Microbiota Imbalance Research Articles

Polysaccharides derived from golden mushroom (Cantharellus cibarius Fr.) modulate gut microbiota and enhance intestinal barrier function to ameliorate dextran sulfate sodium-induced colitis in mice

IntroductionInflammatory bowel disease (IBD), including ulcerative colitis, is marked by intestinal barrier disruptions, immune system dysregulation, and an imbalance in the gut microbiota. The golden chanterelle mushroom, Cantharellus cibarius Fr., a popular edible mushroom, has shown potential therapeutic benefits. This study examines the therapeutic potential of a crude polysaccharide extract obtained from C. cibarius Fr. (CCP) on intestinal barrier integrity, inflammatory cytokine levels, and gut microbiota composition in a murine model of colitis induced by dextran sulfate sodium (DSS).MethodsTo induce colitis BALB/c mice were provided to consume autoclaved water with 3% DSS for 7 days, followed by 14 days of CCP supplementation. To assess the effects of CCP, histological analysis of colon tissue was performed, gene expression, inflammatory responses, tight junction proteins expression, gut barrier integrity, and cytokines levels were measured and analyzed and 16S rRNA sequencing were evaluated.Results and DiscussionCCP treatment alleviates colitis symptoms by improving body weight, and enhancing intestinal integrity through increased mucin-2 and tight junction protein expression. Additionally, CCP administration regulates the altered immune response by mitigating the expression of pro-inflammatory cytokines and upregulating anti-inflammatory cytokines. Furthermore, CCP supplementation effectively modulates DSS-induced dysbiosis as demonstrated by 16S rRNA sequencing results. These findings suggest that crude polysaccharides from the golden chanterelle mushroom, C. cibarius Fr., hold promise for treating colitis, via strengthening the intestinal barrier, regulating inflammatory responses, and reshaping the gut dysbiosis in a DSS-induced colitis model. CCP offers a novel approach for managing colitis, as a chronic inflammatory condition.

In Vitro Evaluation of Probiotic Activities and Anti-Obesity Effects of Enterococcus faecalis EF-1 in Mice Fed a High-Fat Diet

This research sought to assess the anti-obesity potential of Enterococcus faecalis EF-1. An extensive and robust in vitro methodology confirmed EF-1’s significant potential in combating obesity, probably due to its excellent gastrointestinal tract adaptability, cholesterol-lowering property, bile salt hydrolase activity, α-glucosidase inhibition, and fatty acid absorption ability. Moreover, EF-1 exhibited antimicrobial activity against several pathogenic strains, lacked hemolytic activity, and was sensitive to all antibiotics tested. To further investigate EF-1’s anti-obesity properties in vivo, a high-fat diet (HFD) was used to induce obesity in C57BL/6J mice. Treatment with EF-1 (2 × 109 CFU/day) mitigated HFD-induced body weight gain, reduced adipose tissue weight, and preserved liver function. EF-1 also ameliorated obesity-associated microbiota imbalances, such as decreasing the Firmicutes/Bacteroidetes ratio and boosting the levels of bacteria (Faecalibacterium, Mucispirillum, Desulfovibrio, Bacteroides, and Lachnospiraceae_NK4A136_group), which are responsible for the generation of short-chain fatty acids (SCFAs). Concurrently, the levels of total SCFAs were elevated. Thus, following comprehensive safety and efficacy assessments in vitro and in vivo, our results demonstrate that E. faecalis EF-1 inhibits HFD-induced obesity through the regulation of gut microbiota and enhancing SCFA production. This strain appears to be a highly promising candidate for anti-obesity therapeutics or functional foods.

Uso de prebióticos y probióticos en el tratamiento de la obesidad: un estudio de revisión

Obesity is one of the most prevalent health problems in the world, with figures of about 641 million people. The usual treatment for this condition is the reduction of calories from the diet, use of medications or surgical interventions. Obesity is associated with an imbalance in the intestinal microbiota. Prebiotics are non-digestible compounds of dietary fibers. Probiotics are living organisms that confer benefits to the individual. The objective was to determine the efficacy of the consumption of prebiotics and probiotics for the treatment of obesity. A systematic review of 9 scientific articles selected from Web of Science, Pubmed, Taylor and Francis, Dialnet and Scielo was performed. The review revealed that the use of pre and probiotics contributes to the reduction of weight, BMI and waist circumference in people with obesity, as well as the reduction of some biochemical markers associated with obesity. It is suggested that supplementation with prebiotics and probiotics may be an alternative as an adjuvant in the treatment of obesity. However, more studies are needed to support their use.

Intestinal Microbiota and Its Influence on Human Health and Autism Spectrum Disorder (ASD)

Introduction: The intestinal microbiota plays a crucial role in human health, influencing digestion, metabolism, immune system development, and even behavior. This review aims to explore the relationship between gut microbiota and Autism Spectrum Disorder (ASD), emphasizing its potential role in the development and manifestation of ASD symptoms through immunological and metabolic pathways. Methods: Data for this review were obtained from PubMed and Science Direct, covering literature from 2011 to 2024. Inclusion criteria focused on original studies, systematic reviews, and meta-analyses discussing gut microbiota composition, dysbiosis, and its relationship with ASD. Articles were selected based on relevance, language (English or Portuguese), and the presence of empirical data. Results: The review identified 36 articles that highlight the diversity and vital functions of the gut microbiota. Dysbiosis, an imbalance in the gut microbiota, is associated with gastrointestinal issues, metabolic disorders, and neuropsychiatric conditions, including ASD. Studies indicate that children with ASD have distinct gut microbiota compositions, with reduced diversity and specific bacterial imbalances. These changes may contribute to ASD symptoms through the gut-brain axis, affecting neurotransmitter production and immune responses. Discussion: Maintaining a balanced gut microbiota is essential for overall health, and modulating the microbiota may offer therapeutic benefits for managing ASD symptoms. The changes in gut microbiota observed in individuals with ASD suggest a potential link between gut health and neuropsychiatric symptoms, highlighting the importance of dietary and probiotic interventions in maintaining gut health. Conclusion: This review underscores the potential of the gut microbiota as a therapeutic target in ASD and the importance of dietary and probiotic interventions in maintaining gut health. Further research is necessary to fully understand these interactions and develop effective microbiota-based treatments, emphasizing the need for personalized approaches in clinical applications.

Global research trajectories in gut microbiota and functional constipation: a bibliometric and visualization study

BackgroundFunctional constipation (FC) negatively impacts quality of life and is associated with gut microbiota (GM) imbalances. Despite the growing interest in this area, a thorough analysis of research trends is missing. This study uses bibliometric methods to assess the global research on GM’s role in FC, pinpointing key topics, impactful studies, and prominent researchers to guide future research and identify gaps.MethodsIn our study, we conducted a performance analysis and science mapping using bibliometric indicators such as publication trends, author and institutional contributions, productivity, impact, keyword analysis, and collaboration networks. We employed software tools like VOSviewer, Biblioshiny, CiteSpace, and SCImago Graphica to automate the assessment of metrics including country, institutional, and journal distribution, authorship, keyword frequency, and citation patterns.ResultsFrom 2013 to 2024, annual publications on GM and FC rose from 29 to 252, with a slight decrease to 192 in 2024. Average citations per publication peaked at 11.12 in 2021, declining to 6.43 by 2024. China led in research output (37.8%), followed by the United States (14.4%) and Japan (7.5%). Bibliometric analysis identified key authors like CHEN W and ZHANG H, with 30 and 27 articles, respectively. Jiangnan University and Harvard University were top contributors, with 131 and 81 articles. Keywords analysis revealed “constipation,” “gut microbiota,” and “probiotic” as central themes, with a shift toward “gut microbiota” and “intestinal flora” in recent years. This study provides a comprehensive overview of the research landscape, highlighting leading authors, institutions, and evolving research priorities in the field.ConclusionOur review synthesizes current GM and FC research, guiding future studies. It suggests exploring GM in various GI disorders, the impact of lifestyle and drugs on GM, advanced research techniques, and probiotics/prebiotics for FC. There’s also a focus on therapies targeting GM’s effect on the gut-brain axis, paving the way for improved FC management.

Pasteurized Akkermansia muciniphila Ameliorates Preeclampsia in Mice by Enhancing Gut Barrier Integrity, Improving Endothelial Function, and Modulating Gut Metabolic Dysregulation

Preeclampsia (PE) is a serious complication of pregnancy linked to endothelial dysfunction and an imbalance in the gut microbiota. While Akkermansia muciniphila (AKK) has shown promise in alleviating PE symptoms, the use of live bacteria raises safety concerns. This study explored the potential of pasteurized A. muciniphila (pAKK) as a safer alternative for treating PE, focusing on its effects on endothelial function and metabolic regulation. A PE mouse model was induced via the nitric oxide synthase inhibitor L-NAME, followed by treatment with either pAKK or live AKK. Fecal metabolomic profiling was performed via liquid chromatography–tandem mass spectrometry (LC-MS/MS), and in vivo and in vitro experiments were used to assess the effects of pAKK on endothelial function and metabolic pathways. pAKK exhibited therapeutic effects comparable to those of live AKK in improving L-NAME-induced PE-like phenotypes in mice, including enhanced gut barrier function and reduced endotoxemia. pAKK also promoted placental angiogenesis by restoring endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production. The in vitro experiments further confirmed that pAKK alleviated L-NAME-induced NO reduction and endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). Metabolomic analysis revealed that both pAKK and live AKK reversed metabolic disturbances in PE by modulating key metabolites and pathways related to unsaturated fatty acid biosynthesis, folate, and linoleic acid metabolism. As a postbiotic, pAKK may support existing treatments for preeclampsia by improving gut barrier function, restoring endothelial function, and regulating metabolic dysregulation, offering a safer alternative to live bacteria. These findings highlight the potential clinical value of pAKK as an adjunctive therapy in managing PE.

Pickled radish alleviates the progression of colitis in mice by reducing inflammation and repairing intestinal barrier

Scope: Pickled radish is a traditional fermented food known for its health benefits, however, evidence supporting its role in regulating gastrointestinal function is limited. This study aimed to investigate the beneficial effect of pickled radish on DSS-induced colitis in mice. Method and Results: Divide the mice into four groups: control, DSS model, low-dose (DSS+ 5 % pickled radish powder), and high-dose (DSS+ 10 % pickled radish powder). Colitis was induced by 3 % DSS administration in drinking water for eight days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory markers were measured to evaluate the effects of pickled radish on colitis. The results indicate that pickled radish significantly eased symptoms of colitis in mice induced by DSS, dose-dependently reducing DAI, reversed colon shortening, alleviating pathological damage to colon tissue and inflammatory response. Mechanistic investigation revealed that pickled radish upregulated the expression of tight junction-related genes (Zo-1, E-cadherin) and down-regulated inflammation-related genes (Il-1β, Il-6, TNF-α). Moreover, low-dose pickled radish significantly reversed the imbalance of gut microbiota and increased SCFAs. Conclusion: These findings suggest the potential of pickled radish in functional foods targeting the improvement of gastrointestinal health.

Therapeutic Potential of Syzygium aromaticum in Gut Dysbiosis via TMAO Associated Diabetic Cardiomyopathy.

Dysbiosis of the gastrointestinal microbiota is not only related to the pathogenesis of intestinal disorders but also associated with extra-intestinal diseases. Various studies have revealed the role of an imbalance of intestinal microbiota and their metabolites including bile acids, indole derivatives, polyamines, and trimethylamine in the progression of various diseases. The elevated plasma level of the oxidized form of trimethylamine is associated with the increased risk of cardiovascular diseases. Literature supports that herbal medicines can modulate human health by altering the diversity of gut microbiota and their metabolites and proposes the use of prebiotics to improve dysbiotic conditions as a new way of therapeutic strategy. In silico studies including drug likeliness, toxicity prediction, and molecular interaction of phytochemicals against trimethylamine lyase enzyme have been done. Antimicrobial activity of extracts of selected plant i.e. Syzygium aromaticum was done by disc diffusion and the protective effects of plant compounds were examined on trimethylamine-n-oxide a bacterial metabolic product and high glucose induced toxicity. The current study has found that the phytochemicals of S. aromaticum identified as nontoxic and followed the standard rules of drug likeliness and showed a significant binding affinity against trimethylamine-n-oxide producing enzymes. Furthermore, S. aromaticum extract was found to have antimicrobial potential and cardioprotective effects by reducing the production of intracellular reactive oxygen species and correcting the distorted nuclear morphology in the presence of high trimethylamine-n-oxide. Conclusively, our study explored the herbal intervention in intestinal dysbiosis and suggested a natural therapy against dysbiosis associated with cardiac disease, and S, aromaticum was found to have exceptional cardioprotective potential against TMAO induced gut dysbiosis, which provides a novel future therapeutic intervention for treating cardiovascular complications.

Mulberry leaf extract ameliorates high-fat diet-induced obesity in mice by regulating the gut microbiota and metabolites

The increasing prevalence of obesity presents a notable challenge to global health. Mulberry leaves enriched with biologically active substances hold promise for alleviating obesity. This research assessed the efficacy of mulberry leaf extract (MLE) in mitigating obesity and metabolic disturbances in mice fed a high-fat diet (HFD). The results demonstrated that MLE, administered at both low (167 mg/kg) and high (333 mg/kg) doses, decreased weight gain and fat accumulation, improved glucose metabolism, enhanced insulin sensitivity, and reduced inflammation. Analysis of fecal samples via 16S rRNA sequencing revealed that MLE corrected the gut microbiota imbalance caused by HFD, lowering the Firmicutes/Bacteroidota ratio as well as increasing the relative abundances of Bifidobacterium, Faecalibaculum, Coriobacteriaceae_UCG-002, and Dubosiella. Additionally, serum non-targeted metabolomics analysis identified 19 key differential metabolites associated with MLE treatment, which were primarily related to glycerophospholipid metabolism and tryptophan metabolism. Correlation analysis revealed negative associations between Dubosiella and Coriobacteriaceae_UCG-002 with specific phospholipids, and positive associations of 5-hydroxyindoleacetate and quinoline-4,8-diol with Bifidobacterium and Coriobacteriaceae_UCG-002. These findings suggest that MLE is effective in treating obesity and underscores its potential as a functional food.

Microbiome and Chronic Disease

The origin of “microbiota” can be dated back to early 1900s. It was found that a vast number of microorganisms, including bacteria, yeasts, and viruses, coexist in various sites of the human body (gut, skin, lung, oral cavity). The gut microbiome, in particular, has been closely linked to metabolic conditions such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). Dysbiosis, or an imbalance in the gut microbiota, can impair the gut's ability to regulate metabolism, insulin sensitivity, and inflammation. Key mechanisms by which the microbiome affects metabolic diseases include: Short-chain fatty acids (SCFAs), inflammation and energy harvest. The gut microbiome is crucial for regulating metabolism, energy balance, and immune function. Disruptions in the gut microbiome have been associated with conditions such as obesity, type 2 Diabetes and non-alcoholic fatty liver disease (NAFLD).Maintaining a healthy microbiome through a balanced diet, regular exercise, and careful use of antibiotics can help reduce the risk of conditions like obesity, type 2 diabetes, cardiovascular disease, autoimmune disorders, and even some cancers. As research in this area continues to evolve, the microbiome may become a key target for the prevention and treatment of chronic diseases.

Probiotics Application in the Treatment of Autoimmune Diseases and Enhancement of Efficacy Through Genetic Engineering

The development of multidrug resistance in most pathogenic microorganisms and the rapidly increasing prevalence of non-communicable diseases are becoming major health concerns worldwide. Among non-communicable diseases, autoimmune diseases are caused mainly by imbalances in the gut microbiota (dysbiosis). Gut microbiota colonization and immune system establishment started in the early years of life. A defect in the gut microbiota predominantly affects the proper functioning of immune cells. Hence, restoring gut dysbiosis has received considerable attention for the last few decades as a potential therapeutic option. In this regard, probiotics have been the focus of research during recent decades because of their safe history of use along with fermented foods and beverages. Currently, advanced research is being conducted on the use of probiotics as immunomodulatory mediators and for the amelioration of gut dysbiosis as therapeutic adjuncts in the treatment of autoimmune diseases. In addition, probiotics are genetically engineered to enhance treatment efficacy and to develop live biotherapeutics (LBP). In this review, research articles summarizing findings in autoimmune disease treatment via probiotic strains, emphasizing type 1 diabetes, rheumatoid arthritis, Graves' disease, systemic lupus erythematosus and inflammatory bowel disease in both clinical trials and animal models, were reviewed. Finally, promising results of genetic engineering of probiotics for use as biosensors, delivery of therapeutic proteins, and diagnosis of infections were reported.

Significant difference in gut microbiota Bifidobacterium species but not Lactobacillus species in colorectal cancer patients in comparison with healthy volunteers using quantitative real-time PCR.

Colorectal cancer (CRC), with a growing incidence trend, is one of the most diagnosed cancers and the second cause of cancer-related deaths worldwide. The literature has frequently focused attention on the correlation between the gut microbiota imbalance and CRC. The genera Lactobacillus and Bifidobacterium have recently received increasing attention because of their potential in restoring alterations in the gut microflora. Therefore, this study aimed to quantitatively evaluate the presence of lactobacilli and bifidobacterial strains in the fecal samples of CRC patients compared to healthy volunteers. From 2018 to 2019, 25 confirmed CRC patients and 25 age- and gender-matched control subjects were enrolled in the study. Bacterial DNA was extracted from the fecal samples and the presence of lactobacilli and bifidobacterial strains were quantitatively determined using quantitative real-time PCR using genus-specific 16S rDNA primers. A significant decline in the abundance of bifidobacteria in CRC patients compared to healthy individuals (p value<0.003) was observed; however, no significant difference was observed between the two groups regarding the abundance of lactobacilli (p value<0.163). Correlation analysis showed a positive association between the lack of genetic history of CRC and the numbers of gut bifidobacteria and lactobacilli. As a putative gut probiotic, depletion of bifidobacteria showed significant correlation to the development and progression of CRC; therefore, therapeutic use of these probiotic bacteria could be considered a possible adjuvant approach in disease management through modulation of the microbiota.

Optimizing Lactiplantibacillus plantarum viability in the gastrointestinal tract and its impact on gut microbiota-brain axis through zein microencapsulation.

Evidence suggests that Lactiplantibacillus plantarum (LP) can positively influence gut microbiota, subsequently affecting brain function via the gut-brain axis. However, the oral administration of LP may subject it to damage from gastric acid. To address this issue, a microencapsulation system was developed to protect LP and enhance its viability in the gastrointestinal tract. In the study, zein-microencapsulated LP (MLP) was prepared using the phase separation method. We found that the optimal conditions to encapsulate LP (9logCFU/mL) were a zein concentration of 10mg/mL and a zein-to-bacteria mass ratio of 5:1. Scanning electron microscopy and dynamic light scattering analysis demonstrated that MLP exhibited a microstructure with an approximate diameter of 4µm. Findings also revealed that microencapsulation markedly improved the in vitro survival rate of LP compared to free cells and allowed for controlled release. Subsequent in vivo studies in mice showed that this encapsulation not only boosted the colonization of LP but also ameliorated the imbalance of gut microbiota associated with depression. An analysis of the intestinal microbiota in mice identified 13 genera that exhibited significant shifts in abundance due to the depressive states. The administration of MLP reversed these microbial changes, underscoring its therapeutic potential. Additionally, the study examined the expression of pro-inflammatory cytokines. The administrated MLP was found to reverse the inflammation in both the intestine and hippocampus of mice with depression. Behavioral assessments in mouse models corroborated the efficacy of MLP in preventing depression, positioning it as a promising daily supplement.

Integrative analysis of gut microbiome and host transcriptome reveal novel molecular signatures in Hashimoto's thyroiditis

BackgroundHashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets.MethodsWe recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT.ResultsIntegrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis.ConclusionOur study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Dihydromyricetin Alleviates Non-Alcoholic Fatty Liver Disease by Modulating Gut Microbiota and Inflammatory Signaling Pathways.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition that is strongly linked to gut microbiota imbalance and chronic inflammation. This study aims to explore the preventive effects of dihydromyricetin (DHM) on NAFLD by modulating the intestinal flora and the TLR4/NF-κB signaling pathway. Fifty male C57BL/6J mice were randomly assigned to five groups: a normal control group, a model group, and three DHM treatment groups receiving low (500 mg/kg), medium (750 mg/kg), and high doses (1,000 mg/kg). NAFLD was induced using a high-fat diet, and DHM was administered for 8 weeks. ELISA measured serum levels of LPS, IL-1β, and TNF-α, while Western Blot assessed liver expression of TLR4 and NF-κB p65. Changes in intestinal flora composition were analyzed using high-throughput 16S rRNA sequencing. The results showed that DHM treatment significantly reduced serum levels of LPS, IL-1β, and TNF-α, decreasing the liver expression of TLR4 and NF-κB p65. Intestinal flora analysis indicated a notable increase in beneficial bacteria, especially in the medium and high-dose groups. DHM treatment also significantly improved liver pathology, reducing fat deposition and inflammatory cell infiltration. In conclusion, DHM effectively prevents the progression of NAFLD by improving gut microbiota balance and suppressing inflammatory signaling pathways.

Effect of Brassica rapa L. Polysaccharide on Lewis Lung Cancer Mice by Inflammatory Regulation and Gut Microbiota Modulation.

Lung cancer is the leading cause of cancer-related fatalities globally, related to inflammatory and gut microbiota imbalance. Brassica rapa L. polysaccharide (BP) is a functional compound, which is utilized by the gut microbiota to regulate immunity and metabolism. However, the effect of BP on lung cancer and whether it affects the "gut-lung" axis remains unclear. This study explored the intervention of BP in Lewis lung cancer (LLC) mice and its effect on the gut microbiota. The results revealed that BP reduced tumor weight and downregulated the expression of Ki67 protein. Additionally, BP reduced the content of inflammatory factors and growth factors, promoting tumor cell apoptosis and inhibiting the growth of LLC. The intervention of BP suppressed intestinal inflammation, preserved intestinal barrier integrity, and augmented the level of beneficial microbiota, such as Blautia and Bifidobacterium. Furthermore, BP significantly increased the production of short-chain fatty acids (SCFAs), particularly butyrate and propionate. A correlation analysis showed significant correlations among the gut microbiota, SCFAs, inflammatory factors, and tight junction proteins. A functional analysis indicated that BP promoted amino acid metabolism and fatty acid metabolism. These findings suggested that BP had the potential to act as prebiotics to prevent disease and improve lung cancer progression by regulating the gut microbiota.

Interaction Between Early Meals (Big-Breakfast Diet), Clock Gene mRNA Expression, and Gut Microbiome to Regulate Weight Loss and Glucose Metabolism in Obesity and Type 2 Diabetes.

The circadian clock gene system plays a pivotal role in coordinating the daily rhythms of most metabolic processes. It is synchronized with the light-dark cycle and the eating-fasting schedule. Notably, the interaction between meal timing and circadian clock genes (CGs) allows for optimizing metabolic processes at specific times of the day. Breakfast has a powerful resetting effect on the CG network. A misaligned meal pattern, such as skipping breakfast, can lead to a discordance between meal timing and the endogenous CGs, and is associated with obesity and T2D. Conversely, concentrating most calories and carbohydrates (CH) in the early hours of the day upregulates metabolic CG expression, thus promoting improved weight loss and glycemic control. Recently, it was revealed that microorganisms in the gastrointestinal tract, known as the gut microbiome (GM), and its derived metabolites display daily oscillation, and play a critical role in energy and glucose metabolism. The timing of meal intake coordinates the oscillation of GM and GM-derived metabolites, which in turn influences CG expression, playing a crucial role in the metabolic response to food intake. An imbalance in the gut microbiota (dysbiosis) can also reciprocally disrupt CG rhythms. Evidence suggests that misaligned meal timing may cause such disruptions and can lead to obesity and hyperglycemia. This manuscript focuses on the reciprocal interaction between meal timing, GM oscillation, and circadian CG rhythms. It will also review studies demonstrating how aligning meal timing with the circadian clock can reset and synchronize CG rhythms and GM oscillations. This synchronization can facilitate weight loss and improve glycemic control in obesity and those with T2D.

Succinate exacerbates mastitis in mice via extracellular vesicles derived from the gut microbiota: a potential new mechanism for mastitis

BackgroundA high grain diet causes an ecological imbalance in the gut microbiota and serves as an important endogenous trigger of mastitis in dairy cows, but the underlying mechanisms are unclear. Our previous study revealed that subacute rumen acidosis (SARA)-associated mastitis has distinct metabolic profiles in the rumen, especially a significant increase in succinate, but the role of succinate in the pathogenesis of mastitis remains unclear.ResultsSuccinate treatment exacerbates low-grade endotoxemia-induced mastitis in mice. Specifically, succinate increased the production of gut microbiota-extracellular vehicles (mEVs) containing lipopolysaccharides, which can diffuse across the damaged intestinal barrier into the mammary glands. Administration of mEVs promotes mammary inflammation via activation of the TLR4/NF-κB pathway.ConclusionsOur findings suggest that succinate promotes mastitis through the proliferation of enteric pathogens and mEVs production, suggesting a potential strategy for mastitis intervention on the basis of intestinal metabolic regulation and pathogen inhibition. The role of mEVs in interspecific communication has also been elucidated.Graphical

HOW THE ENDOCRINE SYSTEM AND MICROBIOTA EXPLAIN THE EMOTIONS BIOCHEMISTRY AND THEIR IMPACT IN HEALTH

Emotional reactions stimulate neural circuits and biological pathways that produce neurotransmitters, affecting homeostasis and promoting disease. Health and emotions communicate, establishing a bidirectional cause-and-effect pathway. The composition of the microbiota also affects health and emotions, interacting through metabolites, such as short-chain fatty acids (SCFA), with the host's biochemistry. Certain genera of bacteria act in different ways on the host's homeostasis, keeping the immune system constantly vigilant and acting on the synthesis of neurotransmitters, such as serotonin and dopamine, which are responsible for well-being. When the host is in homeostasis, the synthesis of neurotransmitters is normal, which keeps the intestinal microbiota in balance. However, when the organism is out of balance, this synthesis is impaired; decreasing the concentration of the initial compounds for the production of neurotransmitters, which leads to a reduction in the concentration of neurotransmitters and exaggerated activation of the HPA axis, inducing an imbalance in the intestinal microbiota, generating dysbiosis. Due to dysbiosis, the synthesis of neurotransmitters is impaired, leading the host to develop mental disorders such as depression, anxiety and chronic stress; which contributes to the state of imbalance of the organism, harming mental and physical health. By adequately restoring the intestinal microbiota, the hyperactivation of the HPA axis decreases, returning the body to homeostasis, resulting in the improvement of symptoms of depression, anxiety and chronic stress; leaving the organism healthy, both mentally and physically. Therefore, in this study we contextualize emotional research from a historical and descriptive perspective and present the main models of emotional identification. Focusing on basic emotions, we research the relationship of emotional states with the HPA axis and the microbiota, as well as how the bacteria present in the intestine affect the well-being of the host. Finally, we discuss our analysis presenting the bidirectional relationship between the endocrine system, microbiota and emotions.

Impact of Gut Microbiota on the Development of Diseases

Aim: The aim of this article is to review the latest scientific research on the influence of intestinal microbiota on the development of diseases. In this article we will discuss the importance of the intestinal microbiota, the differences in the composition of the microbiota between healthy and sick people and the relationship between the intestinal microbiota and metabolic, inflammatory, cardiovascular and neurodegenerative diseases. Abbreviated description of the state of knowledge: The gut microbiota plays a key role in human health by influencing the development and progression of various diseases. Numerous studies have shown that an imbalance in gut microbiota, called dysbiosis, may be linked to a number of conditions. Intestinal microflora interacts with the immune system, modulates inflammation and influences metabolic pathways, which emphasizes its importance in the development of diseases. Conclusions: Intestinal microflora is crucial to health, regulating immune, metabolic and neurological functions. Dysbiosis, i.e. disturbance of the balance of intestinal microflora, is associated with diseases such as type 2 diabetes, obesity, inflammatory bowel diseases, allergies, autoimmune diseases and neuropsychiatric disorders. Healthy microflora, influenced by diet, pH and nutrients, are essential for metabolism, immune system regulation and neuronal communication. Recently, scientists have become interested in the possibility of using this knowledge in treatment. Appropriate dietary management, probiotic supplementation and fecal microflora transplantation show promising potential. Future research should focus on elucidating the specific mechanisms by which the gut microbiota influences disease processes and developing targeted therapies to exploit the therapeutic potential of the microbiota.