Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.

To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.

Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and cardiomyopathy among others, remain the leading cause of global morbidity and mortality. Despite advances in treatment, the complex pathophysiology of CVDs necessitates innovative approaches to improve patient outcomes. Recent research has uncovered a dynamic interplay between mitochondria and gut microbiota, fundamentally altering our understanding of cardiovascular health. However, while existing studies have primarily focused on individual components of this axis, this review examines the bidirectional communication between these biological systems and their collective impact on cardiovascular health. Mitochondria, serving as cellular powerhouses, are crucial for maintaining cardiovascular homeostasis through oxidative phosphorylation (OXPHOS), calcium regulation, and redox balance. Simultaneously, the gut microbiota influences cardiovascular function through metabolite production, barrier integrity maintenance, and immune system modulation. The mitochondria-gut microbiota axis operates through various molecular mechanisms, including microbial metabolites such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFA), and secondary bile acids, which directly influence mitochondrial function. Conversely, mitochondrial stress signals and damage-associated molecular patterns (DAMPs) affect gut microbial communities and barrier function. Key signalling pathways, including AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the silent information regulator 1-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1-PGC-1α) axis, integrate these interactions, highlighting their role in CVD pathogenesis. Understanding these interactions has revealed promising therapeutic targets, suggesting new therapies aimed at both mitochondrial function and gut microbiota composition. Thus, this review provides a comprehensive framework for leveraging the mitochondria-gut microbiota axis in providing newer therapeutics for CVDs by targeting the AMPK/SIRT-1/PGC-1α/NF-κB signalling.

The gut microbiota plays an important role in maintaining host health by affecting various physiological functions. Among the diverse microbial communities in the gut, prophages are integral components of bacterial genomes, contributing significantly to bacterial evolution, ecology and pathogenicity. Prophages are capable of switching to lytic cycles in response to various internal and external factors. Factors that induce prophage induction include DNA damage, oxidative stress, nutrient availability, host immune response, quorum sensing, diet, secondary metabolites, antibiotics, and lifestyle changes. Prophage induction could contribute to both gut homeostasis and dysbiosis. Importantly, the connections between prophage induction and disorders such as inflammatory bowel disease, ulcerative colitis, and bacterial vaginosis highlight the dual roles of prophages in both health and disease. Although therapeutic approaches such as phage therapy (PT), fecal microbiota transplants (FMT), and fecal virome transplants (FVT) have gained attention, the concept of dietary prophage induction therapy offers a novel, targeted method to modulate gut microbiota. In spite of recent advances in understanding the role of prophages in gut health, the exact mechanisms by which they influence gut health remain only partially understood. Therefore, further research is needed to elucidate additional molecular mechanisms of prophage induction pathways and to explore their implications for gut microbiota dynamics and disease associations. This review discusses the molecular mechanisms and key factors that trigger prophage induction in the gut. Insights into these processes could lead to innovative therapeutic strategies that utilize prophages to support gut health.

Gut microbiota plays a critical role in maintaining human health by regulating digestion, metabolism, and immune function. Emerging research highlights the potential of dietary interventions, particularly dietary fiber (DF) and polyphenols, in modulating gut microbiota composition and function. DF serves as a fermentable substrate for beneficial gut bacteria, promoting the production of short-chain fatty acids (SCFAs). Polyphenols, a diverse group of bioactive compounds selectively modulate microbial populations and contribute to the production of bioactive metabolites with host health benefits. Importantly, the interplay between DF and polyphenols creates a synergistic effect within the gut microbiome, shaping microbial diversity, enhancing SCFAs production, and strengthening gut barrier function, which together support metabolic and immune homeostasis. This review systematically explores the synergistic effects of DF-polyphenol combinations on gut microbiota modulation, microbial metabolites, and their implications for overall health. The combined effects of DF and polyphenols hold promise for targeted nutritional strategies in preventing metabolic disorders and improving gut health. Moreover, the extent of these benefits is influenced by the structural characteristics of DF, the source and dosage of polyphenols, and individual gut microbiota composition. Further research is warranted to optimize DF-polyphenol interactions and facilitate their applications in personalized nutrition and functional food development.

In patients with alcohol-associated cirrhosis, the intestinal microbiome composition is disturbed with a loss of beneficial functions and an increase in pathobionts. These changes are associated with disease severity and decompensation, due in part to the exacerbation of liver inflammation by an altered microbiome. Microbes or their antigens may translocate to the liver to potentiate the activation of immune cells and thereby contribute to inflammatory injury. Moreover, microbes may aggravate liver disease through the production of toxins or metabolites, via the effects on bile acids or the intestinal immune system.

Sarcopenic obesity is a multifactorial disorder commonly found in elderly individuals. One contributing factor is gut microbiota dysbiosis. This study compared the abundance of certain bacteria in elderly individuals with obesity and sarcopenic obesity.

The study included 50 elderly individuals over 65 with a body mass index (BMI) of over 30 kg/m², both sexes. Participants were divided into two groups, each with 25 individuals, based on the diagnosis of sarcopenia using the EWGSOP2 criteria. Individuals with underlying diseases, those using antibiotics, and those with a history of gastrointestinal surgery were excluded. Stool samples were stored at -80 °C, and DNA was extracted using standard kits. Bacterial DNA sample quality was assessed using a Nanodrop device. Bacterial frequency was measured using qPCR. The log cfu for each bacteria was calculated and compared in both groups using an independent t-test. Spearman measured the correlation between bacterial genera and physical performance in SPSS 26.

The case group had a significantly higher average age (70.96) than the control group (68.32). The average BMI was the same in both groups. The frequency of Escherichia (p-value = 0.046) and Bifidobacterium (p-value = 0.017) was significantly higher in the case group. There was no significant difference in the frequency of Lactobacillus and Akkermansia.

The study uncovered substantial differences in gut microbiota composition between elderly individuals experiencing sarcopenic obesity and those with obesity alone. The findings suggest that dysbiosis, characterized by an excessive presence of Bifidobacterium, Escherichia, and Akkermansia, may be associated with sarcopenic obesity.

The online version contains supplementary material available at 10.1007/s40200-025-01584-x.

The gut microbiome early in life plays a crucial role in development of the host and affects health throughout life. The definition of a healthy microbiome early in life has not been established, and the underlying mechanism of how a young host selects appropriate microbes for colonization remains unclear. Understanding the mechanism may provide insights into novel preventive and therapeutic strategies by correcting dysbiosis early in life. We employed germ-free mice early in life (4 weeks of age) and later in life (10 weeks of age) for fecal microbiota transfer (FMT) from specific pathogen-free mice. We performed age-unmatched FMT between recipients early in life and donors early or later in life, in addition to common age-matched FMT. Age-matched FMT resulted in significantly different bacterial compositions between recipients early vs. later in life. When the gut microbiome from donors early or later in life was transferred to recipients early in life, bacterial compositions of recipients from donors later in life were similar to those of recipients from donors early in life. This finding suggests that the host early in life has mechanisms to select microbes appropriate for age from the exposed microbiome. We hypothesized that the age-specific intestinal environment promotes age-appropriate intestinal microbiome colonization and examined gene expression in the intestinal mucosa of germ-free mice. We observed that gene expression profiles were different between early vs. later in life. Correlation analysis demonstrated that genera Lachnospiraceae NK4A136 group and Roseburia were positively correlated to genes expressed predominantly early in life, but negatively with genes expressed predominantly later in life. We confirmed that the relative abundance of these genera was significantly higher in specific pathogen-free mice early in life compared with mice later in life. The characteristic gene expression of the intestinal mucosa early in life might play roles in selecting specific bacteria in the intestinal microbiome early in life.

The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response and fibrosis is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via infection with the pathogenic bacterial species enterotoxigenic Bacteroides fragilis (ETBF) and implanted particulate material (mean particle size <600 μm) of the synthetic polymer polycaprolactone (PCL) into a distal muscle injury. ETBF infection in mice led to increased neutrophil and γδ T cell infiltration into the PCL implant site. ETBF infection alone promoted systemic inflammation, increased levels of neutrophils in lymphoid tissues, and altered skeletal muscle gene expression. At the PCL implant site, we found significant changes in the transcriptome of sorted stromal cells between infected and control mice, including differences related to ECM components such as proteoglycans and glycosaminoglycans. However, we did not observe ETBF-induced differences in fibrosis levels. These results demonstrate the ability of the gut microbiota to mediate long-distance effects such as immune and stromal responses to a distal biomaterial implant.

Elevated plasma levels of trimethylamine N-oxide (TMAO)-a compound derived from diet and the gut microbiome-have been widely studied for their association with diabetes risk and their potential role in disease pathophysiology and complications. However, clinical studies, both prospective and retrospective, have yielded conflicting results. For example, elevated levels of TMAO are frequently linked to an increased risk of cardiovascular and renal complications in individuals with diabetes. However, the robustness and independence of these associations differ across study populations and are influenced by the degree of adjustment for confounding risk factors. Considering insulin's regulatory effect on FMO3 activity in liver cells, TMAO may serve as a marker of hepatic insulin resistance, which could partially explain its association with diabetes risk. The role of TMAO in diabetes pathology remains controversial; while some studies emphasize its detrimental impact on insulin sensitivity and the progression of diabetes-related complications, others suggest potential protective effects. Investigating the largely unexplored role of TMAO's precursor, trimethylamine, may help elucidate these discrepancies. This review consolidates clinical and experimental findings to clarify TMAO's complex mechanistic contributions to diabetes pathology.

Symbiotic microbiota in vertebrates play critical roles in establishing and enhancing host resistance to pathogenic infections as well as maintaining host homeostasis. The interactions and mechanisms of commensal microbiota-mediated mucosal immune systems have been extensively studied in mammals and, to a lesser extent, in birds. However, despite several studies emphasizing the role of mucosal microbiota in controlling pathogen infections in teleost fish, limited knowledge exists regarding the core microbiota and the mechanisms by which they contribute to resistance against viral infections.

Our findings suggest that viral infections shape clinical manifestations of varying severity in infected fish. An increased abundance of Bacillus spp. in the mild phenotype indicates its crucial role in influencing fish immunity during viral infections. To confirm that Bacillus spp. act as a core contributor against viral infection in fish, we isolated a representative strain of Bacillus spp. from largemouth bass (Micropterus salmoides), which was identified as Bacillus velezensis (Bv), and subsequently conducted feeding trials. Our study demonstrated that dietary supplementation with Bv significantly reduced mortality from largemouth bass virus (LMBV) infection in bass by enhancing host immunity and metabolism as well as by regulating the microbial community. Furthermore, multi-omics analysis elucidated the mechanism by which Bacillus spp. confer resistance to viral infections by regulating the production of diglyceride (DG) during lipid metabolism.

Our study provides the first evidence that Bacillus spp. are a core microbiota for combating viral infections in teleost fish, shedding light on the conserved functions of probiotics as a core microbiota in regulating microbial homeostasis and mucosal immunity across the vertebrate lineage.

Digestive diseases have a high incidence worldwide, with various geographic, age, and gender factors influencing the occurrence and development of the diseases. The main etiologic factors involve genetics, environment, lifestyle, and dietary habits. In a low-oxygen environment, however, the body's tissue cells activate hypoxia-inducible factor (HIF), which produces different inflammatory mediators. Hypoxia impacts health at the molecular level by modulating cellular stress responses, metabolic pathways, and immune functions. It also alters gene expression and cellular behavior, thereby affecting gastrointestinal function. Under normal physiological conditions, the gastrointestinal mucus system serves as a crucial protective barrier, defending against mechanical injury, pathogenic invasion, and exposure to harmful chemicals. The integrity and functionality of this barrier are dependent on the synthesis and regulation of mucins and mucus, which are influenced by multiple factors. Additionally, the composition and diversity of the gastric microbiota are shaped by factors such as Helicobacter pylori infection, diet, and lifestyle. A balanced gastric microbiota supports gastrointestinal health and fortifies the mucus barrier. However, hypoxia can disrupt this equilibrium, leading to inflammation, alterations in the mucus layer, and destabilization of the gastric microbiota. Understanding the interplay between hypoxia, the mucus system, and the gastric microbiota is essential for identifying novel therapeutic strategies. Future research should elucidate the mechanisms through which hypoxia influences these systems and develop interventions to mitigate its adverse effects on gastrointestinal health. We examined the impact of hypoxia on the gastrointestinal mucus system and gastric microbiota, highlighting its implications for human health and potential therapeutic approaches.

The Manila clam (Ruditapes philippinarum) is an ecologically and economically important species. Recently, a novel disease of Manila clam with abnormal gill colour has emerged, leading to growth inhibition and death in severe cases. In this study, a multi-omics approach was used to investigate the underlying mechanisms of abnormal gill colour in Manila clam and its association with gut microbiota. High-throughput sequencing revealed a reduction in the uniformity of gut microbiota in diseased clams, with increased abundance of Pseudomonas and Pseudoaltermonas. Network and null model analyses revealed a decline in microbiota stability and a shift toward deterministic assembly in diseased clams. Transcriptomic analysis revealed different gene expression profiles in the gills of healthy and diseased Manila clams, including down-regulation of several immune-related genes such as genes encoding heat shock proteins and involved in Toll and Imd signalling pathways. A total of 38 specialists were identified in the gut microbiota of diseased Manila clams based on their specificity and occupancy. Four of them (two Psychrobacter, one Pseudoaltermonas and one Halomonas) were closely correlated with the expression of gill genes associated with abnormal gill colour. In addition, a gene encoding a major vault protein was identified as the keystone of abnormal gill colour through the network of host genes and their gut microbiota. This study revealed the substantial variation in gut microbiota and gill gene expression in Manila clam with abnormal gill colour and provided insights into the complex host-microbiota interactions involved in disease development.

The human gut microbiota, a diverse community of beneficial normal flora microorganisms, significantly influences physiological function and the immune response. Various microbiota strains have shown promise in supporting clinical treatment of chronic diseases, including cancer, by potentially providing antioxidative and anti-tumorigenic effects in both in vivo and in vitro studies. Breast cancer, which ranks amongst the top five cancer types common worldwide and particularly in Mediterranean countries, has been showing high incidence and prevalence. In breast cancer, microbiota composition, hormonal dynamics, and dietary choices are believed to play significant roles. Hence, the Mediterranean diet, known for its microbiota-friendly features, emerges as a potential protective factor against breast cancer development, highlighting the potential for personalized dietary strategies in cancer prevention. This comprehensive review highlights the emerging mechanisms by which probiotics support our immune system during different physiological activities. It also discusses their potential role, along with nutrition intervention, in improving essential clinical treatment outcomes in breast cancer patients and survivors, suggesting potential supportive strategies that go hand in hand with clinical strategies. Unfortunately, very little research addresses the possible clinical implications of probiotics and dietary habits on breast cancer, despite the promising results, calling for further studies and actions.

The human microbiota, consisting of trillions of bacteria from six main phyla, produces peptide and non-peptide secondary metabolites which have antibacterial properties vital to medicine and biotechnology. These metabolites influence biological processes linked to diseases, yet much remains unknown. This review explores their structures and functions, aiming to spur novel metabolite discovery and advance drug development.

Anthocyanins (Anthos; flower and kyanos; blue) are natural coloring compounds from the flavonoids class that include cyanidin, peonidin, delphinidin, malvidin, pelargonidin, and petunidin. Recently, the role of anthocyanins in disease prevention, especially inflammation, diabetes, cancer, neuro-disorders, hepato-renal protective, and immuno-modulation properties has been highlighted. The current review covered the literature on the pharmacokinetics and pharmacological effects of anthocyanins, especially absorption, distribution, metabolism, and excretion (ADME). The discussion on molecular mechanisms underlying their therapeutic effects is the limelight of the article. The GLUT1, GLUT3, SGLT1, SMCT1, and SMCT2 are the main carriers involved in the transportation of anthocyanins in the gastrointestinal tract. The anthocyanins exert their anticancer effects by reducing the expression of IL-6, IL-1β, TNF-β, COX-2, downregulation of NF-kB, EZH2, MDR1, Akt, and modulation of P13K/AKT and AMPK/mTOR pathways. The reduction in α-amylase and α-glucosidase and improved FFAR1 activity results in antidiabetic effects. The regulation of PGC-1α/NRF2/TFAM, p-PI3K/Akt/GSK3β, and Nrf2/HO-1 prevents neurodegeneration. The anthocyanins impose hepato-renal protective effects via ameliorating NLRP3 inflammasome, inhibiting MDA, GSSG, iNOS, HO-1, ICAM-1, β2-microglobulin, and MPO activity, and improved SOD, CAT, and GSH activity. Anthocyanins promote beneficial gut microbiota and enhance SCFA production, thus inhibiting pro-inflammatory markers. The immuno-modulatory impact of anthocyanins involves the reduction of CRP, P-selectin, C1q, and C4. Anthocyanins reduce LDL, VLDL, TGs, and TC via improved GBA and upregulation of ATP6 V0C, ZO-1, and ATG4D expression. The WHO/FAO suggested that 2.5 mg/kg/day of grape-skin extracts of anthocyanins are safe, and China recommended that 50 mg/day of anthocyanins are safe for consumption. In a nutshell, the multifaceted health benefits of anthocyanins make them promising candidates for disease prevention and therapeutic interventions.

Modulation of the gut microbiota has emerged as a promising approach for addressing the gastrointestinal and neurodevelopmental symptoms associated with autism spectrum disorder (ASD). Consequently, this study aimed to evaluate the impact of four formulated synbiotics comprising Limoscilactobacillus fermentum K73, high-oleic palm oil and whey, on the gut microbiota composition of Colombian children with and without ASD. These components were encapsulated through high-shear emulsification and spray drying. The four synbiotics and their individual components were subjected to in vitro digestion and fermentation using samples of Colombian children gut microbiota. Short-chain fatty acids (SCFAs), including lactic, acetic, propionic, and butyric acids, were quantified using HPLC-DAD, while serotonin was determined by an ELISA kit after in vitro fermentations. Changes in microbial structure were assessed by the sequencing of the 16S rRNA gene via next-generation sequencing (NGS). The results revealed a decrease in the abundance of genera like Bacteroides and Dorea in ASD-associated samples after the treatment with the synbiotics. Conversely, an increase in the relative abundance of probiotic-related genera, including Lactobacillus, Streptococcus, and Anaerostipes, was observed. Furthermore, the analysis of SCFAs and serotonin indicated that the synbiotic intervention resulted in an elevated butyric acid and microbial serotonin synthesis, alongside a decrease in propionic acid, which is changes considered beneficial in the context of ASD. This evidence suggests that synbiotics of L. fermentum K73 could represent a promising live biotherapeutic strategy for modulating the gut microbiota of children with ASD.

The study evaluated the effectiveness of a synbiotic blend containing Lactococcus lactis KA-FF 1-4 and Fibersol-2 in modulating gut microbiota and inhibiting vancomycin-resistant Enterococcus (VRE). Compared to probiotic or prebiotic treatments alone, the synbiotic blend significantly altered the gut microbiota composition, increasing beneficial bacteria like Blautia, Clostridium, Parabacteroides, Prevotella, and Roseburia, while reducing VRE abundance. Moreover, the synbiotic treatment showed an increase in short-chain fatty acid (SCFA) concentrations, particularly acetate, propionate, and butyrate. Correlation analysis revealed that enriched taxa in the synbiotic treatment were positively associated with higher SCFA levels. These findings highlight the potential of synbiotic formulations in improving gut microbiota balance and combating antibiotic-resistant pathogens like VRE.

Gut health is essential to the overall well-being of a human being due to its implication on digestion, the performance of the immune system, and nutritional absorption. The gut microbiota represents an intricate ecology of bacteria, fungi, and viruses, important in regulating the immune response and maintaining intestinal health. Fruit-based diets have developed as an essential constituent in gut health, and current studies highlight nutrition in modulating gut microbiota composition and activity. Rich in fiber, polyphenols, vitamins, and antioxidants, fruits also expand immunological function, subordinate inflammation in the stomach, and boost microbial diversity. The article reviews the benefits of fruit-derived dietary fibers, which assist as prebiotics in fostering the development of beneficial gut microbiota and decreasing intestinal inflammation. These antioxidants in fruits include flavonoids and carotenoids, whose immunomodulatory properties are under investigation for therapeutic use in autoimmune diseases, infections, and inflammatory bowel disease (IBD). Some fruits of particular interest include bananas, apples, citrus, and berries, as studies have consistently shown their immunomodulatory and gastrointestinal effects. There are still barriers to increasing fruit intake, including socioeconomic restrictions and the need for personalized nutritional counseling. The review fills an existing gap in the literature. It encourages enhanced immune and gastrointestinal well-being by combining the most recent research with practical recommendations on implementing fruit-based diets into daily nutrition.

Over the past few decades, there has been a surge in global study on the relationship between gut microbiota and human health. Numerous human illnesses have been linked to dysbiosis. Gram-positive firmicutes and Gram-negative bacteroidetes are the two leading bacterial phyla that make up 90% of the gut microbiome. Many symbionts in the gut environment establish intricate relationships with host defense to stop both local and non-native dangerous bacteria from colonizing and invading. Dysbiosis alters the paracellular route and damages the epithelium, enabling them to penetrate the epithelium and come into contact with the immune cells. Impaired intestinal barrier function, immune regulation mediated by metabolites derived from the gut microbiota, posttranslational modification of host proteins such as increased citrullination, regulation of the gut microbiota's effect on immune cells, intestinal epithelial cell autophagy, interaction between the microbiome and human leukocyte antigen alleles, and interaction with microRNAs are some of the mechanisms involved in rheumatoid arthritis (RA). The gut microbiota, Prevotella copri, and Collinsella spp. were shown to be higher in the early/preclinical phases of RA, while Bacteroidetes, Bifidobacteria, and Eubacterium rectale were found to be lower. Probiotic-based early dietary intervention may reduce inflammation and slow the rate of joint deterioration, and such intervention can also aid in the restoration of gut microbiota equilibrium. This review article describes the gut microbial dysbiosis and role of probiotics in RA.

Inflammation significantly influences the development of gastrointestinal (GI) diseases such as inflammatory bowel diseases (IBD)and ulcerative colitis, which disrupts normal digestive functions, leading to tissue damage and various symptoms. This research explores the preventive effects of quinoa polysaccharides (QPS) on lipopolysaccharide (LPS)-induced systemic acute inflammation in mice and their mechanism of action. The findings revealed that QPS alleviated LPS-induced inflammation symptoms, enhanced the mice behavior score and their immune organ index, reduced pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) levels, elevated the expression level of tight junction proteins (ZO-1, MUC2). Additionally, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were improved via QPS administration. Further, our research suggested that QPS enhanced the diversity and abundance of gut microbiota compared to that of LPS mice, leading to an increase in the short-chain fatty acids in mice feces. Linear discriminant analysis (LDA) effect size (LEfSe) showed that QPS administration could lead to a range of gut biomarkers, promoting the enhancement of polysaccharide-metabolizing bacteria. The results of 16S rRNA sequencing indicated that QPS alleviates LPS-induced inflammation by enhancing the richness of beneficial bacteria such as Bacteroides and Lactobacillus. Linear discriminant analysis (LDA) effect size (LEfSe) showed that QPS administration could lead to a range of gut biomarkers, promoting the enhancement of polysaccharide-metabolizing bacteria. UPLC Q-TOF-MS was performed to analyze metabolites in the fecal samples. LPS administration significantly altered metabolite levels detected in mice feces in which some metabolites have decreased such as xanthosine and hypoxanthine while an increase in some metabolites in mice that received QPS, metabolomics analysis showed the beneficial effects of QPS primarily mediated via amino and bile acid-related metabolism pathways. Our research could offer the basis for further studies and applications of quinoa polysaccharides.

Despite a decline in global incidence, gastric cancer (GC) remains a major health concern. The development of GC is a sequential, multistage maladaptive process involving numerous different factors. Understanding the complexity of GC development is crucial for early detection, effective treatment, and, ultimately, prevention. In this respect, identifying the impact of risk factors contributing to the emergence or progression of GC, such as Helicobacter pylori infection, host and bacterial genetics, alcohol consumption, smoking, and preserved foods, will aid in combatting this disease. In this review, we focus on recent developments in understanding the role of the microbiome, dysfunctional molecular pathways, and immune evasion in gastric pathophysiology. We also highlight challenges and advances in treatment of GC.

The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.

Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.

In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.

Diet modulates gut microbiome composition and function. However, determining causal links between diet-gut microbiome interactions and human health is complicated by inconsistencies in the evidence, arising partially from variability in research methods and reporting. Widespread adoption of standardized best practices would advance the field but require those practices to be identified, consolidated, and discussed. This umbrella review aimed to identify recommended best practices, define existing gaps, and collate considerations for conducting research on diet-gut microbiome interactions and their impact on human health outcomes. Reviews meeting inclusion criteria and published after 2013 were identified using a systematic search. Recommendations, considerations, and gaps relating to the best practices associated with study design, participant selection, dietary intervention/assessment, biological sample collection, and data analysis and reporting were extracted and consolidated. Eight narrative reviews were included. Several general points of agreement were identified, and a recurring theme was that best practices are dependent upon the research aims, outcomes, and feasibility. Multiple gaps were also identified. Some, such as suboptimal diet assessment methods and lack of validated dietary intake biomarkers, are particularly relevant to nutrition science. Others, including defining a "healthy" gut microbiome and the absence of standardized sample and data collection/analysis protocols, were relevant specifically to gut microbiome research. Gaps specific to diet-gut microbiome research include the underrepresentation of microbiome-modulating dietary components in food databases, lack of knowledge regarding interventions eliciting changes in the gut microbiome to confer health benefits, lack of in situ measurement methods, and the need to further develop and refine statistical approaches for integrating diet and gut microbiome data. Future research and cross-disciplinary exchange will address these gaps and evolve the best practices. In the interim, the best practices and considerations discussed herein, and the publications from which that information was extracted provide a roadmap for conducting diet-gut microbiome research. This trial was registered at PROSPERO as CRD42023437645.

Cardiovascular diseases (CVDs), including heart failure (HF), hypertension, myocardial infarction (MI), and atherosclerosis, are increasingly linked to gut microbiota dysbiosis and its metabolic byproducts. HF, affecting over 64 million individuals globally, is associated with systemic inflammation and gut barrier dysfunction, exacerbating disease progression. Similarly, hypertension and MI correlate with reduced microbial diversity and an abundance of pro-inflammatory bacteria, contributing to vascular inflammation and increased cardiovascular risk. Atherosclerosis is also influenced by gut dysbiosis, with key microbial metabolites such as trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs) playing crucial roles in disease pathogenesis. Emerging evidence highlights the therapeutic potential of natural compounds, including flavonoids, omega-3 fatty acids, resveratrol, curcumin, and marine-derived bioactives, which modulate the gut microbiota and confer cardioprotective effects. These insights underscore the gut microbiota as a critical regulator of cardiovascular health, suggesting that targeting dysbiosis may offer novel preventive and therapeutic strategies. Further research is needed to elucidate underlying mechanisms and optimize microbiome-based interventions for improved cardiovascular outcomes.

Probiotics are live bacteria that provides numerous healthy and beneficial effects to the consumers. The present study aimed to investigate the effect of a probiotic candidate Staphylococcus epidermidis SAS1, in immunoregulation and obesity management.

: This probiotic candidate was isolated from a soil sample collected from a region of fruit waste decomposition. In vitro cytotoxicity was assessed using the THP-1 (human leukemia monocytic cell line) cells using MTT assay.

An IC50 value of 47.52 ± 0.18 μg/mL and cell shrinkage were observed along with the release of cellular content of THP-1 cells. The higher production of reactive oxygen species and lesser release of interleukins (IL-4, 5, and 13) are attributed to the antiallergic potential of this strain. Furthermore, in vitro cytotoxicity evaluation using 3T3-L1 cells identified this strain as a promising candidate for anti-obesity treatment. The observed IC50 value was 514.4 ± 0.061 μg/mL.

This extract was shown to have good lipase-inhibiting enzyme activity and was reported to prevent adipogenesis, depicted by increased HDL levels and decreased LDL and triglyceride levels. These results suggested that Staphylococcus epidermidis SAS1 may have therapeutic use in the treatment of obesity and allergies.

Stress in dog breeding leads to significant physiological and psychological burdens, including anxiety, reduced appetite, weakened immune function, gut microbiota imbalance, and even death. Currently, there are various pharmacological interventions for stress management, but few focus on gut health. This study evaluates the potential of a novel strain, Enterococcus faecium Kimate-X, in alleviating transport stress and improving gut health in dogs, providing an alternative to traditional pharmacological treatments. In vitro experiments showed that Kimate-X significantly enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) while reducing the levels of malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in RAW 264.7 macrophage cells. In vivo, dogs supplemented with Kimate-X exhibited significantly lower cortisol levels after transport, indicating reduced stress. Metagenomic analysis revealed increased gut microbiota diversity and higher concentrations of short-chain fatty acids (acetate, propionate, and butyrate) in fecal samples. This study systematically uncovers the mechanism by which Enterococcus faecium Kimate-X alleviates transport stress through modulation of the gut microbiota. These findings provide new scientific evidence supporting the use of probiotics as a novel approach to stress management in animals.

Systemic hypertension is a major risk factor for cardiovascular disease and remains challenging to manage despite the widespread use of antihypertensive medications and lifestyle modifications. This review explores the role of gut microbiota in hypertension development and regulation, highlighting key mechanisms such as inflammation, gut-brain axis modulation, and bioactive metabolite production. We also assess the potential of microbiota-targeted therapies for hypertension management.

Emerging evidence indicates that microbial dysbiosis, high-salt diets, and gut-derived metabolites such as short-chain fatty acids (SCFAs) and bile acids significantly influence blood pressure regulation. Preclinical and early clinical studies suggest that interventions targeting gut microbiota, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), and dietary modifications, may help modulate hypertension. However, variability in gut microbiota composition among individuals and limited human trial data pose challenges to translating these findings into clinical practice. While microbiota-based therapies show promise for hypertension management, further research is needed to establish their efficacy and long-term effects. Large-scale, standardized clinical trials are crucial for understanding the therapeutic potential and limitations of gut microbiota interventions. A deeper understanding of the gut-hypertension axis could lead to novel, personalized treatment strategies for hypertension.

Multiple sclerosis (MS) is a well-known, chronic autoimmune disorder of the central nervous system (CNS) involving demyelination and neurodegeneration. Research previously conducted in the area of the gut microbiome has highlighted it as a critical contributor to MS pathogenesis. Changes in the commensal microbiota, or dysbiosis, have been shown to affect immune homeostasis, leading to elevated levels of pro-inflammatory cytokines and disruption of the gut-brain axis. In this review, we provide a comprehensive overview of interactions between the gut microbiota and MS, especially focusing on the immunomodulatory actions of microbiota, such as influencing T-cell balance and control of metabolites, e.g., short-chain fatty acids. Various microbial taxa (e.g., Prevotella and Faecalibacterium) were suggested to lay protective roles, whereas Akkermansia muciniphila was associated with disease aggravation. Interventions focusing on microbiota, including probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary therapies to normalize gut microbial homeostasis, suppress inflammation and are proven to improve clinical benefits in MS patients. Alterations in gut microbiota represent opportunities for identifying biomarkers for early diagnosis, disease progression and treatment response monitoring. Further studies need to be conducted to potentially address the interplay between genetic predispositions, environmental cues, and microbiota composition to get the precise mechanisms of the gut-brain axis in MS. In conclusion, the gut microbiota plays a central role in MS pathogenesis and offers potential for novel therapeutic approaches, providing a promising avenue for improving clinical outcomes in MS management.

The gut microbiome, a complex community of microorganisms residing in the intestinal tract, plays a dual role in colorectal cancer (CRC) development, acting both as a contributing risk factor and as a protective element. This review explores the mechanisms by which gut microbiota contribute to CRC, emphasizing inflammation, oxidative stress, immune evasion, and the production of genotoxins and microbial metabolites. Fusobacterium nucleatum, Escherichia coli (pks+), and Bacteroides fragilis promote tumorigenesis by inducing chronic inflammation, generating reactive oxygen species, and producing virulence factors that damage host DNA. These microorganisms can also evade the antitumor immune response by suppressing cytotoxic T cell activity and increasing regulatory T cell populations. Additionally, microbial-derived metabolites such as secondary bile acids and trimethylamine-N-oxide (TMAO) have been linked to carcinogenic processes. Conversely, protective microbiota, including Lactobacillus, Bifidobacterium, and Faecalibacterium prausnitzii, contribute to intestinal homeostasis by producing short-chain fatty acids (SCFAs) like butyrate, which exhibit anti-inflammatory and anti-carcinogenic properties. These beneficial microbes enhance gut barrier integrity, modulate immune responses, and inhibit tumor cell proliferation. Understanding the dynamic interplay between pathogenic and protective microbiota is essential for developing microbiome-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation, to prevent or treat CRC. Future research should focus on identifying microbial biomarkers for early CRC detection and exploring personalized microbiome-targeted therapies. A deeper understanding of host-microbiota interactions may lead to innovative strategies for CRC management and improved patient outcomes.

The microbiome of the gut is a complex ecosystem that contains a wide variety of microbial species and functional capabilities. The microbiome has a significant impact on health and disease by affecting endocrinology, physiology, and neurology. It can change the progression of certain diseases and enhance treatment responses and tolerance. The gut microbiota plays a pivotal role in human health, influencing a wide range of physiological processes. Recent advances in computational tools and artificial intelligence (AI) have revolutionized the study of gut microbiota, enabling the identification of biomarkers that are critical for diagnosing and treating various diseases. This review hunts through the cutting-edge computational methodologies that integrate multi-omics data-such as metagenomics, metaproteomics, and metabolomics-providing a comprehensive understanding of the gut microbiome's composition and function. Additionally, machine learning (ML) approaches, including deep learning and network-based methods, are explored for their ability to uncover complex patterns within microbiome data, offering unprecedented insights into microbial interactions and their link to host health. By highlighting the synergy between traditional bioinformatics tools and advanced AI techniques, this review underscores the potential of these approaches in enhancing biomarker discovery and developing personalized therapeutic strategies. The convergence of computational advancements and microbiome research marks a significant step forward in precision medicine, paving the way for novel diagnostics and treatments tailored to individual microbiome profiles. Investigators have the ability to discover connections between the composition of microorganisms, the expression of genes, and the profiles of metabolites. Individual reactions to medicines that target gut microbes can be predicted by models driven by artificial intelligence. It is possible to obtain personalized and precision medicine by first gaining an understanding of the impact that the gut microbiota has on the development of disease. The application of machine learning allows for the customization of treatments to the specific microbial environment of an individual.

This comprehensive review explores the evolving role of probiotic-based foods and beverages, highlighting their potential as functional and "future foods" that could significantly enhance nutrition, health, and overall well-being. These products are gaining prominence for their benefits in gut health, immune support, and holistic wellness. However, their future success depends on addressing critical safety concerns and navigating administrative complexities. Ensuring that these products "do more good than harm" involves rigorous evaluations of probiotic strains, particularly those sourced from the human gastrointestinal tract. Lactic acid bacteria (LABs) serve as versatile and effective functional starter cultures for the development of probiotic foods and beverages. The review emphasizes the role of LABs as functional starter cultures and the development of precision probiotics in advancing these products. Establishing standardized guidelines and transparent practices is essential, requiring collaboration among regulatory bodies, industry stakeholders, and the scientific community. The review underscores the importance of innovation in developing "friendly bacteria," "super probiotics," precision fermentation, and effective safety assessments. The prospects of functional probiotic-based foods and beverages rely on refining these elements and adapting to emerging scientific advancements. Ultimately, empowering consumers with accurate information, fostering innovation, and maintaining stringent safety standards will shape the future of these products as trusted and beneficial components of a health-conscious society. Probiotic-based foods and beverages, often infused with LABs, a "friendly bacteria," are emerging as "super probiotics" and "future foods" designed to "do more good than harm" for overall health.

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by joint inflammation and skin lesions. Recent research has underscored the critical role of gut microbiota-comprising bacteria, fungi, viruses, and archaea-in the pathogenesis and progression of PsA. This narrative review synthesizes the latest findings on the influence of gut microbiota on PsA, focusing on mechanisms such as immune modulation, microbial dysbiosis, the gut-joint axis, and its impact on treatment. Advances in high-throughput sequencing and metagenomics have revealed distinct microbial profiles associated with PsA. Studies show that individuals with PsA have a unique gut microbiota composition, differing significantly from healthy controls. Alterations in the abundance of specific bacterial taxa, including a decrease in beneficial bacteria and an increase in potentially pathogenic microbes, contribute to systemic inflammation by affecting the intestinal barrier and promoting immune responses. This review explores the impact of various factors on gut microbiota composition, including age, hygiene, comorbidities, and medication use. Additionally, it highlights the role of diet, probiotics, and fecal microbiota transplantation as promising strategies to modulate gut microbiota and alleviate PsA symptoms. The gut-skin-joint axis concept illustrates how gut microbiota influences not only gastrointestinal health but also skin and joint inflammation. Understanding the complex interplay between gut microbiota and PsA could lead to novel, microbiome-based therapeutic approaches. These insights offer hope for improved patient outcomes through targeted manipulation of the gut microbiota, enhancing both diagnosis and treatment strategies for PsA.

This Perspective article explores the challenges associated with the direct application of photobiomodulation (PBM) to the gut and presents a novel hypothesis for indirect gut health modulation through oral microbiome alteration. Given the difficulties in delivering PBM effectively to deep gastrointestinal tissues, an alternative approach involves targeting the oral microbiome, which has a demonstrated relationship with the gut microbiome. Research indicates that PBM applied to the oral cavity could selectively alter microbial composition. This alteration may, via the oral-gut microbiome axis, indirectly impact gut health. This hypothesis, supported by preliminary studies, suggests that oral PBM could offer a promising non-invasive strategy for managing gut-related disorders. Furthermore, there may be a link between the oral microbiome and brain diseases. Given the proximity to the brain, PBM-induced changes in the oral microbiota could indirectly help prevent neurological disorders. However, further investigation is necessary to comprehensively elucidate the underlying mechanisms and therapeutic implications of this approach.

This editorial comments on the article by Wu et al in the World Journal of Gastroenterology. The article explored the relationship between mesenteric adipose tissue, creeping fat, inflammation, and gut microbiota in Crohn's disease (CD). We discussed three key aspects of the interaction between gut microbiota and inflammatory bowel disease (IBD): The physiological functions of the gut microbiota, the potential role of probiotics in IBD treatment; and the effect of fecal microbiota transplantation (FMT) in combating IBD. IBD, comprising CD and ulcerative colitis (UC), is influenced by the gut microbiota. Changes in gut microbiota composition disrupt intestinal function and promote chronic inflammation, but the exact mechanisms remain unclear. Probiotics have demonstrated some efficacy in inducing remission in UC, though their effectiveness in CD is still debated. FMT shows promise in treating IBD, especially UC, by restoring gut microbiota diversity and inducing clinical remission. As for CD, FMT has potential, but more studies are needed to confirm its long-term effectiveness and safety. Dietary approaches may help manage IBD symptoms or disease activity, but patient adherence is crucial. Clinicians and researchers must recognize the importance of the gut microbiota and the need for personalized therapies targeting microbial imbalances.

The gut microbiota is pivotal to chickens' overall health, influencing digestion, nutrient absorption, and immune function. Dietary compounds significantly impact gut microbiota composition. House crickets (Acheta domesticus) have emerged as an alternative protein source for animal feed, rich in proteins and beneficial fatty acids. This study compared the gut microbiota in the cecum and ileum of Thai indigenous chicken breeds (Betong Chicken, white feather with black bone chicken, and black feather with black bone chicken) fed with or without house crickets. Using Oxford Nanopore Technology of 16S rDNA, this study found a similar relative abundance of gut bacteria across groups, with dominant bacteria including Firmicute, Bacteroidetes, Proteobacteria, and Actinobacteria. LEfSe analysis identified differential abundance of beneficial bacteria, such as Ruminococcaceae, Rikenella, and Deferribacteres, in the cecum of the black feather with black bone chicken after cricket feeding. Additionally, Lactobacillaceae exhibited differential abundance in the ileum of this breed post-cricket diet. Consequently, this study provides new data into the gut microbiota of Thai indigenous chickens. It suggests that house cricket diets did not significantly alter microbiota diversity but may enhance beneficial bacteria in certain breeds.

Standard clinical parameters like tumor size, age, lymph node status, and molecular markers are used to predict progression risk and treatment response. However, exploring additional markers that reflect underlying biology could offer a more comprehensive understanding of the tumor microenvironment (TME). The TME influences tumor development, progression, disease severity, and survival, with tumor-associated bacteria posited to play significant roles. Studies on tumor-associated microbiota have focused on high bacterial-load sites such as the gut, oral cavity, and stomach, but interest is growing in non-gastrointestinal (GI) solid tumors, such as breast, lung, and pancreas. Microbe-based biomarkers, including Helicobacter pylori, human papillomavirus (HPV), and hepatitis B and C viruses, have proven valuable in predicting gastric, cervical, and renal cancers.

Potential of prognostic and predictive bacterial biomarkers in non-GI solid tumors and the methodologies used.

Advances in techniques like 16S rRNA gene sequencing, qPCR, immunostaining, and in situ hybridization have enabled detailed analysis of difficult-to-culture microbes in solid tumors. However, to ensure reliable results, it is critical to standardize protocols, accurately align reads, address contamination, and maintain proper sample handling. This will pave the way for developing reliable bacterial markers that enhance prognosis, prediction, and personalized treatment planning.

Metabolic syndrome (MetS) is a complex disorder characterized by a cluster of metabolic risk factors. Recent research highlights the gut microbiome's role in metabolic regulation, suggesting that modulation through probiotics, prebiotics, and synbiotics may provide a novel approach to managing MetS. This umbrella review aims to integrate insights from existing meta-analyses to explore how changes in gut microbiota influence key body measurement indicators in individuals with MetS.

A systematic search of PubMed, Scopus, and Web of Science databases identified meta-analyses that assessed the impact of probiotics, prebiotics, or synbiotics on anthropometric indices in MetS patients.

The results indicated that microbial therapy leads to a significant reduction in body mass index (BMI) (SMD: -0.22; 95% CI: -0.35 to -0.09; P < 0.01) and waist circumference (WC) (SMD: -0.47; 95% CI: -0.80 to -0.15; P < 0.01). However, microbial therapy did not significantly affect body fat mass (SMD: -0.30; 95% CI: -0.64 to 0.02; P = 0.06), body fat percentage (SMD: -0.29; 95% CI: -0.62 to 0.03; P = 0.07), waist-to-hip ratio (SMD: -0.09; 95% CI: -0.46 to 0.28; P = 0.63), and weight (SMD: -0.06; 95% CI: -0.21 to 0.08; P = 0.37).

Gut microbial modulation, mainly through probiotics and synbiotics, shows promise in reducing BMI and WC in MetS patients. However, its effects on other anthropometric indices remain uncertain, warranting further high-quality research to fully understand microbial interventions' therapeutic potential.

Rumen flatulence is a diet-related rumen disease in ruminants. This study induced a rumen flatulence model in Xizang sheep using alfalfa (HRF) and wheatgrass (MRF). The aim was to understand the rumen microbiota diversity in healthy and pathological states, host-microbiota interactions, and the molecular mechanisms of rumen flatulence. Results showed that the pH in the HRF and MRF groups was lower than that in the natural grass group (LRF). SCFA concentrations varied between groups: in HRF, 2-BA and CA increased; in MRF, 4-MVA and 5-MCA rose. Microbial analysis indicated that the alpha- and beta-diversity of HRF and MRF groups were lower than LRF's, with different microbial compositions. Transcriptome analysis revealed many differentially expressed genes (DEGs). Compared to MRF, HRF had 348 upregulated and 511 downregulated DEGs. Versus LRF, MRF had 201 upregulated and 185 downregulated DEGs, while HRF had 128 upregulated and 238 downregulated DEGs. Spearman's correlation analysis showed that there was a positive correlation between Butyrivibrio, Quinella, and specific genes. These findings reveal the potential mechanism of rumen flatulence in Xizang sheep and provide new insights into the prevention and treatment of the disease.IMPORTANCEThe research used a high-protein diet to induce a model to understand the diversity of rumen microbiota and its interaction with the host, as well as exploring the molecular mechanisms of rumen flatulence.

Half of all epilepsy cases in both humans and canines are identified as idiopathic. Of these cases, 30 to 40% remain treatment-refractory to antiepileptic medications. Several human and dog studies have demonstrated low-carbohydrate diets and dietary medium-chain triglyceride (MCT) supplementation are effective for seizure reduction, with some patients achieving a seizure-free status. Recent evidence suggests the gut-brain axis has an important role in the pathology of neurological disease among both humans and dogs. Altered gut microbiota may have a major role in treatment-refractory epilepsy. This case report describes a dog with treatment-refractory epilepsy experiencing cluster seizures triggered by an altered gut microbiome despite therapeutic drug concentrations of multiple agents. Consideration of an underlying gastrointestinal disorder should be investigated in patients with treatment-refractory epilepsy, despite therapeutic concentrations of several antiepileptic medications. Dietary and gastrointestinal health-promoting interventions for epilepsy should also be considered before add-on pharmacotherapy or euthanasia. For difficult epilepsy cases, we suggest exploring the role of a limited-ingredient, low-carbohydrate diet, MCT supplementation, and/or pre/probiotics to augment pharmacotherapeutic strategies. This information may be critically valuable in designing high-quality, diet-based therapies for epileptic dogs. Key clinical message: Gastrointestinal workup, dietary changes to a low-carbohydrate diet, supplementation with MCTs, and addition of pre/probiotics could be considered to augment pharmacotherapeutic strategies in treatmentrefractory epilepsy cases in dogs.

Oxidative stress (OS) and gut microbiota are crucial factors influencing human health, each playing a significant role in the development and progression of chronic diseases. This review provides a comprehensive analysis of the complex interplay between these two factors, focusing on how an imbalance between reactive oxygen species (ROS) and antioxidants leads to OS, disrupting cellular homeostasis and contributing to a range of conditions, including metabolic disorders, cardiovascular diseases, neurological diseases, and cancer. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, is essential for regulating immune responses, metabolic pathways, and overall health. Dysbiosis, an imbalance in the gut microbiota composition, is closely associated with chronic inflammation, metabolic dysfunction, and various diseases. This review highlights how the gut microbiota influences and is influenced by OS, complicating the pathophysiology of many conditions. Furthermore, emerging evidence has identified extracellular vesicles (EVs) as critical facilitators of cellular crosstalk between the OS and gut microbiota. EVs also play a crucial role in signaling between the gut microbiota and host tissues, modulating immune responses, inflammation, and metabolic processes. The signaling function of EVs holds promise for the development of targeted therapies aimed at restoring microbial balance and mitigating OS. Personalized therapeutic approaches, including probiotics, antioxidants, and fecal microbiota transplantation-based strategies, can be used to address OS-related diseases and improve health outcomes. Nonetheless, further research is needed to study the molecular mechanisms underlying these interactions and the potential of innovative interventions to offer novel strategies for managing OS-related diseases and enhancing overall human health.