Alteration of the gut microbiota in rhesus monkey with spontaneous osteoarthritis

Abstract Background The spontaneous osteoarthritis (OA) in rhesus macaque is similar to OA in human, which maintains an upright body posture and shows very similar biomechanical properties of bones to humans. At present, there is no good treatment for OA. This study aims to explore relationship between OA and intestinal microbiota, and provide a reference for the treatment of clinical OA. Results We collected colonic contents of the 20 rhesus macaque (6–15 years old, female) for intestinal microbiota analysis by metagenomics sequencing, of which 10 were spontaneous OA monkeys and 10 were normal monkeys. Our results showed the diversity of gut microbiota in monkeys with OA was decreased compared to the normal monkeys (p = 0.16). Mollicutes, Tenericutes, Coprobacillus and Faecalitalea may be biomarkers for the monkeys of OA. Lactobacillus found significantly increased in OA monkeys. Prevotella and Ruminococcus were higher in the normal group than OA group. Zinc/manganese transport system permease protein (p = 0.0011) and Cyclopropane-fatty-acyl-phospholipid synthase (p = 0.0012) are a microbiota metabolic pathway related to cartilage production. Conclusions Our results indicate that the diversity and composition of intestinal microbiota in monkeys with OA are different compared to the normal monkeys. we have found microbes that may be a biomarker for the diagnosis of osteoarthritis. Functional analysis of the microbiota also predicts cartilage damage in the monkeys with osteoarthritis. Non-human primates are closely related to humans, so this study can provide a reference for the development of drugs for the treatment of OA.

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Alteration of the Gut Microbiota in Rhesus Monkey with Spontaneous Osteoarthritis

10.21203/rs.3.rs-612619/v1 ◽

2021 ◽

Author(s):

Yaping Yan ◽

Xiaoyan Yi ◽

Yanchao Duan ◽

Bin Jiang ◽

Tianzhuang Huang ◽

...

Keyword(s):

Rhesus Macaque ◽

Intestinal Microbiota ◽

Biomarker Discovery ◽

Cartilage Damage ◽

Antibiotic Use ◽

Living Environment ◽

Genomic Features ◽

Linear Discriminant ◽

R Packages

Abstract Background Osteoarthritis (OA) can cause stiffness and chronic pain, which affect patients' health and quality of life. Emerging evidence suggests the microbiome plays an important role in the pathogenesis of OA. However, there are very few studies on the intestinal microbiota of OA. The spontaneous osteoarthritis in rhesus macaque is similar to osteoarthritis in human. The artificially reared macaques showed that captivity “humanizes” the primate microbiome can also better control the diet and drug use. Methods We collected colonic contents of the rhesus macaque with spontaneous OA for intestinal microbiota analysis by metagenomics sequencing. The data were analyzed using R packages. The genomic features were identified by a metagenomic biomarker discovery approach called linear discriminant analysis effect size. Results Our results indicate that the diversity and composition of intestinal microbiota in monkeys with OA are different compared to the normal monkeys. Prevotellaceae and Lactobacillus was significantly decreased in the monkeys with osteoarthritis. Lactobacillales, Lactobacillaceae, Mycoplasmataceae and Lactobacillus were significantly increased in the monkeys with OA. Functional analysis of the microbiota also predicts cartilage damage in the monkeys with osteoarthritis. Conclusions Our results are largely consistent with the composition of microbiota in cartilage of OA patients. Our results exclude the effects of food, living environment, and antibiotic use, so we have found some microbes that can be a biomarker for the diagnosis of osteoarthritis.

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Modulation of Gut Microbiota for the Prevention and Treatment of COVID-19

Journal of Clinical Medicine ◽

10.3390/jcm10132903 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2903

Author(s):

Jiezhong Chen ◽

Luis Vitetta

Keyword(s):

Clinical Trials ◽

Trace Elements ◽

Gut Microbiota ◽

Human Health ◽

Intestinal Microbiota ◽

Narrative Review ◽

Bacterial Metabolites ◽

Gut Dysbiosis ◽

Prevention And Treatment

The gut microbiota is well known to exert multiple benefits on human health including protection from disease causing pathobiont microbes. It has been recognized that healthy intestinal microbiota is of great importance in the pathogenesis of COVID-19. Gut dysbiosis caused by various reasons is associated with severe COVID-19. Therefore, the modulation of gut microbiota and supplementation of commensal bacterial metabolites could reduce the severity of COVID-19. Many approaches have been studied to improve gut microbiota in COVID-19 including probiotics, bacterial metabolites, and prebiotics, as well as nutraceuticals and trace elements. So far, 19 clinical trials for testing the efficacy of probiotics and synbiotics in COVID-19 prevention and treatment are ongoing. In this narrative review, we summarize the effects of various approaches on the prevention and treatment of COVID-19 and discuss associated mechanisms.

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Gut microbiota composition and arterial stiffness measured by pulse wave velocity: case–control study protocol (MIVAS study)

BMJ Open ◽

10.1136/bmjopen-2020-038933 ◽

2021 ◽

Vol 11 (2) ◽

pp. e038933

Author(s):

Rita Salvado ◽

Sandra Santos-Minguez ◽

Cristina Agudo-Conde ◽

Cristina Lugones-Sanchez ◽

Angela Cabo-Laso ◽

...

Keyword(s):

Arterial Stiffness ◽

Gut Microbiota ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Intestinal Microbiota ◽

Pulse Wave ◽

Case Control Study ◽

Case Control ◽

Microbiota Composition ◽

Control Study

IntroductionIntestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness.Methods and analysisAn observational case—control study will be developed. Cases will be defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), Cardio-Ankle Vascular Index (CAVI), brachial ankle pulse wave velocity (ba or ba-PWV) above the 90th percentile, for age and sex, of the reference population. Controls will be selected from the same population as cases. The study will be developed in Primary Healthcare Centres. We will select 500 subjects (250 cases and 250 controls), between 45 and 74 years of age. Cases will be selected from a database that combines data from EVA study (Spain) and Guimarães/Vizela study (Portugal). Measurements: cf-PWV will be measured using the SphygmoCor system, CAVI, ba-PWV and Ankle-Brachial Index will be determined using VaSera device. Gut microbiome composition in faecal samples will be determined by 16S ribosomal RNA sequencing. Lifestyle will be assessed by food frequency questionnaire, adherence to the Mediterranean diet and IPAQ (International Physical Activity Questionnaire). Body composition will be evaluated by bioimpedance.Ethics and disseminationThe study has been approved by ‘Committee of ethics of research with medicines of the health area of Salamanca’ on 14 December 2018 (cod. 2018-11-136) and the ’Ethics committee for health of Guimaraes’ (Portugal) on 15 October 2019 (ref: 67/2019). All study participants will sign an informed consent form agreeing to participate in the study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow a better description of gut microbiota in patients with arterial stiffness.Trial registration detailsClinicalTrials.gov, identifier NCT03900338

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A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽

10.3390/nu13072428 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2428

Author(s):

Małgorzata Guz ◽

Witold Jeleniewicz ◽

Anna Malm ◽

Izabela Korona-Glowniak

Keyword(s):

Colorectal Cancer ◽

Gastrointestinal Tract ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Knowledge ◽

Vital Role ◽

Disease States ◽

Health And Disease ◽

Dietary Components ◽

Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

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Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice

mSphere ◽

10.1128/msphere.00492-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 9

Author(s):

Alessandro Tanca ◽

Antonio Palomba ◽

Cristina Fraumene ◽

Valeria Manghina ◽

Michael Silverman ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Time Window ◽

High Resolution Mass Spectrometry ◽

Nod Mice ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Diabetic Mice ◽

Nonobese Diabetic ◽

Nonobese Diabetic Mice

ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD) at 10 weeks of age in the time window between insulitis development and T1D onset. The gut microbiota of NOD mice were investigated by analyzing stool samples with a metaproteogenomic approach, comprising both 16S rRNA gene sequencing and microbial proteome profiling through high-resolution mass spectrometry. A depletion of Firmicutes (particularly, several members of Lachnospiraceae) in the NOD gut microbiota was observed compared to the level in the Eα16/NOD mice microbiota. Moreover, the analysis of proteins actively produced by the gut microbiota revealed different profiles between NOD and Eα16/NOD mice, with the production of butyrate biosynthesis enzymes being significantly reduced in diabetic mice. Our results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate. IMPORTANCE Alterations of the gut microbiota early in age have been hypothesized to impact T1D autoimmune pathogenesis. In the NOD mouse model, protection from T1D has been found to operate via modulation of the composition of the intestinal microbiota during a critical early window of ontogeny, although little is known about microbiota functions related to T1D development. Here, we show which gut microbial functions are specifically associated with protection from T1D in the time window between insulitis development and T1D onset. In particular, we describe that production of butyrate biosynthesis enzymes is significantly reduced in NOD mice, supporting the hypothesis that modulating the gut microbiota butyrate production may influence T1D development.

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Gut microbiome dysbiosis in anorexia nervosa

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0014.8601 ◽

2021 ◽

Vol 75 ◽

pp. 283-291

Author(s):

Agata Janczy ◽

Magdalena Landowska ◽

Zdzisław Kochan

Keyword(s):

Anorexia Nervosa ◽

Gut Microbiota ◽

Body Mass ◽

Intestinal Microbiota ◽

Gut Microbiome ◽

Dietary Habits ◽

Eating Habits ◽

Current Knowledge ◽

Functional Gastrointestinal Disorders

Anorexia nervosa (AN) is described as an eating disorder, which is characterized by malnutrition, a fear of gaining body mass, and a disturbed self-body image. This disease is dependent on biological, psychological and socio-cultural factors. Among the various biological factors, the importance of intestinal microbiota has recently attracted much attention. Identification of the gut microbiota dysbiosis in patients with AN has opened new and promising research directions. Recent observations focus in particular on the association between intestinal microorganisms and the occurrence of functional gastrointestinal disorders associated with anorexia, anxiety and depression, as well as the regulation of eating habits. The composition of the gut microbiota differs between patients with AN and individuals with normal body mass. This is due to the incorrect diet of patients; on the other hand, there is growing interest in the role of intestinal microbiota in the pathogenesis of AN, its changes through re-nutrition practices, and in particular the modulation of intestinal microbiological composition by means of nutritional interventions or the use of preand probiotics as standard supplements therapy of eating disorders. There is a need for further research about the microbiome - intestine - brain axis. Furthermore, consequences of changes in dietary habits as part of AN treatment are also unknown. However, better knowledge about the relationship between the gut microbiome and the brain can help improve the treatment of this disorder. This review aims to present the current knowledge about the potential role of intestinal microbiota in the pathogenesis, course and treatment of AN.

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Integrated Fecal Microbiome and Serum Metabolomics Analysis Reveals Abnormal Changes in Rats with Immunoglobulin A Nephropathy and the Intervention Effect of Zhen Wu Tang

Frontiers in Pharmacology ◽

10.3389/fphar.2020.606689 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jicheng Li ◽

Yiwen Cao ◽

Ruirui Lu ◽

Honglian Li ◽

Yu Pang ◽

...

Keyword(s):

Gut Microbiota ◽

Renal Disease ◽

Intestinal Microbiota ◽

Renal Damage ◽

Immunoglobulin A ◽

Metabolic Phenotype ◽

Immunoglobulin A Nephropathy ◽

Metabolic Phenotypes ◽

Potential Relationship ◽

Rdna Sequencing

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.

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The Immunomodulatory Effect of the Gut Microbiota in Kidney Disease

Journal of Immunology Research ◽

10.1155/2021/5516035 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Mingxuan Chi ◽

Kuai Ma ◽

Jing Wang ◽

Zhaolun Ding ◽

Yunlong Li ◽

...

Keyword(s):

Kidney Disease ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Ischemia Reperfusion Injury ◽

Therapeutic Potential ◽

Kidney Diseases ◽

Ischemia Reperfusion ◽

Intestinal Flora ◽

Inflammatory Factors ◽

Renal Diseases

The human gut microbiota is a complex cluster composed of 100 trillion microorganisms, which holds a symbiotic relationship with the host under normal circumstances. Intestinal flora can facilitate the treatment of human metabolic dysfunctions and interact with the intestinal tract, which could influence intestinal tolerance, immunity, and sensitivity to inflammation. In recent years, significant interests have evolved on the association of intestinal microbiota and kidney diseases within the academic circle. Abnormal changes in intestinal microbiota, known as dysbiosis, can affect the integrity of the intestinal barrier, resulting in the bacterial translocation, production, and accumulation of dysbiotic gut-derived metabolites, such as urea, indoxyl sulfate (IS), and p-cresyl sulfate (PCS). These processes lead to the abnormal activation of immune cells; overproduction of antibodies, immune complexes, and inflammatory factors; and inflammatory cell infiltration that can directly or indirectly cause damage to the renal parenchyma. The aim of this review is to summarize the role of intestinal flora in the development and progression of several renal diseases, such as lupus nephritis, chronic kidney disease, diabetic nephropathy, and renal ischemia-reperfusion injury. Further research on these mechanisms should provide insights into the therapeutic potential of regulating intestinal flora and intervening related molecular targets for the abovementioned nephropathy.

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Particle Radiation Side-Effects: Intestinal Microbiota Composition Shapes Interferon-γ-Induced Osteo-Immunogenicity

Radiation Research ◽

10.1667/rade-21-00068.1 ◽

2021 ◽

Author(s):

Irene Maier ◽

Paul M Ruegger ◽

Julia Deutschmann ◽

Thomas H. Helbich ◽

Peter Pietschmann ◽

...

Keyword(s):

Bone Marrow ◽

Small Intestine ◽

Side Effects ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Interferon Γ ◽

Microbiota Composition ◽

Particle Radiation ◽

Bacterial Indicator ◽

Radiation Induced

Microbiota can both negatively and positively impact radiation-induced bone loss. Our prior research showed that compared to mice with conventional gut microbiota (CM), mice with restricted gut microbiota (RM) reduced inflammatory tumor necrosis factor (TNF) in bone marrow, interleukin (IL)-17 in blood, and chemokine (C-C motif) ligand 20 (CCL20) in bone marrow under anti-IL-17 treatment. We showed that Muribaculum intestinale was more abundant in intestinal epithelial cells (IECs) from the small intestine of female RM mice and positively associated with augmented skeletal bone structure. Female C57BL/6J pun RM mice, which were injected with anti-IL-17 antibody one day before exposure to 1.5 Gy 28Si ions of 850 MeV/u, showed high trabecular numbers in tibiae at 6 weeks postirradiation. Irradiated CM mice were investigated for lower interferon-γ and IL-17 levels in the small intestine than RM mice. IL-17 blockage resulted in bacterial indicator phylotypes being different between both microbiota groups before and after irradiation. Analysis of the fecal bacteria were performed in relation to bone quality and body weight, showing reduced tibia cortical thickness in irradiated CM mice (–15%) vs. irradiated RM mice (–9.2%). Correlation analyses identified relationships among trabecular bone parameters (TRI-BV/TV, Tb.N, Tb.Th, Tb.Sp) and Bacteroides massiliensis, Muribaculum sp. and Prevotella denticola. Turicibacter sp. was found directly correlated with trabecular separation in anti-IL-17 treated mice, whereas an unidentified Bacteroidetes correlated with trabecular thickness in anti-IL-17 neutralized and radiation-exposed mice. We demonstrated radiation-induced osteolytic damage to correlate with bacterial indicator phylotypes of the intestinal microbiota composition, and these relationships were determined from the previously discovered dose-dependent particle radiation effects on cell proliferation in bone tissue. New translational approaches were designed to investigate dynamic changes of gut microbiota in correlation with conditions of treatment and disease as well as mechanisms of systemic side-effects in radiotherapy.

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Influence of the Intestinal Microbiota on Colonization Resistance to Salmonella and the Shedding Pattern of Naturally Exposed Pigs

mSystems ◽

10.1128/msystems.00021-19 ◽

2019 ◽

Vol 4 (2) ◽

Cited By ~ 9

Author(s):

Héctor Argüello ◽

Jordi Estellé ◽

Finola C. Leonard ◽

Fiona Crispie ◽

Paul D. Cotter ◽

...

Keyword(s):

Public Health ◽

16S Rrna ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Control ◽

Growing Pigs ◽

Microbiota Composition ◽

Core Microbiome ◽

The Core ◽

The Impact

ABSTRACT Salmonella colonization and infection in production animals such as pigs are a cause for concern from a public health perspective. Variations in susceptibility to natural infection may be influenced by the intestinal microbiota. Using 16S rRNA compositional sequencing, we characterized the fecal microbiome of 15 weaned pigs naturally infected with Salmonella at 18, 33, and 45 days postweaning. Dissimilarities in microbiota composition were analyzed in relation to Salmonella infection status (infected, not infected), serological status, and shedding pattern (nonshedders, single-point shedders, intermittent-persistent shedders). Global microbiota composition was associated with the infection outcome based on serological analysis. Greater richness within the microbiota postweaning was linked to pigs being seronegative at the end of the study at 11 weeks of age. Members of the Clostridia, such as Blautia, Roseburia, and Anaerovibrio, were more abundant and part of the core microbiome in nonshedder pigs. Cellulolytic microbiota (Ruminococcus and Prevotella) were also more abundant in noninfected pigs during the weaning and growing stages. Microbial profiling also revealed that infected pigs had a higher abundance of Lactobacillus and Oscillospira, the latter also being part of the core microbiome of intermittent-persistent shedders. These findings suggest that a lack of microbiome maturation and greater proportions of microorganisms associated with suckling increase susceptibility to infection. In addition, the persistence of Salmonella shedding may be associated with an enrichment of pathobionts such as Anaerobiospirillum. Overall, these results suggest that there may be merit in manipulating certain taxa within the porcine intestinal microbial community to increase disease resistance against Salmonella in pigs. IMPORTANCE Salmonella is a global threat for public health, and pork is one of the main sources of human salmonellosis. However, the complex epidemiology of the infection limits current control strategies aimed at reducing the prevalence of this infection in pigs. The present study analyzes for the first time the impact of the gut microbiota in Salmonella infection in pigs and its shedding pattern in naturally infected growing pigs. Microbiome (16S rRNA amplicon) analysis reveals that maturation of the gut microbiome could be a key consideration with respect to limiting the infection and shedding of Salmonella in pigs. Indeed, seronegative animals had higher richness of the gut microbiota early after weaning, and uninfected pigs had higher abundance of strict anaerobes from the class Clostridia, results which demonstrate that a fast transition from the suckling microbiota to a postweaning microbiota could be crucial with respect to protecting the animals.

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