Gut microbiome dysbiosis alleviates the progression of osteoarthritis in mice

Abstract Gut microbiota dysbiosis has been studied under the pathological conditions of osteoarthritis (OA). However, the effect of antibiotic-induced gut flora dysbiosis on OA remains incompletely understood at present. Herein, we used a mouse (8 weeks) OA model of destabilization of the medial meniscus (DMM) and gut microbiome dysbiosis induced by antibiotic treatment with ampicillin and neomycin for 8 weeks. The results show that antibiotic-induced intestinal microbiota dysbiosis reduced the serum level of lipopolysaccharide (LPS) and the inflammatory response, such as suppression of the levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which can lead to decreased matrix metalloprotease-13 (MMP-13) expression and improvement of OA after joint injury. In addition, trabecular thickness (Tb.Th) and osteophyte scores were increased significantly in antibiotic-induced male mice compared with female mice. We further used network correlation analysis to verify the effect of gut microbiota dysbiosis on OA. Therefore, the present study contributes to our understanding of the gut–joint axis in OA and reveals the relationship between the inflammatory response, sex and gut microbiota, which may provide new strategies to prevent the symptoms and long-term sequelae of OA. Conclusion: Our data showed that gut microbiome dysbiosis alleviates the progression of OA.

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Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris

Frontiers in Nutrition ◽

10.3389/fnut.2021.761978 ◽

2021 ◽

Vol 8 ◽

Author(s):

Chaonan Sun ◽

Ling Chen ◽

Huan Yang ◽

Hongjiang Sun ◽

Zhen Xie ◽

...

Keyword(s):

Gut Microbiota ◽

Abdominal Distension ◽

Fecal Microbiota ◽

Ultraviolet B ◽

Healthy Controls ◽

Gastrointestinal Discomfort ◽

Delayed Recovery ◽

The Relationship ◽

Gut Microbiota Dysbiosis

Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development.Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls.Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively).Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.

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Dysbiotic Gut Microbiota and Dysregulation of Cytokine Profile in Children and Teens With Autism Spectrum Disorder

Frontiers in Neuroscience ◽

10.3389/fnins.2021.635925 ◽

2021 ◽

Vol 15 ◽

Author(s):

Xia Cao ◽

Kevin Liu ◽

Jun Liu ◽

Yen-Wenn Liu ◽

Li Xu ◽

...

Keyword(s):

Gut Microbiota ◽

Inflammatory Cytokines ◽

Gut Microbiome ◽

Plasma Levels ◽

Autism Spectrum ◽

Tnf Α ◽

Healthy Control ◽

Ifn Γ ◽

The Relationship ◽

Pro Inflammatory Cytokines

Inflammation and the gut-brain axis have been implicated in the pathogenesis of autism spectrum disorders (ASDs). To further understand the relationship between aberrant immune responses and dysbiotic features of the gut microbiome in ASD, we enrolled 45 ASD individuals and 41 healthy control subjects with ages ranging from 2 to 19 years. We found that ASD group subjects have significantly higher plasma levels of IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, TNF-β, and IFN-γ when compared to healthy controls (FDR-adjusted p < 0.05). The plasma levels of pro-inflammatory cytokines IFN-γ and IL-6 are found to be further associated with several largely pathogenic gut microbiota uniquely detected in subjects with ASD. Furthermore, the ASD gut microbiome is characterized by reduced levels of several beneficial microbiota, including Bacteroides (FDR-adjusted p < 0.01) and Lachnospiraceae (FDR-adjusted p < 0.001). Analysis of Lachnospiraceae family and genus level taxa suggested that relative abundances of such taxa are negatively correlated with pro-inflammatory signaling cytokines IFN-γ and IL-6, particularly in subjects with severe ASD as defined by CARS (p < 0.05). Several largely pathogenic genera are determined to be associated with the pro-inflammatory cytokines IFN-γ and IL-6 (FDR-adjusted p < 0.1). Additionally, IL-4 is significantly negatively correlated with CARS total score (p < 0.05). Based on such results, we propose that the association between the disturbances of specific cytokines and alterations in gut microbiota abundance observed in children and adolescents with ASD provides additional evidence on the induction of aberrant pro-inflammatory mechanisms in ASD and its early diagnosis.

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Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris

10.1101/2020.11.16.20232025 ◽

2020 ◽

Author(s):

Chaonan Sun ◽

Ling Chen ◽

Huan Yang ◽

Hongjiang Sun ◽

Zhen Xie ◽

...

Keyword(s):

Gut Microbiota ◽

Abdominal Distension ◽

Fecal Microbiota ◽

Healthy Controls ◽

Gastrointestinal Discomfort ◽

Delayed Recovery ◽

The Relationship ◽

Term Management ◽

Gut Microbiota Dysbiosis

AbstractBackgroundPsoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis.ObjectivesWe intend to further investigate the relationship between intestinal microbiota and psoriasis development.MethodsWe first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between psoriatic patients and general population. Then variation of gut microbiota in psoriatic patients (un)treated with Acitretin was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines of mouse psoriasiform models, which were transplanted with fecal microbiota from psoriatic patients or healthy controls.Results(1) 85.53% of psoriatic patients versus 58.08% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g. abdominal distension, constipation) were significantly higher in patients, compared with controls (p<0.05). Increased fart and constipation were significantly correlated with psoriasis (p<0.05, respectively). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus and Blautia genus were significantly decreased with psoriasis improvement, which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microflora transplantation showed significantly delayed recovery of psoriasiform dermatitis and less reduction of IL-17A, than those receiving healthy microflora or blank control (p<0.05 and p<0.01, respectively).ConclusionsMultiple evidences we provided here demonstrate the involvement of gut microbiota in psoriasis development. The strategy based on gut microbiota is expected to be a promising supplementary for long-term management of psoriasis.

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Persistence and reversibility of arsenic-induced gut microbiome and metabolome shifts in rats after 30-days recovery duration

10.21203/rs.3.rs-29645/v1 ◽

2020 ◽

Author(s):

Xiaoyan Du ◽

Jie Zhang ◽

Karl-Werner Schramm ◽

Qingyu Huang ◽

Meiping Tian ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Arsenic Exposure ◽

Male Rats ◽

Recovery Duration ◽

Contaminated Drinking Water ◽

Important Host ◽

Novel Strategy ◽

The Relationship

Abstract Background: The metabolites of gut microbiome are important host-health regulating factors and can be easily interrupted by the host exposure to environmental pollution via ingestion route. Arsenic contaminated drinking water is one of the most serious environmental problems worldwide. Therefore, the arsenic-induced alterations of gut microbiome and the metabolome, especially the persistence and reversibility parts of the alterations after the long-term arsenic exposure will be interesting to know. Results: We investigated the relationship between gut microbiota and its related metabolites in male rats both after the 30-days arsenic treatment and 30-days recovery duration. The composition and diversity of gut microbiota were affected significantly by the treatment, but they presented partial improvement in recovery duration. Moreover, arsenic exposure induced the significant changes of 73 metabolites, which involved in the metabolism of glycerophospholipid, linoleic acid, as well as the biosynthesis of phenylalanine, tyrosine and tryptophan. Although it had a persistent effect, the restoration of glycerophospholipid metabolism was observed in the 30-days recovery. Integration analysis further correlated the arsenic impacting microbes with some important differential metabolites, but only Lactobacillus associated with the decreases of phosphatidylethanolamine(34:1) , 16alpha-hydroxydehydroepiandrosterone 3-sulfate, seryltryptophan and alanyltyrosine in the recovery. Lactobacillus strains have potential to work as protective agents against arsenic toxicity by restoring perturbed glycerophospholipid metabolism. Conclusions: Arsenic significantly modified gut microbiome and metabolome, but arsenic-induced disruptions of gut microbiome and metabolome are reversible to some extent after a 30-days recovery. The deeper understanding of correlation of altered gut microbiome and metabolome could be a novel strategy to combat arsenic-induced disease.

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Bifico Relieves Irritable Bowel Syndrome By Regulating Gut Microbiota Dysbiosis and Inflammatory Cytokines in an Animal Model

10.21203/rs.3.rs-717837/v1 ◽

2021 ◽

Author(s):

Yanlin Zhou ◽

Fan Zhang ◽

Liqi Mao ◽

Tongfei Feng ◽

Kaijie Wang ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Inflammatory Cytokines ◽

Short Chain Fatty Acids ◽

Intragastric Administration ◽

Protein Levels ◽

Tnf Α ◽

Irritable Bowel ◽

Factor Α ◽

Gut Microbiota Dysbiosis

Abstract Gut microbiota dysbiosis, a core pathophysiology of irritable bowel syndrome (IBS), is closely related to immunological and metabolic functions. Gut microbiota-based therapeutics have been recently explored in several studies. Bifico is a probiotic cocktail widely used in gastrointestinal disorders which relate to the imbalance of gut microbiota. However, the efficacy and potential mechanisms of Bifico treatment in IBS remains incompletely understood. In this animal experiment, IBS mice received Bifico by intragastric administration. Subsequently, abdominal withdrawal reflex (AWR) scores showed a protective effect of Bifico in IBS mice. Then 16S rDNA, 1H nuclear magnetic resonance (1H-NMR) and western blot assays were performed to analyze alterations of gut microbiota, microbiome metabolites and inflammatory cytokines, respectively. Results suggested that while Bifico did not increase gut microbial diversity, it could change the composition of gut microbiota which were characterized by an increase of Proteobacteria phylum and Actinobacteria phylum, Muribaculum genera, Bifidobacterium genera and a decrease of Parabacteroides genera, Sutterella genera and Lactobacillus genera. Moreover, Bifico elevated the concentration of short-chain fatty acids (SCFAs) and reduced protein levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). From further Spearman's correlation analysis, Bifidobacterium genera were positively correlated with SCFAs including propionate, butyrate, valerate and negatively correlated with IL-6 and TNF-α. In conclusion, this study demonstrated that Bifico could alleviate symptoms of IBS mice through regulation of the gut microbiota, elevating production of SCFAs and reducing the colonic inflammatory response. Therefore, Bifico may have utility in clinical practice.

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Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽

10.3390/life11030246 ◽

2021 ◽

Vol 11 (3) ◽

pp. 246

Author(s):

Felix C.F. Schmitt ◽

Martin Schneider ◽

William Mathejczyk ◽

Markus A. Weigand ◽

Jane C. Figueiredo ◽

...

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Gut Microbiota ◽

Gut Microbiome ◽

Tumor Resection ◽

Microbial Composition ◽

Colorectal Cancer Surgery ◽

Long Term Changes ◽

Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

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Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation

Communications Biology ◽

10.1038/s42003-021-01741-x ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Travis T. Sims ◽

Molly B. El Alam ◽

Tatiana V. Karpinets ◽

Stephanie Dorta-Estremera ◽

Venkatesh L. Hegde ◽

...

Keyword(s):

Cervical Cancer ◽

Radiation Therapy ◽

Gut Microbiota ◽

Cancer Patients ◽

Gut Microbiome ◽

Compositional Variation ◽

Short Term ◽

Microbiome Diversity ◽

Term Survivor

AbstractDiversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought to determine if diversity and composition of the gut microbiome was independently associated with survival in cervical cancer patients receiving chemoradiation. Our study demonstrates that the diversity of gut microbiota is associated with a favorable response to chemoradiation. Additionally, compositional variation among patients correlated with short term and long-term survival. Short term survivor fecal samples were significantly enriched in Porphyromonas, Porphyromonadaceae, and Dialister, whereas long term survivor samples were significantly enriched in Escherichia Shigella, Enterobacteriaceae, and Enterobacteriales. Moreover, analysis of immune cells from cervical tumor brush samples by flow cytometry revealed that patients with a high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ over the course of radiation therapy. Modulation of the gut microbiota before chemoradiation might provide an alternative way to enhance treatment efficacy and improve treatment outcomes in cervical cancer patients.

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Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

Nutrients ◽

10.3390/nu13051426 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1426

Author(s):

Mauro Lombardo ◽

Giovanni Aulisa ◽

Daniele Marcon ◽

Gianluca Rizzo ◽

Maria Grazia Tarsisano ◽

...

Keyword(s):

Gut Microbiota ◽

Fish Consumption ◽

Plasma Levels ◽

Cooking Methods ◽

Saltwater Fish ◽

Increased Risk ◽

Mediator Role ◽

Fish And Shellfish ◽

The Relationship

Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.

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Chlorogenic Acid and Geniposide Combination Prevents NASH in Rats Fed High-fat diet via Microbiota and TLR4-LPS Pathway

10.21203/rs.3.rs-238577/v1 ◽

2021 ◽

Author(s):

Zhijia Zhou ◽

Lingxia Xu ◽

Shaoliang Zhang ◽

Shilin Xu ◽

Yanmiao Yang ◽

...

Keyword(s):

Gut Microbiota ◽

Chlorogenic Acid ◽

Inflammatory Cytokines ◽

High Fat Diet ◽

Oral Treatment ◽

Variable Region ◽

High Fat ◽

Tnf Α ◽

Abundance And Diversity ◽

Factor Α

Abstract Objective: Chlorogenic acid and geniposide (CG) are derived from traditional Chinese medicine, Yinchenhao Recipe (QCHR), and can improve the clinical efficacy of NASH patients. This study investigated the effects of CG on NASH and expounded its Potential mechanism of action through the LPS-TLR4 pathway and microbiota. Methods: Rats were randomized into Control (C), Model (M), Chlorogenic Acid and Geniposide (CG), Pioglitazone (PH) and Bifico (B) groups. After an 8-week high-fat diet (HFD), CG, PH and B oral treatment were initiated and carried out for a further 8 weeks. The stool samples were used in a16S rDNA V4 highly variable region measurement method in order to regulate the role of CG in gut microbiota. The concentrations of triglyceride (TG), cholesterol (CHO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in LPS were detected by the corresponding methods. Results: Observations were made that CG significantly improved the pathology of the liver and terminal ileum tissue. The accumulation of TG and the content of inflammatory cytokines in the liver were significantly decreased and the abundance of Proteobacteria was significantly down-regulated. The expression of TLR4, AP-1, MyD88, and phosphorylated NF-κB p65 were significantly decreased. All the findings above indicated that CG was highly effective in improving the composition of gut microbiota, decreasing the production of endogenous LPS, and reducing the secretion of inflammatory cytokines through the gut-liver axis.Conclusion: CG can regulate the abundance and diversity of the intestinal microbial community and improve liver inflammation and steatosis in NASH rats by reducing LPS-TLR4-mediated inflammation.

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Aggravation of endotoxin-induced disseminated intravascular coagulation and cytokine activation in heterozygous protein-C–deficient mice

Blood ◽

10.1182/blood-2002-10-3254 ◽

2003 ◽

Vol 101 (12) ◽

pp. 4823-4827 ◽

Cited By ~ 108

Author(s):

Marcel Levi ◽

Janine Dörffler-Melly ◽

Pieter Reitsma ◽

Harry Büller ◽

Sandrine Florquin ◽

...

Keyword(s):

Inflammatory Response ◽

Disseminated Intravascular Coagulation ◽

Protein C ◽

Activated Protein C ◽

Intravascular Coagulation ◽

Cytokine Activation ◽

Tnf Α ◽

Single Allele ◽

Factor Α ◽

Heterozygous Deficiency

Abstract In the pathogenesis of sepsis and disseminated intravascular coagulation (DIC), dysfunctional anticoagulant pathways are important. The function of the protein C system in DIC is impaired because of low levels of protein C and down-regulation of thrombomodulin. The administration of (activated) protein C results in an improved outcome in experimental and clinical studies of DIC. It is unknown whether congenital deficiencies in the protein C system are associated with more severe DIC. The aim of the present study was to investigate the effect of a heterozygous deficiency of protein C on experimental DIC in mice. Mice with single-allele targeted disruption of the protein C gene (PC+/–) mice and wild-type littermates (PC+/+) were injected with Escherichia coli endotoxin (50 mg/kg) intraperitoneally. PC+/–mice had more severe DIC, as evidenced by a greater decrease in fibrinogen level and a larger drop in platelet count. Histologic examination showed more fibrin deposition in lungs, kidneys, and liver in mice with a heterozygous deficiency of protein C. Interestingly, PC+/– mice had significantly higher levels of proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, indicating an interaction between the protein C system and the inflammatory response. Survival was lower at 12 and 24 hours after endotoxin in the PC+/– mice. These results confirm the important role of the protein C system in the coagulative-inflammatory response on endotoxemia and may suggest that congenital deficiencies in the protein C system are associated with more severe DIC and adverse outcome in sepsis.

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