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Nature Communications Apr 2023Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show...
Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.
Topics: Humans; Mice; Male; Animals; Pyroptosis; Liver Cirrhosis; Liver; Hepatocytes; Bile Acids and Salts; Caspases; Mice, Inbred C57BL
PubMed: 37005411
DOI: 10.1038/s41467-023-37459-z -
Signal Transduction and Targeted Therapy Jan 2023The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be...
The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.
Topics: Mice; Animals; Dysbiosis; Vascular Endothelial Growth Factor A; Aminoquinolines; Cytokines; Psoriasis; Mice, Transgenic; Inflammation; Phenotype; Fatty Acids
PubMed: 36710269
DOI: 10.1038/s41392-022-01219-0 -
Gut Microbes 2021Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However,...
Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to "leak" into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.
Topics: Animals; Bacteroidetes; Brain; Brain-Gut Axis; Depression; Dysbiosis; Gastrointestinal Microbiome; Indoleamine-Pyrrole 2,3,-Dioxygenase; Intestines; Kynurenine; Male; Mice; Neurotransmitter Agents; Probiotics; Restraint, Physical; Tryptophan
PubMed: 33535879
DOI: 10.1080/19490976.2020.1869501 -
Cell Host & Microbe Apr 2023Phages are highly abundant in the human gut, yet most of them remain uncultured. Here, we present a gut phage isolate collection (GPIC) containing 209 phages for 42...
Phages are highly abundant in the human gut, yet most of them remain uncultured. Here, we present a gut phage isolate collection (GPIC) containing 209 phages for 42 commensal human gut bacterial species. Genome analysis of the phages identified 34 undescribed genera. We discovered 22 phages from the Salasmaviridae family that have small genomes (∼10-20 kbp) and infect Gram-positive bacteria. Two phages from a candidate family, Paboviridae, with high prevalence in the human gut were also identified. Infection assays showed that Bacteroides and Parabacteroides phages are specific to a bacterial species, and strains of the same species also exhibit substantial variations in phage susceptibility. A cocktail of 8 phages with a broad host range for Bacteroides fragilis strains effectively reduced their abundance in complex host-derived communities in vitro. Our study expands the diversity of cultured human gut bacterial phages and provides a valuable resource for human microbiome engineering.
Topics: Humans; Bacteriophages; Gastrointestinal Microbiome; Bacteria; Microbiota; Symbiosis
PubMed: 37054680
DOI: 10.1016/j.chom.2023.03.013 -
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 -
Gut Microbes 2021is the type strain for the genus , a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in... (Review)
Review
is the type strain for the genus , a group of gram-negative anaerobic bacteria that commonly colonize the gastrointestinal tract of numerous species. First isolated in the 1930s from a clinical specimen as , the strain was re-classified to form the new genus in 2006. Currently, the genus consists of 15 species, 10 of which are listed as 'validly named' (, and ) and 5 'not validly named' (, and ) by the List of Prokaryotic names with Standing in Nomenclature. The genus has been associated with reports of both beneficial and pathogenic effects in human health. Herein, we review the literature on the history, ecology, diseases, antimicrobial resistance, and genetics of this bacterium, illustrating the effects of on human and animal health.
Topics: Animals; Anti-Bacterial Agents; Bacteroidetes; Drug Resistance, Bacterial; Gastrointestinal Microbiome; Gram-Negative Bacterial Infections; Humans; Phylogeny; Probiotics
PubMed: 34196581
DOI: 10.1080/19490976.2021.1922241 -
Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities.Scientific Reports Sep 2019The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and... (Randomized Controlled Trial)
Randomized Controlled Trial
The gut microbiota (GM) is related to obesity and other metabolic diseases. To detect GM markers for obesity in patients with different metabolic abnormalities and investigate their relationships with clinical indicators, 1,914 Chinese adults were enrolled for 16S rRNA gene sequencing in this retrospective study. Based on GM composition, Random forest classifiers were constructed to screen the obesity patients with (Group OA) or without metabolic diseases (Group O) from healthy individuals (Group H), and high accuracies were observed for the discrimination of Group O and Group OA (areas under the receiver operating curve (AUC) equal to 0.68 and 0.76, respectively). Furthermore, six GM markers were shared by obesity patients with various metabolic disorders (Bacteroides, Parabacteroides, Blautia, Alistipes, Romboutsia and Roseburia). As for the discrimination with Group O, Group OA exhibited low accuracy (AUC = 0.57). Nonetheless, GM classifications to distinguish between Group O and the obese patients with specific metabolic abnormalities were not accurate (AUC values from 0.59 to 0.66). Common biomarkers were identified for the obesity patients with high uric acid, high serum lipids and high blood pressure, such as Clostridium XIVa, Bacteroides and Roseburia. A total of 20 genera were associated with multiple significant clinical indicators. For example, Blautia, Romboutsia, Ruminococcus2, Clostridium sensu stricto and Dorea were positively correlated with indicators of bodyweight (including waistline and body mass index) and serum lipids (including low density lipoprotein, triglyceride and total cholesterol). In contrast, the aforementioned clinical indicators were negatively associated with Bacteroides, Roseburia, Butyricicoccus, Alistipes, Parasutterella, Parabacteroides and Clostridium IV. Generally, these biomarkers hold the potential to predict obesity-related metabolic abnormalities, and interventions based on these biomarkers might be beneficial to weight loss and metabolic risk improvement.
Topics: Adult; Biomarkers; Body Mass Index; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged; Obesity
PubMed: 31530820
DOI: 10.1038/s41598-019-49462-w -
Nature Communications Nov 2023Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides...
Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.
Topics: Animals; Humans; Mice; Case-Control Studies; Diabetes Mellitus, Type 2; Dietary Fiber; Insulin Resistance
PubMed: 38007572
DOI: 10.1038/s41467-023-43622-3 -
Frontiers in Psychiatry 2019Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder...
Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. A PubMed literature search combined the terms "depression," "depressive disorder," "stool," "fecal," "gut," and "microbiome" to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Six eligible studies were found in which 50 taxa exhibited differences ( < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-, and -were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum , in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (, and ), six were lower (, and ), and six were divergent (, and ). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.
PubMed: 30804820
DOI: 10.3389/fpsyt.2019.00034 -
Nutrients Mar 2020Autism spectrum disorder (ASD) is a public health problem and has a prevalence of 0.6%-1.7% in children. As well as psychiatric symptoms, dysbiosis and gastrointestinal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Autism spectrum disorder (ASD) is a public health problem and has a prevalence of 0.6%-1.7% in children. As well as psychiatric symptoms, dysbiosis and gastrointestinal comorbidities are also frequently reported. The gut-brain microbiota axis suggests that there is a form of communication between microbiota and the brain underlying some neurological disabilities. The aim of this study is to describe and compare the composition of gut microbiota in children with and without ASD.
METHODS
Electronic databases were searched as far as February 2020. Meta-analyses were performed using RevMan5.3 to estimate the overall relative abundance of gut bacteria belonging to 8 phyla and 17 genera in children with ASD and controls.
RESULTS
We included 18 studies assessing a total of 493 ASD children and 404 controls. The microbiota was mainly composed of the phyla Bacteroidetes, Firmicutes, and Actinobacteria, all of which were more abundant in the ASD children than in the controls. Children with ASD showed a significantly higher abundance of the genera , , , and and a lower percentage of and .
DISCUSSION
This meta-analysis suggests that there is a dysbiosis in ASD children which may influence the development and severity of ASD symptomatology. Further studies are required in order to obtain stronger evidence of the effectiveness of pre- or probiotics in reducing autistic behaviors.
Topics: Autism Spectrum Disorder; Bacteria; Child; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Male
PubMed: 32192218
DOI: 10.3390/nu12030792