Gut microbiota dysbiosis characterized by abnormal elevation of Lactobacillus in patients with immune-mediated necrotizing myopathy.

Aim: The gut microbiota plays an important role in human health. In this study, we aimed to investigate whether and how gut microbiota communities are altered in patients with immune-mediated necrotizing myopathy (IMNM) and provide new ideas to further explore the pathogenesis of IMNM or screen for its clinical therapeutic targets in the future. Methods: The gut microbiota collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta-diversity analyses were applied to examine the bacterial diversity and community structure. Welch's t test was performed to identify the significantly abundant taxa of bacteria between the two groups. Spearman correlation analysis was performed to analyze the correlation between gut microbiota and clinical indicators. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P < 0.05 was considered statistically significant. Results: Nineteen IMNM patients and 23 HCs were included in the analysis. Among IMNM patients, 94.74% (18/19) of them used glucocorticoids, while 57.89% (11/19) of them used disease-modifying antirheumatic drugs (DMARDs), and the disease was accessed by MITAX (18.26 ± 8.62) and MYOACT (20.68 ± 8.65) scores. Participants in the groups were matched for gender and age. The diversity of the gut microbiota of IMNM patients differed and decreased compared to that of HCs (Chao1, Shannon, and Simpson indexes: p < 0.05). In IMNM patients, the relative abundances of Bacteroides, Roseburia, and Coprococcus were decreased, while that of Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies, anti-Ro52 antibodies, and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP, and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, the prediction model was built using the top five differential genera, which was verified using a ROC curve (area under the curve (AUC): 87%, 95% confidence interval: 73%-100%). Conclusion: We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and is correlated with systemic autoimmune features.

The Interplay between Medical Plants and Gut Microbiota in Cancer.

The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and probiotics, hygiene status, and other environmental factors. Dysbiosis, a disruption of the normal crosstalk between the host and the microbes, is associated with obesity, diabetes, cancer, and cardiovascular diseases, is linked to a reduction of anti-inflammatory bacteria like Lactobacillus and Roseburia, and to an increase in the growth of proinflammatory species like Ruminococcus gnavus and Bacteroidetes. Some plants possess anticancer properties and various studies have reported that some of these are also able to modulate the gut microbiota. The aim of this work is to evaluate the crucial relationship between medical plants and gut microbiota and the consequences on the onset and progression of cancer. In vivo studies about hematological malignancies showed that beta-glucans tie to endogenous antibeta glucan antibodies and to iC3b, an opsonic fragment of the central complement protein C3, leading to phagocytosis of antibody-targeted neoplastic cells and potentiation of the cytotoxic activity of the innate immune system if administered together with monoclonal antibodies. In conclusion, this review suggests the potential use of medical plants to improve gut dysbiosis and assist in the treatment of cancer.

Adlercreutzia equolifaciens Is an Anti-Inflammatory Commensal Bacterium with Decreased Abundance in Gut Microbiota of Patients with Metabolic Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) affects about 20-40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can lead to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observe that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy for liver diseases.

Unraveling the Impact of Gut and Oral Microbiome on Gut Health in Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) is a complex disorder characterized by chronic inflammation of the gastrointestinal tract (GIT). IBD mainly includes two distinct diseases, namely Crohn's disease and ulcerative colitis. To date, the precise etiology of these conditions is not fully elucidated. Recent research has shed light on the significant role of the oral and gut microbiome in the development and progression of IBD and its collective influence on gut health. This review aims to investigate the connection between the oral and gut microbiome in the context of IBD, exploring the intricate interplay between these microbial communities and their impact on overall gut health. Recent advances in microbiome research have revealed a compelling link between the oral and gut microbiome, highlighting their pivotal role in maintaining overall health. The oral cavity and GIT are two interconnected ecosystems that harbor complex microbial communities implicated in IBD pathogenesis in several ways. Reduction in diversity and abundance of beneficial bacterial species with the colonization of opportunistic pathogens can induce gut inflammation. Some of these pathogens can arise from oral origin, especially in patients with oral diseases such as periodontitis. It is essential to discern the mechanisms of microbial transmission, the impact of oral health on the gut microbiome, and the potential role of dysbiosis in disease development. By elucidating this relationship, we can enhance our understanding of IBD pathogenesis and identify potential therapeutic avenues for managing the disease. Furthermore, innovative strategies for modulating the oral and gut microbiome can promote health and prevent disease occurrence and progression.

Combination of Gut Microbial Features and the Proteomic Pattern Revealed Changes in Specific Intestinal Luminal Factors and Mechanisms of Their Regulation of Gluten Allergy.

Recent research consensus has highlighted the role of intestinal luminal factors in the association between intestinal microenvironment homeostasis and food allergy. However, the association between intestinal immune homeostasis and food allergy-related proteomic features remains elusive. In this study, we aimed to investigate the changes in gluten allergy (GA)-defined phenotypes and endotypes and intestinal microenvironment factors in BALB/c mice and linked GA to colonic proteomic signatures. Combined with increased allergy and diarrhea scores, intense antibody responses and abnormalities in T-cell cytokine production were induced in mice. GA-associated disruption of intestinal microenvironment homeostasis was underlined by the increased colonic pH, decreased intestinal antioxidant capacity, impaired intestinal barrier function, and decreased production and imbalanced proportions of short-chain fatty acids. 16S rRNA amplicon sequencing showed that the gut microbiota dysbiosis in mice was characterized by significant enrichment of six bacterial taxonomic units, including Prevotellaceae, Escherichia Shigella, Alloprevotella, Escherichia coli, Bacteroides vulgatus, and Lachnospiraceae bacterium DW59, which was correlated with immune end points. Using a label-free proteomics quantitative approach, 24 differentially expressed proteins linking GA-induced gut dysbiosis were identified, with four of them enriched in the serine endopeptidase inhibitor activity pathway. The development of GA in mice was associated with changes in specific intestinal luminal factors and may be mediated by serine protease activity-associated metabolic routes.

Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.

Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.

Unraveling mechanistic insights into the role of microbiome in neurogenic hypertension: A comprehensive review.

Neurogenic hypertension, a complex and multifactorial cardiovascular disorder, is known to be influenced by various genetic, environmental, and lifestyle factors. In recent years, there has been growing interest in the role of the gut microbiome in hypertension pathogenesis. The bidirectional communication between the gut microbiota and the central nervous system, known as the microbiota-gut-brain axis, has emerged as a crucial mechanism through which the gut microbiota exerts its influence on neuroinflammation, immune responses, and blood pressure regulation. Recent studies have shown how the microbiome has a substantial impact on a variety of physiological functions, such as cardiovascular health. The increased sympathetic activity to the gut may cause microbial dysbiosis, increased permeability of the gut, and increased inflammatory reactions by altering a number of intestinal bacteria producing short-chain fatty acids (SCFAs) and the concentrations of lipopolysaccharide (LPS) in the plasma. Collectively, these microbial metabolic and structural compounds stimulate sympathetic stimulation, which may be an important stage in the onset of hypertension. The result is an upsurge in peripheral and central inflammatory response. In addition, it has recently been shown that a link between the immune system and the gut microbiota might play a significant role in hypertension. The therapeutic implications of the gut microbiome including probiotic usage, prebiotics, dietary modifications, and fecal microbiota transplantation in neurogenic hypertension have also been found. A large body of research suggests that probiotic supplementation might help reduce chronic inflammation and hypertension that have an association with dysbiosis in the gut microbiota. Overall, this review sheds light on the intricate interplay between the gut microbiome and neurogenic hypertension, providing valuable insights for both researchers and clinicians. As our knowledge of the microbiome's role in hypertension expands, novel therapeutic strategies and diagnostic biomarkers may pave the way for more effective management and prevention of this prevalent cardiovascular disorder. Exploring the potential of the microbiome in hypertension offers an exciting avenue for future research and offers opportunities for precision medicine and improved patient care.

Diarrheal-associated gut dysbiosis in cancer and inflammatory bowel disease patients is exacerbated by Clostridioides difficile infection.

Introduction: Low diversity gut dysbiosis can take different forms depending on the disease context. In this study, we used shotgun metagenomic sequencing and gas chromatography-mass spectrometry (GC-MS) to compared the metagenomic and metabolomic profiles of Clostridioides (Clostridium) difficile diarrheal cancer and inflammatory bowel disease (IBD) patients and defined the additive effect of C. difficile infection (CDI) on intestinal dysbiosis. Results: The study cohort consisted of 138 case-mix cancer patients, 43 IBD patients, and 45 healthy control individuals. Thirty-three patients were also infected with C. difficile. In the control group, three well-known enterotypes were identified, while the other groups presented with an additional Escherichia-driven enterotype. Bacterial diversity was significantly lower in all groups than in healthy controls, while the highest level of bacterial species richness was observed in cancer patients. Fifty-six bacterial species had abundance levels that differentiated diarrheal patient groups from the control group. Of these species, 52 and 4 (Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, and Ruminococcus gnavus) were under-represented and over-represented, respectively, in all diarrheal patient groups. The relative abundances of propionate and butyrate were significantly lower in fecal samples from IBD and CDI patients than in control samples. Isobutyrate, propanate, and butyrate concentrations were lower in cancer, IBD, and CDI samples, respectively. Glycine and valine amino acids were over- represented in diarrheal patients. Conclusion: Our data indicate that different external and internal factors drive comparable profiles of low diversity dysbiosis. While diarrheal-related low diversity dysbiosis may be a consequence of systemic cancer therapy, a similar phenotype is observed in cases of moderate to severe IBD, and in both cases, dysbiosis is exacerbated by incidence of CDI.

Unique microbial landscape in the human oropharynx during different types of acute respiratory tract infections.

BACKGROUND: Secondary bacterial infections and pneumonia are major mortality causes of respiratory viruses, and the disruption of the upper respiratory tract (URT) microbiota is a crucial component of this process. However, whether this URT dysbiosis associates with the viral species (in other words, is viral type-specific) is unclear. RESULTS: Here, we recruited 735 outpatients with upper respiratory symptoms, identified the infectious virus types in 349 participants using multiplex RT-PCR, and profiled their upper respiratory microbiome using the 16S ribosomal RNA gene and metagenomic gene sequencing. Microbial and viral data were subsequently used as inputs for multivariate analysis aimed at revealing viral type-specific disruption of the upper respiratory microbiota. We found that the oropharyngeal microbiota shaped by influenza A virus (FluA), influenza B virus (FluB), respiratory syncytial virus (RSV), and human rhinovirus (HRV) infections exhibited three distinct patterns of dysbiosis, and Veillonella was identified as a prominent biomarker for any type of respiratory viral infections. Influenza virus infections are significantly correlated with increased oropharynx microbiota diversity and enrichment of functional metabolic pathways such as L-arginine biosynthesis and tetracycline resistance gene tetW. We used the GRiD algorithm and found the predicted growth rate of common respiratory pathogens was increased upon influenza virus infection, while commensal bacteria, such as Streptococcus infantis and Streptococcus mitis, may act as a colonization resistance to the overgrowth of these pathogens. CONCLUSIONS: We found that respiratory viral infections are linked with viral type-specific disruption of the upper respiratory microbiota, particularly, influenza infections uniquely associated with increased microbial diversity and growth rates of specific pathogens in URT. These findings are essential for clarifying the differences and dynamics of respiratory microbiota in healthy participants and acute respiratory viral infections, which contribute to elucidating the pathogenesis of viral-host-bacterial interactions to provide insights into future studies on effective prevention and treatment of respiratory tract infections. Video Abstract.

How Do Microorganisms Influence the Development of Endometriosis? Participation of Genital, Intestinal and Oral Microbiota in Metabolic Regulation and Immunopathogenesis of Endometriosis.

Microorganisms inhabiting the human body play an extremely key role in its proper functioning, as well as in the development of the immune system, which, by maintaining the immune balance, allows you to enjoy health. Dysbiosis of the intestinal microbiota, or in the oral cavity or reproductive tract, understood as a change in the number and diversity of all microorganisms inhabiting them, may correlate with the development of many diseases, including endometriosis, as researchers have emphasized. Endometriosis is an inflammatory, estrogen-dependent gynecological condition defined by the growth of endometrial cells outside the uterine cavity. Deregulation of immune homeostasis resulting from microbiological disorders may generate chronic inflammation, thus creating an environment conducive to the increased adhesion and angiogenesis involved in the development of endometriosis. In addition, research in recent years has implicated bacterial contamination and immune activation, reduced gastrointestinal function by cytokines, altered estrogen metabolism and signaling, and abnormal progenitor and stem cell homeostasis, in the pathogenesis of endometriosis. The aim of this review was to present the influence of intestinal, oral and genital microbiota dysbiosis in the metabolic regulation and immunopathogenesis of endometriosis.

Hyperglycemia is associated with duodenal dysbiosis and altered duodenal microenvironment.

The gut microbiome influences the pathogenesis and course of metabolic disorders such as diabetes. While it is likely that duodenal mucosa associated microbiota contributes to the genesis and progression of increased blood sugar, including the pre-diabetic stage, it is much less studied than stool. We investigated paired stool and duodenal microbiota in subjects with hyperglycemia (HbA1c ≥ 5.7% and fasting plasma glucose > 100 mg/dl) compared to normoglycemic. We found patients with hyperglycemia (n = 33) had higher duodenal bacterial count (p = 0.008), increased pathobionts and reduction in beneficial flora compared to normoglycemic (n = 21). The microenvironment of duodenum was assessed by measuring oxygen saturation using T-Stat, serum inflammatory markers and zonulin for gut permeability. We observed that bacterial overload was correlated with increased serum zonulin (p = 0.061) and higher TNF-α (p = 0.054). Moreover, reduced oxygen saturation (p = 0.021) and a systemic proinflammatory state [increased total leukocyte count (p = 0.031) and reduced IL-10 (p = 0.015)] characterized the duodenum of hyperglycemic. Unlike stool flora, the variability in duodenal bacterial profile was associated with glycemic status and was predicted by bioinformatic analysis to adversely affect nutrient metabolism. Our findings offer new understanding of the compositional changes in the small intestine bacteria by identifying duodenal dysbiosis and altered local metabolism as potentially early events in hyperglycemia.

Impact of Gut Bacterial Metabolites on Psoriasis and Psoriatic Arthritis: Current Status and Future Perspectives.

There is growing evidence that supports a role of gut dysbiosis in the pathogenesis of psoriasis (Pso). Thus, probiotic supplementation and fecal microbiota transplantation may serve as promising preventive and therapeutic strategies for patients with Pso. One of the basic mechanisms through which the gut microbiota interacts with the host is through bacteria-derived metabolites, usually intermediate or end products produced by microbial metabolism. In this study, we provide an up-to-date review of the most recent literature on microbial-derived metabolites and highlight their roles in the immune system, with a special focus on Pso and one of its most common comorbidities, psoriatic arthritis.

Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms.

Microbiota dysbiosis and metabolic syndrome, consequences of a non-adequate diet, generate a feedback pathogenic state implicated in Alzheimer's disease development. The lower production of short chain fatty acids (SCFAs) under dysbiosis status leads to lipid homeostasis deregulation and decreases Angptl4 release and AMPK activation in the adipose tissue, promoting higher lipid storage (adipocyte hypertrophy) and cholesterol levels. Also, low SCFA generation reduces GPR41 and GPR43 receptor activation at the adipose tissue (increasing leptin release and leptin receptor resistance) and intestinal levels, reducing the release of GLP-1 and YPP. Therefore, lower satiety sensation and energy expenditure occur, promoting a weight gaining environment mediated by higher food intake and lipid storage, developing dyslipemia. In this context, higher glucose levels, together with higher free fatty acids in the bloodstream, promote glycolipotoxicity, provoking a reduction in insulin released, insulin receptor resistance, advanced glycation products (AGEs) and type 2 diabetes. Intestinal dysbiosis and low SCFAs reduce bacterial biodiversity, increasing lipopolysaccharide (LPS)-producing bacteria and intestinal barrier permeability. Higher amounts of LPS pass to the bloodstream (endotoxemia), causing a low-grade chronic inflammatory state characterized by higher levels of leptin, IL-1ß, IL-6 and TNF-α, together with a reduced release of adiponectin and IL-10. At the brain and neuronal levels, the generated insulin resistance, low-grade chronic inflammation, leptin resistance, AGE production and LPS increase directly impact the secretase enzymes and tau hyperphosphorylation, creating an enabling environment for ß-amyloid senile plaque and tau tangled formations and, as a consequence, Alzheimer's initiation, development and maintenance.

Microbiota dysbiosis associated with type 2 diabetes-like effects caused by chronic exposure to a mixture of chlorinated persistent organic pollutants in zebrafish.

Mixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 µg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance and richness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 µg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, Bifidobacterium adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host-microbiome interactions.

Role of nutrients in modulating microbiota and immunity in COVID-19 disease.

COVID-19 is a novel disease with a broad range of clinical patterns. Several patients show dysbiosis in the intestinal tract, with evidence of reduced beneficial bacteria, such as Bifidobacteria and Lactobacilli. It is well established that human gut microbiota dysbiosis is associated with several clinical conditions, including respiratory tract diseases due to the gut-lung axis. This narrative review discusses the role of nutrients in the relationship between the gut microbiota and the immune response in SARS-CoV-2 infection. In particular, we will focus on the benefits offered by vitamins and micronutrients on different aspects of COVID-19 disease while also discussing which diets seem to provide the most advantages.

Intratumor microbiota: Occult participants in the microenvironment of multiple myeloma.

More recently, microbiota was detected in several tumorous tissues including multiple myeloma (MM), but the roles of which is still under-studied as paucity of research on tumor biology. Moreover, we also detected the presence of microbiota in the bone marrow of patients with MM by 2bRAD-M sequencing technology, which is an incurable hematological malignancy characterized by accumulation of abnormal plasma cells in the bone marrow. However, the roles of intratumor microbiota in tumor disease remains poorly understood. In this review, we critically reviewed recent literature about microbiota in the tumorigenesis and progression of MM. Importantly, we proposed that the emergence of microbiota in the microenvironment of multiple myeloma may be attributed to microbial dysbiosis and impaired intestinal barrier, due to the increased prevalence of MM in patients with obesity and diabetes, of which the characteristic phenotype is gut microbial dysbiosis and impaired intestinal barrier. When the intestinal barrier is damaged, dysbiotic microbiota and their metabolites, as well as dysregulated immune cells, may participate in the reshaping of the local immune microenvironment, and play pivotal roles in the tumorigenesis and development of multiple myeloma, probably by migrating to the bone marrow microenvironment from intestine. We also discuss the emerging microbiological manipulation strategies to improve long-term outcomes of MM, as well as the prospective of the state-of-the-art techniques to advance our knowledge about the biological implication in the microbiome in MM.

Liposomal Epigallocatechin-3-Gallate for the Treatment of Intestinal Dysbiosis in Children with Autism Spectrum Disorder: A Comprehensive Review.

Autism Spectrum Disorder (ASD) is characterized by varying degrees of difficulty in social interaction and communication. These deficits are often associated with gastrointestinal symptoms, indicating alterations in both intestinal microbiota composition and metabolic activities. The intestinal microbiota influences the function and development of the nervous system. In individuals with ASD, there is an increase in bacterial genera such as Clostridium, as well as species involved in the synthesis of branched-chain amino acids (BCAA) like Prevotella copri. Conversely, decreased amounts of Akkermansia muciniphila and Bifidobacterium spp. are observed. Epigallocatechin-3-gallate (EGCG) is one of the polyphenols with the greatest beneficial activity on microbial growth, and its consumption is associated with reduced psychological distress. Therefore, the objective of this review is to analyze how EGCG and its metabolites can improve the microbial dysbiosis present in ASD and its impact on the pathology. The analysis reveals that EGCG inhibits the growth of pathogenic bacteria like Clostridium perfringens and Clostridium difficile. Moreover, it increases the abundance of Bifidobacterium spp. and Akkermansia spp. As a result, EGCG demonstrates efficacy in increasing the production of metabolites involved in maintaining epithelial integrity and improving brain function. This identifies EGCG as highly promising for complementary treatment in ASD.

Antibiotic-induced gut microbiota dysbiosis has a functional impact on purine metabolism.

BACKGROUND: Dysbiosis of the gut microbiota is closely linked to hyperuricemia. However, the effect of the microbiome on uric acid (UA) metabolism remains unclear. This study aimed to explore the mechanisms through which microbiomes affect UA metabolism with the hypothesis that modifying the intestinal microbiota influences the development of hyperuricemia. RESULTS: We proposed combining an antibiotic strategy with protein-protein interaction analysis to test this hypothesis. The data demonstrated that antibiotics altered the composition of gut microbiota as UA increased, and that the spectrum of the antibiotic was connected to the purine salvage pathway. The antibiotic-elevated UA concentration was dependent on the increase in microbiomes that code for the proteins involved in purine metabolism, and was paralleled by the depletion of bacteria-coding enzymes required for the purine salvage pathway. On the contrary, the microbiota with abundant purine salvage proteins decreased hyperuricemia. We also found that the antibiotic-increased microbiota coincided with a higher relative abundance of bacteria in hyperuricemia mice. CONCLUSIONS: An antibiotic strategy combined with the prediction of microbiome bacterial function presents a feasible method for defining the key bacteria involved in hyperuricemia. Our investigations discovered that the core microbiomes of hyperuricemia may be related to the gut microbiota that enriches purine metabolism related-proteins. However, the bacteria that enrich the purine salvage-proteins may be a probiotic for decreasing urate, and are more likely to be killed by antibiotics. Therefore, the purine salvage pathway may be a potential target for the treatment of both hyperuricemia and antibiotic resistance.

The Diagnostic Potential of the Human Blood Microbiome: Are We Dreaming or Awake?

Human blood has historically been considered a sterile environment. Recently, a thriving microbiome dominated by Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes phyla was detected in healthy blood. The localization of these microbes is restricted to some blood cell populations, particularly the peripheral blood mononuclear cells and erythrocytes. It was hypothesized that the blood microbiome originates from the skin-oral-gut axis. In addition, many studies have evaluated the potential of blood microbiome dysbiosis as a prognostic marker in cardiovascular diseases, cirrhosis, severe liver fibrosis, severe acute pancreatitis, type 2 diabetes, and chronic kidney diseases. The present review aims to summarize current findings and most recent evidence in the field.

Association between vaginal microbiota and the progression of ovarian cancer.

Ovarian cancers, especially high-grade serous ovarian cancer (HGSOC), are one of the most lethal age-independent gynecologic malignancies. Although pathogenic microorganisms have been demonstrated to participate in the pathogenesis of multiple types of tumors, their potential roles in the development of ovarian cancer remain unclear. To gain an insight into the microbiome-associated pathogenesis of ovarian cancer and identify potential diagnostic biomarkers, we applied different techniques to analyse the microbiome and serum metabolome of different resources. We found that the vaginal microbiota in ovarian cancer mouse models was under dysbiosis, with altered metabolite configurations that may result from amino acid or lysophospholipid metabolic processes. Local therapeutic intervention with a broad spectrum of antibiotics was effective in reversing microbiota dysbiosis and suppressing carcinogenic progression. As the ovary is situated deeply in the pelvis, it is difficult to directly monitor the ovarian microbial community. Our findings provide alternative options for utilizing the vaginal bacteria as noninvasive biomarkers, such as Burkholderia (area under the curve = 0.8843, 95% confidence interval: 0.743-1.000), which supplement the current invasive diagnostic methods for monitoring ovarian cancer progression and contribute to the development of advanced microbe-based diagnosis and adjuvant therapies.