver Injury Caused by Chronic Alcohol Consumption

Alcoholic liver injury is a serious risk to human health. Probiotics have become a popular form of treatment. Lacticaseibacillus casei Grx12 and Limosilactobacillus fermentum Grx07 isolated from the gut of long-lived people in Rugao, Jiangsu, were studied to determine their protective effects and possible mechanisms of action on alcoholic liver injury. The results showed that rat serum ALT and AST were restored, and liver injury was reduced after the probiotics intervention. The level of antioxidant enzymes and antioxidants such as SOD, GSH and GSH-Px in the rat liver was significantly increased (p < 0.05), which reduces the level of MDA, a peroxidation product in the liver, and thus alleviates liver oxidative stress. L. casei Grx12 and L. fermentum Grx07 also could significantly enhance the expression of Nrf2 protein in the rat liver to regulate the anti-oxidative stress response in the body and cells (p < 0.05). The levels of ADH, Na+-K+-ATPase and Ca2+-ATPase in the rat liver were significantly increased (p < 0.05), which enhanced the body’s metabolism of alcohol. The rat serum LPS and liver TNF-α, IL-6, VEGF, TGF-β1 and NF-κB levels were significantly reduced (p < 0.05), indicating that the probiotics could relieve liver inflammation. The results of this study indicate that L. casei Grx12 and L. fermentum Grx07 have certain protective effects on alcoholic liver injury in rats, likely because of their antioxidant properties and ability to prevent oxidative stress and relieve inflammation.

Elevated levels of alcohol dehydrogenase aggravate ethanol-evoked cardiac remodeling and contractile anomalies through FKBP5-yap-mediated regulation of ferroptosis and ER stress

Alcohol intake provokes severe organ injuries including alcoholic cardiomyopathy with hallmarks of cardiac remodeling and contractile defects. This study examined the toxicity of facilitated ethanol metabolism in alcoholism-evoked changes in myocardial morphology and contractile function, insulin signaling and various cell death domains using cardiac-selective overexpression of alcohol dehydrogenase (ADH). WT and ADH mice were offered an alcohol liquid diet for 12 weeks prior to assessment of cardiac geometry, function, ER stress, apoptosis and ferroptosis. Alcohol intake provoked pronounced glucose intolerance, cardiac remodeling and contractile anomalies with apoptosis, ER stress, and ferroptosis, the effects were accentuated by ADH with the exception of global glucose intolerance. Hearts from alcohol ingesting mice displayed dampened insulin-stimulated phosphorylation of insulin receptor (tyr1146) and IRS-1 (tyrosine) along with elevated IRS-1 serine phosphorylation, the effect was augmented by ADH. Alcohol challenge dampened phosphorylation of Akt and GSK-3β, and increased phosphorylation of c-Jun and JNK, the effects were accentuated by ADH. Alcohol challenge promoted ER stress, FK506 binding protein 5 (FKBP5), YAP, apoptosis and ferroptosis, the effects were exaggerated by ADH. Using a short-term ethanol challenge model (3 g/kg, i.p., twice in three days), we found that inhibition of FKBP5-YAP signaling or facilitated ethanol detoxification by Alda-1 alleviated ethanol cardiotoxicity. In vitro study revealed that the ethanol metabolite acetaldehyde evoked cardiac contractile anomalies, lipid peroxidation, and apoptosis, the effects of which were mitigated by Alda-1, inhibition of ER stress, FKBP5 and YAP. These data suggest that facilitated ethanol metabolism via ADH exacerbates alcohol-evoked myocardial remodeling, functional defects, and insulin insensitivity possibly through a FKBP5-YAP-associated regulation of ER stress and ferroptosis.

Effects of Ca2+ signal on the activities of key enzymes and expression of related genes in yeast ethanol metabolism and mitochondrial function during high sugar fermentation.

During high sugar fermentation, yeast is mainly affected by high sugar stress in the early stage. It becomes jointly affected by high sugar and ethanol stress as ethanol accumulates during fermentation. Ca2+, as the second messenger of the cell, mediates various metabolic processes. In this study, the effects of the Ca2+ signal on the activities of key enzymes, expression of related genes of ethanol metabolism, and mitochondrial function were investigated. The results showed a significant increase in the activities of enzymes related to ethanol metabolism in yeast cells under a high sugar environment. Ca2+ significantly promoted the activities of enzymes related to mitochondrial respiratory metabolism and regulated the carbon flow between ethanol metabolism and the tricarboxylic acid cycle. The high sugar environment affected the expression of genes related to carbon metabolism, while the addition of Ca2+ stabilized the expression of related genes. Ca2+ signal participated in ethanol and mitochondrial metabolism and regulated the key enzymes and related gene expression to enhance the resistance of yeast to stress during high sugar fermentation. © 2024 Society of Chemical Industry.

Disulfiraminės psichozės atvejis

Introduction. Disulfiram is one of three medications approved by the Federal Drug Administration (FDA) to treat alcohol dependence. Patients tend to abstain from alcohol to avoid the unpleasant effects of alcohol toxicity. There may be some side effects, the most common of which are drowsiness, unusual tiredness, headache, metallic taste in mouth, skin rashes, decreased libido. Disulfiram induced psychosis is a psychiatric side effect that occurs very rarely.
 Case report. We report the case of a 33-year-old patient with nearly 15 years history of psychiatric personality disorder and alcohol dependence. Approximately 4 days of alcohol abstinence, as an inpatient he was administered disulfiram. After two weeks, the patient began to feel some side effects. He was admitted to hospital and was diagnosed with disulfiram induced psychosis.
 Discussion. The effect of disulfiram on alcohol metabolism was noticed in the 1940s. It should be used only by motivated patients who must be fully informed about the alcohol-disulfiram reaction. Disulfiram should only be started after about 10 days of sobriety, and the recommended dosage is 500 mg/day. The drug should be used with caution in people with a history of heart disease, diabetes mellitus, hypothyroidism, cerebral damage, nephritis, liver cirrhosis, epilepsy. Caution is recommended for patients who use benzodiazepines, some antibiotics, anticoagulants, tricyclic antidepressants. There may be some adverse effects, more serious ones include changes in vision, numbness, pain or weakness in the limbs, liver cell damage, peripheral neuropathy, seizures – but these are considered to be very rare. Psychiatric side effects may include mood changes, psychotic reactions, memory impairment. Reliable data is lacking, but cases of disulfiram induced psychosis are considered to be rare. Patients taking disulfiram should be monitored carefully.

Alcohol Promotes Lipogenesis in Sebocytes-Implications for Acne.

The oral consumption of alcohol (ethanol) has a long tradition in humans and is an integral part of many cultures. The causal relationship between ethanol consumption and numerous diseases is well known. In addition to the well-described harmful effects on the liver and pancreas, there is also evidence that ethanol abuse triggers pathological skin conditions, including acne. In the present study, we addressed this issue by investigating the effect of ethanol on the energy metabolism in human SZ95 sebocytes, with particular focus on qualitative and quantitative lipogenesis. It was found that ethanol is a strong trigger for lipogenesis, with moderate effects on cell proliferation and toxicity. We identified the non-oxidative metabolism of ethanol, which produced fatty acid ethyl esters (FAEEs), as relevant for the lipogenic effect-the oxidative metabolism of ethanol does not contribute to lipogenesis. Correspondingly, using the Seahorse extracellular flux analyzer, we found an inhibition of the mitochondrial oxygen consumption rate as a measure of mitochondrial ATP production by ethanol. The ATP production rate from glycolysis was not affected. These data corroborate that ethanol-induced lipogenesis is independent from oxygen. In sum, our results give a causal explanation for the prevalence of acne in heavy drinkers, confirming that alcoholism should be considered as a systemic disease. Moreover, the identification of key factors driving ethanol-dependent lipogenesis may also be relevant in the treatment of acne vulgaris.

Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity

BackgroundAlcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout.MethodsThis research was conducted using the UK Biobank resource. The association of alcohol consumption with serum urate and gout was tested among 458,405 European participants. Candidate SNPs were identified by comparing serum urate, gout, and alcohol consumption GWAS for shared signals of association. Multivariable-adjusted linear and logistic regression analyses were conducted with the inclusion of interaction terms to identify SNP-alcohol consumption interactions for association with serum urate level, hyperuricaemia, and gout. The nature of these interactions was characterised using genotype-stratified association analyses.ResultsAlcohol consumption was associated with elevated serum urate and gout. For serum urate level, non-additive interactions were identified between alcohol consumption and rs1229984 at the ADH1B locus (P = 3.0 × 10−44) and rs6460047 at the MLXIPL locus (P = 1.4 × 10−4). ADH1B also demonstrated interaction with alcohol consumption for hyperuricaemia (P = 7.9 × 10−13) and gout (P = 8.2 × 10−9). Beer intake had the most significant interaction with ADH1B for association with serum urate and gout among men, while wine intake had the most significant interaction among women. In the genotype-stratified association analyses, ADH1B and MLXIPL were associated with serum urate level and ADH1B was associated with hyperuricaemia and gout among consumers of alcohol but not non-consumers.ConclusionsIn this large study of European participants, novel interactions with alcohol consumption were identified at ADH1B and MLXIPL for association with serum urate level and at ADH1B for association with hyperuricaemia and gout. The association of ADH1B with serum urate and gout may occur through the modulation of alcohol metabolism rate among consumers of alcohol.

Gene Expression of Ethanol and Acetate Metabolic Pathways in the Acinetobacter baumannii EmaSR Regulon.

Previous studies have confirmed the involvement of EmaSR (ethanol metabolism a sensor/regulator) in the regulation of Acinetobacter baumannii ATCC 19606 ethanol and acetate metabolism. RNA-seq analysis further revealed that DJ41_568-571, DJ41_2796, DJ41_3218, and DJ41_3568 regulatory gene clusters potentially participate in ethanol and acetate metabolism under the control of EmaSR. This study fused the EmaSR regulon promoter segments with reporter genes and used fluorescence expression levels to determine whether EmaSR influences regulon expression in ethanol or acetate salt environments. The enzymatic function and kinetics of significantly regulated regulons were also studied. The EmaSR regulons P2796 and P3218 exhibited > 2-fold increase in fluorescence expression in wild type compared to mutant strains in both ethanol and acetate environments, and PemaR demonstrated a comparable trend. Moreover, increases in DJ41_2796 concentration enhanced the conversion of acetate and succinyl-CoA into acetyl-CoA and succinate, suggesting that DJ41_2796 possesses acetate: succinyl-CoA transferase (ASCT) activity. The kcat/KM values for DJ41_2796 with potassium acetate, sodium acetate, and succinyl-CoA were 0.2131, 0.4547, and 20.4623 mM-1s-1, respectively. In A. baumannii, EmaSR controls genes involved in ethanol and acetate metabolism, and the EmaSR regulon DJ41_2796 was found to possess ASCT activity.

The protective effect of Enteromorpha prolifera polysaccharide on alcoholic liver injury in C57BL/6 mice

An alcohol-induced liver injury model was induced in C57BL/6 mice to assess the protective efficacy of Enteromorpha prolifera polysaccharides (EP) against liver damage. Histological alterations in the liver were examined following hematoxylin-eosin (H&E) staining. Biochemical assay kits and ELISA kits were employed to analyze serum and liver biochemical parameters, as well as the activity of antioxidant enzymes and alcohol metabolism-related enzymes. The presence of oxidative stress-related proteins in the liver was detected using western blotting. Liquid chromatography and mass spectrometry were used to profile serum metabolites in mice. The findings demonstrated that EP-H (100 mg/Kg) reduced serum ALT and AST activity by 2.31-fold and 2.32-fold, respectively, when compared to the alcohol-induced liver injury group. H&E staining revealed a significant attenuation of microvesicular steatosis and ballooning pathology in the EP-H group compared to the model group. EP administration was found to enhance alcohol metabolism by regulating metabolite-related enzymes (ADH and ALDH) and decreasing CYP2E1 expression. EP also modulated the Nrf2/HO-1 signaling pathway to bolster hepatic antioxidant capacity. Furthermore, EP restored the levels of lipid metabolites (Glycine, Butanoyl-CoA, and Acetyl-CoA) to normalcy. In summary, EP confers protection to the liver through the regulation of antioxidant activity and lipid metabolites in the murine liver.

Efficacy of Jiuzao polysaccharides in ameliorating alcoholic fatty liver disease and modulating gut microbiota

Jiuzao, the residue from Baijiu production, has shown radical scavenging properties in prior investigations, suggesting its potential as a hepatoprotective agent against acute liver damage. This study reveals that Jiuzao polysaccharides ameliorated liver morphological damage in zebrafish larvae afflicted with alcoholic fatty liver disease (AFLD), as evidenced by Oil red O, H&E, and Nile red staining. These polysaccharides notably modulated antioxidant enzyme levels and lipid peroxidation components. The real-time quantitative polymerase chain reactions analyses illustrated the significant impact of Jiuzao polysaccharides on genes integral to ethanol and lipid metabolism. The 16 S rRNA results showed that Jiuzao polysaccharides could improve the intestinal flora in zebrafish larvae exposed to ethanol. In summary, Jiuzao polysaccharides efficaciously mitigate liver lipid accumulation, enhance ethanol metabolism, and reduce oxidative stress by downregulating genes involved in AFLD development. They also regulate the changes in gut microbiota, providing further protection against acute alcoholic liver insult in zebrafish larvae.

Food and alcohol disturbance among people who have undergone bariatric surgery.

There have been numerous investigations of aberrant eating and substance abuse among patients who have undergone bariatric surgery, which affects the metabolism and the pharmacokinetics of alcohol. However, there is a dearth of literature considering the complex interplay between changes in post-surgery food and alcohol consumption. Furthermore, despite the increasing recognition of issues surrounding replacing food consumption with alcohol consumption (Food and Alcohol Disturbance [FAD]), most emerging research has focused on young adult populations. This perspective reviews and synthesizes the small but growing body of research on the interplay between food and alcohol consumption, particularly FAD, and considers its application to bariatric surgery in general. There are unique considerations for patients who have undergone bariatric surgery. Patients experience altered gastric anatomy, which affects food and alcohol metabolism, and are advised to abstain from drinking alcohol after surgery. After reviewing the available literature, this perspective highlights future directions for research and practice in bariatric surgery.

Acetic Acid: An Underestimated Metabolite in Ethanol-Induced Changes in Regulating Cardiovascular Function.

Acetic acid is a bioactive short-chain fatty acid produced in large quantities from ethanol metabolism. In this review, we describe how acetic acid/acetate generates oxidative stress, alters the function of pre-sympathetic neurons, and can potentially influence cardiovascular function in both humans and rodents after ethanol consumption. Our recent findings from in vivo and in vitro studies support the notion that administration of acetic acid/acetate generates oxidative stress and increases sympathetic outflow, leading to alterations in arterial blood pressure. Real-time investigation of how ethanol and acetic acid/acetate modulate neural control of cardiovascular function can be conducted by microinjecting compounds into autonomic control centers of the brain and measuring changes in peripheral sympathetic nerve activity and blood pressure in response to these compounds.

Insight into the binding characteristics of epigallocatechin-3-O-gallate and alcohol dehydrogenase: Based on the spectroscopic and molecular docking analysis

Alcohol dehydrogenase (ADH) is one of the pivotal enzymes for alcohol metabolism, which plays an important role in many physiological processes. In this study, the activation effects of epigallocatechin-3-O-gallate (EGCG) on ADH and the characteristics of the interaction were investigated via biochemical method, spectroscopy methods, and molecular docking. The results demonstrated that EGCG significantly increased the catalytic activity of ADH with a 33.33% activation rate and that EGCG blending slightly altered the microenvironment surrounding ADH aromatic amino acids, with an increase in the quantity of β-sheet and a decrease in the α-helix. Through the thermal stability analysis, it is further shown that the interaction of the two affects the intra-molecular hydrogen bond formation of the protein, and the conformation is partially extended. Besides, a total of 8 residues in ADH participated in the docking with EGCG, among which Asp-227, Lys-231, Glu-234, Gly-365 and Glu-366 participated in the formation of hydrogen bonds. At the same time, EGCG and amino group of Lys-231 form a noncovalent bond through cation-π interaction. In particular, hydrogen bonding was beneficial to keep the stability of EGCG-ADH, which was the primary driver of ADH activity activation. The results supply a new way for EGCG to activate ADH and a theoretical basis for the development of anti-alcoholism products.

The Preventative Effect of Chitooligosaccharides against Chronic Alcoholic Liver Disease by Regulating Alcohol Metabolism, Fatty Acid Metabolism, and Intestinal Barrier Damage

Since chronic alcoholic liver disease (ALD) is a significant global health concern, several studies have shown that chitooligosaccharides (COS) exhibit hepatoprotective effects. This paper examined the COS protective effect on chronic ALD mice. Results showed that COS improved the lipid accumulation, liver injury, and oxidative stress levels in the mice while inhibiting cytochrome P450 protein 2E1 (CYP2E1) expression in the liver and promoting alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH1) expression, indicating that COS could ameliorate alcohol metabolism. Moreover, COS intervention also enhanced the antioxidant capacity of the liver and upregulated peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1), silent information regulator 1 (SIRT1), HO-1, and nuclear factor-erythroid 2-related factor 2 (NRF2) protein levels. In addition, COS increased peroxisome proliferator-activated receptor α (PPARα), acyl-CoA oxidase (ACOX), acyl-CoA synthetase long-chain family member (ACSL), carnitine palmitoyltransferase 1A (CPT-1A), and carnitine palmitoyltransferase 2 (CPT2) protein levels by upregulating the fatty acid β oxidation pathway and restoring mitochondrial genesis. From a liver-gut axis perspective, COS enhanced intestinal barrier function by increasing the adhesion junction (AJ) and intestinal tight junction (TJ) protein expression. Therefore, COS displayed a protective ability against chronic ALD. The results provide a theoretical basis for utilizing supplemental dietary COS as a functional food alternative for treating chronic ALD.

Oral Administration of Alcohol-Tolerant Lactic Acid Bacteria Alleviates Blood Alcohol Concentration and Ethanol-Induced Liver Damage in Rodents.

Excessive alcohol consumption can have serious negative consequences on health, including addiction, liver damage, and other long-term effects. The causes of hangovers include dehydration, alcohol and alcohol metabolite toxicity, and nutrient deficiency due to absorption disorders. Additionally, alcohol consumption can slow reaction times, making it more difficult to rapidly respond to situations that require quick thinking. Exposure to a large amount of ethanol can also negatively affect a person's righting reflex and balance. In this study, we evaluated the potential of lactic acid bacteria (LAB) to alleviate alcohol-induced effects and behavioral responses. Two LAB strains isolated from kimchi, Levilactobacillus brevis WiKim0168 and Leuconostoc mesenteroides WiKim0172, were selected for their ethanol tolerance and potential to alleviate hangover symptoms. Enzyme activity assays for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were then conducted to evaluate the role of these bacteria in alcohol metabolism. Through in vitro and in vivo studies, these strains were assessed for their ability to reduce blood alcohol concentrations and protect against alcohol-induced liver damage. The results indicated that these LAB strains possess significant ethanol tolerance and elevate ADH and ALDH activities. LAB administration remarkably reduced blood alcohol levels in rats after excessive alcohol consumption. Moreover, the LAB strains showed hepatoprotective effects and enhanced behavioral outcomes, highlighting their potential as probiotics for counteracting the adverse effects of alcohol consumption. These findings support the development of functional foods incorporating LAB strains that can mediate behavioral improvements following alcohol intake.

Inhibitory Effects of Jiuzao Polysaccharides on Alcoholic Fatty Liver Formation in Zebrafish Larvae and Their Regulatory Impact on Intestinal Microbiota.

The liver is critical in alcohol metabolism, and excessive consumption heightens the risk of hepatic damage, potentially escalating to hepatitis and cirrhosis. Jiuzao, a by-product of Baijiu production, contains a rich concentration of naturally active polysaccharides known for their antioxidative properties. This study investigated the influence of Laowuzeng Jiuzao polysaccharide (LJP) on the development of ethanol-induced alcoholic fatty liver. Zebrafish larvae served as the model organisms for examining the LJPs hepatic impact via liver phenotypic and biochemical assays. Additionally, this study evaluated the LJPs effects on gene expression associated with alcoholic fatty liver and the composition of the intestinal microbiota through transcriptomic and 16 S rRNA gene sequencing analyses, respectively. Our findings revealed that LJP markedly mitigated morphological liver damage and reduced oxidative stress and lipid peroxidation in larvae. Transcriptome data indicated that LJP ameliorated hepatic fat accumulation and liver injury by enhancing gene expression involved in alcohol and lipid metabolism. Furthermore, LJP modulated the development of alcoholic fatty liver by altering the prevalence of intestinal Actinobacteriota and Firmicutes, specifically augmenting Acinetobacter while diminishing Chryseobacterium levels. Ultimately, LJP mitigated alcohol-induced hepatic injury by modulating gene expression related to ethanol metabolism, lipid metabolism, and inflammation and by orchestrating alterations in the intestinal microbiota.

A critical review of ethanol effects on neuronal firing: A metabolic perspective.

Ethanol metabolism is relatively understudied in neurons, even though changes in neuronal metabolism are known to affect their activity. Recent work demonstrates that ethanol is preferentially metabolized over glucose as a source of carbon and energy, and it reprograms neurons to a state of reduced energy potential and diminished capacity to utilize glucose once ethanol is exhausted. Ethanol intake has been associated with changes in neuronal firing and specific brain activity (EEG) patterns have been linked with risk for alcohol use disorder (AUD). Furthermore, a haplotype of the inwardly rectifying potassium channel subunit, GIRK2, which plays a critical role in regulating excitability of neurons, has been linked with AUD and shown to be directly regulated by ethanol. At the same time, overexpression of GIRK2 prevents ethanol-induced metabolic changes. Based on the available evidence, we conclude thatthe mechanisms underlying the effects of ethanol on neuronal metabolism are a novel target for developing therapies for AUD.

Nonelectroactive clostridium obtains extracellular electron transfer-capability after forming chimera with Geobacter.

Extracellular electron transfer (EET) of microorganisms is a major driver of the microbial growth and metabolism, including reactions involved in the cycling of C, N, and Fe in anaerobic environments such as soils and sediments. Understanding the mechanisms of EET, as well as knowing which organisms are EET-capable (or can become so) is fundamental to electromicrobiology and geomicrobiology. In general, Gram-positive bacteria very seldomly perform EET due to their thick non-conductive cell wall. Here, we report that a Gram-positive Clostridium intestinale (C.i) attained EET-capability for ethanol metabolism only after forming chimera with electroactive Geobacter sulfurreducens (G.s). Mechanism analyses demonstrated that the EET was possible after the cell fusion of the two species was achieved. Under these conditions, the ethanol metabolism pathway of C.i was integrated by the EET pathway of G.s, by which achieved the oxidation of ethanol for the subsequent reduction of extracellular electron acceptors in the coculture. Our study displays a new approach to perform EET for Gram-positive bacteria via recruiting the EET pathway of an electroactive bacterium, which suggests a previously unanticipated prevalence of EET in the microbial world. These findings also provide new perspectives to understand the energetic coupling between bacterial species and the ecology of interspecies mutualisms.

Pathology of Ketoacidosis in Emergency of Diabetic Ketoacidosis and Alcoholic Ketoacidosis: A Retrospective Study.

This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, β-hydroxybutyric acid, and β-hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.