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Cell Metabolism Oct 2023Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic...
Non-alcoholic fatty liver disease (NAFLD) is regarded as a pandemic that affects about a quarter of the global population. Recently, host-gut microbiota metabolic interactions have emerged as distinct mechanistic pathways implicated in the development of NAFLD. Here, we report that a group of gut microbiota-modified bile acids (BAs), hyodeoxycholic acid (HDCA) species, are negatively correlated with the presence and severity of NAFLD. HDCA treatment has been shown to alleviate NAFLD in multiple mouse models by inhibiting intestinal farnesoid X receptor (FXR) and upregulating hepatic CYP7B1. Additionally, HDCA significantly increased abundances of probiotic species such as Parabacteroides distasonis, which enhances lipid catabolism through fatty acid-hepatic peroxisome proliferator-activated receptor alpha (PPARα) signaling, which in turn upregulates hepatic FXR. These findings suggest that HDCA has therapeutic potential for treating NAFLD, with a unique mechanism of simultaneously activating hepatic CYP7B1 and PPARα.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; PPAR alpha; Liver; Deoxycholic Acid; Bile Acids and Salts
PubMed: 37591244
DOI: 10.1016/j.cmet.2023.07.011 -
Immunity Feb 2023The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations...
The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.
Topics: Pregnancy; Female; Humans; Animals; Mice; Gastrointestinal Microbiome; Pyroptosis; NLR Family, Pyrin Domain-Containing 3 Protein; Macrophages; Sepsis; Inflammation
PubMed: 36792573
DOI: 10.1016/j.immuni.2023.01.015 -
Nature Communications Apr 2022Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut...
Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, resulting in a distinct serum bile acid profile characterized by depleting the proportion of non-12α-hydroxylated bile acids, ursodeoxycholic acid and lithocholic acid. Downregulation of UCP1 expression in brown adipose tissue and decreased serum GLP-1 were observed in the weight-rebound mice. Moreover, treatment with Parabacteroides distasonis or non-12α-hydroxylated bile acids ameliorated weight regain via increased thermogenesis. Our results highlighted the gut microbiota-bile acid crosstalk in rebound weight gain and Parabacteroides distasonis as a potential probiotic to prevent rapid post-CR weight gain.
Topics: Animals; Bacteroidetes; Bile Acids and Salts; Caloric Restriction; Diet, High-Fat; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Weight Gain
PubMed: 35440584
DOI: 10.1038/s41467-022-29589-7 -
International Journal of Molecular... Apr 2021Numerous scientific studies in recent years have shown significant skin and gut dysbiosis among patients with psoriasis. A significant decrease in microbiome... (Review)
Review
Numerous scientific studies in recent years have shown significant skin and gut dysbiosis among patients with psoriasis. A significant decrease in microbiome alpha-diversity (abundance of different bacterial taxa measured in one sample) as well as beta-diversity (microbial diversity in different samples) was noted in psoriasis skin. It has been proven that the representation of , spp., and is decreased and , , spp., and spp. increased in the psoriasis skin in comparison to healthy skin. Alterations in the gut microbiome in psoriasis are similar to those observed in patients with inflammatory bowel disease. In those two diseases, the , spp., spp., and were underrepresented, while the abundance of sp., sp., sp., , sp., and sp. was increased. Several research studies provided evidence for the significant influence of psoriasis treatments on the skin and gut microbiome and a positive influence of orally administered probiotics on the course of this dermatosis. Further research is needed to determine the influence of the microbiome on the development of inflammatory skin diseases. The changes in microbiome under psoriasis treatment can serve as a potential biomarker of positive response to the administered therapy.
Topics: Arthritis, Psoriatic; Dysbiosis; Gastrointestinal Microbiome; Humans; Probiotics; Psoriasis; Skin
PubMed: 33924414
DOI: 10.3390/ijms22083998 -
Emerging Microbes & Infections Dec 2022Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, its role in sepsis-related liver injury (SLI) in the elderly is...
Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, its role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic-aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analysed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analysed by histopathology, immunofluorescence, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under gut microbiota. Importantly, FMT assay showed that rats gavaged with faeces from metformin-treated SLI rats displayed less severe liver damage and colon barrier dysfunctions than those gavaged with faeces from SLI rats. The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats was different. In particular, the proportion of and was higher in SLI rats than sham-operated and metformin-treated SLI rats; while metformin could increase the proportion of , , and in aged SLI rats. Additionally, and correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic-aged rats, which may be an effective therapy for SLI.
Topics: Animals; Gastrointestinal Microbiome; Liver; Metformin; RNA, Ribosomal, 16S; Rats; Sepsis
PubMed: 35191819
DOI: 10.1080/22221751.2022.2045876 -
Journal of Food and Drug Analysis Jul 2019Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many... (Review)
Review
Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many important reports have highlighted the changes in the gut microbiota (dysbiosis) are closely related to development of intra- and extra-intestinal, chronic inflammation related diseases such as colitis, obesity/metabolic syndromes, diabetes mellitus, liver diseases, cardiovascular diseases and also cancer and neurodegenerative diseases. To circumvent these difficulties, the strategy of modulating the structure of the gut microbiota has been under intensive study and shed more light on amelioration of these inflammation related diseases. While traditional probiotics generally show marginal ameliorative effects, emerging next generation probiotics start to reveal as new preventive and therapeutic tools. Recent studies have unraveled many potential next generation probiotics (NGP). These include Prevotella copri and Christensenella minuta that control insulin resistance, Parabacteroides goldsteinii, Akkermansia muciniphila and Bacteroides thetaiotaomicron that reverse obesity and insulin resistance, Faecalibacterium prausnitzii that protects mice against intestinal diseases, and Bacteroides fragilis that reduces inflammation and shows anticancer effect. New agents will soon be revealed for targeted therapy on specific inflammation related diseases. The important roles of next generation probiotics and gut microbiota normobiosis on the maintenance of intestinal integrity and homeostasis are emphasized.
Topics: Animals; Cardiovascular Diseases; Colitis; Diabetes Mellitus; Gastrointestinal Microbiome; Humans; Inflammation; Liver Diseases; Metabolic Syndrome; Neoplasms; Neurodegenerative Diseases; Obesity; Probiotics
PubMed: 31324278
DOI: 10.1016/j.jfda.2018.12.011 -
International Journal of Molecular... Nov 2022There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological... (Review)
Review
There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.
Topics: Humans; Gastrointestinal Microbiome; Nervous System Diseases; Parkinson Disease; Microbiota; Akkermansia; Multiple Sclerosis; Prevotella; Clostridiaceae; Clostridiales; Stroke
PubMed: 36430144
DOI: 10.3390/ijms232213665 -
Nature Microbiology Aug 2023Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary...
Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by C-inulin. Integration of C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease.
Topics: Animals; Mice; Non-alcoholic Fatty Liver Disease; Inulin; Fatty Acids; Inflammation; Dietary Fiber
PubMed: 37386075
DOI: 10.1038/s41564-023-01418-7 -
Translational Psychiatry May 2023Postoperative delirium is a common postoperative complication in older patients, and its pathogenesis and biomarkers remain largely undetermined. The gut microbiota has... (Review)
Review
Postoperative delirium is a common postoperative complication in older patients, and its pathogenesis and biomarkers remain largely undetermined. The gut microbiota has been shown to regulate brain function, and therefore, it is vital to explore the association between gut microbiota and postoperative delirium. Of 220 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy under general or spinal anesthesia, 86 participants were included in the data analysis. The incidence (primary outcome) and severity of postoperative delirium were assessed for two days. Fecal swabs were collected from participants immediately after surgery. The 16S rRNA gene sequencing was used to assess gut microbiota. Principal component analyses along with a literature review were used to identify plausible gut microbiota, and three gut bacteria were further studied for their associations with postoperative delirium. Of the 86 participants [age 71.0 (69.0-76.0, 25-75% percentile of quartile), 53% female], 10 (12%) developed postoperative delirium. Postoperative gut bacteria Parabacteroides distasonis was associated with postoperative delirium after adjusting for age and sex (Odds Ratio [OR] 2.13, 95% Confidence Interval (CI): 1.09-4.17, P = 0.026). The association between delirium and both Prevotella (OR: 0.59, 95% CI: 0.33-1.04, P = 0.067) and Collinsella (OR: 0.57, 95% CI: 0.27-1.24, P = 0.158) did not meet statistical significance. These findings suggest that there may be an association between postoperative gut microbiota, specifically Parabacteroides distasonis, and postoperative delirium. However, further research is needed to confirm these findings and better understand the gut-brain axis's role in postoperative outcomes.
Topics: Humans; Female; Aged; Male; Emergence Delirium; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Bacteroidetes
PubMed: 37160886
DOI: 10.1038/s41398-023-02450-1 -
Nutrients Oct 2022Gestational diabetes mellitus (GDM)is one of the most common perinatal pathologies, with a prevalence of 5-20% depending on the population or diagnostic standards. It is... (Review)
Review
Gestational diabetes mellitus (GDM)is one of the most common perinatal pathologies, with a prevalence of 5-20% depending on the population or diagnostic standards. It is diagnosed when glucose intolerance is first detected during pregnancy. In the pathogenesis of GDM, genetic, environmental, and pregnancy-related factors (excessive fat storage and increased adipokine and cytokine secretion) play important roles. A growing amount of scientific data has indicated the role of gut microbiota (GM) dysbiosis in the development of glucose intolerance during pregnancy. Previous studies have indicated that, in comparison to healthy pregnant women, GDM individuals have a greater abundance of bacteria belonging to the genera , and and a lower number of bacteria belonging to the genera , and . Recently, many studies have focused on treating GDM with methods targeting GM. Several previous studies have analyzed the effect of probiotics on the course of GDM, but their data are inconclusive. In view of this state, the aim of the study was to collect and comprehensively discuss current knowledge regarding the role of probiotic supplementation in preventing and treating GDM. According to the analyzed data, probiotics have a positive influence on glycemic control and are a promising tool for lowering the frequency of GDM. However, further studies must be conducted to determine the optimal model of probiotic therapy (strain, dose, time of intervention, etc.) in pregnant women with GDM.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Glucose Intolerance; Probiotics; Adipokines; Cytokines
PubMed: 36296986
DOI: 10.3390/nu14204303