The Rationale for Sulforaphane Favourably Influencing Gut Homeostasis and Gut-Organ Dysfunction: A Clinician's Hypothesis.

Given the increasing scientific, clinical and consumer interest in highly prevalent functional gastrointestinal disorders, appropriate therapeutic strategies are needed to address the many aspects of digestive dysfunction. Accumulating evidence for the crucifer-derived bioactive molecule sulforaphane in upstream cellular defence mechanisms highlights its potential as a therapeutic candidate in targeting functional gastrointestinal conditions, as well as systemic disorders. This article catalogues the evolution of and rationale for a hypothesis that multifunctional sulforaphane can be utilised as the initial step in restoring the ecology of the gut ecosystem; it can do this primarily by targeting the functions of intestinal epithelial cells. A growing body of work has identified the colonocyte as the driver of dysbiosis, such that targeting gut epithelial function could provide an alternative to targeting the microbes themselves for the remediation of microbial dysbiosis. The hypothesis discussed herein has evolved over several years and is supported by case studies showing the application of sulforaphane in gastrointestinal disorders, related food intolerance, and several systemic conditions. To the best of our knowledge, this is the first time the effects of sulforaphane have been reported in a clinical environment, with several of its key properties within the gut ecosystem appearing to be related to its nutrigenomic effects on gene expression.

The Gut-Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology.

The intestine is considered to be a vital digestive organ to absorb nutrients and is the largest immune organ, while numerous microorganisms coexist with the host. It is well known that the complex interactions between the gut microbiota and the host's immune system inevitably affect the function of other organs, creating an "axis" between them. During the past few years, a new technique based mainly on microfluidics and cell biology has been developed to emulate the structure, function, and microenvironment of the human gut, called the "gut-on-chip". This microfluidic chip provides insight into key aspects of gut function in health and disease, such as the gut-brain axis, gut-liver axis, gut-kidney axis, and gut-lung axis. In this review, we first describe the basic theory of the gut axis and the various composition and parameter monitoring of the gut microarray systems, as well as summarize the development and emerging advances in the gut-organ-on-chip, with a focus on the host-gut flora and nutrient metabolism, and highlight their role in pathophysiological studies. In addition, this paper discusses the challenges and prospects for the current development and further use of the gut-organ-on-chip platform.

The central and biodynamic role of gut microbiota in critically ill patients.

Gut microbiota plays an essential role in health and disease. It is constantly evolving and in permanent communication with its host. The gut microbiota is increasingly seen as an organ, and its failure, reflected by dysbiosis, is seen as an organ failure associated with poor outcomes. Critically ill patients may have an altered gut microbiota, namely dysbiosis, with a severe reduction in "health-promoting" commensal intestinal bacteria (such as Firmicutes or Bacteroidetes) and an increase in potentially pathogenic bacteria (e.g. Proteobacteria). Many factors that occur in critically ill patients favour dysbiosis, such as medications or changes in nutrition patterns. Dysbiosis leads to several important effects, including changes in gut integrity and in the production of metabolites such as short-chain fatty acids and trimethylamine N-oxide. There is increasing evidence that gut microbiota and its alteration interact with other organs, highlighting the concept of the gut-organ axis. Thus, dysbiosis will affect other organs and could have an impact on the progression of critical diseases. Current knowledge is only a small part of what remains to be discovered. The precise role and contribution of the gut microbiota and its interactions with various organs is an intense and challenging research area that offers exciting opportunities for disease prevention, management and therapy, particularly in critical care where multi-organ failure is often the focus. This narrative review provides an overview of the normal composition of the gut microbiota, its functions, the mechanisms leading to dysbiosis, its consequences in an intensive care setting, and highlights the concept of the gut-organ axis.

The impact of gut microbiota on morbidities in preterm infants.

The gut microbiota undergoes substantial development from birth, and its development in the initial years of life has a potentially lifelong effect on the health of the individual. However, various factors can disrupt the development of the gut microbiota, leading to a condition known as dysbiosis, particularly in preterm infants. Current studies involving adults have suggested that the gut microbiota not only influences the gut but also has multidimensional effects on remote organs; these pathways are often referred to as the gut-organ axis. Imbalance of the gut microbiota may lead to the development of multiple diseases. Recent studies have revealed that gut dysbiosis in preterm infants may cause several acute morbidities-such as necrotizing enterocolitis, late-onset sepsis, bronchopulmonary dysplasia, and retinopathy of prematurity-and it may also influence long-term outcomes including neurodevelopment and somatic growth. This review mainly presents the existing evidence regarding the relationships between the gut microbiota and these morbidities in preterm infants and explores the role of the gut-organ axis in these morbidities. This paper thus offers insights into the future perspectives on microbiota interventions for promoting the health of preterm infants.

Friend or Foe: Exploring the Relationship between the Gut Microbiota and the Pathogenesis and Treatment of Digestive Cancers.

Digestive cancers are among the leading causes of cancer death in the world. However, the mechanisms of cancer development and progression are not fully understood. Accumulating evidence in recent years pointing to the bidirectional interactions between gut dysbiosis and the development of a specific type of gastrointestinal cancer is shedding light on the importance of this "unseen organ"-the microbiota. This review focuses on the local role of the gut microbiota imbalance in different digestive tract organs and annexes related to the carcinogenic mechanisms. Microbiota modulation, either by probiotic administration or by dietary changes, plays an important role in the future therapies of various digestive cancers.

Global research trends on the links between gut microbiota and radiotherapy: a bibliometric analysis (2004-2023).

Background: There is a crosstalk between gut microbiota and radiotherapy. The aim of this study is to use bibliometric analysis to explore the research status and development trends of research on gut microbiota and radiotherapy. Methods: A literature search regarding publications on gut microbiota and radiotherapy from 2004 to 2023 was retrieved. CiteSpace and VOSviewer were used to conduct the bibliometric analysis. The growth rate of publications, leading countries and institutions, preferred journals, top authors and co-cited authors, top co-cited references, keywords and citation were analyzed in this study. Results: A total of 2821 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2017. The USA and China had the most publications and made great contributions to this field. The Chinese Academy of Sciences stood out as the institution with the highest number of publications, followed by the Chinese Academy of Medical Sciences & Peking Union Medical College. The most influential authors were Fan Saijun and Li Yuan. PLoS One had the most publications and the most total citations. Highly cited papers and high-frequency keywords illustrated the current status and trends. Furthermore, analysis of keyword with burst revealed that immunotherapy, acid, intestinal barrier, therapy, immunotherapy, fecal microbiota transplantation, etc, are at the forefront of research in this area. Conclusion: This study provides an overview of research on gut microbiota and radiotherapy, highlighting influential contributors, impactful publications, and emerging trends. Our finding suggests avenues for further exploration to improve clinical outcomes.

Impacts of PFOS, PFOA and their alternatives on the gut, intestinal barriers and gut-organ axis.

With the restricted use of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), a number of alternatives to PFOS and PFOA have attracted great interest. Most of the alternatives are still characterized by persistence, bioaccumulation, and a variety of toxicity. Due to the production and use of these substances, they can be detected in the atmosphere, soil and water body. They affect human health through several exposure pathways and especially enter the gut by drinking water and eating food, which results in gut toxicity. In this review, we summarized the effects of PFOS, PFOA and 9 alternatives on pathological changes in the gut, the disruption of physical, chemical, biological and immune barriers of the intestine, and the gut-organ axis. This review provides a valuable understanding of the gut toxicity of PFOS, PFOA and their alternatives as well as the human health risks of emerging contaminants.

New insights into the intestinal barrier through "gut-organ" axes and a glimpse of the microgravity's effects on intestinal barrier.

Gut serves as the largest interface between humans and the environment, playing a crucial role in nutrient absorption and protection against harmful substances. The intestinal barrier acts as the initial defense mechanism against non-specific infections, with its integrity directly impacting the homeostasis and health of the human body. The primary factor attributed to the impairment of the intestinal barrier in previous studies has always centered on the gastrointestinal tract itself. In recent years, the concept of the "gut-organ" axis has gained significant popularity, revealing a profound interconnection between the gut and other organs. It speculates that disruption of these axes plays a crucial role in the pathogenesis and progression of intestinal barrier damage. The evaluation of intestinal barrier function and detection of enterogenic endotoxins can serve as "detecting agents" for identifying early functional alterations in the heart, kidney, and liver, thereby facilitating timely intervention in the disorders. Simultaneously, consolidating intestinal barrier integrity may also present a potential therapeutic approach to attenuate damage in other organs. Studies have demonstrated that diverse signaling pathways and their corresponding key molecules are extensively involved in the pathophysiological regulation of the intestinal barrier. Aberrant activation of these signaling pathways and dysregulated expression of key molecules play a pivotal role in the process of intestinal barrier impairment. Microgravity, being the predominant characteristic of space, can potentially exert a significant influence on diverse intestinal barriers. We will discuss the interaction between the "gut-organ" axes and intestinal barrier damage, further elucidate the signaling pathways underlying intestinal barrier damage, and summarize alterations in various components of the intestinal barrier under microgravity. This review aims to offer a novel perspective for comprehending the etiology and molecular mechanisms of intestinal barrier injury as well as the prevention and management of intestinal barrier injury under microgravity environment.

Akkermansia muciniphila improve cognitive dysfunction by regulating BDNF and serotonin pathway in gut-liver-brain axis.

BACKRGROUND: Akkermansia muciniphila, a next-generation probiotic, is known as a cornerstone regulating the gut-organ axis in various diseases, but the underlying mechanism remains poorly understood. Here, we revealed the neuronal and antifibrotic effects of A. muciniphila on the gut-liver-brain axis in liver injury. RESULTS: To investigate neurologic dysfunction and characteristic gut microbiotas, we performed a cirrhosis cohort (154 patients with or without hepatic encephalopathy) and a community cognition cohort (80 participants in one region for three years) and validated the existence of cognitive impairment in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic injury mouse model. The effects of the candidate strain on cognition were evaluated in animal models of liver injury. The expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors was accessed in patients with fibrosis (100 patients) according to the fibrosis grade and hepatic venous pressure gradient. The proportion of A. muciniphila decreased in populations with hepatic encephalopathy and cognitive dysfunction. Tissue staining techniques confirmed gut-liver-brain damage in liver injury, with drastic expression of BDNF and serotonin in the gut and brain. The administration of A. muciniphila significantly reduced tissue damage and improved cognitive dysfunction and the expression of BDNF and serotonin. Isolated vagus nerve staining showed a recovery of serotonin expression without affecting the dopamine pathway. Conversely, in liver tissue, the inhibition of injury through the suppression of serotonin receptor (5-hydroxytryptamine 2A and 2B) expression was confirmed. The severity of liver injury was correlated with the abundance of serotonin, BDNF, and A. muciniphila. CONCLUSIONS: A. muciniphila, a next-generation probiotic, is a therapeutic candidate for alleviating the symptoms of liver fibrosis and cognitive impairment.

Double-side role of short chain fatty acids on host health via the gut-organ axes.

Short chain fatty acids (SCFA) exist in dietary foods and are produced by the fermentation of gut microbiota, and are considered an important element for regulating host health. Through blood circulation, SCFA produced in the gut and obtained from foods have an impact on the intestinal health as well as vital organs of the host. It has been recognized that the gut is the "vital organ" in the host. As the gut microbial metabolites, SCFA could create an "axis" connecting the gut and to other organs. Therefore, the "gut-organ axes" have become a focus of research in recent years to analyze organism health. In this review, we summarized the sources, absorption properties, and the function of SCFA in both gut and other peripheral tissues (brain, kidney, liver, lung, bone and cardiovascular) in the way of "gut-organ axes". Short chain fatty acids exert both beneficial and pathological role in gut and other organs in various ways, in which the beneficial effects are more pronounced. In addition, the beneficial effects are reflected in both preventive and therapeutic effects. More importantly, the mechanisms behinds the gut and other tissues provided insight into the function of SCFA, assisting in the development of novel preventive and therapeutic strategies for maintaining the host health.

Exploring the gut microbiome: probiotics, prebiotics, synbiotics, and postbiotics as key players in human health and disease improvement.

The human gut microbiome accompanies us from birth, and it is developed and matured by diet, lifestyle, and environmental factors. During aging, the bacterial composition evolves in reciprocal communication with the host's physiological properties. Many diseases are closely related to the gut microbiome, which means the modulation of the gut microbiome can promote the disease targeting remote organs. This review explores the intricate interaction between the gut microbiome and other organs, and their improvement from disease by prebiotics, probiotics, synbiotics, and postbiotics. Each section of the review is supported by clinical trials that substantiate the benefits of modulation the gut microbiome through dietary intervention for improving primary health outcomes across various axes with the gut. In conclusion, the review underscores the significant potential of targeting the gut microbiome for therapeutic and preventative interventions in a wide range of diseases, calling for further research to fully unlock the microbiome's capabilities in enhancing human health.

The Gut-Organ Axis within the Human Body: Gut Dysbiosis and the Role of Prebiotics.

The human gut microbiota (GM) is a complex microbial ecosystem that colonises the gastrointestinal tract (GIT) and is comprised of bacteria, viruses, fungi, and protozoa. The GM has a symbiotic relationship with its host that is fundamental for body homeostasis. The GM is not limited to the scope of the GIT, but there are bidirectional interactions between the GM and other organs, highlighting the concept of the "gut-organ axis". Any deviation from the normal composition of the GM, termed "microbial dysbiosis", is implicated in the pathogenesis of various diseases. Only a few studies have demonstrated a relationship between GM modifications and disease phenotypes, and it is still unknown whether an altered GM contributes to a disease or simply reflects its status. Restoration of the GM with probiotics and prebiotics has been postulated, but evidence for the effects of prebiotics is limited. Prebiotics are substrates that are "selectively utilized by host microorganisms, conferring a health benefit". This study highlights the bidirectional relationship between the gut and vital human organs and demonstrates the relationship between GM dysbiosis and the emergence of certain representative diseases. Finally, this article focuses on the potential of prebiotics as a target therapy to manipulate the GM and presents the gaps in the literature and research.

Multiomics implicate gut microbiota in low cypermethrin (CP) exposure induced multiorgan toxicological effects in pubertal male rats.

Cypermethrin (CP), widely used as a broad-spectrum pesticide, has raised concerns over its frequent presence in the environment and potential health risks. The present study focused on incorporating the gut-organ axis theory to reinterpret the toxicological effects and mechanisms following CP exposure at environmentally relevant concentrations (0.1 mg/kg/d and 0.5 mg/kg/d) in pubertal male rats. The results showed alterations in histopathological and organosomatic indices in the liver, brain, and epididymis. Through multiomics network analysis, it was found that Lachnospiraceae and Ruminococcaceae may contribute to the alteration in serum L-carnitine and trigonelline, leading to hepatic lipid accumulation following CP exposure. Additionally, Ruminococcaceae, Lachnospiraceae, and Porphyromonadaceae were associated with CP-induced glutamatergic hypofunction and overproduction of TNF-α, potentially contributing to the brain neurotoxicity. Overall, the study provides important insights into the potential mechanisms underlying CP-induced toxicity and highlights the need for continued research to fully understand the implications for CP-induced health risks. The incorporation of the gut-organ axis theory in the study provides a promising avenue for future research into the potential interactions between gut microbiota and organ toxicity, and the potential for targeted interventions to mitigate the adverse effects of environmental toxins.

Extensive Summary of the Important Roles of Indole Propionic Acid, a Gut Microbial Metabolite in Host Health and Disease.

Increasing evidence suggests that metabolites produced by the gut microbiota play a crucial role in host-microbe interactions. Dietary tryptophan ingested by the host enters the gut, where indole-like metabolites such as indole propionic acid (IPA) are produced under deamination by commensal bacteria. Here, we summarize the IPA-producing bacteria, dietary patterns on IPA content, and functional roles of IPA in various diseases. IPA can not only stimulate the expression of tight junction (TJ) proteins to enhance gut barrier function and inhibit the penetration of toxic factors, but also modulate the immune system to exert anti-inflammatory and antioxidant effects to synergistically regulate body physiology. Moreover, IPA can act on target organs through blood circulation to form the gut-organ axis, which helps maintain systemic homeostasis. IPA shows great potential for the diagnosis and treatment of various clinical diseases, such as NAFLD, Alzheimer's disease, and breast cancer. However, the therapeutic effect of IPA depends on dose, target organ, or time. In future studies, further work should be performed to explore the effects and mechanisms of IPA on host health and disease to further improve the existing treatment program.

Gut Microbiota Dynamics in Relation to Long-COVID-19 Syndrome: Role of Probiotics to Combat Psychiatric Complications.

Increasing numbers of patients who recover from COVID-19 report lasting symptoms, such as fatigue, muscle weakness, dementia, and insomnia, known collectively as post-acute COVID syndrome or long COVID. These lasting symptoms have been examined in different studies and found to influence multiple organs, sometimes resulting in life-threating conditions. In this review, these symptoms are discussed in connection to the COVID-19 and long-COVID-19 immune changes, highlighting oral and psychiatric health, as this work focuses on the gut microbiota's link to long-COVID-19 manifestations in the liver, heart, kidney, brain, and spleen. A model of this is presented to show the biological and clinical implications of gut microbiota in SARS-CoV-2 infection and how they could possibly affect the therapeutic aspects of the disease. Probiotics can support the body's systems in fighting viral infections. This review focuses on current knowledge about the use of probiotics as adjuvant therapies for COVID-19 patients that might help to prevent long-COVID-19 complications.

New Insights into the Relationship between Gut Microbiota and Radiotherapy for Cancer.

Cancer is the second most common cause of death among humans in the world, and the threat that it presents to human health is becoming more and more serious. The mechanisms of cancer development have not yet been fully elucidated, and new therapies are changing with each passing day. Evidence from the literature has validated the finding that the composition and modification of gut microbiota play an important role in the development of many different types of cancer. The results also demonstrate that there is a bidirectional interaction between the gut microbiota and radiotherapy treatments for cancer. In a nutshell, the modifications of the gut microbiota caused by radiotherapy have an effect on tumor radiosensitivity and, as a result, affect the efficacy of radiotherapy and show a certain radiation toxicity, which leads to numerous side effects. What is of new research significance is that the "gut-organ axis" formed by the gut microbiota may be one of the most interesting potential mechanisms, although the relevant research is still very limited. In this review, we combine new insights into the relationship between the gut microbiota, cancer, and radiotherapy. Based on our current comprehensive understanding of this relationship, we give an overview of the new cancer treatments based on the gut microbiota.

Molecular Mechanism of Polysaccharides Extracted from Chinese Medicine Targeting Gut Microbiota for Promoting Health.

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity, type 2 diabetes mellitus, heart failure, and non-alcoholic fatty liver disease. Polysaccharides extracted from Chinese medicine (CM) can not only alleviate pathological status but also promote health by anti-inflammatory, regulating immunity, lowering blood glucose and lipids, anti-cancer, and anti-oxidation. The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment. In addition, they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota. This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics for promoting health.

Butyrate producers, "The Sentinel of Gut": Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics.

Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-ß signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and ß-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.

Short chain fatty acid: a messenger of gut-organ axis for disease regulation / 药学学报

Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.