A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems of the body. Recent research on the gut microbiota dysbiosis associated with SLE patients has gained traction and warranted further exploration. It has not been determined whether the change in the gut microbiota is a cause of SLE or a symptom of SLE. However, based on the physiological and pathophysiological role of the bacteria in the gut microbiome, as levels of the bacteria rise or fall, symptomatology in SLE patients could be affected. This review analyzes the recent studies that examined the changes in the gut microbiota of SLE patients and highlights the correlations between gut dysbiosis and the clinical manifestations of SLE. A systematic search strategy was developed by combining the terms "SLE," "systemic lupus erythematosus," and "gut microbiome." Biomedical Reference Collection, CINAHL, Medline ProQuest, and PubMed Central databases were searched by combining the appropriate keywords with "AND." Only full-text, English-language articles were searched. The articles were restricted from 2013 to 2023. Only peer-reviewed controlled studies with both human and animal trials were included in this scoping review. Review articles, non-English articles, editorials, case studies, and duplicate articles from the four databases were excluded. Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. Among the bacterial species increased were Clostridium, Lactobacilli, Streptococcus, Enterobacter, and Klebsiella. The bacterial species that decreased were Bifidobacteria, Prevotella, and the Firmicutes/Bacteroidetes ratio. Literature shows that Clostridium is one of several bacteria found in abundance, from pre-disease to the diseased state of SLE. Lachnospiraceae and Ruminococcaceae are both part of the family of butyrate-producing anaerobes that are known for their role in strengthening the skin barrier function and, therefore, may explain the cutaneous manifestations of SLE patients. Studies have also shown that the Firmicutes/Bacteroidetes ratio is significantly depressed, which may lead to appetite changes and weight loss seen in SLE patients. Based on the established role of these bacteria within the gut microbiome, the disruption in the gut ecosystem could explain the symptomatology common in SLE patients. By addressing these changes, our scoping review encourages further research to establish a true causal relationship between the bacterial changes in SLE patients as well as furthering the scope of microbiota changes in other systems and autoimmune diseases.

Exploration of the impact of dysbiosis in the gut microbiota on microbial composition in children's neurodevelopment.

OBJECTIVE: To investigate the impact of gut microbiota dysbiosis on neurodevelopment in children. METHODS: This study included 338 children aged 0-3 years admitted to our hospital from January to December 2022, The children were divided into a normal neurodevelopment group (169 cases) and a poor neurodevelopment group (169 cases). Basic personal information and clinical data were collected through a detailed questionnaire, and the microbial composition in fecal samples was analyzed using 16S rRNA gene sequencing. RESULTS: Children in the poor neurodevelopment group showed a significant decrease in gut microbiota diversity compared to those in the normal neurodevelopment group (Shannon index, p < 0.05). The abundance of Bifidobacterium and Veillonella genera significantly decreased (p < 0.05), while the abundance of Streptococcus genus increased significantly (p < 0.05). CONCLUSION: There is an association between gut microbiota dysbiosis and poor neurodevelopment in children. The increased abundance of Streptococcus genus and decreased abundance of Bifidobacterium and Veillonella genera in the gut microbiota may be potential risk factors for poor neurodevelopment in preterm infants. Future research should further explore the potential beneficial effects of gut microbiota modulation on neurodevelopment in children.

Association between increased and decreased gut microbiota abundance and Parkinson's disease: A systematic review and subgroup meta-analysis.

OBJECTIVE: The objective of the study was to systematically investigate the association between gut microbiota (GM) abundance and Parkinson's disease (PD). METHODS: PubMed, Medline, Cochrane Library and other literature datebase platforms were searched for eligible studies in the English-language from conception to March 1, 2024. Studies evaluating the association between GM and PD were included. The results of the included studies were analyzed using a random effects model with calculation of the mean difference (MD) with the 95 % confidence interval to quantify the incidence of differences in abundance of various bacterial families in PD patients. Continuous models were used to analyze the extracted data. RESULTS: A total of 14 studies with 1045 PD cases and 821 healthy controls were included for data extraction and meta-analysis. All the included studies exhibited reasonable quality. The included studies reported the data on the ratios of 10 families of GM. Of these 10 microbiota families, Bifidobacteriaceae, Ruminococcaceae, Rikenellaceae, Lactobacillaceae, Verrucomicrobiaceae and Christensenellaceae were found to have increased ratios according to the pooled ratios, while Prevotellaceae, Lachnospiraceae, Erysipelotrichaceae and Faecalibacterium were decreased in PD cases. CONCLUSION: Patients in the PD cohort exhibited distinctive microbiota compositions compared to healthy individuals, with unique differential patterns in gut microbiome abundance at the phylum, family, and genus levels that may be associated wtih PD pathogenesis.

Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Gut-Derived Exosomes Mediate the Microbiota Dysbiosis-Induced Spermatogenesis Impairment by Targeting Meioc in Mice.

Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non-reproductive tissue-originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single-cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR-211-5p in gut-derived circulating exosomes, which inhibited the expression of meiosis-specific with coiled-coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut-derived exosomes in connecting the "gut-testis" axis.

Effects of Salmonella Typhimurium Infection on the Gut Microbiota of Cherry Valley Meat Ducks.

Salmonella infection causes serious economic losses, threatens food safety, and is one of the most important diseases threatening meat duck farming. The gut microbiome is critical in providing resistance against colonization by exogenous microorganisms. Studying the relationship between Salmonella and gut microbiota can help us better understand the threat of the pathogenic mechanism of Salmonella and provide a more scientific theoretical basis for its prevention and treatment. This study uses Salmonella Typhimurium as the research object and Cherry Valley meat duck as the model with which to study the impact of Salmonella infection on ducks. In this field trial, 2 × 108 CFUs Salmonella Typhimurium were administered to 3-day-old ducks. After infection, duck viscera were collected to detect the colonization of Salmonella, and cecal contents were collected to analyze the changes in gut microbiota. The results show that Salmonella Typhimurium can colonize ducks three days after infection and alter the gut microbiota composition, mainly by increasing the abundance of Ruminococcaceae and Lachnospiraceae. In conclusion, Salmonella Typhimurium infection significantly alters the intestinal microbiota of ducks and poses a serious public health risk.

Glyphosate: Impact on the microbiota-gut-brain axis and the immune-nervous system, and clinical cases of multiorgan toxicity.

Glyphosate (GLP) and GLP-based herbicides (GBHs), such as polyethoxylated tallow amine-based GLP surfactants (GLP-SH), developed in the late 70', have become the most popular and controversial agrochemicals ever produced. Nowadays, GBHs have reached 350 million hectares of crops in over 140 countries, with an annual turnover of 5 billion and 11 billion USD in the U.S.A. and worldwide, respectively. Because of the highly efficient inhibitory activity of GLP targeted to the 5-enolpyruvylshikimate-3-phosphate synthase pathway, present in plants and several bacterial strains, the GLP-resistant crop-based genetic agricultural revolution has decreased famine and improved the costs and quality of living in developing countries. However, this progress has come at the cost of the 50-year GBH overuse, leading to environmental pollution, animal intoxication, bacterial resistance, and sustained occupational exposure of the herbicide farm and companies' workers. According to preclinical and clinical studies covered in the present review, poisoning with GLP, GLP-SH, and GBHs devastatingly affects gut microbiota and the microbiota-gut-brain (MGB) axis, leading to dysbiosis and gastrointestinal (GI) ailments, as well as immunosuppression and inappropriate immunostimulation, cholinergic neurotransmission dysregulation, neuroendocrinal system disarray, and neurodevelopmental and neurobehavioral alterations. Herein, we mainly focus on the contribution of gut microbiota (GM) to neurological impairments, e.g., stroke and neurodegenerative and neuropsychiatric disorders. The current review provides a comprehensive introduction to GLP's microbiological and neurochemical activities, including deviation of the intestinal Firmicutes-to-Bacteroidetes ratio, acetylcholinesterase inhibition, excitotoxicity, and mind-altering processes. Besides, it summarizes and critically discusses recent preclinical studies and clinical case reports concerning the harmful impacts of GBHs on the GI tract, MGB axis, and nervous system. Finally, an insightful comparison of toxic effects caused by GLP, GBH-SH, and GBHs is presented. To this end, we propose a first-to-date survey of clinical case reports on intoxications with these herbicides.

Disrupting the gut microbiota/metabolites axis by Di-(2-ethylhexyl) phthalate drives intestinal inflammation via AhR/NF-κB pathway in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer known for its environmental endocrine-disrupting properties, posing potential risks to various organs. However, the precise impact of DEHP on intestinal health and its contribution to the initiation of intestinal inflammation remains elucidated. This study aims to investigate the underlying mechanisms of DEHP-induced intestinal inflammation in mice, specifically focusing on the complex interplay between the gut microbiota-metabolite axis and associated pathophysiological alterations. Our findings showed that DEHP-induced damage of multiple organs systemically, as indicated by abnormal liver and kidney biochemical markers, along with a disrupted ileum morphology. Additionally, DEHP exposure disrupted gut barrier function, causing intestinal inflammation characterized by bacterial translocation and alterations in defense and inflammation-related gene expressions. Moreover, 16S rRNA analysis suggested that DEHP-induced gut microbial remodeling is characterized by an upregulation of detrimental bacteria (Erysipelotrichaceae) and a downregulation of beneficial bacteria (Muribaculaceae, Ruminococcaceae, and Lachnospiraceae). Metabolomics analysis revealed DEHP perturbed gut metabolic homeostasis, particularly affecting the degradation of aromatic compounds, which generated an aberrant activation of the AhR and NF-κB, subsequently causing intestinal inflammation. Consequently, our results elucidate the mechanistic link between disrupted gut microbiota and metabolome and the initiation of DEHP-induced intestinal inflammation, mediated through the AhR/NF-κB signaling pathway.

When smoke meets gut: deciphering the interactions between tobacco smoking and gut microbiota in disease development.

Tobacco smoking is a prevalent and detrimental habit practiced worldwide, increasing the risk of various diseases, including chronic obstructive pulmonary disease (COPD), cardiovascular disease, liver disease, and cancer. Although previous research has explored the detrimental health effects of tobacco smoking, recent studies suggest that gut microbiota dysbiosis may play a critical role in these outcomes. Numerous tobacco smoke components, such as nicotine, are found in the gastrointestinal tract and interact with gut microbiota, leading to lasting impacts on host health and diseases. This review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and functionality. We also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host health. Furthermore, this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

Adipokines and Bacterial Metabolites: A Pivotal Molecular Bridge Linking Obesity and Gut Microbiota Dysbiosis to Target.

Adipokines are essential mediators produced by adipose tissue and exert multiple biological functions. In particular, adiponectin, leptin, resistin, IL-6, MCP-1 and PAI-1 play specific roles in the crosstalk between adipose tissue and other organs involved in metabolic, immune and vascular health. During obesity, adipokine imbalance occurs and leads to a low-grade pro-inflammatory status, promoting insulin resistance-related diabetes and its vascular complications. A causal link between obesity and gut microbiota dysbiosis has been demonstrated. The deregulation of gut bacteria communities characterizing this dysbiosis influences the synthesis of bacterial substances including lipopolysaccharides and specific metabolites, generated via the degradation of dietary components, such as short-chain fatty acids, trimethylamine metabolized into trimethylamine-oxide in the liver and indole derivatives. Emerging evidence suggests that these bacterial metabolites modulate signaling pathways involved in adipokine production and action. This review summarizes the current knowledge about the molecular links between gut bacteria-derived metabolites and adipokine imbalance in obesity, and emphasizes their roles in key pathological mechanisms related to oxidative stress, inflammation, insulin resistance and vascular disorder. Given this interaction between adipokines and bacterial metabolites, the review highlights their relevance (i) as complementary clinical biomarkers to better explore the metabolic, inflammatory and vascular complications during obesity and gut microbiota dysbiosis, and (ii) as targets for new antioxidant, anti-inflammatory and prebiotic triple action strategies.

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.

Dextran sulfate sodium-induced gut microbiota dysbiosis aggravates liver injury in mice with S100-induced autoimmune hepatitis.

Recently, the incidence of autoimmune hepatitis (AIH) has gradually increased, and the disease can eventually develop into cirrhosis or even hepatoma if left untreated. AIH patients are often characterized by gut microbiota dysbiosis, but whether gut microbiota dysbiosis contributes to the progression of AIH remains unclear. In this study, we investigate the role of gut microbiota dysbiosis in the occurrence and development of AIH in mice with dextran sulfate sodium salt (DSS) induced colitis. C57BL/6J mice were randomly divided into normal group, S100-induced AIH group, and DSS+S100 group (1 % DSS in the drinking water), and the experimental cycle lasted for four weeks. We demonstrate that DSS administration aggravates hepatic inflammation and disruption of the intestinal barrier, and significantly changes the composition of gut microbiota in S100-induced AIH mice, which are mainly characterized by increased abundance of pathogenic bacteria and decreased abundance of beneficial bacteria. These results suggest that DSS administration aggravates liver injury of S100-induced AIH, which may be due to DSS induced gut microbiota dysbiosis, leading to disruption of the intestinal barrier, and then, the microbiota translocate to the liver, aggravating hepatic inflammation.

Acupuncture as multi-targeted therapy for the multifactorial disease obesity: a complex neuro-endocrine-immune interplay.

The prevalence of obesity has reached pandemic dimensions. It is associated with multiple comorbidities and is becoming a clinical and public health threat. Obesity is a multifactorial disease with a complex pathophysiology and interplay of various systems. A strong interplay exists between the neuro-endocrine system, the immune system with systemic chronic low-grade inflammation, and microbiome dysbiosis that can lead to the development of obesity, which in turn can exacerbate each of these factors, hence creating a vicious cycle. The conventional treatment with lifestyle modifications such as diet, physical exercise, pharmacotherapy, and bariatric surgery does not always result in sufficient weight control thus paving the way for other strategies. As one such strategy, acupuncture is increasingly used worldwide to treat obesity. This narrative review outlines the evidence for this neuro-endocrine-immune interplay in the pathophysiology of obesity. Furthermore, the existing experimental and clinical evidence of acupuncture as a multi-targeted therapy for obesity is explained and future research perspectives are discussed.

Oral probiotics increased the proportion of Treg, Tfr, and Breg cells to inhibit the inflammatory response and impede gestational diabetes mellitus.

BACKGROUND: Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM. METHODS: GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels. RESULTS: GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-ß and IL-10, preventing inflammation and preserving mouse pregnancy. CONCLUSION: Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.

Gut Microbiome Dysbiosis as a Potential Risk Factor for Idiopathic Toe-Walking in Children: A Review.

Idiopathic toe walking (ITW) occurs in about 5% of children. Orthopedic treatment of ITW is complicated by the lack of a known etiology. Only half of the conservative and surgical methods of treatment give a stable positive result of normalizing gait. Available data indicate that the disease is heterogeneous and multifactorial. Recently, some children with ITW have been found to have genetic variants of mutations that can lead to the development of toe walking. At the same time, some children show sensorimotor impairment, but these studies are very limited. Sensorimotor dysfunction could potentially arise from an imbalanced production of neurotransmitters that play a crucial role in motor control. Using the data obtained in the studies of several pathologies manifested by the association of sensory-motor dysfunction and intestinal dysbiosis, we attempt to substantiate the notion that malfunction of neurotransmitter production is caused by the imbalance of gut microbiota metabolites as a result of dysbiosis. This review delves into the exciting possibility of a connection between variations in the microbiome and ITW. The purpose of this review is to establish a strong theoretical foundation and highlight the benefits of further exploring the possible connection between alterations in the microbiome and TW for further studies of ITW etiology.

Thioredoxin/Glutaredoxin Systems and Gut Microbiota in NAFLD: Interplay, Mechanism, and Therapeutical Potential.

Non-alcoholic fatty liver disease (NAFLD) is a common clinical disease, and its pathogenesis is closely linked to oxidative stress and gut microbiota dysbiosis. Recently accumulating evidence indicates that the thioredoxin and glutaredoxin systems, the two thiol-redox dependent antioxidant systems, are the key players in the NAFLD's development and progression. However, the effects of gut microbiota dysbiosis on the liver thiol-redox systems are not well clarified. This review explores the role and mechanisms of oxidative stress induced by bacteria in NAFLD while emphasizing the crucial interplay between gut microbiota dysbiosis and Trx mediated-redox regulation. The paper explores how dysbiosis affects the production of specific gut microbiota metabolites, such as trimethylamine N-oxide (TMAO), lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), amino acids, bile acid, and alcohol. These metabolites, in turn, significantly impact liver inflammation, lipid metabolism, insulin resistance, and cellular damage through thiol-dependent redox signaling. It suggests that comprehensive approaches targeting both gut microbiota dysbiosis and the thiol-redox antioxidant system are essential for effectively preventing and treating NAFLD. Overall, comprehending the intricate relationship between gut microbiota dysbiosis and thiol-redox systems in NAFLD holds significant promise in enhancing patient outcomes and fostering the development of innovative therapeutic interventions.

The role of macrophages in polycystic ovarian syndrome and its typical pathological features: A narrative review.

Polycystic ovarian syndrome (PCOS) is the most common endocrine and metabolic disorder in women of childbearing age, with ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology (PCOM) as the clinical features. Androgen excess, insulin resistance, obesity, adipose tissue dysfunction, ovulatory dysfunction, and gut microbiota dysbiosis are the main pathological features and pathogenesis of PCOS and are related to systemic chronic low-grade inflammation and chronic ovarian tissue inflammation in PCOS. With the advances in immune-endocrine interaction studies, research on the role of immune cells in the occurrence and development of PCOS is gradually increasing. As the core of innate immunity, macrophages play an indispensable role in systemic inflammatory response. Meanwhile, they are involved in maintaining the stability and function of the ovary as the most abundant immune cells in ovarian tissue. Studies in humans and mice have found that the polarization of macrophages into M1 type plays multiple roles in the pathogenesis of PCOS. This review describes the distribution characteristics of macrophage subpopulations in patients and animal models with PCOS, discusses the role of macrophage-related metabolic inflammation in PCOS, and summarizes the relationship between macrophages and PCOS-related pathological features and its possible mechanisms, to further understand the pathogenesis of PCOS and reveal the role of macrophages in it. In addition, research on immune-endocrine interactions can also provide direction for finding new therapeutic targets for PCOS.

Pediatric Autoimmune or Primary Sclerosing Cholangitis: Metronidazole Effectiveness on Biochemical Data, Bile Acid Profile, and Gut Microbiota: A Pilot Study.

Objectives: Autoimmune hepatitis and primary sclerosing cholangitis (PSC) can both be present, resulting in autoimmune sclerosing cholangitis (ASC). PSC physiopathology could be based on the cross-talk between gut microbiota and bile acids (BAs); antibiotics are an innovative therapy. This pilot study assesses metronidazole (MTZ)'s effectiveness in ASC or PSC patients according to the stage of the disease, and its effects on biochemical parameters, BA profiles, and gut microbiota. Methods: ASC or PSC patients from Cliniques universitaires Saint-Luc's pediatric hepato-gastroenterology division were enrolled retrospectively and prospectively; both datasets were merged. MTZ was administered over at least 14 days on top of standard treatment (ursodeoxycholic acid, azathioprine, and steroids). Fecal and blood samples were collected before (T0) and at MTZ day 14 (T14). Sustained biochemical remission was defined by the reduction of transaminases (AST and ALT), gamma-glutamyl transferase (GGT), and CRP until 12 months post-MTZ. Results: A total of 18 patients (mean age, 13.2 ± 4.5 years) were enrolled (13 ASC and 5 PSC), and divided in remission or relapse patients. CRP, AST, ALT, and GGT levels decreased post-MTZ in both groups (excepting GGT in relapse patients), with decreases between T0 and T14 being significant for AST and ALT. Relapse patients were older (P = 0.0351) and in late-disease stage, with mainly large-duct PSC (P = 0.0466). In remission patients, the mean plasma relative abundance of hydrophilic BA increased by +6.3% (P = 0.0391) after MTZ. Neither at baseline nor T14, there were significant differences in gut microbiota recorded. Conclusion: These data are likely indicative of long-term benefits following MTZ therapy at early-stage ASC or PSC, with increased hydrophilic BA abundance. Multicenter prospective studies are needed.

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization.

We have previously demonstrated abnormal gut microbial composition in castration-resistant prostate cancer (CRPC) patients, here we revealed the mechanism of gut microbiota-derived short-chain fatty acids (SCFAs) as a mediator linking CRPC microbiota dysbiosis and prostate cancer (PCa) progression. By using transgenic TRAMP mouse model, PCa patient samples, in vitro PCa cell transwell and macrophage recruitment assays, we examined the effects of CRPC fecal microbiota transplantation (FMT) and SCFAs on PCa progression. Our results showed that FMT with CRPC patients' fecal suspension increased SCFAs-producing gut microbiotas such as Ruminococcus, Alistipes, Phascolarctobaterium in TRAMP mice, and correspondingly raised their gut SCFAs (acetate and butyrate) levels. CRPC FMT or SCFAs supplementation significantly accelerated mice's PCa progression. In vitro, SCFAs enhanced PCa cells migration and invasion by inducing TLR3-triggered autophagy that further activated NF-κB and MAPK signalings. Meanwhile, autophagy of PCa cells released higher level of chemokine CCL20 that could reprogramme the tumor microenvironment by recruiting more macrophage infiltration and simultaneously polarizing them into M2 type, which in turn further strengthened PCa cells invasiveness. Finally in a cohort of 362 PCa patients, we demonstrated that CCL20 expression in prostate tissue was positively correlated with Gleason grade, pre-operative PSA, neural/seminal vesical invasion, and was negatively correlated with post-operative biochemical recurrence-free survival. Collectively, CRPC gut microbiota-derived SCFAs promoted PCa progression via inducing cancer cell autophagy and M2 macrophage polarization. CCL20 could become a biomarker for prediction of prognosis in PCa patients. Intervention of SCFAs-producing microbiotas may be a useful strategy in manipulation of CRPC.

Sleep Deprivation and Gut Microbiota Dysbiosis: Current Understandings and Implications.

Gut microbiota comprises the microbial communities inhabiting our gastrointestinal (GI) tracts. Accordingly, these complex communities play a fundamental role in many host processes and are closely implicated in human health and diseases. Sleep deprivation (SD) has become increasingly common in modern society, partly owing to the rising pressure of work and the diversification of entertainment. It is well documented that sleep loss is a significant cause of various adverse outcomes on human health including immune-related and metabolic diseases. Furthermore, accumulating evidence suggests that gut microbiota dysbiosis is associated with these SD-induced human diseases. In this review, we summarize the gut microbiota dysbiosis caused by SD and the succedent diseases ranging from the immune system and metabolic system to various organs and highlight the critical roles of gut microbiota in these diseases. The implications and possible strategies to alleviate SD-related human diseases are also provided.