The role of gut microbiota in prostate inflammation and benign prostatic hyperplasia and its therapeutic implications.

Background: The gut microbiota thrives in a complex ecological environment and its dynamic balance is closely related to host health. Recent studies have shown that the occurrence of various diseases including prostate inflammation is related to the dysregulation of the gut microbiome. Objective: This review focus on the mechanisms by which the gut microbiota induces prostate inflammation and benign prostatic hyperplasia and its therapeutic implications. Materials and methods: Publications related to gut microbiota, prostate inflammation, and benign prostatic hyperplasia (BPH) until April 2023 were systematically reviewed. The research questions were formulated using the Problem, Intervention, Comparison/Control, and Outcome (PICO) frameworks. Results: Fifteen articles covering the relationship between the gut microbiota and prostate inflammation/BPH, the mechanisms by which the gut microbiota influences prostate inflammation and BPH, and potential therapeutic approaches targeting the gut microbiota for these conditions were included. Conclusion: Short-chain fatty acids (SCFAs), which are metabolites of the intestinal microbiota, protect the integrity of the intestinal barrier, regulate immunity, and inhibit inflammation. However, dysregulation of the gut microbiota significantly reduces the SCFA content in feces and impairs the integrity of the gut barrier, leading to the translocation of bacteria and bacterial components such as lipopolysaccharide, mediating the development of prostate inflammation through microbe-associated molecular patterns (MAMPs).

Biotics as novel therapeutics in targeting signs of skin ageing via the gut-skin axis.

Skin ageing is a phenomenon resulting from the aggregative changes to skin structure and function and is clinically manifested by physical features such as wrinkles, hyperpigmentation, elastosis, telangiectasia, and deterioration of skin barrier integrity. One of the main drivers of skin ageing, UV radiation, negatively influences the homeostasis of cells and tissues comprising the skin by triggering production of immune-mediated reactive oxygen species (ROS) and pro-inflammatory cytokines, as well as a various hormones and neuropeptides. Interestingly, an established link between the gut and the skin coined the 'gut-skin axis' has been demonstrated, with dysbiosis and gut barrier dysfunction frequently observed in certain inflammatory skin conditions and more recently, implicated in skin ageing. Therapeutic use of 'biotics' including prebiotics, probiotics, postbiotics, and synbiotics, which modulate the gut microbiota and production of microbially associated metabolites, influence the activity of the gut mucosal and immune systems and are showing promise as key candidates in addressing signs of skin ageing. In this review we aim to focus on the structure and function of the gut-skin axis and showcase the recent in-vitro and clinical evidence demonstrating the beneficial effects of select biotics in targeting signs of skin ageing and discuss the proposed mechanisms mediated via the gut-skin axis underpinning these effects.

Involvement of autophagy and gut dysbiosis in ambient particulate matter-induced colonic inflammation.

Ambient fine particulate matter (PM2.5), a vital environmental toxicant, not only adversely affects the cardiovascular and respiratory systems but also potentially exhibits an association with intestinal inflammation and colorectal cancer (CRC). The underlying molecular mechanisms of PM2.5 impacts on CRC are still unclear. In this study, we utilized collected ambient PM2.5 and standard reference material SRM2786 to investigate the toxic effects on the colon through in vivo chronic exposure mouse and in vitro cell culture models. We employed a chronic mouse exposure model to clarify the colonic injury and gut microbiome biomarkers. Prolonged exposure to PM2.5 via oropharyngeal aspiration led to a significant rise in colonic epithelial proliferation and reduced colon length in mice. It triggered characteristics indicative of gut microbiota dysbiosis linked to inflammatory bowel disease. The gut microbiome alternations may serve as a biomarker indicating the colonic health impacts of PM2.5 exposure. PM2.5 and SRM2786-induced cytotoxicity manifested as autophagy dysregulation-mediated abnormal proliferation, IL-8 production, p62/SQSTM1 accumulation, and lysosomal membrane damage in human colon cells WiDr and Caco-2. Both PM2.5 and SRM2786 exposures led to the accumulation of p62/SQSTM1 and compromised lysosomal membrane integrity, showing impaired autophagic flux in WiDr and Caco-2 cells. Finally, we examined the correlations between atmospheric PM2.5 data and biomarkers of colonic inflammation in human population. The serum level of IL-8 was significantly correlated with regional anthropogenic pollutants. In conclusion, our findings elucidate that ambient PM2.5 exhibits adverse effects on colon health manifested as inflammation, aberrant proliferation, and gut dysbiosis, potentially mediated through autophagy dysregulation, thereby highlighting the importance of further research on the impact of environmental pollutants on gastrointestinal health.

Impact of different gastric acid suppressants on chronic unpredictable mild stress-induced cognitive impairment in rats: A possible involvement of gut dysbiosis.

Recently, clinical evidence indicates that gastric acid suppressants are associated with an increased risk of the development of cognitive impairment and dementia, especially in elderly patients and those with mild cognitive impairment. Therefore, the aim of this research was to explore the impact of different gastric acid suppressants use, famotidine (Famo), esomeprazole (Esome) and vonoprazan (Vono) in the absence or the presence of chronic unpredictable mild stress (CUMS) on several memory tasks with examination of the role of gut dysbiosis. In the present study, rats received famotidine (3.7 mg/kg/day, p.o.) or esomeprazole (3.7 mg/kg/day, p.o.) or vonoprazan (1.85 mg/kg/day, p.o.) for 7 weeks with or without exposure to CUMS. Remarkably, CUMS with different acid suppressants caused a significant decrease in all memory tasks in late CUMS in the current investigation. CUMS with acid suppressants also revealed a marked alteration in the fecal Firmicutes/Bacteroidetes ratio compared to CUMS alone. This gut microbiome alteration was associated with an alteration in gut membrane integrity, as revealed by colonic histopathology and an elevation of systemic inflammatory markers. Besides, upregulation of hippocampal amyloid ß and p-tau proteins and modification of brain histopathology were noticed. Our findings support the detrimental effect of gastric acid suppressants, especially proton pump inhibitors, on cognitive impairment in the presence of stress, with the possible involvement of gut dysbiosis.

Disturbance of gut microbiota aggravates the inflammatory response and damages the vascular endothelial function in patients with preeclampsia.

OBJECTIVE: To investigate the influence of intestinal flora imbalance on inflammatory factors in the serum and vascular endothelial functionality in individuals with preeclampsia (PE). METHODS: From January 2022 to December 2023, a total of 58 individuals with PE (PE group) and 60 healthy controls (CON group) were included in this study; they were matched for age and pre-pregnancy Body Mass Index (BMI). A comparison was made between the two groups in terms of the general data and the number of unique intestinal flora. Additionally, clinical blood measures, serum inflammatory factors, and vascular endothelial function were also assessed and compared between the groups. RESULTS: Age, gestational age, and pre-pregnancy BMI were similar between the PE and control group. However, diastolic and systolic blood pressure were significantly higher in the PE group. The abundance of Lactobacillus, Bifidobacterium, Enterobacter, and Enterococcus. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were considerably higher in the PE group compared to the CON group, but Interleukin-4 (IL-4) was noticeably lower, and the amount of White blood cells (WBC), neutrophil count (N) and lymphocyte count (L) in the PE group were significantly higher than those in the CON group. In the PE group, serum vascular endothelin (ET) and soluble endoglin (sEng) were higher than in the CON group, vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels were considerably lower than in the CON group, and the levels of TC, TG, LDL-C and HDL-C were significantly higher in the PE group than in the CON group. The presence of Lactobacillus and Bifidobacterium was inversely associated with levels of TNF-α, IL-6, Interleukin-10 (IL-10), ET, and sEng, and positively associated with levels of IL-4, VEGF, and NO. Nevertheless, there was a positive correlation between the abundance of Enterobacterium and Enterococcus with the levels of TNF-α, IL-6, IL-10, ET, and sEng. Conversely, there was a negative correlation between the abundance of Enterobacterium and Enterococcus and the levels of IL-4, VEGF, and NO. CONCLUSION: Patients with PE exhibited dysbiosis of intestinal flora, characterized by altered gut microbiota diversity, increased serum pro-inflammatory factors, and impaired vascular endothelial function.

Elevated muramyl dipeptide by sialic acid-facilitated postantibiotic pathobiont expansion contributes to gut dysbiosis-induced mastitis in mice.

INTRODUCTION: In responses to antibiotics exposure, gut dysbiosis is a risk factor not only for pathogen infection but also for facilitating pathobiont expansion, resulting in increased inflammatory responses in the gut and distant organs. However, how this process is regulated has not been fully elucidated. OBJECTIVES: In this study, we investigated the role of sialic acid, a host-derived carbohydrate, in the pathogenesis of gut dysbiosis-derived inflammation in distant organs. METHODS: Ampicillin (Amp)-induced gut dysbiotic mice were treated with N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) for three weeks to assess the role of sialic acids in mastitis. The underlying mechanism by which sialic acids regulate mastitis was explored using 16S rRNA sequencing, transcriptomics and employed multiple molecular approaches. RESULTS: Administration of Neu5Ac and Neu5Gc exacerbated gut dysbiosis-induced mastitis and systemic inflammation. The gut dysbiosis caused by Amp was also aggravated by sialic acid. Notably, increased Enterococcus expansion, which was positively correlated with inflammatory markers, was observed in both Neu5Ac- and Neu5Gc-treated gut dysbiotic mice. Treatment of mice with Enterococcus cecorum (E. cecorum) aggravated gut dysbiosis-induced mastitis. Mechanically, sialic acid-facilitated E. cecorum expansion promoted muramyl dipeptide (MDP) release, which induced inflammatory responses by activating the NOD2-RIP2-NF-κB axis. CONCLUSIONS: Collectively, our data reveal a role of sialic acid-facilitated postantibiotic pathobiont expansion in gut dysbiosis-associated inflammation, highlighting a potential strategy for disease prevention by regulating the MDP-NOD2-RIP2 axis.

Tanshinone IIA Exerts Cardioprotective Effects Through Improving Gut-Brain Axis Post-Myocardial Infarction.

Myocardial infarction (MI) is a lethal cardiovascular disease worldwide. Emerging evidence has revealed the critical role of gut dysbiosis and impaired gut-brain axis in the pathological progression of MI. Tanshinone IIA (Tan IIA), a traditional Chinese medicine, has been demonstrated to exert therapeutic effects for MI. However, the effects of Tan IIA on gut-brain communication and its potential mechanisms post-MI are still unclear. In this study, we initially found that Tan IIA significantly reduced myocardial inflammation, apoptosis and fibrosis, therefore alleviating hypertrophy and improving cardiac function following MI, suggesting the cardioprotective effect of Tan IIA against MI. Additionally, we observed that Tan IIA improved the gut microbiota as evidenced by changing the α-diversity and ß-diversity, and reduced histopathological impairments by decreasing inflammation and permeability in the intestinal tissues, indicating the substantial improvement of Tan IIA in gut function post-MI. Lastly, Tan IIA notably reduced lipopolysaccharides (LPS) level in serum, inflammation responses in paraventricular nucleus (PVN) and sympathetic hyperexcitability following MI, suggesting that restoration of Tan IIA on MI-induced brain alterations. Collectively, these results indicated that the cardioprotective effects of Tan IIA against MI might be associated with improvement in gut-brain axis, and LPS might be the critical factor linking gut and brain. Mechanically, Tan IIA-induced decreased intestinal damage reduced LPS release into serum, and reduced serum LPS contributes to decreased neuroinflammation with PVN and sympathetic inactivation, therefore protecting the myocardium against MI-induced injury.

Bacterial extracellular vesicles at the interface of gut microbiota and immunity.

Bacterial extracellular vesicles (BEVs) are nano-sized lipid-shielded structures released by bacteria and that play an important role in intercellular communication. Their broad taxonomic origins and varying cargo compositions suggest their active participation in significant biological mechanisms. Specifically, they are involved in directly modulating microbial ecosystems, competing with other organisms, contributing to pathogenicity, and influencing the immunity of their hosts. This review examines the mechanisms that underlie the modulatory effects of BEVs on gut dynamics and immunity. Understanding how BEVs modulate microbiota composition and functional imbalances is crucial, as gut dysbiosis is implicated not only in the pathogenesis of various gastrointestinal, metabolic, and neurological diseases, but also in reducing resistance to colonization by enteric pathogens, which is particularly concerning given the current antimicrobial resistance crisis. This review summarizes recent advancements in the field of BEVs to encourage further research into these enigmatic entities. This will facilitate a better understanding of intra- and interkingdom communication phenomena and reveal promising therapeutic approaches.

Gut Dysbiosis and Dietary Interventions in Rheumatoid Arthritis-A Narrative Review.

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. The pathogenesis of RA is complex and involves interactions between articular cells, such as fibroblast-like synoviocytes, and immune cells. These cells secrete pro-inflammatory cytokines, chemokines, metalloproteinases and other molecules that together participate in joint degradation. The current evidence suggests the important immunoregulatory role of the gut microbiome, which can affect susceptibility to diseases and infections. An altered microbiome, a phenomenon known as gut dysbiosis, is associated with the development of inflammatory diseases. Importantly, the profile of the gut microbiome depends on dietary habits. Therefore, dietary elements and interventions can indirectly impact the progression of diseases. This review summarises the evidence on the involvement of gut dysbiosis and diet in the pathogenesis of RA.

NLRP3 Inflammasome and Gut Dysbiosis Linking Diabetes Mellitus and Inflammatory Bowel Disease.

Diabetes mellitus and inflammatory bowel disease are chronic conditions with significant overlap in their pathophysiology, primarily driven by chronic inflammation. Both diseases are characterized by an aberrant immune response and disrupted homeostasis in various tissues. However, it remains unclear which disease develops first, and which one contributes to the other. Diabetes mellitus increases the risk of inflammatory bowel disease and inflammatory bowel disease may increase the risk of developing diabetes. This review focuses on comprehensively discussing the factors commonly contributing to the pathogenesis of diabetes mellitus and inflammatory bowel disease to draw a relationship between them and the possibility of targeting common factors to attenuate the incidence of one if the other is present. A key player in the intersection of diabetes mellitus and inflammatory bowel disease is the NLRP3 inflammasome, which regulates the production of pro-inflammatory cytokines leading to prolonged inflammation and tissue damage. Additionally, toll-like receptors via sensing microbial components contribute to diabetes mellitus and inflammatory bowel disease by initiating inflammatory responses. Gut dysbiosis, a common link in both diseases, further intensifies inflammation and metabolic dysfunction. Alterations in gut microbiota composition affect intestinal permeability and immune modulation, perpetuating a vicious cycle of inflammation and disease progression by changing protein expression. The overlap in the underlying inflammatory mechanisms has led to the potential of targeting mediators of chronic inflammation using anti-inflammatory drugs and biologics that benefit both conditions or attenuate the incidence of one in the presence of the other.

The signatures and crosstalk of gut microbiome, mycobiome, and metabolites in decompensated cirrhotic patients.

Background: Numerous studies have confirmed that gut microbiota plays a crucial role in the progression of cirrhosis. However, the contribution of gut fungi in cirrhosis is often overlooked due to the relatively low abundance. Methods: We employed 16S ribosomal RNA sequencing, internal transcribed spacer sequencing, and untargeted metabolomics techniques to investigate the composition and interaction of gut bacteria, fungi, and metabolites in cirrhotic patients. Results: Cirrhotic patients exhibited significant differences in the diversity and composition of gut microbiota and their metabolites in cirrhotic patients compared to healthy individuals. Increase in pathogenic microbial genera and a decrease in beneficial microbial genera including bacteria and fungi were observed. Various clinical indexes were closely connected with these increased metabolites, bacteria, fungi. Additionally, endoscopic treatment was found to impact the gut microbiota and metabolites in cirrhotic patients, although it did not significantly alter the gut ecology. Finally, we constructed a cirrhosis diagnostic model based on different features (bacteria, fungi, metabolites, clinical indexes) with an AUC of 0.938. Conclusion: Our findings revealed the characteristics of gut microbial composition and their intricate internal crosstalk in cirrhotic patients, providing cutting-edge explorations of potential roles of gut microbes in cirrhosis.

Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients.

Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.

Association of bacterial overgrowth in the small intestine with cortical thickness and functional connectivity in Parkinson's disease involving mild cognitive impairment.

This study explored potential associations of bacterial overgrowth in the small intestine, as detected based on levels of hydrogen and methane in breath after lactulose consumption, with cortical thickness and resting-state functional connectivity in different brain regions. Prospective comparison of 35 patients with Parkinson's disease (PD) involving mild cognitive impairment, 35 patients with PD with normal cognitive function and 17 healthy controls showed the largest level of hydrogen alone and the largest combined level of hydrogen and methane in patients with mild cognitive impairment. The comparison also revealed a significant negative correlation between those levels and thickness of the right insular cortex. Mild cognitive patients showed different functional connectivity between the right insula and cognition-related brain networks from normal cognitive patients. Our results suggest that bacterial overgrowth in the small intestine may contribute to cortical thinning and alterations in resting-state functional connectivity in PD involving mild cognitive impairment. These insights support and deepen previous observations implicating the gut-brain axis in the neurological disorder.

Intestinal permeability disturbances: causes, diseases and therapy.

Nowadays, a pathological increase in the permeability of the intestinal barrier (the so-called leaky gut) is increasingly being diagnosed. This condition can be caused by various factors, mainly from the external environment. Damage to the intestinal barrier entails a number of adverse phenomena: dysbiosis, translocation of microorganisms deep into the intestinal tissue, immune response, development of chronic inflammation. These phenomena can ultimately lead to a vicious cycle that promotes the development of inflammation and further damage to the barrier. Activated immune cells in mucosal tissues with broken barriers can migrate to other organs and negatively affect their functioning. Damaged intestinal barrier can facilitate the development of local diseases such as irritable bowel disease, inflammatory bowel disease or celiac disease, but also the development of systemic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, hepatitis, and lupus erythematosus, neurodegenerative or psychiatric conditions, or metabolic diseases such as diabetes or obesity. However, it must be emphasized that the causal links between a leaky gut barrier and the onset of certain diseases often remain unclear and require in-depth research. In light of recent research, it becomes crucial to prevent damage to the intestinal barrier, as well as to develop therapies for the barrier when it is damaged. This paper presents the current state of knowledge on the causes, health consequences and attempts to treat excessive permeability of the intestinal barrier.

Correlation of gut microbial diversity to sight-threatening diabetic retinopathy.

PURPOSE: To determine the association of gut microbiome diversity and sight-threatening diabetic retinopathy (STDR) amongst patients with pre-existing diabetes. METHODS: A cross-sectional study was performed, wherein 54 participants selected in total were placed into cases cohort if diagnosed with STDR and those without STDR but had a diagnosis of diabetes mellitus of at least 10-year duration were taken as controls. Statistical analysis comparing the gut microbial alpha diversity between cases and control groups as well as patients differentiated based on previously hypothesized Bacteroidetes/Firmicutes(B/F) ratio with an optimal cut-off 1.05 to identify patients with STDR were performed. RESULTS: Comparing gut microbial alpha diversity did not show any difference between cases and control groups. However, statistically significant difference was noted amongst patients with B/F ratio ≥1.05 when compared to B/F ratio < 1.05; ACE index [Cut-off < 1.05:773.83 ± 362.73; Cut-off > 1.05:728.03 ± 227.37; p-0.016]; Chao1index [Cut-off < 1.05:773.63 ± 361.88; Cut-off > 1.05:728.13 ± 227.58; p-0.016]; Simpson index [Cut-off < 1.05:0.998 ± 0.001; Cut-off > 1.05:0.997 ± 0.001; p-0.006]; Shannon index [Cut-off < 1.05:6.37 ± 0.49; Cut-off > 1.05:6.10 ± 0.43; p-0.003]. Sub-group analysis showed that cases with B/F ratio ≥ 1.05, divided into proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME), showed decreased diversity compared to controls (B/F ratio < 1.05). For PDR, all four diversity indices significantly decreased (p < 0.05). However, for CSME, only Shannon and Simpson indices showed significant decrease in diversity (p < 0.05). CONCLUSIONS: Based on clinical diagnosis, decreasing gut microbial diversity was observed among patients with STDR, although not statistically significant. When utilizing B/F ratio, the decreasing gut microbial diversity in STDR patients seems to be associated due to species richness and evenness in PDR when compared to decreasing species richness in CSME.

The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice.

BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy. METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB+Iba1+ and lipopolysaccharide (LPS)+Iba1+ cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone. CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.

Gut Dysbiosis in Patients With Fontan Circulation.

BACKGROUND: The process underlying Fontan pathophysiology is multifactorial and may include gut dysbiosis (GD). We investigated the presence of GD and elucidated its correlation with Fontan pathophysiology. METHODS AND RESULTS: Gut microbiomes of 155 consecutive patients with Fontan pathophysiology and 44 healthy individuals were analyzed using 16S rRNA sequencing of bacterial DNA extracted from fecal samples. GD was evaluated on the basis of α and ß diversities of the gut microbiome and was compared with natural log-transformed C-reactive protein, hemodynamics, von Willebrand factor antigen (a bacterial translocation marker), Mac-2 binding protein glycosylation isomer (a liver fibrosis indicator), peak oxygen uptake, and heart failure hospitalization. Patients with Fontan exhibited GD in terms of α and ß diversities as compared with controls (P<0.01). Reduced α diversity was associated with a failed hemodynamic phenotype, hypoxia, high natural log-transformed C-reactive protein levels, and elevated von Willebrand factor antigen and Mac-2 binding protein glycosylation isomer levels (P<0.05-0.01). In addition to elevated von Willebrand factor antigen and hypoxia, decreased α diversity was independently correlated with a high natural log-transformed C-reactive protein level (P<0.05), which was associated with liver imaging abnormalities and a heightened risk of heart failure hospitalization (P<0.01 for both). CONCLUSIONS: Patients with Fontan pathophysiology exhibited GD compared with healthy individuals, and GD was linked to failed hemodynamics and systemic inflammation with a poor prognosis. Therefore, GD may play a pivotal role in a failing Fontan status, including Fontan-associated liver disease, through GD-associated systemic inflammation.

Gut Microbiota Modulation in the Management of Chronic Obstructive Pulmonary Disease: A Literature Review.

Chronic obstructive pulmonary disease (COPD) represents a significant global health burden, characterized by progressive airflow limitation and exacerbations that significantly impact patient morbidity and mortality. Recent research has investigated the interplay between the gut and the lungs, known as the gut-lung axis, highlighting the role of the gut microbiome in COPD pathogenesis. Dysbiosis, characterized by microbial imbalance, has implications for COPD, influencing disease progression and susceptibility to exacerbations. This comprehensive review integrates current scientific literature on gut microbiota modulation as a therapeutic avenue for COPD management. Through a thorough discussion of studies investigating probiotics, prebiotics, synbiotics, antibiotics, dietary fiber, and fecal microbiota transplantation, this review summarizes the influence of these interventions on COPD via the gut-lung axis through the modulation of systemic inflammation, mucosal immunity, and metabolic processes. The interventions highlighted here show potential in preventing COPD exacerbations, preserving lung function, and improving patient quality of life. By compiling the latest scientific evidence, this review provides a comprehensive framework for physicians and researchers to deduce the effectiveness of gut microbiome modulation as an adjunctive therapeutic strategy in COPD management.

Synbiotic supplementation ameliorates anxiety and myocardial ischaemia-reperfusion injury in hyperglycaemic rats by modulating gut microbiota.

Hyperglycaemia, hyperlipidaemia, hypertension and obesity are the main risk factors affecting the development and prognosis of ischaemic heart disease, which is still an important cause of death today. In our study, male Sprague-Dawley rats were fed either a standard diet (SD) or a high fat and high carbohydrate diet (HF-HCD) for 8 weeks and streptozotocin (STZ) was injected at the seventh week of the feeding period. In one set of rats, a mixture of a prebiotic and probiotics (synbiotic, SYN) was administered by gavage starting from the beginning of the feeding period. Experimental myocardial ischaemia-reperfusion (30 min/60 min) was induced at the end of 8 weeks. Hyperglycaemia, hypertension and increased serum low-density lipoprotein levels occurred in SD- and HF-HCD-fed and STZ-treated rats followed for 8 weeks. Increased density of the Proteobacteria phylum was observed in rats with increased blood glucose levels, indicating intestinal dysbiosis. The severity of cardiac damage was highest in the dysbiotic HF-HCD-fed hyperglycaemic rats, which was evident with increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumour necrosis factor-α, and interleukin-6 levels, along with a decrease in ST-segment resolution index. SYN supplementation to either a normal or a high-fat high-carbohydrate diet improved gut dysbiosis, reduced anxiety, decreased CK-MB and cTnI levels, and alleviated myocardial ischaemia-reperfusion injury in hyperglycaemic rats.

Roundup-Induced Gut Dysbiosis, Irrelevant to Aromatic Amino Acid Deficiency, Impairs the Gut Function in Rats.

Glyphosate, the most popular herbicide globally, has long been considered safe for mammals. However, whether glyphosate can disturb gut microbiota via inhibiting aromatic amino acid (AAA) synthesis has been under debate recently. Here, we evaluated the impacts of chronic exposure to Roundup on gut health with the addition of AAA and explored the mechanism behind Roundup-induced gut dysfunction by performing fecal microbiota transplantation. 500 mg/kg·bw of Roundup, independent of AAA deficiency, caused severe damage to gut function, as characterized by gut microbial dysbiosis, oxidative stress damage, intestinal inflammation, and histopathological injury, particularly in female rats. Notably, similar to Roundup, Roundup-shaped gut microbiome evidently damaged serum, cecum, and colon profiling of oxidative stress biomarkers (malonaldehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and H2O2). Moreover, it induced 0.65-, 3.29-, and 2.36-fold increases in colonic IL-1ß, IL-6, and TNF-α levels, and 0.34-fold decreases in the IL-10 level. Upon transplanting healthy fecal microbiota to Roundup-treated rats, they exhibited a healthier gut microenvironment with mitigated inflammation, oxidative damage, and intestinal injury. Overall, our findings provide new insights into the safety of Roundup, highlight the crucial role of gut microbiota in Roundup-induced gut dysfunction, and pave the way for developing gut-microbiota-based strategies to address Roundup-related safety issues.