Fatty Acids Research Articles

Progress in Investigating the Relationship between Omega-3 Polyunsaturated Fatty Acids and Coronary Heart Disease (CHD)

Coronary heart disease (CHD) is a globally common cardiovascular disorder, characterized by atherosclerotic lesions in the coronary arteries, leading to narrowing or blockage of the vessels, which subsequently causes myocardial ischemia, hypoxia, and even necrosis. This condition significantly impacts the daily life of patients and represents a major contributor to both morbidity and mortality on a global scale. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), Principally extracted from marine pisces and certain plants, have been increasingly shown in recent years to be closely associated with various pathophysiological mechanisms related to CHD, which holds significant value in the prevention and treatment of CHD. This review offers a comprehensive summary of the sources of ω-3 PUFA, explores the pathophysiological mechanisms of CHD, and offers an in-depth analysis of the multifaceted contribution of ω-3 PUFA in mitigating the susceptibility to CHD, particularly focusing on their effects on lipid metabolism, endothelial function, and inflammatory pathways, thereby contributing new research perspectives for the tactics for the risk mitigation and administration of CHD, including both preventive measures and therapeutic interventions.

Design, Synthesis, and In-Silico Analysis of Thiazole-Embedded Schiff Base Derivatives for Breast Cancer Therapeutic Potential

Thiazole-derived Schiff base compounds possess significant pharmacological properties, influencing various enzymes in metabolic pathways and exhibiting antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. This study delves into the synthesis, characterization, and in-silico analysis of ten thiazole-embedded Schiff base derivatives (TZ1-10), benchmarking them against five Food and Drug Administration (FDA)-approved breast cancer drugs. Molecular docking against multiple therapeutic targets related to fatty acid synthase and cell proliferation (PDB IDs: 4FX3, 4OAR, 3NUP, and 3ERT) alongside ADME and Lipinski rule assessments were conducted. Compounds TZ6 and TZ8 emerged as promising candidates with docking scores of -8.0 kcal/mol and -8.2 kcal/mol respectively against the 4FX3 protein. These findings contribute to a deeper understanding of thiazole-embedded Schiff base derivatives, showcasing their potential for future medicinal and scientific applications.

Severe Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Patients on Chronic Hemodialysis—Reconsidering the Relationship with Thrombo-Inflammation and Oxidative Stress

Background/Objectives: Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship between the levels of a broad spectrum of thrombo-inflammatory and oxidative stress-related biomarkers and the presence and level of ESA hyporesponsiveness in patients undergoing regular chronic hemodialysis. Methods: This cross-sectional study included 96 patients treated with chronic hemodialysis. Levels of several thrombo-inflammatory and oxidative stress-related biomarkers, as well as demographic, clinical, and laboratory analyses, were collected and analyzed based on the calculated value of the ESA-hyporesponsiveness index (EHRI). Results: In the analyzed sample, 58 patients received ESAs. Of all the investigated parameters, only body mass index (BMI), level of plasminogen activator inhibitor-1, and level of L-type fatty acid binding protein (L-FABP) were observed as significant predictors of EHRI. A significant diagnostic potential for ESA resistance has been observed in BMI and L-FABP between ESA-resistant and ESA-non-resistant groups of patients (p = 0.004, area under the curve 0.763 and p = 0.014, area under the curve 0.712, respectively) with the cut-off values of 25.46 kg/m2 and 5355.24 ng/mL, respectively. Having a BMI of 25.46 kg/m2 or less and an L-FABP level higher than 5355.24 ng/mL were observed as significant predictors of ESA resistance (odds ratio 9.857 and 6.125, respectively). Conclusions: EHRI was positively predicted by low BMI and high levels of plasminogen activator inhibitor-1 and L-FABP. High levels of L-FABP and low BMI have been observed as strong predictors of ESA resistance.

The ability in managing reactive oxygen species affects Escherichia coli persistence to ampicillin after nutrient shifts.

This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on Escherichia coli and how the switch from different carbon sources to fatty acids influences the formation of persister-resilient bacterial cells resistant to antibiotics. The findings reveal a striking variation in survival rates, with a significant number of cells surviving ampicillin treatment after transitioning from glucose to oleic acid. The key revelation is the role of reactive oxygen species (ROS) in cell killing, particularly after switching from gluconeogenic carbons. The timing of ROS bursts aligns with the rapid killing phase, highlighting the critical impact of oxidative stress regulation on persistence frequency. This research provides valuable insights into bacterial persistence mechanisms, offering potential avenues for targeted therapeutic interventions to combat bacterial resistance effectively.

Assessment of cardiac and skeletal muscle metabolites using 1H-MRS and chemical-shift encoded magnetic resonance imaging: Impact of diabetes, RAGE, and DIAPH1.

Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used 1H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice. Nine cohorts of male mice, with six mice per cohort, were used: wild type non-diabetic control mice (WT-NDM), WT-diabetic (WT-DM) mice, Ager knockout non-diabetic (RKO-NDM) and diabetic mice (RKO-DM), Diaph1 knockout non-diabetic (DKO-NDM), and diabetic mice (DKO-DM), WT-NDM mice treated with vehicle, WT-DM mice treated with vehicle, and WT-DM mice treated with RAGE229 (antagonist of RAGE-DIAPH1 interaction). A Point Resolved Spectroscopy (PRESS) sequence for 1H-MRS, and multi-echo gradient recalled echo (GRE) for CSE were employed. Triglycerides, and free fatty acids in the heart and hind limb obtained from MRS and MRI were compared to those measured using biochemical assays. Two-sided t-test, non-parametric Kruskal-Wallis Test, and one-way ANOVA were employed for statistical analysis. We report that the results were well-correlated with significant differences using MRI and biochemical assays between WT-NDM and WT-DM, as well as within the non-diabetic groups, and within the diabetic groups. Deletion of Ager or Diaph1, or treatment with RAGE229 attenuated diabetes-associated increases in triglycerides in the heart and hind limb in mice. These results suggest that the employment of 1H-MRS/MRI is a feasible non-invasive modality to monitor metabolic dysfunction in T1D and the metabolic consequences of interventions that block RAGE and DIAPH1.

Influence of Gut Microflora on Eating Disorders

Eating disorders (EDs) have attracted extensive attention worldwide as a disease that seriously affects eating behaviour and weight control. The impact and pathogenesis of the gut microbiota in EDs remain important research directions and have sparked interest in developing treatments for these conditions. This review examines the intricate interactions between the gut microbiota and the gut-brain (GB) axis, and Eds focuses on bulimia nervosa (BN), binge eating disorder (BED), and anorexia nervosa (AN). According to the findings, the pathophysiology of AN and BED is correlated with lower levels of short-chain fatty acids (SCFAs) and beneficial bacteria in the gut microbiota. In addition, as a key mediator, the GB axis affects the neural pathways and behaviours between the brain and the gut, thereby exacerbating EDs symptoms. This review highlights the potential of gut microbiota-targeted therapies as adjunctive treatments for EDs. However, this study also has certain limitations. For example, more investigation is required to explore the clear mechanism and causal relationship between the gut microbiome and other EDs. Future studies should clarify the function of gut bacteria in EDs and advance treatment strategies.

Dry eye disease – how our lifestyle choices can affect the disease?

Introduction: In today’s world, we know how important it is to keep healthy habits because many diseases begin with daily lifestyle choices. Dry eye disease is a disease of the ocular surface and there are many risk factors, that lead to developing this disorder. As the possible factors we can underline deficiency of vitamin D or Omega-3 fatty acids, lack of physical exercise, long screen time, or smoking tobacco. Aim of the study: This review seeks to highlight the issue of dry eye disease linked to everyday routines by examining clinical trial outcomes. Furthermore, it offers an analysis of potential strategies to prevent ocular alterations by critically evaluating the existing data. State of knowledge: The listed lifestyle choices cause a higher risk of developing dry eye disease and affect ocular health on many levels, leading to unpleasant feelings and affecting people’s lives. However, with some lifestyle changes, the risk of developing this disease can be decreased, and negative symptoms can be minimized. It is important to remember vitamin D, and Omega-3 supplementation, daily physical activity, minimalization of the time spent in front of the visual display terminals, and quitting smoking. Conclusions: Many daily habits are connected to developing dry eye disease, and it is very important to remember about the small daily changes, which can decrease the risk of the disease.

Improvement of Phosphorus Removal from Wastewater Through Fermentation of Low-Concentrated Wastewater Sludge and Increased Production of Volatile Fatty Acids

This article presents the results of a two-stage study: the first stage involved assessing the dependence of the increase or decrease in the concentration of volatile fatty acids (VFAs) on external factors and then assessing the relationship between the VFA concentration in the supernatant after fermentation and the processing characteristics (temperature, mixing mode, alkalinity, pH, nitrogen and phosphorus content). The greatest increase in VFAs (content up to 285 mg/L in the supernatant) was achieved at a temperature in the range of 28 to 38 °C with constant mixing of the sludge. Based on the results of the second stage, a conclusion was made on the efficiency of using a particular substrate depending on the concentration of phosphorus phosphates in the incoming wastewater. The study results showed that 7.54 mg/L of phosphorus can be removed with a given probability (for activated sludge, raw sludge and wastewater). It is recommended to compensate for the excess of this concentration by dosing the acetic acid solution at a rate of 3800 meq/L of VFA per 1 mg/L of phosphorus phosphates. The literature does not contain any results of parallel studies of the operation of a controlled bioreactor with artificial external feeding and acidified VFA. The results of the study can be applied in planning sludge acidification systems in the technological scheme of wastewater treatment and sludge processing.

Amycolatopsis melonis sp. nov., a novel protease-producing and cellulose-degrading actinobacterium isolated from soil.

A novel protease-producing and cellulose-degrading actinobacterium, designated strain NEAU-NG30T, was isolated from a melon rhizosphere soil sample collected in Harbin, Heilongjiang Province, China, and established its status using a polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain NEAU-NG30T was closely related to Amycolatopsis bullii DSM 45802T (98.7%) and Amycolatopsis vancoresmycina DSM 44592T (98.3%). The phospholipid profile contained diphosphatidylglycerol, phosphatidyl methylethanolamine, phosphatidylethanolamine and phosphatidylinositol. The diagnostic sugars in cell hydrolysates were determined to be galactose and arabinose. Cell walls contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinone was MK-9(H4). The major fatty acids were iso-C15:0 and iso-C16:0. Meanwhile, genome analysis of sequences revealed a genome size of 9 338 250 bp and a DNA G+C content of 71.6%. In addition, the average nucleotide identity values and the level of digital DNA-DNA hybridization between strain NEAU-NG30T and its reference strains fall below the thresholds typically used for delineating prokaryote species. According to phenotypic, chemotaxonomic and genotypic studies, it is indicated that strain NEAU-NG30T is considered to be a novel species of the genus Amycolatopsis, for which the name Amycolatopsis melonis sp. nov. is proposed, with NEAU-NG30T (=MCCC 1K08677T=JCM 35654T) as the type strain.

Sustainable Abiotic-Biotic Dechlorination of Perchloroethene with Sulfidated Nanoscale Zero-Valent Iron as Electron Donor Source.

Combining organohalide-respiring bacteria with nanoscale zero-valent iron (nZVI) represents a promising approach for remediating chloroethene-contaminated aquifers. However, limited information is available regarding their synergistic dechlorinating ability for chloroethenes when nZVI is sulfidated (S-nZVI) under the organic electron donor-limited conditions typically found in deep aquifers. Herein, we developed a combined system utilizing a mixed culture containing Dehalococcoides (Dhc) and S-nZVI particles, which achieved sustainable dechlorination with repeated rounds of spiking with 110 μM perchloroethene (PCE). The relative abundance of Dhc considerably increased from 5.2 to 91.5% after five rounds of spiking with PCE, as evidenced by 16S rRNA gene amplicon sequencing. S-nZVI corrosion generated hydrogen as an electron donor for Dhc and other volatile fatty acid (VFA)-producing bacteria. Electron balance analysis indicated that 68.1% of electrons from Fe0 consumed in S-nZVI were involved in dechlorination, and 6.2, 1.1, and 3.2% were stored in formate, acetate, and other VFAs, respectively. The produced acetate possibly served as a carbon source for Dhc. Metagenomic analysis revealed that Desulfovibrio, Syntrophomonas, Clostridium, and Mesotoga were likely involved in VFA production. These findings provide valuable insights into the synergistic mechanisms of biotic and abiotic dechlorination, with important implications for sustainable remediation of electron donor-limited aquifers contaminated by chloroethenes.

In vitro validation of colon delivery of vitamin B2 through a food grade multi-unit particle system.

Colon target delivery of active ingredients is frequently applied in pharmaceutical products. However, in functional food and beverage applications, dietary supplements, and medical nutrition, formats targeting colonic delivery to improve human health are rare. Nevertheless, there is emerging evidence for beneficial effects of colonic delivered nutrients on gut microbiota and host health which increases the demand for sustainable food grade materials that are regulatory approved for application. In this paper, we describe a double layer coated multi-unit particle system (MUPS) with a diameter of approximately 730 microns consisting of food grade materials: shellac as outer layer, alginate as inner layer, cellulose as a core and riboflavin as active ingredient. The suitability of the MUPS for colonic delivery was tested in three well-established in vitro digestion and fermentation models: the USP Apparatus 3 and the TNO Intestinal Models 1 and 2 (TIM-1 and TIM-2). All systems confirmed the integrity of the MUPS under simulated upper gastrointestinal tract conditions with approximately 90% of the active ingredient being released under simulated ileal-colonic conditions. The TIM-2 model also showed the effects of riboflavin loaded MUPS on the microbiome composition with an increase in the production of short-chain fatty acids, acetate and butyrate. The results of these experiments provide a reliable basis for validation of this vitamin-loaded food grade MUPS in future human clinical trials. In addition, following the recent announcement of the European Commission to restrict intentionally added microplastics to products, the materials used in the described formulation offer an environmentally friendly alternative to often applied methyl acrylate based coatings.

Whole-Genome Metagenomic Analysis of Functional Profiles in the Fecal Microbiome of Farmed Sows with Different Reproductive Performances

Recent studies suggested an association between the reproductive performance of sows and their gut microbiota. To understand how the gut microbiota affect the reproductive performances of sows, we conducted a whole-genome metagenomic analysis on the fecal microbial functional profiles of sows with high and low reproductive performances. We used 60 sows from six farms (10 sows/farm), including 30 sows from three farms with higher reproductive performances (the mean number of weaned piglets/sow/year) (group H) and 30 sows from three farms with lower performances (group L). Fecal microbial DNA was subjected to a whole-genome metagenomic analysis. Biomarker exploration analysis identified “carbohydrate transport and metabolism” as the most discriminative function enriched in group H. Further analysis of carbohydrate-active enzymes revealed that the fecal microbiome of group H had a greater capacity to degrade dietary fiber, specifically cellulose and pectin. Group H also exhibited higher fecal short-chain fatty acid (SCFA) concentrations than group L, with the abundances of cellulose- and pectin-degrading genes showing significant positive correlations with fecal SCFA concentrations. Taxonomic analysis indicated greater contributions of Prevotella, Treponema, Ruminococcus, and Fibrobacter to cellulose and pectin degradation in the fecal microbiome in group H. In conclusion, higher reproductive performances of sows were, at least in part, associated with a greater microbial capacity for degrading cellulose and pectin, resulting in a higher SCFA production in the hindgut.

Topical Application of Melatonin in a Grapeseed Oil-based Microemulsion Accelerated Wound Healing in Rat Models

Objective: Melatonin has been associated with accelerated tissue regeneration and grapeseed oil has abundant unsaturated fatty acids, particularly linoleic acid that makes it a strong antioxidant, having the potential to promote wound healing by enhancing the presence of free radicals at the wound site. The study is aimed to evaluate the potential of a microemulsion gel using grapeseed oil as the organic phase and melatonin encapsulated in the vesicles to exhibit synergistic wound healing in Swiss albino rats. Materials and Method: Microemulsion containing grapeseed oil encapsulating melatonin was developed using the water-titration method. The surfactant and co-surfactant ratio (Smix) were fixed at 1:1. A pseudo-ternary diagram was used to determine the microemulsion zone and the developed microemulsion was further incorporated in carbopol 934P gel. The formulations were evaluated for their physicochemical properties and cytotoxicity assay. The optimized formulation was topically applied to cutaneous wounds of Swiss albino rat models. 30 Swiss albino rats were divided into five groups of 6 animals each: (i) Negative control group, (ii) Standard marketed formulation treated group, (iii) Optimized microemulsion containing Grapeseed oil and melatonin treated group, (iv) Grapeseed oil treated group and (v) Melatonin treated group. All the rats in each group were topically applied with the desired formulations daily for up to 14 days. Results: The treatment with a formulation comprising 10.18% Grapeseed oil, 24.88% water, and 64.94% Smix exhibited the highest entrapment efficiency of 86.65 ± 1.88% with an enhanced in vitro drug release of up to 83.02 ± 1.09%, also demonstrating first-order release kinetics. Furthermore, it did not inhibit L929 mouse fibroblast cell proliferation up to 500 μg/mL and promoted wound closure prior to other groups. Additionally, increased tissue maturation with higher collagen deposition was mostly seen by day 7. Thus demonstrating it is suitable for dermal application and sustained release of melatonin. The in vivo wound healing study and histological investigations on rat models demonstrated comparable results as observed in the marketed formulation of melatonin. Conclusion: The results showed that GSO oil based microemulsion encapsulating MEL could be a promising wound treatment option to exhibit accelerated wound healing effects.

FABP7: A Potential Diagnostic and Prognostic Biomarker for Clear Cell Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is highly heterogeneous, with distinct patient management between clear cell RCC (ccRCC) and non-ccRCC groups. Previous bioinformatics and machine learning techniques identified fatty acid binding protein 7 (FABP7) as a potential ccRCC biomarker. However, FABP7 expression studies between ccRCC and non-ccRCC were incomplete. This study aimed to assess FABP7 as a biomarker for distinguishing between ccRCC and non-ccRCC tissue samples. FABP7 expression was evaluated via immunohistochemical staining in 58 RCC cases, including 43 ccRCC and 15 non-ccRCC cases. Staining results were interpreted using H-scores; scores above the cut-off were deemed positive. The correlation between FABP7 expression and clinicopathological RCC features was investigated. FABP7 positivity was 48.8% in ccRCC and only 13.3% in non-ccRCC cases, with weak positivity in non-ccRCC tissues. FABP7 expression significantly differed between ccRCC and non-ccRCC (p<0.05). This finding was confirmed in a TCGA dataset. However, FABP7 expression was not correlated with other RCC clinicopathological features in our dataset. TCGA results linked FABP7 expression to tumor stage and disease-free survival in patients with ccRCC. This study preliminarily evaluated FABP7 as a differential diagnostic biomarker in RCC subtyping, showing higher expression in ccRCC than non-ccRCC. FABP7 may serve as a potential diagnostic and prognostic biomarker for ccRCC.

Upcycling Milk Industry Byproducts into Tenebrio molitor Larvae: Investigation on Fat, Protein, and Sugar Composition

Edible insects represent a growing sector of the food industry and have a low carbon footprint. Noteworthy, insects can upcycle different leftovers and byproducts into high-quality nutrients. Herein, the larvae of the edible insect Tenebrio molitor (TML) were fed using local milk industry byproducts. Mozzarella whey and whey permeate obtained in cheese production were used to formulate three alternative diets. Both byproducts are rich in sugars, in particular the disaccharide lactose and the monosaccharides glucose and galactose. Two of the three diets did not interfere with biometric data and vitality, while the use of whey permeate alone significantly reduced development. At the end of the trial, the proximate composition of TML was strongly affected, with an increased protein content of up to +7% and a favorable fat composition. The analysis of secondary metabolites revealed the accumulation of different compounds, in particular monounsaturated fatty acids (MUFAs), amino acids, and the disaccharide trehalose, essential for the correct larval development and pupation. In conclusion, the present study demonstrates that milk industry byproducts can be upcycled as feed for TML, maintaining an optimal nutrient composition and favorably increasing the protein content.

Roseobacter sinensis sp. nov., a marine bacterium capable to synthesize arachidonic acid.

Strain WL0113T was isolated from surface seawater of the coast of Lianyungang, Jiangsu province, PR China. Strain WL0113T shared highest 16S rRNA gene sequence similarity with Roseobacter insulae YSTF-M11T (98.8%), followed by R. cerasinus AI77T (98.8%), R. ponti MM-7T (98.0%). Strain WL0113T was Gram-stain-negative, cream, aerobic, non-motile and coccoid- to oval-shaped, and able to grow at pH 6.5-9.0 (optimum, pH 7.0-8.0), at 10-37°C (optimum, 28°C) and in the presence of 1-5% (w/v; optimum, 2.5%) NaCl. Ubiquinone-10 was detected as dominant. The main fatty acids (> 5%) of the strain WL0113T were C16:0, iso-C17:0 3OH, C20:4ω6,9,12,15c (arachidonic acid), and summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids include phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, glycophospholipid, unknown aminolipid, unknown phospholipid, and two unknown polar lipids. The ANI and dDDH values between strain WL0113T and Roseobacter cerasinus were 80.4% and 23.0%, respectively. The genomic DNA G + C content of strain WL0113T was 63.1%. Based on these data, it is proposed that strain WL0113T represent novel species of the genus Roseobacter, for which the name Roseobacter sinensis sp. nov. is proposed. The type strain is WL0113T (= GDMCC 1.3082T = JCM 35567T).

MTORC1 and 2 adrenergic regulation and function in brown adipose tissue.

Brown adipose tissue (BAT) thermogenesis results from the uncoupling of mitochondrial inner membrane proton gradient mediated by the uncoupling protein 1 (UCP-1), which is activated by lipolysis-derived fatty acids. Norepinephrine (NE) secreted by sympathetic innervation not only activates BAT lipolysis and UCP-1, but uniquely in brown adipocytes, promotes "futile" metabolic cycles and enhances BAT thermogenic capacity by increasing UCP-1 content, mitochondrial biogenesis and brown adipocyte hyperplasia. NE exerts these actions by triggering signaling in the canonical G protein coupled b adrenergic receptors, cAMP and protein kinase A (PKA) pathway which, in brown adipocyte, is under a complex and intricated crosstalk with important growth-promoting signaling pathways such as those of mechanistic target of rapamycin (mTOR) complexes 1 (mTORC1) and 2 (mTORC2). This article reviews evidence suggesting that mTOR complexes are modulated by and participate in the thermogenic, metabolic, and growth-promoting effects elicited by NE in BAT and discusses current gaps and future directions in this field of research.

Enterotype-Specific Effects of Red Beetroot (Beta vulgaris L.) Powder and Betanin on Human Gut Microbiota: A Preliminary Study Based on In Vitro Fecal Fermentation Model

Red beetroots, rich in betanin, may act as prebiotics and impact gut microbiota. Because the human gut microbiota is unique to each person, the effectiveness of prebiotics varies with the enterotype. In this study, we hypothesized that the effects of red beetroot powder (RP) and betanin pigment (BP) would differ depending on the enterotype. Fecal samples from 30 subjects were analyzed and categorized into three enterotypes: Phocaeicola, Prevotella, and Bifidobacterium. Feces were collected from one representative subject from each enterotype cluster for fermentation. Results showed that RP and BP affected microbiota composition and short-chain fatty acid (SCFA) production differently across enterotypes. The Bifidobacterium cluster showed significantly reduced alpha diversity, with the direction of change in the gut microbiota composition being different from that of other subjects. Additionally, SCFAs significantly increased, with the highest increase in the Bifidobacterium cluster. In this cluster, metabolic pathways related to SCFAs (i.e., starch and sucrose metabolism and glycolysis/gluconeogenesis) were altered. Conversely, Prevotella-dominant feces exhibited fewer changes in SCFAs and a lower increase in Bifidobacterium abundance than the others. These findings highlight that RP and BP elicit enterotype-specific responses in the gut microbiota composition and SCFA production, emphasizing the importance of enterotypes in personalized nutrition.

Oral supplementation of heat-killed Enterococcus faecalis strain EC-12 relieves gastrointestinal discomfort and alters the gut microecology in academically stressed students.

Stress significantly affects gastrointestinal and mental health, and the gut microbiota plays a pivotal role in this process. Enterococcus faecalis strain EC-12 (EC-12) is a lactic acid bacterium that has several health benefits. To investigate the impact of oral supplementation with heat-killed EC-12 on the discomfort caused by stress, a randomised, double-blind, placebo-controlled trial was conducted with students under academic stress taking EC-12 (n= 14) or a placebo (n= 13) daily for one week. Improvement in the students' symptoms was assessed using the visual analogue scale. Faecal microbiota was characterised by next-generation sequencing of 16S rRNA genes, and faecal metabolites and short-chain fatty acids were analysed using a GC-MS metabolomics approach. Significant improvements in abdominal pain and rumbling of the stomach were found in the EC-12 group compared to the placebo group, but no changes were observed in mental symptoms or salivary cortisol levels. The relative abundance of E. faecalis significantly increased in the EC-12 group after the trial; however, the composition and diversity of the gut microbiota did not change significantly. Functional analysis of the gut microbiota suggested that EC-12 intake alters specific metabolic pathways. Although the levels of faecal short-chain fatty acids did not change between the groups before and after the trial, EC-12 intake altered the composition of faecal metabolites, with a significant increase in tryptamine levels. The ratio of students with improved symptoms to those with increased tryptamine levels was calculated based on the number of students with elevated faecal tryptamine levels who showed symptomatic improvements. The ratio of improved rumbling stomach was higher than that of other types of digestive discomfort. These results suggest that oral supplementation with EC-12 has a potentially beneficial effect on stress-induced gastrointestinal discomfort, which may occur through alterations in gut microbiota composition and metabolism. This study was registered at the University Hospital Medical Information Network Center (UMIN) under the UMIN ID: UMIN000048184.

Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells in synergistic improvement of aging related disorders in a senescence-accelerated mouse model

BackgroundThe prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.MethodsSAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.ResultsHUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.ConclusionThe administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.