Intestinal Microbiota In Patients Research Articles

Changes in the intestinal microbiota of multiple myeloma patients living in high‑altitude and cold regions analyzed using 16s rRNA high‑throughput sequencing.

Multiple myeloma (MM) is a plasma cell clonal disease and these plasma cells can survive in the gut. The intestinal microbiota is a complex ecosystem and its dysfunction can release persistent stimulus signals that trigger genetic mutations and clonal evolution in the gut. The present study analyzed the intestinal microbiota in fecal samples of MM patients in high-altitude and cold regions of China using 16s rRNA sequencing and analyzed significantly enriched species at the phylum and genus levels. Although no significant difference in the alpha diversity was observed between the MM and control groups, a significant difference was noted in the beta diversity. A total of 15 significant differential bacteria at the genus level were found between the two groups, among which Bacteroides, Streptococcus, Lactobacillus and Alistipes were significantly enriched in the MM group. The present study also constructed a disease diagnosis model using Random Forest analysis and verified its accuracy using receiver operating characteristic analysis. In addition, using correlation analysis, it demonstrated that the composition of the intestinal microbiota in patients with MM was associated with complement levels. Notably, the present study predicted that the signaling and metabolic pathways of the intestinal microbiota affected MM progression through Kyoto Encyclopedia of Genes and Genomes functional analysis. The present study provides a new approach for the prevention and treatment of MM, in which the intestinal microbiota may become a novel therapeutic target for MM.

Inflammation in the pathogenesis of neurodegenerative diseases

Summary
 Introduction. Neurodegenerative diseases (ND) are common chronic disorders associated with progressive damage to the nervous tissue system. The participation of the immune system in the development of neurodegenerative diseases was confirmed by data on the activation of microglia, the presence of an imbalance in the composition and phenotype of peripheral immune cells and the presence of disorders of humoral immunity, dysbiosis of the intestinal microbiota in patients with this pathology.
 Discussion. It has been established that inflammation plays a key role in the pathogenesis of diseases associated with progressive damage to the nervous system. The article analyzes the mechanisms of development of “subclinical” chronic inflammation that leads to the development of old age and related diseases, including neurodegenerative pathology. At least three groups of factors associated with old age play a role in the formation of a “proinflammatory status”: mitochondrial dysfunction, the development of an age-related “proinflammatory” status of the immune system, and chronic stress. Mitochondrial dysfunction is associated primarily with disruption of mitophagy processes: failure of quality control mechanisms as a result of disruption of mitophagy processes leads to the accumulation of terminally damaged mitochondria, which become a threat to cell survival. Inadequate removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and the development of inflammatory diseases. A high level of deletions in the mitochondrial genetic apparatus that accumulates with age inevitably leads to increased formation of reactive oxygen species, which in turn are assumed to be one of the leading activators of the cytosolic NLRP3 protein, the main component of inflammasomes. Increased inflammosome formation ultimately leads to caspase-1-dependent production of proinflammatory interleukins. Age-related inflammatory imbalance is associated with the fact that during life the immune system, the main protective mechanism of which is the inflammatory response, copes with constant antigenic attacks. However, over time, upon reaching a certain threshold, the reaction of the immune system becomes excessive, characterized by increased production of coagulation factors, proinflammatory cytokines, acute phase proteins of inflammation, prostaglandins and leukotrienes.
 Conclusion. Immunological changes that develop during chronic (long-term) stress are the result of a disruption of the homeostatic connection between the neuroendocrine and immune systems, leading to the formation of an inflammatory background that complements the “pro-inflammatory status” that develops as a result of age-related changes in the immune system and disruption of mitophagy mechanisms.

The effect of anti-TNF drugs on the intestinal microbiota in patients with spondyloarthritis, rheumatoid arthritis, and inflammatory bowel diseases.

Spondyloarthritis (SpA), rheumatoid arthritis (RA), and inflammatory bowel diseases (IBD) are chronic inflammatory autoimmune diseases that are associated with alterations in the composition of the intestinal microbiota (i.e., dysbiosis). For SpA and RA, a gut-joint-enthesis axis is hypothesized and recent data suggests that dysbiosis may contribute directly to initiating and perpetuating joint and spine inflammation. Biologic drugs targeting tumor necrosis factor (TNF) are effective in treating these diseases and have been shown to partially restore the disrupted microbiome. Hence, drugs that affect both the intestinal and joint components of these diseases, such as anti-TNF drugs, may act on the intestinal microbiome. However, despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent, and predictors of patient outcomes have not been identified. In this narrative review, we summarize recent research on the downstream effects of anti-TNF drugs on the intestinal microbiota in SpA, RA, and IBD. We also discuss whether these changes could have a role as predictive biomarkers of anti-TNF response.

Changes in the intestinal microbiota of individuals with non-alcoholic fatty liver disease based on sequencing: An updated systematic review and meta-analysis.

Alterations in the composition and abundance of the intestinal microbiota occur in non-alcoholic fatty liver disease (NAFLD). However, the results are inconsistent because of differences in the study design, subject area, and sequencing methodology. In this study, we compared the diversity and abundance of the intestinal microbiota of patients with NAFLD and healthy individuals through a systematic review and meta-analysis. Three databases (PubMed, EMBASE, and Cochrane Library) were searched from their inception to March 20, 2023. A meta-analysis was performed using Stata software to analyze variations in the richness and abundance of the intestinal microbiota in patients with NAFLD. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for quality assessment. A total of 28 articles were included. Shannon diversity was reduced in patients with NAFLD (SMD = -0.24 (95% CI -0.43-0.05, I2 = 71.7%). The relative abundance of Ruminococcus, Faecalibacterium, and Coprococcus all decreased, with total SMDs of -0.96 (95% CI -1.29 to -0.63, I2 = 4.8%), -1.13 (95% CI -2.07 to -0.19, I2 = 80.5%), and -1.66 (95% CI -3.04 to -0.28, I2 = 91.5%). Escherichia was increased in individuals with NAFLD (SMD = 1.78, 95% CI 0.12 to 3.45, I2 = 94.4%). Increasing the species diversity and altering the abundance of specific gut microbiota, including Coprococcus, Faecalibacterium, Ruminococcus, and Escherichia, may be beneficial for improving NAFLD.

The gut microbiota posttranslationally modifies IgA1 in autoimmune glomerulonephritis.

Mechanisms underlying the disruption of self-tolerance in acquired autoimmunity remain unclear. Immunoglobulin A (IgA) nephropathy is an acquired autoimmune disease where deglycosylated IgA1 (IgA subclass 1) auto-antigens are recognized by IgG auto-antibodies, forming immune complexes that are deposited in the kidneys, leading to glomerulonephritis. In the intestinal microbiota of patients with IgA nephropathy, there was increased relative abundance of mucin-degrading bacteria, including Akkermansia muciniphila. IgA1 was deglycosylated by A. muciniphila both in vitro and in the intestinal lumen of mice. This generated neo-epitopes that were recognized by autoreactive IgG from the sera of patients with IgA nephropathy. Mice expressing human IgA1 and the human Fc α receptor I (α1KI-CD89tg) that underwent intestinal colonization by A. muciniphila developed an aggravated IgA nephropathy phenotype. After deglycosylation of IgA1 by A. muciniphila in the mouse gut lumen, IgA1 crossed the intestinal epithelium into the circulation by retrotranscytosis and became deposited in the glomeruli of mouse kidneys. Human α-defensins-a risk locus for IgA nephropathy-inhibited growth of A. muciniphila in vitro. A negative correlation observed between stool concentration of α-defensin 6 and quantity of A. muciniphila in the guts of control participants was lost in patients with IgA nephropathy. This study demonstrates that gut microbiota dysbiosis contributes to generation of auto-antigens in patients with IgA nephropathy and in a mouse model of this disease.

Microbiome and its relevance to indigenous inflammatory bowel diseases in China

BackgroundInflammatory Bowel Disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Although dysbiosis is implicated in its pathogenesis, deep sequencing and oral microbiota study in Chinese IBD patients is absent. AimTo explore the role of oral / intestinal microbiota in patients with IBD and the potential associations therein. MethodsClinical data, fecal and saliva samples were harvested from 80 patients with IBD (Crohn's disease, CD, n = 69; Ulcerative colitis, UC, n = 11) and 24 normal controls. Microbiomics (16S rRNA sequencing and 16S rRNA full-length sequencing) were used to detect and analyze the difference between IBD patients and normal control. ResultsCompared with normal controls, a higher abundance of the intestinal Shigella spp. (Shigella flexneri and Shigella sonnei, which were positively relate to the severity of IBD), lower abundance of intestinal probiotics (Prevotella, Faecalibacterium and Roseburia), and higher abundance of oral Neisseria were present in IBD patients with microbiome. The higher inflammation-related markers, impaired hepatic and renal function, and dyslipidaemia were present in patients with IBD. A higher intake of red meat and increased abundance of Clostridium in the gut were found in CD patients, while the elevated abundance of Ruminococcus in the gut was showed in UC ones. The bacterial composition of saliva and fecal samples was completely different, yet there was some correlation in the distribution of dominant probiotics. ConclusionEnteric dysbacteriosis and the infections of pathogenic bacteria (Shigella) may associate with the occurrence or development of IBD.

The effect of budesonide combined with bifidobacteria and lactobacilli on lung function and gut microbiota of patients with chronic obstructive pulmonary disease.

To explore the effects of budesonide combined with Bifidobacteria and Lactobacilli on the lung function and intestinal microbiota of patients with chronic obstructive pulmonary disease (COPD). Clinical data of 124 COPD patients admitted to Fengcheng Hospital, Fengxian District, Shanghai from February 2021 to February 2023 were retrospectively analyzed. Patients either received budesonide treatment alone (n=59, control group) or budesonide combined with Bifidobacteria and Lactobacilli (n=65, observation group). Levels of lung function indicators, symptom relief time, gut microbiota levels, and quality of life were compared between the two groups before and after the treatment. After two weeks of treatment, the improvement of lung function in the observation group was better than that in the control group (P<0.05). Compared to budesonide treatment alone, combined budesonide, Bifidobacteria, and Lactobacilli treatment were associated with shorter symptom relief time (P<0.05), and with more significant improvement of intestinal microbiota level (P<0.05) and the quality of life (P<0.05). Budesonide combined with Bifidobacteria and Lactobacilli can effectively alleviate clinical symptoms, regulate intestinal microbiota, improve lung function and the quality of life of COPD patients.

ECCO Grant Analysis of the tolerogenic role of the liver in controlling intestinal inflammation

Abstract Background and Aims There is a close anatomical connection between the liver and the intestine. This connection is further highlighted by the association between Primary Sclerosing Cholangitis (PSC) and Inflammatory Bowel Disease (IBD). Interestingly, PSC-associated IBD (PSC/IBD) presents with milder colitis symptoms compared to Crohn's disease and Ulcerative Colitis. We hypothesize that PSC has a protective impact on IBD, which is mediated by Foxp3+ regulatory T cells. This hypothesis is supported by our preliminary data. However, the mechanism by which PSC induces tolerance in the intestine remains unknown and answering this question is the aim of this proposal. Methods In Objective 1, we will test the hypothesis that changes in the intestinal microbiota mediate the protective effects of PSC on IBD. We will compare the intestinal microbiota in patients with PSC/IBD and IBD. This analysis will be complemented by functional experiments. Specifically, we aim to engraft germ-free wild type (WT) mice with fecal microbiota from PSC/IBD and IBD patients, as well as from Mdr2-deficient and WT mice. In these mouse models, we will analyze the effect of the microbiota on effector and regulatory T cells and on colitis susceptibility. In Objective 2, we will test whether changes in the composition of bile acids mediate the protective effects of PSC on IBD. To test this, we will deliver specific bile acids identified by us into Il10-deficient mice and analyze their impact on colitis severity and the intestinal T cell repertoire. Moreover, we will decipher how those bile acids impact the intestinal microbiota. Using in vitro assays, we will further test the direct effect of specific bile acids on T cell differentiation. Anticipated Impact Finally, our long-term aim is to understand how the liver induces immunological tolerance in the intestine. This knowledge could pave the way for new targeted therapies for inflammatory diseases.

Lactobacillus plantarum 24-7 improves postoperative bloating and hard stools by modulating intestinal microbiota in patients with congenital heart disease: a randomized controlled trial.

Gastrointestinal symptoms are a common postoperative complication in patients with congenital heart disease (CHD), affecting their postoperative recovery. Probiotic intervention may be a promising therapeutic approach to alleviate postoperative gastrointestinal symptoms. This study aimed to evaluate the potential of Lactobacillus plantarum 24-7 (L. plantarum 24-7) in mitigating postoperative gastrointestinal symptoms and promoting patient recovery. Adult CHD patients scheduled for surgical intervention were recruited. One hundred and twenty patients were randomized and received L. plantarum or placebo intervention twice daily for ten days. Gastrointestinal symptoms were assessed utilizing the Gastrointestinal Symptom Rating Scale (GSRS). Various postoperative variables were analyzed across both groups. Alterations in gut microbiota were evaluated through 16S rRNA sequencing. 112 patients completed the study, with 55 in the probiotic group and 57 in the placebo group. While the disparity in overall postoperative GSRS scores between the two groups did not reach statistical significance (P = 0.067), marked differences were observed in bloating (P = 0.004) and hard stool (P = 0.030) scores. Furthermore, individuals within the probiotic group exhibited lower postoperative neutrophil counts (P = 0.007) and concurrently higher lymphocyte counts (P = 0.001). Variations in the diversity and composition of postoperative gut microbiota were discerned between the probiotic and placebo groups. Remarkably, no probiotic-related adverse events were documented. Supplementation with L. plantarum was well-tolerated and demonstrated partial efficacy in ameliorating gastrointestinal symptoms in postoperative CHD patients. Modulating the gut microbiota may be a potential mechanism by which L. plantarum exerts clinical benefits.

Experience of inulin use for correcting intestinal microbiota in patients suffering from recurrent vulvovaginal candidiasis: A prospective cohort comparative study

Aim. To evaluate the effectiveness of inulin for the adjustment of intestinal microflora in patients with recurrent vulvovaginal candidiasis (VVC).&#x0D; Materials and methods. A prospective cohort comparative study included 79 women aged 18 to 50 years. They were divided into three groups: the main group included 32 patients receiving complex treatment with a dietary supplement containing inulin derived from the "Extra" variety of Jerusalem artichoke root in combination with fluconazole; the comparison group included 27 patients receiving fluconazole only; and the control group included 20 healthy women. The patients were followed up for 12 months. Examination included stool culture for dysbiosis, complete blood count, urinalysis, blood chemistry (glucose, bilirubin, alanine aminotransferase, aspartate aminotransferase, total protein, urea, creatinine), examination of the vulva and vaginal mucosa, vaginal smear microscopy for microflora, Gram staining, real-time polymerase chain reaction for Mycoplasma hominis, Ureaplasma parvum, Trihomonas vaginalis, Chlamydia traсhomatis, Candida albicans. Subsequently, all subjects every three months underwent a bimanual examination, speculum examination of the cervical mucosa and vagina, Gram staining of vaginal mucosa and cervix swabs, a thorough interview, and history taking. At 12 months, stool was cultured for dysbiosis again, and the data were analyzed.&#x0D; Results. The VVC therapy in the group of inulin-containing dietary supplement was more effective: the recurrence rate was 3 times lower than with the standard treatment regimen.&#x0D; Conclusion. The use of dietary supplement containing inulin derived from the "Extra" variety of Jerusalem artichoke root in complex therapy for recurrent VVC can significantly improve the gut and vagina microflora condition and prevent the recurrence and normalization of stool in patients.

Study of the influence of GLP-1 receptor agonists on the metabolic activity of the intestinal microbiota in patients with type 2 DM

The aim: to investigate the peculiarities of the metabolic activity of the intestinal microbiota in patients with type 2 diabetes under the influence of glucagon-like peptide-1 receptor agonist therapy. Materials and methods: 21 patients with type 2 diabetes mellitus were included in the study, the average age was 57.2±8.53 years (M±SD), the HbA1c level was 8.29±0.88 % (M±SD). Patients were prescribed raGLP-1 at the maximum tolerated dose for 6 months. Before and after the course of treatment, indicators of body composition were determined by the bioelectrical impedance method (TANITA BC-545N analyzer, Japan), characteristics of carbohydrate metabolism and the lipid spectrum of blood serum, as well as the concentration of GLP-1, trimethylamine-N-oxide (TMAO) by the immunoenzymatic method, of short-chain fatty acids (SCFA) by the method of chromatographic research. Results. After 6 months of therapy with liraglutide against the background of a statistically significant decrease in fasting blood glucose and HbA1c levels (p&lt;0.05), a decrease in body mass index and waist circumference (p&lt;0.05), a decrease in the content of visceral (p&lt;0.05 ) and total fat (p&lt;0.05) in patients with type 2 diabetes, there was a decrease in the concentration of TMAO in blood serum (p&lt;0.05) and an increase in the concentration of SCFA: acetic, propionic (p&lt;0.05) in the coprofiltrate and a tendency to increase in the level of butyric acids. Data analysis also established an increase in the concentration of endogenous GLP-1 in the blood (p&lt;0.05). Conclusions. The detected changes in microbial metabolites may indicate a positive effect of raGLP-1 on the composition of the intestinal microbiota and its metabolic activity in patients with T2DM, which in turn contributes to the improvement of endogenous secretion of incretins

The characteristics of intestinal microbiota in patients with chronic schistosomiasis japonica-induced liver fibrosis by 16S rRNA gene sequence.

The intestinal microbiota is known to play a role in the development of liver disease, there is a limited understanding of the intestinal microbiota associated with chronic schistosomiasis japonica. This study sought to explore the characteristics of the intestinal microbiota in patients with chronic schistosomiasis japonica and identify potential biomarkers that could aid diagnosis. A total of 40 residents of Qingshan Island in Yueyang (Hunan, China) were enrolled in this cross-sectional study. These individuals were divided into two groups for analysis of the intestinal microbiota: patients with chronic schistosomiasis japonica-induced liver fibrosis group (CSJ group, n = 10) and a healthy control group (HC group, n = 30). Feces were collected from each participant and analyzed by 16S rRNA gene sequencing, which included species composition analysis at the phylum and family levels, α and β diversity analysis, LEfSe, Kyoto Encyclopedia of Genes and Genome (KEGG) and Clusters of Orthologous Groups of proteins (COG) analysis. Our results indicated that Schistosoma japonicum infection changed the composition and abundance of intestinal microbiota at the phylum and family levels. Compared with the HC group, the α and β diversity results showed that CSJ group had low diversity of species of the intestinal microbiome. LEfSe and relative abundance analysis found that the Prevotella 7, Alloprevotella, and Holdemanella genera were significantly higher in the CSJ group than in the HC group. Meanwhile, the ROC analysis showed that the area under the curve (AUC) of Prevotella 7, Alloprevotella, and Holdemanella genera was 0.779, 0.769, and 0.840, respectively. KEGG and COG analysis showed that the Replication and Repair, and Defense Mechanism pathways correlated strongly with chronic schistosomiasis japonica infection. The current study was the first to explore differences in the intestinal microbiota of patients with chronic schistosomiasis japonica-induced liver fibrosis and healthy people from Qingshan Island, which indicated that Prevotella 7, Alloprevotella, and Holdemanella genera could have a potential value in non-invasive diagnosis of chronic schistosomiasis japonica-induced fibrosis.

Characteristics of the intestinal microbiota in patients with colorectal cancer

AIM: to study the intestinal microbiota and identify its characteristic features in patients with colorectal cancer.PATIENTS AND METHODS: in this study, the composition of the intestinal microbiota in patients with colorectal cancer was analyzed, while the comparison group consisted of patients with non-inflammatory bowel diseases.RESULTS: previous studies have shown the possible role of enterococci and some types of clostridia in stimulating oncogenic processes and, on the contrary, the vital role of lactobacilli and bifidobacteria in intestinal homeostasis maintaining. The aim of this study was to compare the gut microbiota composition in colorectal cancer patients and non-inflammatory bowel diseases patients gut microbita. The proportion of enterococci was increased in patients with colorectal cancer (12.7% in the study group and 7.6% in the control group) on the contrary the proportion of bifidobacteria and obligate anaerobes was decreased (1.5% in the study group and 4% in the control groups) and (3.3 % of the study group and 9.7% in the control group) respectively. Decrease of the microbiota biodiversity was observed for the patients with colorectal cancer that was calculated by the Shannon diversity Index (4.46 in the study group and 4.8 in the control group), also two-fold increase of Pseudomonas aeruginosa share (2.2% in the study group and 1.1% in the control group) was found for this cohort, Clostridium septicum was isolated only from patients with colorectal cancer.CONCLUSION: this study results suggest the diagnostic significance of the species diversity of the intestinal microbiota.

The Effect of Synbiotic Supplementation on Uremic Toxins, Oxidative Stress, and Inflammation in Hemodialysis Patients-Results of an Uncontrolled Prospective Single-Arm Study.

Introduction: Numerous studies to date have shown that the development of dysbiotic gut microbiota is a characteristic finding in chronic kidney disease (CKD). A number of uremic toxins progressively accumulate in the course of CKD, some of them generated by the intestinal microbiome, such as indoxyl sulfate (IS) and p-cresyl sulfate (p-CS). They are found to be involved in the pathogenesis of certain complications of uremic syndrome, including low-grade chronic inflammation and oxidative stress. The aim of the present study is to research the serum concentration of IS and p-CS in end stage renal disease (ESRD) patients undergoing conventional hemodialysis, as well as to study the possibilities of influencing some markers of inflammation and oxidative stress after taking a synbiotic. Materials and Methods: Thirty patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment who were taking a synbiotic in the form of Lactobacillus acidophilus La-14 2 × 1011 (CFU)/g and prebiotic fructooligosaccharides were included in the study. Serum levels of total IS, total p-CS, Interleukin-6 (IL-6), and Malondialdehyde (MDA) were measured at baseline and after 8 weeks. Results. The baseline values of the four investigated indicators in the patients were significantly higher-p-CS (29.26 ± 58.32 pg/mL), IS (212.89 ± 208.59 ng/mL), IL-6 (13.84 ± 2.02 pg/mL), and MDA (1430.33 ± 583.42 pg/mL), compared to the results obtained after 8 weeks of intake, as we found a significant decrease in the parameters compared to the baseline-p-CS (6.40 ± 0.79 pg/mL, p = 0.041), IS (47.08 ± 3.24 ng/mL, p < 0.001), IL-6 (9.14 ± 1.67 pg/mL, p < 0.001), and MDA (1003.47 ± 518.37 pg/mL, p < 0.001). Conclusions: The current study found that the restoration of the intestinal microbiota in patients with CKD significantly decreases the level of certain uremic toxins. It is likely that this favorably affects certain aspects of CKD, such as persistent low-grade inflammation and oxidative stress.

Alteration of Intestinal Microbiota and Hydrogen Sulfide Metabolism in Patients with Hashimoto's Thyroiditis.

To analyze the intestinal microbiota and H2S levels in patients with HT. Twenty euthyroid HT patients and twenty healthy control individuals were recruited. Fecal samples were collected, and the microbiota was examined using 16S RNA gene sequencing. We also collected serum samples to examine the H2S levels. Compared with patients with HT, the ACE and Chao indices were significantly lower in healthy controls (P=0.04, 0.03, respectively). The microbial composition of the HT group differed significantly from that of the healthy group. We observed a significant increase in the proportions of Bacteroides, Fusobacterium, Sutterella, and Veillonella in patients with HT (P < 0.05). Linear discriminant analysis and effect size analysis also revealed that Bacteroides and Ralstonia were enriched in patients with HT. Additionally, patients with HT had significantly lower H2S levels than healthy controls (P < 0.005). The enrichment of H2S anabolism was linked to the alteration of intestinal microbiota in patients with HT. We demonstrated that patients with HT have aberrant intestinal microbiome and that H2S anabolism may contribute to HT pathogenesis.

Efficacy of Biejiajian Pill on Intestinal Microbiota in Patients with Hepatitis B Cirrhosis/Liver Fibrosis: A Randomized Double-Blind Controlled Trial.

To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

Clinical and functional state of the pancreas, liver, and intestinal microbiota in patients with chronic biliary-dependent pancreatitis after cholecystectomy

The purpose of the study: To evaluate the clinical and functional state of the pancreas, liver and intestinal microbiota in patients with chronic biliary- dependent pancreatitis (CKD) after cholecystectomy.Materials and methods. 110 patients with CKD were examined, who were divided into 2 groups: group 1–58 patients (CKD) with a history of cholecystectomy. Group 2–52 patients with CKD with concomitant GI. The control group consisted of 35 practically healthy people. Patients with CKD with preserved gallbladder formed a comparison group with the main group. Cholecystectomy was performed according to urgent indications in most cases, but in some cases it was performed “prophylactically” with asymptomatic GI.All patients underwent:• ultrasound elastometry of the liver on the device “FibroScan” (“EchoSens”, France).• the study of the ability of cells to produce cytokines — TNF-a and TGF-b was determined by the enzyme immunoassay using test systems manufactured by the company “Cytokine” (St. Petersburg) and the company “R&amp;D systems” (USA).• study of the concentration of pancreatic elastase-1 in feces by ELISA using test systems of the company “ScheBoBiotech” (Germany).• determination of the absolute and relative content of FGC (C2-C4) by gas-liquid chromatographic analysis in blood serum and faeces on the Crystal 2000 M chromatograph.Conclusion. In patients with CKD with a history of cholecystectomy, there are more significant violations of the metabolic activity of the intestinal microflora, lipid metabolism, liver fibrosis indicators, the severity of external secretory pancreatic insufficiency (VSN pancreas), which is accompanied by an increase in cytokine levels: TGF-b and TNF-a, an increase in the absolute content of short- chain fatty acids (FFA) in blood serum and feces and multidirectional changes in their spectrum, depending on the severity of the pancreatic VSN, the stage of liver steatosis, cholesterol levels compared with those of patients with CKD with preserved LC.

Compositional and Functional Alterations in Intestinal Microbiota in Patients with Psychosis or Schizophrenia: A Systematic Review and Meta-analysis.

Intestinal microbiota is intrinsically linked to human health. Evidence suggests that the composition and function of the microbiome differs in those with schizophrenia compared with controls. It is not clear how these alterations functionally impact people with schizophrenia. We performed a systematic review and meta-analysis to combine and evaluate data on compositional and functional alterations in microbiota in patients with psychosis or schizophrenia. Original studies involving humans and animals were included. The electronic databases PsycINFO, EMBASE, Web of Science, PubMed/MEDLINE, and Cochrane were systematically searched and quantitative analysis performed. Sixteen original studies met inclusion criteria (1376 participants: 748 cases and 628 controls). Ten were included in the meta-analysis. Although observed species and Chao 1 show a decrease in diversity in people with schizophrenia compared with controls (SMD = -0.14 and -0.66 respectively), that did not reach statistical significance. We did not find evidence for variations in richness or evenness of microbiota between patients and controls overall. Differences in beta diversity and consistent patterns in microbial taxa were noted across studies. We found increases in Bifidobacterium, Lactobacillus, and Megasphaera in schizophrenia groups. Variations in brain structure, metabolic pathways, and symptom severity may be associated with compositional alterations in the microbiome. The heterogeneous design of studies complicates a similar evaluation of functional readouts. The microbiome may play a role in the etiology and symptomatology of schizophrenia. Understanding how the implications of alterations in microbial genes for symptomatic expression and clinical outcomes may contribute to the development of microbiome targeted interventions for psychosis.

Extracellular vesicles derived from the intestinal microbiota of patients with CGD-associated inflammatory bowel disease have pro-inflammatory effects

BackgroundChronic granulomatous disease (CGD) is an inborn error of immunity characterized by mutations in any one of the 6 subunits forming the nicotinamide-adenine dinucleotide phosphate oxidase complex 2 leading to defective phagocyte-derived ROS production. As a result, patients with CGD have recurrent infections and increased inflammation and 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). Although we have previously demonstrated that patients with CGD-IBD have intestinal dysbiosis, its functional impact is poorly understood. Interestingly, intestinal microbes can produce gut microbiota-derived extracellular vesicles (GMEVs) which can cross the intestinal barrier and have systemic and/or end-organ immunomodulatory effects. Yet, the role of GMEVs in patients with CGD has never been evaluated. ObjectiveTo investigate the impact of GMEVs isolated from patients with CGD, with or without CGD-IBD, on intestinal permeability and inflammatory responses using wild type and NOX2-deficient (CYBB-/-) models. MethodsGMEVs were isolated and characterized from fecal samples obtained from 11 patients without CGD-IBD and 11 patients with active CGD-IBD recruited at the National Institutes of Health. Stimulation with GMEVs was performed on HT29, THP1 and CYBB-/- THP1 cell lines, HT29/THP1 co-culture models, and induced pluripotent stem cell-derived human intestinal organoids. TNF-α, IL-6, IL-8, IL-1β, IP-10, GM-CSF and MCP1 gene expression and production were assessed by RT-qPCR and ELISA, respectively. ResultsOur data showed that stimulation with GMEVs from patients with active CGD-IBD increased intestinal permeability compared to cells stimulated with GMEVs from patients without CGD-IBD. In HT29 cells, increased intestinal permeability was associated with increased gene expression and production of IL-8 and IL-1β. IL-8 was similarly increased in intestinal organoids. In THP1 cells, stimulation led to increased gene expression and production of TNF-α, IL-6 and IP-10, while stimulation in CYBB-/- THP1 cells increased TNF-α and MCP1 gene expression. Finally, stimulation of HT29/THP1 cell co-cultures resulted in increased gene expression of TNF-α, IL-6 and GM-CSF. ConclusionsOur results suggest that GMEVs isolated from patients with CGD-IBD may induce pro-inflammatory immune responses in patients with CGD, thereby contributing to their underlying inflammatory pathology. These findings bring forward GMEVs as a possible new therapeutic target for CGD-IBD. [Display omitted]

Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.