Correction: Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation.
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ABSTRACT:
SUBMITTER: Ding P
PROVIDER: S-EPMC9263109 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Accumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.
| S-EPMC8016915 | biostudies-literature
Project description:Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders. To investigate this hypothesis, changes in the gut microbiota, insulin and glucose intolerance, and levels of tissue inflammation were analysed in mice after oral administration of Porphyromonas gingivalis, a representative periodontopathogens. Pyrosequencing revealed that the population belonging to Bacteroidales was significantly elevated in P. gingivalis-administered mice which coincided with increases in insulin resistance and systemic inflammation. In P. gingivalis-administered mice blood endotoxin levels tended to be higher, whereas gene expression of tight junction proteins in the ileum was significantly decreased. These results provide a new paradigm for the interrelationship between periodontitis and systemic diseases.
| S-EPMC4010932 | biostudies-literature
Project description:Chronic sleep fragmentation (SF) commonly occurs in human populations, and although it does not involve circadian shifts or sleep deprivation, it markedly alters feeding behaviors ultimately promoting obesity and insulin resistance. These symptoms are known to be related to the host gut microbiota. Mice were exposed to SF for 4 weeks and then allowed to recover for 2 weeks. Taxonomic profiles of fecal microbiota were obtained prospectively, and conventionalization experiments were performed in germ-free mice. Adipose tissue insulin sensitivity and inflammation, as well as circulating measures of inflammation, were assayed. Effect of fecal water on colonic epithelial permeability was also examined. Chronic SF-induced increased food intake and reversible gut microbiota changes characterized by the preferential growth of highly fermentative members of Lachnospiraceae and Ruminococcaceae and a decrease of Lactobacillaceae families. These lead to systemic and visceral white adipose tissue inflammation in addition to altered insulin sensitivity in mice, most likely via enhanced colonic epithelium barrier disruption. Conventionalization of germ-free mice with SF-derived microbiota confirmed these findings. Thus, SF-induced metabolic alterations may be mediated, in part, by concurrent changes in gut microbiota, thereby opening the way for gut microbiome-targeted therapeutics aimed at reducing the major end-organ morbidities of chronic SF.
| S-EPMC5064361 | biostudies-literature
Project description:Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs -/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.
| S-EPMC6187193 | biostudies-literature
Project description:Imbalance of gut microbiota can induce or aggravate intestinal inflammation. To enhance our understanding of the molecular mechanisms of gut microbiota and inflammatory bowel disease (IBD), we studied the role of repulsive guidance molecule b (RGMb) in gut microbiota and colitis in mice. We generated Rgmb knockout mice and inducible Rgmb knockout mice and induced colitis using dextran sulfate sodium (DSS) in these mice. 16S ribosomal RNA (rRNA) high-throughput sequencing was performed to acquire the gut microbiota composition and abundance. We found that Rgmb deficiency significantly altered the diversity of gut microbiota and also induced dysbiosis. In sharp contrast to the balanced distribution of various bacteria in control mice, Prevotellaceae was almost exhausted in Rgmb-deficient mice under both basal and inflammatory conditions. Correlation analysis indicated that Prevotellaceae was negatively associated with inflammation in Rgmb-deficient mice with colitis. Similar results were obtained at the early inflammatory stage of colitis associated colon cancer (CAC). Taken together, our results reveal that Rgmb deficiency leads to dysbiosis of predominant gut microbiota under basal and inflammatory conditions. Rgmb-deficiency-mediated Prevotellaceae loss may render mice more susceptible to intestinal inflammation. Therefore, RGMb may be a novel potential target for reconstruction of the gut microbiota for the treatment of IBD.
| S-EPMC8113641 | biostudies-literature
Project description:Over the past few decades, the clinical outcomes of patients with cancer have significantly improved mostly owing to the development of effective chemotherapeutic treatments. However, chronic health conditions such as bone mass loss and risk of fragility fractures caused by chemotherapy have also emerged as crucial issues in patients treated for cancer. In this study, we aimed to understand the effect of eribulin mesylate (ERI), a microtubule-targeting agent currently used to treat metastatic breast cancer and certain subtypes of advanced sarcomas, on bone metabolism in mice. The administration of ERI reduced bone mass in mice, mainly by promoting osteoclast activity. Gene expression analysis of skeletal tissues revealed no change in the expression levels of the transcripts for RANK ligand, one of the master regulators of osteoclastogenesis; however, the transcript levels of osteoprotegerin, which neutralizes RANK ligand, were significantly reduced in ERI-treated mice compared with those in vehicle-treated controls, indicating a relative increase in RANK ligand availability after ERI treatment. In line with the increased bone resorption in ERI-treated mice, we found that zoledronate administration effectively suppressed bone loss in these mice. These results reveal a previously unrecognized effect of ERI on bone metabolism and suggest the application of bisphosphonates for patients with cancer undergoing treatment with ERI. Highlights • Eribulin administration led to bone mass loss in mice.• Eribulin-induced bone loss was not secondary to malnutrition or hypogonadism.• Eribulin promoted bone resorption but had little impact on bone formation.• The expression of osteoprotegerin transcripts was reduced in Eribulin-treated mice.• A single administration of Zoledronate completely suppressed bone mass loss induced by Eribulin.
| S-EPMC10248043 | biostudies-literature
Project description:The advent of vaccination and improved hygiene have eliminated many of the deadly infectious pathogens in developed nations. However, the incidences of inflammatory diseases, such as inflammatory bowel disease, asthma, obesity and diabetes are increasing dramatically. Research in the recent decades revealed that it is indeed the lack of early childhood microbial exposure, increase use of antibiotics, as well as increase consumption of processed foods high in carbohydrates and fats, and lacking fibre, which wreak havoc on the proper development of immunity and predispose the host to elevated inflammatory conditions. Although largely unexplored and under-appreciated until recent years, these factors impact significantly on the composition of the gut microbiota (a collection of microorganisms that live within the host mucosal tissue) and inadvertently play intricate and pivotal roles in modulating an appropriate host immune response. The suggestion that shifts in the composition of host microbiota is a risk factor for inflammatory disease raises an exciting opportunity whereby the microbiota may also present as a potential modifiable component or therapeutic target for inflammatory diseases. This review provides insights into the interactions between the microbiota and the immune system, how these affect disease phenotypes, and explore current and emerging therapies that target the gut microbiota as potential treatment for inflammatory diseases.
| S-EPMC4855262 | biostudies-other
Project description:ObjectiveGut microbes and microbe-dependent metabolites (eg, tryptophan-kynurenine-serotonin pathway metabolites) have been linked to systemic inflammation, but the microbiota-metabolite-inflammation axis remains uncharacterised in children. Here we investigated whether gut microbiota features and circulating metabolites (both microbe-dependent and non-microbe-dependent metabolites) associated with circulating inflammation markers in children.MethodsWe studied children from the prospective Gen3G birth cohort who had data on untargeted plasma metabolome (n=321 children; Metabolon platform), gut microbiota (n=147; 16S rRNA sequencing), and inflammation markers (plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1, and tumour necrosis factor-α) measured at 5-7 years. We examined associations of microbial taxa and metabolites-examining microbe-dependent and non-microbe-dependent metabolites separately-with each inflammatory marker and with an overall inflammation score (InfSc), adjusting for key confounders and correcting for multiple comparisons. We also compared the proportion of significantly associated microbe-dependent versus non-microbe-dependent metabolites, identified a priori (Human Microbial Metabolome Database), with each inflammation marker.ResultsOf 335 taxa tested, 149 were associated (qFDR<0.05) with at least one inflammatory marker; 10 of these were robust to pseudocount choice. Several bacterial taxa involved in tryptophan metabolism were associated with inflammation, including kynurenine-degrading Ruminococcus, which was inversely associated with all inflammation markers. Of 1037 metabolites tested, 315 were previously identified as microbe dependent and were more frequently associated with PAI-1 and the InfSc than non-microbe dependent metabolites. In total, 87 metabolites were associated (qFDR<0.05) with at least one inflammation marker, including kynurenine (positively), serotonin (positively), and tryptophan (inversely).ConclusionA distinct set of gut microbes and microbe-dependent metabolites, including those involved in the tryptophan-kynurenine-serotonin pathway, may be implicated in inflammatory pathways in childhood.
| S-EPMC11367355 | biostudies-literature
Project description:The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Thus, the systemic effects of small differences in the oral microbiota are unclear. In this study, we explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects by analyzing the hepatic gene expression and serum metabolomic profiles. The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Samples were collected five weeks after administration. Gut microbial communities were analyzed by 16S ribosomal RNA gene sequencing. Hepatic gene expression profiles were analyzed using a DNA microarray and quantitative polymerase chain reaction. Serum metabolites were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The gut microbial composition at the genus level was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of Neat1, Mt1, Mt2, and Spindlin1, which are involved in lipid and glucose metabolism. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with Bifidobacterium, Atomobium, Campylobacter, and Haemophilus, which are characteristic taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.
2022-08-17 | GSE198570 | GEO
Project description:Systemic chronic hypoxia is a feature of many diseases and may influence the communication between bone marrow (BM) and gut microbiota. Here we analyse patients with cyanotic congenital heart disease (CCHD) who are experiencing chronic hypoxia and characterize the association between bone marrow mesenchymal stem cells (BMSCs) and gut microbiome under systemic hypoxia. We observe premature senescence of BMSCs and abnormal D-galactose accumulation in patients with CCHD. The hypoxia that these patients experience results in an altered diversity of gut microbial communities, with a remarkable decrease in the number of Lactobacilli and a noticeable reduction in the amount of enzyme-degraded D-galactose. Replenishing chronic hypoxic rats with Lactobacillus reduced the accumulation of D-galactose and restored the deficient BMSCs. Together, our findings show that chronic hypoxia predisposes BMSCs to premature senescence, which may be due to gut dysbiosis and thus induced D-galactose accumulation.
| S-EPMC5964076 | biostudies-literature