Search

This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.

The review aimed to investigate the diversity of oral microbiota and its influencing factors, as well as the association of oral microbiota with oral health and the possible effects of dysbiosis and oral disorder. The oral cavity harbors a substantial microbial burden, which is particularly notable compared to other organs within the human body. In usual situations, the microbiota exists in a state of equilibrium; however, when this balance is disturbed, a multitude of complications arise. Dental caries, a prevalent issue in the oral cavity, is primarily caused by the colonization and activity of bacteria, particularly streptococci. Furthermore, this environment also houses other pathogenic bacteria that are associated with the onset of gingival, periapical, and periodontal diseases, as well as oral cancer. Various strategies have been employed to prevent, control, and treat these disorders. Recently, techniques utilizing microbiota, like probiotics, microbiota transplantation, and the replacement of oral pathogens, have caught the eye. This extensive examination seeks to offer a general view of the oral microbiota and their metabolites concerning oral health and disease, and also the resilience of the microbiota, and the techniques used for the prevention, control, and treatment of disorders in this specific area. [ABSTRACT FROM AUTHOR]

Background: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear. Methods: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites. Results: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that Lvaline could alleviate sepsis-induced intestinal damage. Conclusion: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury. [ABSTRACT FROM AUTHOR]

The hepatobiliary system is vital for the biotransformation and disposition of endogenous molecules. Any impairment in the normal functioning of the hepatobiliary system leads to a spectrum of hepatobiliary diseases (HBDs), such as liver cirrhosis, fatty liver, biliary dyskinesia, gallbladder cancer, etc. Especially in pregnancy, HBD may result in increased maternal and fetal morbidity and mortality. Maternal HBD is a burden to the fetus’s growth, complicates fetal development, and risks the mother’s life. In fetal programming, the maternal mechanism is significantly disturbed by multiple factors (especially diet) that influence the development of the fetus and increase the frequency of metabolic diseases later in life. Additionally, maternal under-nutrition or over-nutrition (especially in high-fat, high-carbohydrate, or protein-rich diets) lead to dysregulation in gut hormones (CCK, GLP-1, etc.), microbiota metabolite production (SCFA, LPS, TMA, etc.), neurotransmitters (POMC, NPY, etc.), and hepatobiliary signaling (insulin resistance, TNF-a, SREBPs, etc.), which significantly impact fetal programming. Recently, biotherapeutics have provided a new horizon for treating HBD during fetal programming to save the lives of the mother and fetus. This review focuses on how maternal impaired hepatobiliary metabolic signaling leads to disease transmission to the fetus mediated through the gut–brain axis.

Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i.e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota‐derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota‐derived metabolites, such as short‐chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine‐N‐oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined. [ABSTRACT FROM AUTHOR]

The hepatobiliary system is vital for the biotransformation and disposition of endogenous molecules. Any impairment in the normal functioning of the hepatobiliary system leads to a spectrum of hepatobiliary diseases (HBDs), such as liver cirrhosis, fatty liver, biliary dyskinesia, gallbladder cancer, etc. Especially in pregnancy, HBD may result in increased maternal and fetal morbidity and mortality. Maternal HBD is a burden to the fetus's growth, complicates fetal development, and risks the mother's life. In fetal programming, the maternal mechanism is significantly disturbed by multiple factors (especially diet) that influence the development of the fetus and increase the frequency of metabolic diseases later in life. Additionally, maternal under-nutrition or over-nutrition (especially in high-fat, high-carbohydrate, or protein-rich diets) lead to dysregulation in gut hormones (CCK, GLP-1, etc.), microbiota metabolite production (SCFA, LPS, TMA, etc.), neurotransmitters (POMC, NPY, etc.), and hepatobiliary signaling (insulin resistance, TNF-a, SREBPs, etc.), which significantly impact fetal programming. Recently, biotherapeutics have provided a new horizon for treating HBD during fetal programming to save the lives of the mother and fetus. This review focuses on how maternal impaired hepatobiliary metabolic signaling leads to disease transmission to the fetus mediated through the gut–brain axis. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that the gut microbiota plays a role in insomnia pathogenesis. This study compared the dietary habits and microbiota metabolites of older adults with insomnia of short vs. normal sleep duration (ISSD and INSD, respectively). Data collection included sleep assessment through actigraphy, dietary analysis using the Food Frequency Questionnaire, and metabolomic profiling of stool samples. The results show that ISSD individuals had higher body mass index and a greater prevalence of hypertension. Significant dietary differences were observed, with the normal sleep group consuming more kilocalories per day and specific aromatic amino acids (AAAs) phenylalanine and tyrosine and branch-chain amino acid (BCAA) valine per protein content than the short sleep group. Moreover, metabolomic analysis identified elevated levels of the eight microbiota metabolites, benzophenone, pyrogallol, 5-aminopental, butyl acrylate, kojic acid, deoxycholic acid (DCA), trans-anethole, and 5-carboxyvanillic acid, in the short compared to the normal sleep group. The study contributes to the understanding of the potential role of dietary and microbial factors in insomnia, particularly in the context of sleep duration, and opens avenues for targeted dietary interventions and gut microbiota modulation as potential therapeutic approaches for treating insomnia. [ABSTRACT FROM AUTHOR]

Intratumoral microbiota has become research hotspots, and emerges as a non-negligent new component of tumor microenvironments (TME), due to its powerful influence on tumor initiation, metastasis, immunosurveillance and prognosis despite in low-biomass. The accumulations of microbes, and their related components and metabolites within tumor tissues, endow TME with additional pluralistic features which are distinct from the conventional one. Therefore, it's definitely necessary to comprehensively delineate the sophisticated landscapes of tumor microbe microenvironment, as well as their functions and related underlying mechanisms. Herein, in this review, we focused on the fields of tumor microbe microenvironment, including the heterogeneity of intratumor microbiota in different types of tumors, the controversial roles of intratumoral microbiota, the basic features of tumor microbe microenvironment (i. e., pathogen-associated molecular patterns (PAMPs), typical microbial metabolites, autophagy, inflammation, multi-faceted immunomodulation and chemoresistance), as well as the multidisciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes, microbiota metabolites, antibiotics, synthetic biology and rationally designed biomaterials. We hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial, and facilitate the development of microbes-based tumor-specific treatments. This article focused on the fields of tumor microbe microenvironment, talking about the heterogeneity of intratumoral microbiota, basic features of tumor microbe microenvironment and multidisciplinary approach-based intervention of tumor microbiome. [Display omitted] [ABSTRACT FROM AUTHOR]

The review aimed to investigate the diversity of oral microbiota and its influencing factors, as well as the association of oral microbiota with oral health and the possible effects of dysbiosis and oral disorder. The oral cavity harbors a substantial microbial burden, which is particularly notable compared to other organs within the human body. In usual situations, the microbiota exists in a state of equilibrium; however, when this balance is disturbed, a multitude of complications arise. Dental caries, a prevalent issue in the oral cavity, is primarily caused by the colonization and activity of bacteria, particularly streptococci. Furthermore, this environment also houses other pathogenic bacteria that are associated with the onset of gingival, periapical, and periodontal diseases, as well as oral cancer. Various strategies have been employed to prevent, control, and treat these disorders. Recently, techniques utilizing microbiota, like probiotics, microbiota transplantation, and the replacement of oral pathogens, have caught the eye. This extensive examination seeks to offer a general view of the oral microbiota and their metabolites concerning oral health and disease, and also the resilience of the microbiota, and the techniques used for the prevention, control, and treatment of disorders in this specific area.

BackgroundThe protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear.MethodsFecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman’s correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites.ResultsThe diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage.ConclusionAlterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.

Simple Summary: Feeding technologies, such as probiotics, are widely used in the animal industry for purposes beyond nutritional needs. Probiotic bacteria have been shown to have multiple effects on sow physiology during gestation and lactation, making them a subject of great interest when it comes to animal behavior and welfare. In this study, the use of probiotics mitigated the apathetic state of gestating sows housed in individual cages, in addition to reducing fear and aversion towards humans during interaction tests. The influence was also observed in the progeny, as piglets from sows supplemented with probiotics were less resistant in fear assessments, which may indicate lower stress levels. The findings indicate that the use of probiotics during gestation and lactation can be used as a tool in enhancing animal welfare. The intensification of production systems has resulted in detrimental effects on sow welfare, which can have an adverse influence on their offspring. Considering the relevance of the microbiota–gut–brain axis, probiotics can mitigate such impacts. To investigate the effects of the dietary inclusion of probiotics on the welfare of sows and piglets, 147 multiparous sows were randomly assigned to two groups: a control group or a group supplemented with a multistrain probiotic from the beginning of pregnancy to the end of lactation. The human–animal relationship (HAR), stereotypic behavior, position changes, salivary cortisol, and plasma serotonin levels were assessed in the sows. The piglets' back test behavior and organ weight were analyzed. The probiotic-supplemented sows exhibited a better HAR index (p = 0.017), which indicated reduced aversion towards humans. The frequency of stereotypies was not influenced by the treatments. However, the supplemented sows spent more time standing (p = 0.054) and less time lying down (p = 0.008). The cortisol level of the supplemented sows was 50% lower (p = 0.047) and the serotonin levels were 11% higher (p = 0.034) than control animals. The multistrain piglets were more passive and less resistant (p = 0.076) in the back test. The organ weights were not influenced by treatments. In conclusion, the sows supplemented with probiotics showed less fear and more motivation indicators, while their piglets showed less aggression behaviors. [ABSTRACT FROM AUTHOR]

Lactobacillus johnsonii is a commensal bacterium that has been isolated from vaginal and gastrointestinal (GI) tracts of vertebrate hosts, including humans, rodents, swine, and poultry. Lactobacillus-based probiotic supplements are popular because of the health advantages they offer. Species such as L. johnsonii are particularly interesting due to their potential health-promoting properties. Here, we reviewed the research on specific strains of L. johnsonii that have been studied in the context of health and disease and delved into the underlying mechanisms that aid in preserving host homeostasis. The utilization of L. johnsonii strains has been widely linked to numerous health benefits in the host. These include pathogen antagonism, control of mucosal and systemic immune responses, reduction of chronic inflammation, modulation of metabolic disorders, and enhanced epithelial barrier. These findings suggest that L. johnsonii plays a critical role in maintaining host homeostasis, highlighting its potential as a probiotic. [ABSTRACT FROM AUTHOR]

Lactobacillus johnsonii is a commensal bacterium that has been isolated from vaginal and gastrointestinal (GI) tracts of vertebrate hosts, including humans, rodents, swine, and poultry. Lactobacillus-based probiotic supplements are popular because of the health advantages they offer. Species such as L. johnsonii are particularly interesting due to their potential health-promoting properties. Here, we reviewed the research on specific strains of L. johnsonii that have been studied in the context of health and disease and delved into the underlying mechanisms that aid in preserving host homeostasis. The utilization of L. johnsonii strains has been widely linked to numerous health benefits in the host. These include pathogen antagonism, control of mucosal and systemic immune responses, reduction of chronic inflammation, modulation of metabolic disorders, and enhanced epithelial barrier. These findings suggest that L. johnsonii plays a critical role in maintaining host homeostasis, highlighting its potential as a probiotic.

Simple Summary: The gastrointestinal tract (GIT) is home to a large number of microorganisms, referred to collectively as the GIT microbiota. These microorganisms can be beneficial or potentially harmful to the host. Ensuring a high level of microbial diversity in the GIT, with a high abundance of beneficial and a low abundance of pathogenic microorganisms, is essential for host health. A healthy microbiota is vital at all stages of pig production; however, the post-weaning period is of particular importance. The post-weaning period is a phase during which intestinal dysbiosis can occur, providing an opportunity for harmful microorganisms to colonize and proliferate, leading to poor performance and even mortality. Different microorganisms have different metabolic capabilities, varying in the substrates they break down and the subsequent bioactive metabolites they produce. Therefore, the dietary substrates available to microbes have a significant impact on the microbial composition of the GIT and the subsequent metabolites produced. A prebiotic is a substrate selectively utilized by host microorganisms and conferring a benefit to the host. Prebiotics offer a therapeutic strategy in order to alter the composition of the microbiota, enhancing the proliferation of beneficial microbes and production of host-health-promoting metabolites, which can subsequently limit the proliferation of potentially harmful microbes. There is currently a broad range of different prebiotic classes. These vary in structure and composition and subsequently in the effects exerted on the microbiota. The current review is an overview of the different classes of prebiotics, their potential mode benefits, and the main findings from investigations utilizing them in the pigs' diets to date. Establishing a balanced and diverse microbiota in the GIT of pigs is crucial for optimizing health and performance throughout the production cycle. The post-weaning period is a critical phase, as it is often associated with dysbiosis, intestinal dysfunction and poor performance. Traditionally, intestinal dysfunctions associated with weaning have been alleviated using antibiotics and/or antimicrobials. However, increasing concerns regarding the prevalence of antimicrobial-resistant bacteria has prompted an industry-wide drive towards identifying natural sustainable dietary alternatives. Modulating the microbiota through dietary intervention can improve animal health by increasing the production of health-promoting metabolites associated with the improved microbiota, while limiting the establishment and proliferation of pathogenic bacteria. Prebiotics are a class of bioactive compounds that resist digestion by gastrointestinal enzymes, but which can still be utilized by beneficial microbes within the GIT. Prebiotics are a substrate for these beneficial microbes and therefore enhance their proliferation and abundance, leading to the increased production of health-promoting metabolites and suppression of pathogenic proliferation in the GIT. There are a vast range of prebiotics, including carbohydrates such as non-digestible oligosaccharides, beta-glucans, resistant starch, and inulin. Furthermore, the definition of a prebiotic has recently expanded to include novel prebiotics such as peptides and amino acids. A novel class of -biotics, referred to as "stimbiotics", was recently suggested. This bioactive group has microbiota-modulating capabilities and promotes increases in short-chain fatty acid (SCFA) production in a disproportionally greater manner than if they were merely substrates for bacterial fermentation. The aim of this review is to characterize the different prebiotics, detail the current understating of stimbiotics, and outline how supplementation to pigs at different stages of development and production can potentially modulate the GIT microbiota and subsequently improve the health and performance of animals. [ABSTRACT FROM AUTHOR]

Simple Summary: The gastrointestinal tract (GIT) microbiota refers to the collection of microorganisms that colonize the GIT. The composition and diversity of the GIT microbiota play a fundamental role in animal health and performance and is an area that is becoming increasingly important with recent introduction of new restrictions on antibiotic and antimicrobial use in animal production. Enhancing the establishment of the GIT microbiota in the initial stages of life can improve health and performance, both in the immediate period and later life. Interestingly, the offspring's microbiota is heavily influenced by the maternal microbiota, thereby underlining modulation of the maternal microbiota as a promising strategy to enhance the health and growth of the offspring. A probiotic is a beneficial live microorganism that, when supplemented, has beneficial effects on the host's health. A synbiotic is a combination of a probiotic and another bioactive known as a prebiotic, which is essentially a substrate for beneficial microbes in the gut. Supplementing probiotics or synbiotics in the maternal diet presents a promising strategy to firstly modulate the maternal GIT microbiota, conferring several health benefits to the sow, and secondly to influence the establishment of the offspring's GIT microbiota, conferring several health benefits to the offspring. The current review discusses the importance and suggested mechanisms of action for maternal probiotic and synbiotic supplementation and details key findings from studies that have investigated the effects of maternal probiotic or synbiotic supplementation in pigs. The increasing prevalence of antimicrobial-resistant pathogens has prompted the reduction in antibiotic and antimicrobial use in commercial pig production. This has led to increased research efforts to identify alternative dietary interventions to support the health and development of the pig. The crucial role of the GIT microbiota in animal health and performance is becoming increasingly evident. Hence, promoting an improved GIT microbiota, particularly the pioneer microbiota in the young pig, is a fundamental focus. Recent research has indicated that the sow's GIT microbiota is a significant contributor to the development of the offspring's microbiota. Thus, dietary manipulation of the sow's microbiota with probiotics or synbiotics, before farrowing and during lactation, is a compelling area of exploration. This review aims to identify the potential health benefits of maternal probiotic or synbiotic supplementation to both the sow and her offspring and to explore their possible modes of action. Finally, the results of maternal sow probiotic and synbiotic supplementation studies are collated and summarized. Maternal probiotic or synbiotic supplementation offers an effective strategy to modulate the sow's microbiota and thereby enhance the formation of a health-promoting pioneer microbiota in the offspring. In addition, this strategy can potentially reduce oxidative stress and inflammation in the sow and her offspring, enhance the immune potential of the milk, the immune system development in the offspring, and the sow's feed intake during lactation. Although many studies have used probiotics in the maternal sow diet, the most effective probiotic or probiotic blends remain unclear. To this extent, further direct comparative investigations using different probiotics are warranted to advance the current understanding in this area. Moreover, the number of investigations supplementing synbiotics in the maternal sow diet is limited and is an area where further exploration is warranted. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Pathology is the property of Canadian Association of Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Gut microbiome is a key factor in health and disease transformation, and can metabolize nutrients consumed by human body to produce microbiota metabolites mainly composed of short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), tryptophan metabolites and secondary bile acids (2BAs), which are closely related to ischemic stroke (IS). Ischemic stroke is a refractory brain injury that results in severe loss of function and greatly increases the burden of society and medical system. Experiments have proved that regulating the microbiota metabolites can effectively improve the prognosis of stroke. Therefore, a full understanding of the crosstalk between ischemic stroke and microbiota metabolites will help to formulate the relevant treatment strategies, so as to guide clinical practice. This article summarized the formation and function of microbiota metabolites, the relationship with ischemic stroke, and the possible pathways of action, so as to provide new ideas for future research on ischemic stroke.

Innate immunity of the mucosal surfaces provides the first-line defense from invading pathogens and pollutants conferring protection from the external environment. Innate immune system of the airway epithelium consists of several components including the mucus layer, mucociliary clearance of beating cilia, production of host defense peptides, epithelial barrier integrity provided by tight and adherens junctions, pathogen recognition receptors, receptors for chemokines and cytokines, production of reactive oxygen species, and autophagy. Therefore, multiple components interplay with each other for efficient protection from pathogens that still can subvert host innate immune defenses. Hence, the modulation of innate immune responses with different inducers to boost host endogenous front-line defenses in the lung epithelium to fend off pathogens and to enhance epithelial innate immune responses in the immunocompromised individuals is of interest for hostdirected therapy. Herein, we reviewed possibilities of modulation innate immune responses in the airway epithelium for host-directed therapy presenting an alternative approach to standard antibiotics. [ABSTRACT FROM AUTHOR]

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut–brain axis. While this microbiota–gut–brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota–gut–brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut–brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that the gut microbiota plays a role in insomnia pathogenesis. This study compared the dietary habits and microbiota metabolites of older adults with insomnia of short vs. normal sleep duration (ISSD and INSD, respectively). Data collection included sleep assessment through actigraphy, dietary analysis using the Food Frequency Questionnaire, and metabolomic profiling of stool samples. The results show that ISSD individuals had higher body mass index and a greater prevalence of hypertension. Significant dietary differences were observed, with the normal sleep group consuming more kilocalories per day and specific aromatic amino acids (AAAs) phenylalanine and tyrosine and branch-chain amino acid (BCAA) valine per protein content than the short sleep group. Moreover, metabolomic analysis identified elevated levels of the eight microbiota metabolites, benzophenone, pyrogallol, 5-aminopental, butyl acrylate, kojic acid, deoxycholic acid (DCA), trans-anethole, and 5-carboxyvanillic acid, in the short compared to the normal sleep group. The study contributes to the understanding of the potential role of dietary and microbial factors in insomnia, particularly in the context of sleep duration, and opens avenues for targeted dietary interventions and gut microbiota modulation as potential therapeutic approaches for treating insomnia.

The intensification of production systems has resulted in detrimental effects on sow welfare, which can have an adverse influence on their offspring. Considering the relevance of the microbiota–gut–brain axis, probiotics can mitigate such impacts. To investigate the effects of the dietary inclusion of probiotics on the welfare of sows and piglets, 147 multiparous sows were randomly assigned to two groups: a control group or a group supplemented with a multistrain probiotic from the beginning of pregnancy to the end of lactation. The human–animal relationship (HAR), stereotypic behavior, position changes, salivary cortisol, and plasma serotonin levels were assessed in the sows. The piglets’ back test behavior and organ weight were analyzed. The probiotic-supplemented sows exhibited a better HAR index (p = 0.017), which indicated reduced aversion towards humans. The frequency of stereotypies was not influenced by the treatments. However, the supplemented sows spent more time standing (p = 0.054) and less time lying down (p = 0.008). The cortisol level of the supplemented sows was 50% lower (p = 0.047) and the serotonin levels were 11% higher (p = 0.034) than control animals. The multistrain piglets were more passive and less resistant (p = 0.076) in the back test. The organ weights were not influenced by treatments. In conclusion, the sows supplemented with probiotics showed less fear and more motivation indicators, while their piglets showed less aggression behaviors.

Innate immunity of the mucosal surfaces provides the first-line defense from invading pathogens and pollutants conferring protection from the external environment. Innate immune system of the airway epithelium consists of several components including the mucus layer, mucociliary clearance of beating cilia, production of host defense peptides, epithelial barrier integrity provided by tight and adherens junctions, pathogen recognition receptors, receptors for chemokines and cytokines, production of reactive oxygen species, and autophagy. Therefore, multiple components interplay with each other for efficient protection from pathogens that still can subvert host innate immune defenses. Hence, the modulation of innate immune responses with different inducers to boost host endogenous front-line defenses in the lung epithelium to fend off pathogens and to enhance epithelial innate immune responses in the immunocompromised individuals is of interest for host-directed therapy. Herein, we reviewed possibilities of modulation innate immune responses in the airway epithelium for host-directed therapy presenting an alternative approach to standard antibiotics.

Drug-induced enteritis is an inflammatory disease changing in the morphology and function of the intestine as a result of medicine damage. With the increase in drug abuse in recent years, the incidence of drug-associated enteritis accordingly rises and becomes an important disease affecting the health and life quality of patients. Hence, elucidating the pathogenesis of drug-induced enteritis and finding cost-effective diagnostic and therapeutic tools have become current research focuses. The gut microbiota and metabolites regulate the immune response, playing a key role in the maintenance of homeostasis in the intestine. Numerous studies have found that many medicines can induce intestinal flora disorders, which are closely related to the development of drug-induced enteritis. Therefore, this paper analyses the role of gut microbiota and metabolites in regulating the immune response, and provides basic research direction and clinical reference strategies for drug-induced enteritis, taking into account the existing applications and perspectives. [ABSTRACT FROM AUTHOR]

Neurodegenerative disease is a highly disabling and fatal disease that occurs in the central nervous system. The main population is the middle-aged and the elderly. At present, the pathogenesis of this type of disease is still unclear, and there is no effective treatment strategy. With the deepening of aging, neurodegenerative diseases pose a serious threat to the health of Chinese. As microorganisms living in the gastrointestinal tract, the intestinal flora has a mutually beneficial and symbiotic relationship with the human body and plays a vital role in life and health. The development of neurodegenerative diseases is accompanied by the development of intestinal flora and its related metabolites. This article reviews the mechanism of the interaction between the gut microbiota and its metabolites and neurodegenerative diseases, and discusses the potential value of the gut microbiota in the treatment of neurodegenerative diseases, in order to provide new research directions for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Several disorders have been linked to modifications in the gut microbial imbalance, intestinal epithelium, and host immune system. In this regard, microbiota derived short-chain fatty acids (SCFAs) play a key function in the regulation of histone deacetylases (HDACs), which affect modulation of immunity and regulation of inflammatory responses in the intestine and other organs. Studies examining the metabolites produced by polymicrobial bacterial vaginosis (BV) states and Lactobacillus-dominated microbiota have noted a dramatic reduction of lactic acid and a shift toward SCFA synthesis. Along with higher levels of SCFAs, acetate is typically the main metabolite in the cervicovaginal fluid of women with symptomatic bacterial vaginosis. The fact that SCFAs made by the vaginal microbiota have been shown to exhibit antibacterial and immune-modulating properties suggests that they may have promise as indicators of disease and/or disease susceptibility. In this review, we overview and summarize the current findings on the detrimental or protective roles of microbiota metabolites especially SCFAs in the health and disease of the female reproductive system.

Chronic constipation (CC) is a highly prevalent and burdensome gastrointestinal disorder. Accumulating evidence highlights the link between imbalances in the gut microbiome and constipation. However, the mechanisms by which the microbiome and microbial metabolites affect gut movement remain poorly understood. In this review, we discuss recent studies on the alteration in the gut microbiota in patients with CC and the effectiveness of probiotics in treating gut motility disorder. We highlight the mechanisms that explain how the gut microbiome and its metabolism are linked to gut movement and how intestinal microecological interventions may counteract these changes based on the enteric nervous system, the central nervous system, the immune function, and the ability to modify intestinal secretion and the hormonal milieu. In particular, microbiota-based approaches that modulate the levels of short-chain fatty acids and tryptophan catabolites or that target the 5-hydroxytryptamine and Toll-like receptor pathways may hold therapeutic promise. Finally, we discuss the existing limitations of microecological management in treating constipation and suggest feasible directions for future research. [ABSTRACT FROM AUTHOR]

Depression is a common and complex mental and emotional disorder that causes disability, morbidity, and quite often mortality around the world. Depression is closely related to several physical and metabolic conditions causing metabolic depression. Studies have indicated that there is a relationship between the intestinal microbiota and the brain, known as the gut–brain axis. While this microbiota–gut–brain connection is disturbed, dysfunctions of the brain, immune system, endocrine system, and gastrointestinal tract occur. Numerous studies show that intestinal dysbiosis characterized by abnormal microbiota and dysfunction of the microbiota–gut–brain axis could be a direct cause of mental and emotional disorders. Traditional treatment of depression includes psychotherapy and pharmacotherapy, and it mainly targets the brain. However, restoration of the intestinal microbiota and functions of the gut–brain axis via using probiotics, their metabolites, prebiotics, and healthy diet may alleviate depressive symptoms. Administration of probiotics labeled as psychobiotics and their metabolites as metabiotics, especially as an adjuvant to antidepressants, improves mental disorders. It is a new approach to the prevention, management, and treatment of mental and emotional illnesses, particularly major depressive disorder and metabolic depression. For the effectiveness of antidepressant therapy, psychobiotics should be administered at a dose higher than 1 billion CFU/day for at least 8 weeks.

Background: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear., Methods: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites., Results: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage., Conclusion: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Sun, Qi, Tang, Zhu and Wang.)

Nanomedicine has become one of the most promising technologies to modernize the traditional food. However, not only the public perception of the new technology is uncertain, but also the regulators have not yet to agree on rules that apply globally. The gastrointestinal tract microbiota and its genes (the microbiome) are considered a fundamental part of the human body. The gut microbiota is a major part of the host microbiota and contains approximately 3 × 1013 bacterial cells in a commensal relationship with the host. However, once the gastric ecosystem is altered, various bacterial species (e.g., antibiotic-resistant Enterococcus and Clostridium difficile) can increase and develop pathogenic phenotypes. Recent evidence suggests that the gut microbiota is involved in carcinogenesis and can enhance the activity, efficacy, and toxicity of anticancer therapies. Recently, there is fast-growing concern regarding the effect of nanoparticles on the human gut microbiota. Nanomaterials can enter the human body via skin contact, ingestion, and inhalation. In the present review, the recent advances on the roles of microbiota and nanomaterials in cancer therapy, the microbiota and their metabolic interventions via nanomaterials, microbial inspiration via nanomaterials, and the challenges associated with using nanomaterials in humans and animals is discussed. In short, this review will focus on the current status and future perspectives of gut microbiota targeted nanotechnology for cancer therapy and cancer-related metabolic diseases. The changes in the gut microbiota or microbiome play vital roles in human diseases such as cancer. Traditional microbiome treatments have led to improved cancer treatments in some cases; however, problems such as collateral injury to the symbiotic microbiome and reliability of these treatment methods have led to new technological developments designed specifically for cancer microbiota crossing point. Hence, the prosperousness of nanomaterials in cancer prevention has led to the idea that nanomaterials can alter the cancer-causing microbiome/microbiota and their metabolites as well as alter the cancer microenvironment. Therefore, nanomaterials can be used as novel strategies to treat cancer. However, this emerging research area requires further in vivo clinical trials to determine the exact mechanisms of action involved in treating cancer via nanomaterials. Further studies should explore the connection between nanomaterials, the microbiota, microbial metabolites, cancer and cancer-related microenvironments in animals and humans. Image 1 • Increasing evidence suggested that the gut microbiota dysbiosis influence cancer. • Interaction between nanomaterials and gut microbiota are largely unexplored. • The concept of nanomedicine based approached to alter gut microbiota for cancer therapy has been proposed. • The gut microbiota and nanomedicine might provide new specific biomarkers for cancer therapy. • Future perceptive toward the development of novel nanomedicine for cancer therapy are discussed. [ABSTRACT FROM AUTHOR]

The gut microbiome is rapidly becoming the focus of interest as a possible factor involved in the pathophysiology of neuropsychiatric disorders. Recent understanding of the pathophysiology of schizophrenia emphasizes the role of systemic components, including immune/inflammatory and metabolic processes, which are influenced by and interacting with the gut microbiome. Here we systematically review the current literature on the gut microbiome in schizophrenia-spectrum disorders and in their animal models. We found that the gut microbiome is altered in psychosis compared to healthy controls. Furthermore, we identified potential factors related to psychosis, which may contribute to the gut microbiome alterations. However, further research is needed to establish the disease-specificity and potential causal relationships between changes of the microbiome and disease pathophysiology. This can open up the possibility of. manipulating the gut microbiome for improved symptom control and for the development of novel therapeutic approaches in schizophrenia and related psychotic disorders.

We have analyzed the prebiotic effect of softwood hemicelluloses on specific bacterial species in vitro and on microbiota diversity and metabolism in healthy mice in vivo. The ethanol-precipitated glycans from the softwood hemicellulose autohydrolysate were able to stimulate in vitro the growth of Bifidobacterium adolescentis, but to a much lesser extent than that of adherent-invasive E. coli. B. adolescentis was the best producer of SCFA. When mice were fed with the ethanol precipitate fraction, the relative abundance of Bacteroidetes increased while that of Proteobacteria diminished, suggesting change towards a less obesogenic microbiome. Following treatment, lipid analysis showed a decrease in cholesterol, bile acids and free fatty acids, indicating a potential cardioprotection role. Furthermore, analysis of fermentation metabolites revealed an increase in metabolites important for immune health and well-being. Our results highlight the value of hemicelluloses as a potential source of prebiotics supporting both a healthy digestive tract and immune system.

The gut microbiome is rapidly becoming the focus of interest as a possible factor involved in the pathophysiology of neuropsychiatric disorders. Recent understanding of the pathophysiology of schizophrenia emphasizes the role of systemic components, including immune/inflammatory and metabolic processes, which are influenced by and interacting with the gut microbiome. Here we systematically review the current literature on the gut microbiome in schizophrenia-spectrum disorders and in their animal models. We found that the gut microbiome is altered in psychosis compared to healthy controls. Furthermore, we identified potential factors related to psychosis, which may contribute to the gut microbiome alterations. However, further research is needed to establish the disease-specificity and potential causal relationships between changes of the microbiome and disease pathophysiology. This can open up the possibility of. manipulating the gut microbiome for improved symptom control and for the development of novel therapeutic approaches in schizophrenia and related psychotic disorders. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract There is increasing evidence that the intestinal microbiota plays a mechanistic role in the etiology of non-alcoholic fatty liver disease (NAFLD). Animal and human studies have linked small molecule metabolites produced by commensal bacteria in the gut contribute to not only intestinal inflammation, but also to hepatic inflammation. These immunomodulatory metabolites are capable of engaging host cellular receptors, and may mediate the observed association between gut dysbiosis and NAFLD. This review focuses on the effects and potential mechanisms of three specific classes of metabolites that synthesized or modified by gut bacteria: short chain fatty acids, amino acid catabolites, and bile acids. In particular, we discuss their role as ligands for cell surface and nuclear receptors regulating metabolic and inflammatory pathways in the intestine and liver. Studies reveal that the metabolites can both agonize and antagonize their cognate receptors to reduce or exacerbate liver steatosis and inflammation, and that the effects are metabolite- and context-specific. Further studies are warranted to more comprehensively understand bacterial metabolite-mediated gut-liver in NAFLD. This understanding could help identify novel therapeutics and therapeutic targets to intervene in the disease through the gut microbiota. [ABSTRACT FROM AUTHOR]

Trimethylamine (TMA), trimethylamine- N -oxide (TMAO) and short chain fatty acids (SCFAs), as acetic, propionic, butyric and valeric acids are among the most important products of the gut microbiota (GM) metabolism. The present study is aimed at the determination of TMA, TMAO and SCFAs by a double step headspace-solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, allowing the simultaneous quantitation of both the acidic and basic metabolites in faecal samples. TMAO amount was evaluated after its reduction to TMA by using Fe(II)-EDTA complex as a reagent. Under the fully validated experimental conditions, adequate sensitivity (LOQ 0.011–0.23 µmol g −1 ), good accuracy (79 – 110%) and precision (CV% < 11%) were achieved for all the target analytes. The presented method is successfully applied to the quantitation of the considered gut metabolites in faecal samples from Italian healthy volunteers. [ABSTRACT FROM AUTHOR]

• Microbial metabolites can modulate macrophage activation and polarization, leading to the development and progression of cardiovascular diseases. • Short-chain fatty acids produced by the gut microbiome can promote anti-inflammatory macrophage phenotypes and reduce atherosclerosis development. • Trimethylamine N-oxide (TMAO) produced by the gut microbiome can promote pro-inflammatory macrophage phenotypes and contribute to atherosclerosis development. • Microbial metabolites can modulate the expression of genes involved in macrophage function, such as cholesterol metabolism and inflammation. • Targeting microbial metabolites through dietary interventions, probiotics, or pharmacological approaches may be a potential therapeutic strategy for treating and preventing cardiovascular diseases. The gut microbiome has emerged as a crucial player in developing and progressing cardiovascular diseases (CVDs). Recent studies have highlighted the role of microbial metabolites in modulating immune cell function and their impact on CVD. Macrophages, which have a significant function in the pathogenesis of CVD, are very vulnerable to the effects of microbial metabolites. Microbial metabolites, such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), have been linked to atherosclerosis and the regulation of immune functions. Butyrate has been demonstrated to reduce monocyte migration and inhibit monocyte attachment to injured endothelial cells, potentially contributing to the attenuation of the inflammatory response and the progression of atherosclerosis. On the other hand, TMAO, another compound generated by gut bacteria, has been linked to atherosclerosis due to its impact on lipid metabolism and the accumulation of cholesterol in macrophages. Indole-3-propionic acid, a tryptophan metabolite produced solely by microbes, has been found to promote the development of atherosclerosis by stimulating macrophage reverse cholesterol transport (RCT) and raising the expression of ABCA1. This review comprehensively discusses how various microbiota-produced metabolites affect macrophage polarization, inflammation, and foam cell formation in CVD. We also highlight the mechanisms underlying these effects and the potential therapeutic applications of targeting microbial metabolites in treating CVD. [ABSTRACT FROM AUTHOR]

The human body contains thousands of metabolites derived from mammalian cells, the microbiota, food, and medical drugs. Many bioactive metabolites act through the engagement of G-protein-coupled receptors (GPCRs); however, technological limitations constrain current explorations of metabolite-GPCR interactions. Here, we developed a highly multiplexed screening technology called PRESTO-Salsa that enables simultaneous assessment of nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate. Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRome and uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists. Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactions across 435 human microbiome strains from multiple body sites, revealing conserved patterns of cross-tissue GPCR engagement and activation of CD97/ADGRE5 by the Porphyromonas gingivalis protease gingipain K. These studies thus establish a highly multiplexed bioactivity screening technology and expose a diverse landscape of human, diet, drug, and microbiota metabolome-GPCRome interactions. [Display omitted] • PRESTO-Salsa enables multiplexed bioactivity screening of >300 GPCRs via NGS • Screening of human metabolome- and microbiota secretome-GPCRome interactions • Identification of cross-tissue human microbiome-GPCRome interactions • Porphyromonas gingivalis activates CD97/ADGRE5 via site-specific proteolytic cleavage PRESTO-Salsa is a multiplexed GPCR screening platform that enables the interrogation of GPCRome-wide bioactivities across diverse sample types. This platform was used to explore microbiota-induced GPCR activation and revealed the engagement of an immune cell-associated GPCR by a periodontal pathogen protease. [ABSTRACT FROM AUTHOR]

• A new strategy is proposed for studying the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients. • The new strategy explains why TCM ingredients with low bioavailability could have high activity in vivo. • The active forms of PD with antitussive and expectorant effects are its intestinal microbiota metabolites. The intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue. A new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed. Platycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking. Results showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-β- d -glucopyranosyl platycodigenin, 3-O-β- d -glucopyranosyl isoplatycodigenin, 7‑hydroxyl-3-O-β- d -glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism. The proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity. [Display omitted] [ABSTRACT FROM AUTHOR]

Consumption of organic products is increasing yearly due to perceived health-promoting qualities. Several studies have shown higher amounts of phytochemicals such as polyphenols and carotenoids in foods produced by this type of agriculture than in conventional foods, but whether this increase has an impact on humans still needs to be assessed. A randomized, controlled and crossover study was carried out in nineteen healthy subjects aged 18−40 years, who all followed an organic and conventional healthy diet, both for a 4-week period. Analysis of biological samples revealed a significant increase on the excretion of 4-hydroxybenzoic acid (4-HBA), a phenolic metabolite with biological activity, after the organic intervention. However, no changes were observed in the other variables analyzed.

Innate immunity of the mucosal surfaces provides the first-line defense from invading pathogens and pollutants conferring protection from the external environment. Innate immune system of the airway epithelium consists of several components including the mucus layer, mucociliary clearance of beating cilia, production of host defense peptides, epithelial barrier integrity provided by tight and adherens junctions, pathogen recognition receptors, receptors for chemokines and cytokines, production of reactive oxygen species, and autophagy. Therefore, multiple components interplay with each other for efficient protection from pathogens that still can subvert host innate immune defenses. Hence, the modulation of innate immune responses with different inducers to boost host endogenous front-line defenses in the lung epithelium to fend off pathogens and to enhance epithelial innate immune responses in the immunocompromised individuals is of interest for host-directed therapy. Herein, we reviewed possibilities of modulation innate immune responses in the airway epithelium for host-directed therapy presenting an alternative approach to standard antibiotics., Competing Interests: GHG is a founder and stockholder in Akthelia Pharmaceuticals that holds a patent on APD compounds Patent No. US 9,957,226 B2. The remaining author declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Myszor and Gudmundsson.)

The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MSn. The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism. [ABSTRACT FROM AUTHOR]

Several disorders have been linked to modifications in the gut microbial imbalance, intestinal epithelium, and host immune system. In this regard, microbiota derived short-chain fatty acids (SCFAs) play a key function in the regulation of histone deacetylases (HDACs), which affect modulation of immunity and regulation of inflammatory responses in the intestine and other organs. Studies examining the metabolites produced by polymicrobial bacterial vaginosis (BV) states and Lactobacillus -dominated microbiota have noted a dramatic reduction of lactic acid and a shift toward SCFA synthesis. Along with higher levels of SCFAs, acetate is typically the main metabolite in the cervicovaginal fluid of women with symptomatic bacterial vaginosis. The fact that SCFAs made by the vaginal microbiota have been shown to exhibit antibacterial and immune-modulating properties suggests that they may have promise as indicators of disease and/or disease susceptibility. In this review, we overview and summarize the current findings on the detrimental or protective roles of microbiota metabolites especially SCFAs in the health and disease of the female reproductive system., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Environmental (restraint stress) and dietary (high fructose) factors are key triggers for flares of inflammatory bowel disease; however, the mechanisms involved in this phenomenon are not fully elucidated. This study aimed to investigate the mechanisms by which restraint stress and high fructose damage the intestinal mucosal immune barrier. The feces of C57BL/6J mice were subjected to 16S rRNA and untargeted metabolome sequencing, and the intestinal histological structure was analyzed by immunohistochemistry and immunofluorescence staining. The mRNA and protein levels of the intestinal protein were analyzed by reverse transcription-PCR (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). The metabolites of the microbiota were tested in vitro , and Akkermansia muciniphila was used for colonization in vivo . Dietary fructose exacerbated the development of restraint stress, with an extensive change in the composition of the gut microbiota and microbial metabolites. The disturbance of the microbiota composition led to an increase in the abundance of histamine and a decrease in the abundance of taurine, which inhibited the expression of tight junction and MUC2 proteins, destroyed the function of NLRP6, and reduced intestinal autophagy level; this in turn disrupted the function of colonic goblet cells to secrete mucus, leading to defects in the intestinal mucosal barrier, which ultimately codrives colon autoinflammation. However, A. muciniphila supplementation counteracted damage to the intestinal mucosal barrier by high fructose and restraint stress. Therefore, the gut microbiota and microbiota metabolites play an important role in maintaining microenvironment homeostasis of the intestinal mucosal barrier. IMPORTANCE A high-fructose diet aggravated restraint stress-induced changes in the composition of the intestinal microbiome, in which the abundance of A. muciniphila was significantly increased. The high-fructose diet exacerbated restraint stress-induced the changes in the composition of the microbial metabolites, with taurine abundance being downregulated and histamine abundance upregulated. High fructose and restraint stress induced colonic mucosal immune barrier damage, possibly due to changes in the abundance of the microbial metabolites taurine and histamine. Colonization with A. muciniphila stimulated the expression of the NLRP6 inflammasome and activated autophagy in goblet cells, thereby producing more new mucins, which could protect the intestinal mucosal barrier.

The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MSn. The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism.

Abstract: Grape seed phenolic extract (GSE) is predicted to have health benefits, even though its bioavailability, including digestibility, permeability and ultimate metabolism, are still poorly understood. In vitro gastric and pancreatic digestion and in vitro ileal and faecal fermentation were combined with Caco-2 cell permeability studies for GSE samples. Qualitatively, there was no change in type/number of GSE compounds following gastric and pancreatic digestion and LC–MS analysis. However, the monomers were significantly (P <0.05) increased after gastric digestion, along with a significant (P <0.05) decrease in polymers. In addition, all forms of phenolic compounds decreased following pancreatic digestion. However, none of the original GSE phenolic compounds passed the Caco-2 cell monolayer, since all were recovered in the apical compartment. In contrast, the two intestinal microbiota metabolites with deprotonated molecular weights of [M–H]-165/121 and 193/175, that were found both in the ileal and faecal fermented samples, passed the Caco-2 cell monolayer. [Copyright &y& Elsevier]

A growing body of documents shows microbiota produce metabolites such as short-chain fatty acids (SCFAs) as crucial executors of diet-based microbial influence the host and bacterial pathogens. The production of SCFAs depends on the metabolic activity of intestinal microflora and is also affected by dietary changes. SCFAs play important roles in maintaining colonic health as an energy source, as a regulator of gene expression and cell differentiation, and as an anti-inflammatory agent. Additionally, the regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. This review will present data supporting the diverse functional roles of microbiota-derived butyrate, propionate, and acetate on host cellular activities such as immune modulation, energy metabolism, nervous system, inflammation, cellular differentiation, and anti-tumor effects, among others. On the other hand, we will discuss and summarize data about the role of these SCFAs on the virulence factor of bacterial pathogens. In this regard, receptors and signaling routes for SCFAs metabolites in host and pathogens will be introduced. • One way microbiota influences health and disease is harmful metabolites mediated to prompt disorders or beneficial metabolites that prevent disorder. • Microbiota SCFAs are organic acids including acetate, propionate, and butyrate. • SCFAs play important roles in maintaining colonic host health as energy source, regulator of gene expression, and anti-inflammatory agents. • Besides, SCFAs have been shown to influence bacterial gene expression.. [ABSTRACT FROM AUTHOR]