Manipulation Of Gut Microbiota Research Articles

Protective effect of Acanthus ilicifolius extracts against acute alcoholic liver injury via suppressing TLR4/NF-κB signal pathway and modulating intestinal microbiota in mice

Excessive alcohol consumption is leading to increased rates of liver injury and disease. A new research strategy focuses on manipulating gut microbiota to lessen alcohol-induced harm. This study examined the hepatoprotective effects of extracts from Acanthus ilicifolius (EAI) on acute alcoholic liver injury by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal microbiota in mice. The results showed that EAI dose-dependently reduced alcohol-induced elevations of AST, ALT, and ALP levels. EAI showed significant inhibitory effects on the expressions of TLR4, NF-κB, and pNF-κB proteins. Furthermore, EAI caused a notable reduction in hepatic levels of IL-1β, IL-6, and TNF-α. Supplementation with EAI could ameliorate alcohol-induced dysbiosis of intestinal bacteria. The levels of ALT, AST, and ALP levels were negatively correlated with Ligilactobacillus, Lactobacillus, and Alistipes, but positively correlated with Helicobacter and Bacteroides. Overall, EAI alleviated alcoholic liver injury in mice by inhibiting the TLR4/NF-κB signalling pathway and modulating intestinal bacteria.

What Happens in the Gut during the Formation of Neonatal Jaundice-Underhand Manipulation of Gut Microbiota?

Jaundice is a symptom of high blood bilirubin levels affecting about 80% of neonates. In neonates fed with breast milk, jaundice is particularly prevalent and severe, which is likely multifactorial. With the development of genomics and metagenomics, a deeper understanding of the neonatal gut microbiota has been achieved. We find there are accumulating evidence to indicate the importance of the gut microbiota in the mechanism of jaundice. In this paper, we present new comprehensive insight into the relationship between the microbiota and jaundice. In the new perspective, the gut is a crucial crossroad of bilirubin excretion, and bacteria colonizing the gut could play different roles in the excretion of bilirubin, including Escherichia coli as the main traffic jam causers, some Clostridium and Bacteroides strains as the traffic police, and most probiotic Bifidobacterium and Lactobacillus strains as bystanders with no effect or only a secondary indirect effect on the metabolism of bilirubin. This insight could explain why breast milk jaundice causes a longer duration of blood bilirubin and why most probiotics have limited effects on neonatal jaundice. With the encouragement of breastmilk feeding, our perspective could guide the development of new therapy methods to prevent this side effect of breastfeeding.

Attitudes and Practices of Dietitians Regarding Gut Microbiota in Health-An Online Survey of the European Federation of the Associations of Dietitians (EFAD).

Explorations of the current attitudes and practices of dietitians regarding the gut microbiota in health are scarce. In this online survey, we assessed the attitudes and practices of dietitians across Europe concerning gut microbiome parameters and the manipulation of the gut microbiota. Pre-graduate dietetic students and other professionals were also invited to participate. The potential interest and preferences of the participants for future educational initiatives about the gut microbiota and the educational resources used were further explored. A total of 179 full responses were recorded (dietitians, n = 155), mainly from the southern and western regions. Most of the participants (>90.0%) believed that probiotics and prebiotics have a place in nutritional practice and that fermented foods with live microbial cultures should be a part of food-based dietary guidelines. A strong belief in the beneficial roles of probiotics and prebiotics in some health situations was also reported among the participants. Most of the dietitians recognised the importance of gut microbiota manipulation and advised the use of probiotics and prebiotics in dietary practice, and they felt quite confident applying the relevant information in their daily practice. Nevertheless, misconceptions were identified, and further guideline-oriented education is necessary. The interest in future e-learning initiatives was high among the participants, and the sources of knowledge, educative formats, and potential areas for further educational efforts were indicated.

Enhancing gut microbiota and microbial function with inulin supplementation in children with obesity.

Gut dysbiosis that resulted from the alteration between host-microbe interaction might worsen obesity-induced systemic inflammation. Gut microbiota manipulation by supplementation of prebiotic inulin may reverse metabolic abnormalities and improve obesity. This study aimed to determine whether inulin supplementation improved intestinal microbiota and microbial functional pathways in children with obesity. Children with obesity whose BMI above median + 2SDs were recruited to a randomized, double-blinded placebo-controlled study. The participants aged 7-15 years were assigned to inulin supplement extracted from Thai Jerusalem artichoke (intervention), maltodextrin (placebo), and dietary fiber advice groups. All participants received similar monthly conventional advice and follow-up for 6 months. Fecal samples were collected for gut microbiome analysis using 16S rRNA sequencing. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was performed to infer microbial functional pathways. One hundred and forty-three children with available taxonomic and functional pathway abundance profiles were evaluated. A significant increase in alpha-diversity was observed in the inulin group. Inulin supplementation substantially enhanced Bifidobacterium, Blautia, Megasphaera, and several butyrate-producing bacteria, including Agathobacter, Eubacterium coprostanoligenes, and Subdoligranulum, compared to the other groups. The inulin group showed a significant difference in functional pathways of proteasome and riboflavin metabolism. These changes correlated with clinical and metabolic outcomes exclusively in the inulin group. Inulin supplementation significantly promoted gut bacterial diversity and improved gut microbiota dysbiosis in children with obesity. The modulation of functional pathways by inulin suggests its potential to establish beneficial interactions between the gut microbiota and host physiology. Inulin supplementation could be a strategic treatment to restore the balance of intestinal microbiota and regulate their functions in childhood obesity.

Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids

PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3β in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.

Human Gut Microbiota in Cardiovascular Disease.

The gut ecosystem, termed microbiota, is composed of bacteria, archaea, viruses, protozoa, and fungi and is estimated to outnumber human cells. Microbiota can affect the host by multiple mechanisms, including the synthesis of metabolites and toxins, modulating inflammation and interaction with other organisms. Advances in understanding commensal organisms' effect on human conditions have also elucidated the importance of this community for cardiovascular disease (CVD). This effect is driven by both direct CV effects and conditions known to increase CV risk, such as obesity, diabetes mellitus (DM), hypertension, and renal and liver diseases. Cardioactive metabolites, such as trimethylamine N -oxide (TMAO), short-chain fatty acids (SCFA), lipopolysaccharides, bile acids, and uremic toxins, can affect atherosclerosis, platelet activation, and inflammation, resulting in increased CV incidence. Interestingly, this interaction is bidirectional with microbiota affected by multiple host conditions including diet, bile acid secretion, and multiple diseases affecting the gut barrier. This interdependence makes manipulating microbiota an attractive option to reduce CV risk. Indeed, evolving data suggest that the benefits observed from low red meat and Mediterranean diet consumption can be explained, at least partially, by the changes that these diets may have on the gut microbiota. In this article, we depict the current epidemiological and mechanistic understanding of the role of microbiota and CVD. Finally, we discuss the potential therapeutic approaches aimed at manipulating gut microbiota to improve CV outcomes. © 2024 American Physiological Society. Compr Physiol 14:5449-5490, 2024.

Inulin supplementation exhibits increased muscle mass via gut-muscle axis in children with obesity: double evidence from clinical and in vitro studies.

Gut microbiota manipulation may reverse metabolic abnormalities in obesity. Our previous studies demonstrated that inulin supplementation significantly promoted Bifidobacterium and fat-free mass in obese children. We aimed to study gut-muscle axis from inulin supplementation in these children. In clinical phase, the plasma samples from 46 participants aged 7-15years, were analyzed for muscle biomarkers before and after 6-month inulin supplementation. In parallel, the plausible mechanism of muscle production via gut-muscle axis was examined using macrophage cell line. Bifidobacterium was cultured in semi-refined medium with inulin used in the clinical phase. Cell-free supernatant was collected and used in lipopolysaccharide (LPS)-induced macrophage cell line to determine inflammatory and anti-inflammatory gene expression. In clinical phase, IL-15 and creatinine/cystatin C ratio significantly increased from baseline to the 6th month. In vitro study showed that metabolites derived from Bifidobacterium capable of utilizing inulin contained the abundance of SCFAs. In the presence of LPS, treatment from Bifidobacterium + inulin downregulated TNF-α, IL-6, IL-1β, and iNOS, but upregulated FIZZ-1 and TGF-β expression. Inulin supplementation promoted the muscle biomarkers in agreement with fat-free mass gain, elucidating by Bifidobacterium metabolites derived from inulin digestion showed in vitro anti-inflammatory activity and decreased systemic pro-inflammation, thus promoting muscle production via gut-muscle axis response.Clinical Trial Registry number: NCT03968003.

Gut-lung axis and asthma: A historical review on mechanism and future perspective.

Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed. The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

Gum odina prebiotic induced gut modulation for the treatment of colon cancer on Swiss albino mice: By using capecitabine loaded biopolymeric microsphere

A complex illness with a current global hazard, colon cancer has many different manifestations. The efficacy of colon cancer therapy can be affected by the bacteria in the digestive tract. It is hypothesised that novel prebiotics like Gum Odina is emerging as preventative therapy to fight chronic gut illnesses by gut microbiota modulatory therapy when compared to traditional intervention. The first-line chemotherapy drug for colon cancer, capecitabine, lacks a carrier that can extend its half-life. Here, we use the prebiotic gum odina – sodium alginate conjugate to create a capecitabine loaded biopolymeric microspheres, which were previously established as excellent tools for colon cancer therapy. The accelerated stability study exhibited that the alteration in physicochemical properties was found to be negligible. When administered orally to mice with colon cancer, capecitabine raises intra-tumoral capecitabine concentration and slows drug elimination in the blood. Optimized formulation improves anti-tumor immunity over free capecitabine and decrease the tumor volume from 8 ± 6.59 mm3 to 5.21 ± 2.79 mm3. This prebiotics based microsphere combine's gut microbiota manipulation with chemotherapy to offer a potentially effective colon cancer treatment.

Exploring the Potential of Humoral Immune Response to Commensal Bifidobacterium as a Biomarker for Human Health, including Both Malignant and Non-Malignant Diseases: A Perspective on Detection Strategies and Future Directions.

In this comprehensive review, we explore the pivotal role of commensal Bifidobacterium (c-BIF) as potent non-self-antigens through antigenic mimicry, along with exploring the potential of humoral immune responses for both malignant and non-malignant disease. c-BIF, a predominant component of the human gut microbiome encompassing around 90% of the human genome, has emerged as a pivotal player in human biology. Over recent decades, there has been extensive research elucidating the intricate connections between c-BIF and various facets of human health, with particular emphasis on their groundbreaking impact on anti-cancer effects and the management of non-malignant diseases. The multifaceted role of c-BIF is explored, ranging from enhancing anti-tumor immunity to improving the efficacy of anti-cancer and anti-infectious disease strategies, and serving as predictive biomarkers for various diseases. Recent studies highlight not only c-BIF's promotion of anti-tumor immunity but also their role in enhancing the efficacy of immune checkpoint inhibitors. The review emphasizes the promising avenue of manipulating the gut microbiota, particularly c-BIF, for modulating cancer immunotherapy with targeted effects on tumor cells while minimizing harm to normal tissue. In the context of infectious and inflammatory diseases, the crucial role of c-BIFs in the management of COVID-19 symptoms is examined, emphasizing their impact on the severity of and immune response to COVID-19. Furthermore, c-BIF exhibits preventive and therapeutic effects on Human Papillomaviruses (HPV) and shows promise in improving inflammatory bowel diseases. The potential application of c-BIF as a biomarker for immunotherapy is explored, with a specific emphasis on its predictive and prognostic value in cancer. Suggestions are made regarding the use of humoral immune responses to cytotoxic T lymphocyte (CTL) epitope peptides that share motifs with c-BIF, proposing them as potential markers for predicting overall survival in diverse cancer patients. In conclusion, c-BIF emerges as a crucial and multifaceted determinant of human health, across anti-tumor immunity to infectious and inflammatory disease management. The manipulation of c-BIF and gut microbiota presents a promising avenue for advancing therapeutic strategies, particularly in the realm of cancer immunotherapy. Additionally, this review highlights the significance of c-BIF as potent non-self-antigens via antigenic mimicry, emphasizing the importance of robust humoral immune responses against c-BIF for preventing various diseases, including inflammatory conditions. Elevated levels of circulating antibodies against c-BIF in healthy individuals may serve as potential indicators of lower risks for malignant and non-malignant diseases.

The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications.

The concept of a 'microbiota-gut-brain axis' has recently emerged as an important player in the pathophysiology of Parkinson disease (PD), not least because of the reciprocal interaction between gut bacteria and medications. The gut microbiota can influence levodopa kinetics, and conversely, drugs administered for PD can influence gut microbiota composition. Through a two-step enzymatic pathway, gut microbes can decarboxylate levodopa to dopamine in the small intestine and then dehydroxylate it to m-tyramine, thus reducing availability. Inhibition of bacterial decarboxylation pathways could therefore represent a strategy to increase levodopa absorption. Other bacterial perturbations common in PD, such as small intestinal bacterial overgrowth and Helicobacter pylori infection, can also modulate levodopa metabolism, and eradication therapies may improve levodopa absorption. Interventions targeting the gut microbiota offer a novel opportunity to manage disabling motor complications and dopa-unresponsive symptoms. Mediterranean diet-induced changes in gut microbiota composition might improve a range of non-motor symptoms. Prebiotics can increase levels of short-chain fatty acid-producing bacteria and decrease pro-inflammatory species, with positive effects on clinical symptoms and levodopa kinetics. Different formulations of probiotics showed beneficial outcomes on constipation, with some of them improving dopamine levels; however, the most effective dosage and duration and long-term effects of these treatments remain unknown. Data from faecal microbiota transplantation studies are preliminary, but show encouraging trends towards improvement in both motor and non-motor outcomes.This article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.

Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.

The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD). This mini-review examines current research into GM and FMT as a therapy for depression. Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website Clinicaltrials.gov/controlled-trials.com were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD. Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis. The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.

Current Understanding of Equine Gut Dysbiosis and Microbiota Manipulation Techniques: Comparison with Current Knowledge in Other Species.

Understanding the importance of intestinal microbiota in horses and the factors influencing its composition have been the focus of many studies over the past few years. Factors such as age, diet, antibiotic administration, and geographic location can affect the gut microbiota. The intra- and inter-individual variability of fecal microbiota in horses complicates its interpretation and has hindered the establishment of a clear definition for dysbiosis. Although a definitive causal relationship between gut dysbiosis in horses and diseases has not been clearly identified, recent research suggests that dysbiosis may play a role in the pathogenesis of various conditions, such as colitis and asthma. Prebiotics, probiotics, and fecal microbiota transplantation to modulate the horse's gastrointestinal tract may eventually be considered a valuable tool for preventing or treating diseases, such as antibiotic-induced colitis. This article aims to summarize the current knowledge on the importance of intestinal microbiota in horses and factors influencing its composition, and also to review the published literature on methods for detecting dysbiosis while discussing the efficacy of gut microbiota manipulation in horses.

Nutritional Approaches Targeting Gut Microbiota in Oxidative-Stress-Associated Metabolic Syndrome: Focus on Early Life Programming.

Metabolic syndrome (MetS) denotes a constellation of risk factors associated with the development of cardiovascular disease, with its roots potentially traced back to early life. Given the pivotal role of oxidative stress and dysbiotic gut microbiota in MetS pathogenesis, comprehending their influence on MetS programming is crucial. Targeting these mechanisms during the early stages of life presents a promising avenue for preventing MetS later in life. This article begins by examining detrimental insults during early life that impact fetal programming, ultimately contributing to MetS in adulthood. Following that, we explore the role of oxidative stress and the dysregulation of gut microbiota in the initiation of MetS programming. The review also consolidates existing evidence on how gut-microbiota-targeted interventions can thwart oxidative-stress-associated MetS programming, encompassing approaches such as probiotics, prebiotics, postbiotics, and the modulation of bacterial metabolites. While animal studies demonstrate the favorable effects of gut-microbiota-targeted therapy in mitigating MetS programming, further clinical investigations are imperative to enhance our understanding of manipulating gut microbiota and oxidative stress for the prevention of MetS.

Knowledge of Dietitians on Gut Microbiota in Health-An Online Survey of the European Federation of the Associations of Dietitians (EFAD).

Explorations of current knowledge of dietitians about gut-health interconnection and the role of diet in gut microbiota manipulation are rather scarce in the literature. In this online survey we assessed the perceived and current knowledge of dietitians across Europe about gut microbiota and systemic health, nutrition as a modulator of the gut ecosystem, and the role of probiotics and prebiotics. Pre-graduate dietetic students and other professionals were also invited to participate. A total of 179 full responses were recorded (dietitians, n = 155), mainly from Southern and Western regions. Most participants (>78.0%) reported an average to good level of perceived knowledge, with significant positive correlations between perceived and current knowledge in all sections and overall (p for all <0.05). Nevertheless, a rather low current knowledge scoring of participants about probiotics and prebiotics was observed. Features such as being a dietitian, having a higher educational level as dietitian and working in an academic/research setting were usually associated with higher current knowledge. Further analysis revealed that dietitians had a trend for higher scoring about probiotics and prebiotics compared to pre-graduate students or other professionals. Moreover, for dietitians, working in an academic or research setting was an independent factor for scoring in the highest quartile in all tested sections and overall (p for all <0.05). In conclusion, this online survey shed some light on the current knowledge of dietitians across Europe about gut microbiota parameters, including dietary modulation, highlighting in parallel possible knowledge determinants. Potential areas for future educational efforts in this rather unexplored field were indicated.

Trichuris trichiura infection is associated with changes in gut microbiome composition and function among women of reproductive age from Pemba, Tanzania

Large intestine-dwelling helminths affect microbiome composition. In sub-Saharan Africa, where helminth infections are endemic, the use of chemotherapeutic drugs is the primary strategy for controlling soil-transmitted helminthiases (STHs). However, the emergence of anthelmintic resistance necessitates the urgent exploration of alternative and complementary treatments to achieve the World Health Organization’s goal of eliminating STHs. One promising avenue involves the manipulation of gut microbiota in at-risk populations. This study aimed to enhance the understanding of the interplay between Trichuris trichiura and the gut microbiome. In this study, we used the Mini-FLOTAC technique for parasitological analyses and a shotgun metagenomic sequencing approach to investigate the effect of T. trichiura on the gut microbiome by comparing infected and non-infected women of reproductive age (WRA) from Pemba. Structural and functional analyses of the gut microbiome revealed that T. trichiura infection shaped the host gut microbiome in WRA. Some taxa vary according to infection status. Prevotella genus was more abundant in healthy participants, whereas species such as Weissella cibaria, Leuconostoc citreum (new emergent probiotics), and Leuconostoc lactis (starter) decreased in infected individuals, suggesting the use of potential probiotic treatments to mitigate dysbiosis induced by STHs. Furthermore, the overall number of common fungi, irrespective of species, was significantly higher in the mycobiome of Trichuris infected participants. Functional analysis revealed significant differences in metabolic pathways (p &amp;lt; 0.05), with cholesterol metabolism and pathogenic infections being more abundant in the infected samples than in the non-infected samples. In conclusion, this study sheds light on the intricate interactions between helminth infections and the gut microbiome in the WRA, particularly in STH-endemic regions. The identified associations between specific gut microbial changes and T. trichiura infection may pave the way for innovative complementary treatments to effectively combat STHs.

Adolescent alcohol drinking interaction with the gut microbiome: implications for adult alcohol use disorder.

Reciprocal communication between the gut microbiota and the brain, commonly referred to as the "gut-brain-axis" is crucial in maintaining overall physiological homeostasis. Gut microbiota development and brain maturation (neuronal connectivity and plasticity) appear to be synchronized and to follow the same timeline during childhood (immature), adolescence (expansion) and adulthood (completion). It is important to note that the mesolimbic reward circuitry develops early on, whereas the maturation of the inhibitory frontal cortical neurons is delayed. This imbalance can lead to increased acquirement of reward-seeking and risk-taking behaviors during adolescence, and consequently eventuate in heightened risk for substance abuse. Thus, there is high initiation of alcohol drinking in early adolescence that significantly increases the risk of alcohol use disorder (AUD) in adulthood. The underlying causes for heightened AUD risk are not well understood. It is suggested that alcohol-associated gut microbiota impairment during adolescence plays a key role in AUD neurodevelopment in adulthood. Furthermore, alcohol-induced dysregulation of microglia, either directly or indirectly through interaction with gut microbiota, may be a critical neuroinflammatory pathway leading to neurodevelopmental impairments and AUD. In this review article, we highlight the influence of adolescent alcohol drinking on gut microbiota, gut-brain axis and microglia, and eventual manifestation of AUD. Furthermore, novel therapeutic interventions via gut microbiota manipulations are discussed briefly.

From microbes to medicine: harnessing the gut microbiota to combat prostate cancer.

The gut microbiome (GM) has been identified as a crucial factor in the development and progression of various diseases, including cancer. In the case of prostate cancer, commensal bacteria and other microbes are found to be associated with its development. Recent studies have demonstrated that the human GM, including Bacteroides, Streptococcus, Bacteroides massiliensis, Faecalibacterium prausnitzii, Eubacterium rectale, and Mycoplasma genitalium, are involved in prostate cancer development through both direct and indirect interactions. However, the pathogenic mechanisms of these interactions are yet to be fully understood. Moreover, the microbiota influences systemic hormone levels and contributes to prostate cancer pathogenesis. Currently, it has been shown that supplementation of prebiotics or probiotics can modify the composition of GM and prevent the onset of prostate cancer. The microbiota can also affect drug metabolism and toxicity, which may improve the response to cancer treatment. The composition of the microbiome is crucial for therapeutic efficacy and a potential target for modulating treatment response. However, their clinical application is still limited. Additionally, GM-based cancer therapies face limitations due to the complexity and diversity of microbial composition, and the lack of standardized protocols for manipulating gut microbiota, such as optimal probiotic selection, treatment duration, and administration timing, hindering widespread use. Therefore, this review provides a comprehensive exploration of the GM's involvement in prostate cancer pathogenesis. We delve into the underlying mechanisms and discuss their potential implications for both therapeutic and diagnostic approaches in managing prostate cancer. Through this analysis, we offer valuable insights into the pivotal role of the microbiome in prostate cancer and its promising application in future clinical settings.

Gut microbiota and metabolite interface-mediated hepatic inflammation.

Immunologic and metabolic signals regulated by gut microbiota and relevant metabolites mediate bidirectional interaction between the gut and liver. Gut microbiota dysbiosis, due to diet, lifestyle, bile acids, and genetic and environmental factors, can advance the progression of chronic liver disease. Commensal gut bacteria have both pro- and anti-inflammatory effects depending on their species and relative abundance in the intestine. Components and metabolites derived from gut microbiota-diet interaction can regulate hepatic innate and adaptive immune cells, as well as liver parenchymal cells, significantly impacting liver inflammation. In this mini review, recent findings of specific bacterial species and metabolites with functions in regulating liver inflammation are first reviewed. In addition, socioeconomic and environmental factors, hormones, and genetics that shape the profile of gut microbiota and microbial metabolites and components with the function of priming or dampening liver inflammation are discussed. Finally, current clinical trials evaluating the factors that manipulate gut microbiota to treat liver inflammation and chronic liver disease are reviewed. Overall, the discussion of microbial and metabolic mediators contributing to liver inflammation will help direct our future studies on liver disease.

Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.

The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD. Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition. From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α. Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.