Dysbiosis In Patients Research Articles

A comprehensive guide to assess gut mycobiome and its role in pathogenesis and treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.

P1220 Dysbiosis of the gut microbiota and decreased fecal levels of short-chain fatty acid in patients with Ulcerative Colitis: a hospital-based case-control study

Abstract Background Ulcerative Colitis (UC) is a typical intractable disease whose number of patients is increasing worldwide, and studies have suggested that the gut microbiota and its metabolites are closely involved in its pathogenesis and severity. However, to date, no study has comprehensively compared the microbiomes or metabolomes of UC patients and healthy controls after considering important confounding factors such as age, gender, race, and other lifestyle factors. Therefore, we conducted this clinical study to compare the compositions and diversity of the gut microbiota and the fecal metabolites between age-, sex-, and race-matched patients with Ulcerative Colitis (UC) and those without. Methods In total, 90 outpatients with UC (UC group) and 90 without a history of gastrointestinal diseases and their family members (without UC group) were recruited. Results The UC group had a significantly lower abundance of the genus Bifidobacterium, Faecalibacterium, and Lactobacillus than the without UC group. Furthermore, the UC group had a significantly lower alpha-diversity of the gut microbiota than the without UC group. The UC group had a significantly lower level of fecal SCFAs than the without UC group. These results remained significant after adjusting for sex, age, and smoking status. Furthermore, the expression of a group of genes encoded by the gut bacteria that are involved in the biosynthesis of tetrapyrrole was significantly lower in the UC group than in the without UC group. Conclusion Gut microbiota dysbiosis and low SCFA levels, as well as reduced tetrapyrrole biosynthetic capacity by the gut bacteria, may contribute to the development of UC. Moreover, regardless of the severity, duration, and type of UC, the gut microbiota and its metabolites were in a stable state of dysbiosis in patients with UC.

Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria.

Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. The objective of this work is to examine the alteration of gut microbiota in patients with CS. We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.

Liver Bacterial Colonization in Patients with Obesity and Gut Dysbiosis.

Recently, the link between gut microbiota, liver inflammation, and obesity has become an interesting focus of research. The aim of this study is to show the possible relation between gut microbiota dysbiosis in patients with obesity and the presence of bacterial genomes in their liver biopsies. A prospective study on patients undergoing bariatric surgery was carried out. Anthropometric and metabolic data, comorbidities, stool samples, and hepatic biopsies were collected and analyzed at the time of surgery. The V3-16S rRNA region was sequenced using the Ion Torrent new-generation sequencing platform. In each of the 23 patients enrolled, the bacterial population was analyzed both in the stools and liver. In eight patients (34.7%), Prevotella (62.5%), Bacteroides (50%), Streptococcus (12.5%), and Dalister (12.5%) were found in both samples, simultaneously; in 15 cases, the liver was free from colonization. The statistically significant difference between groups was a Roseburia intestinalis reduction in fecal samples of patients with liver biopsies colonized by bacteria (1% vs 3%; p = 0.0339). To the best of our knowledge, this is the first study reporting the presence of bacterial genome in a liver biopsy on bariatric patients, instead of the microbe-associated molecular patterns. Notably, in literature, the presence of Roseburia intestinalis in stool samples has been shown to prevent intestinal inflammation playing its role in the gut barrier integrity. In our population, the Roseburia reduction was associated with the presence of bacterial genome in the liver, probably related to a greater permeability of the gut and vascular barriers.

A Longitudinal Metagenomic Comparative Analysis of Oral Microbiome Shifts in Patients Receiving Proton Radiation versus Photon Radiation for Head and Neck Cancer.

Due to the radiation-sparing effects on salivary gland acini, changes in the composition of the oral microbiome may be a driver for improved outcomes in patients receiving proton radiation, with potentially worse outcomes in patients exposed to photon radiation therapy. To date, a head-to-head comparison of oral microbiome changes at a metagenomic level with longitudinal sampling has yet to be performed in these patient cohorts. To comparatively analyze oral microbiome shifts during head and neck radiation therapy, a prospective pilot cohort study was performed at the Maryland Proton Treatment Center and the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. A longitudinal metagenomic comparative analysis of oral microbiome shifts was performed at three time points (pre-radiation, during radiation, and immediately post-radiation). Head and neck cancer patients receiving proton radiation (n = 4) were compared to photon radiation (n = 4). Additional control groups included healthy age- and sex-matched controls (n = 5), head and neck cancer patients who never received radiation therapy (n = 8), and patients with oral inflammatory disease (n = 3). Photon therapy patients presented with lower microbial alpha diversity at all timepoints, and there was a trend towards reduced species richness as compared with proton therapy. Healthy controls and proton patients exhibited overall higher and similar diversity. A more dysbiotic state was observed in patients receiving photon therapy as compared to proton therapy, in which oral microbial homeostasis was maintained. Mucositis was observed in 3/4 photon patients and was not observed in any proton patients during radiation therapy. The bacterial de novo pyrimidine biosynthesis pathway and the nitrate reduction V pathway were comparatively higher following photon exposure. These functional changes in bacterial metabolism may suggest that photon exposure produces a more permissive environment for the proliferation of pathogenic bacteria. Oral microbiome dysbiosis in patients receiving photon radiation may be associated with increased mucositis occurrence. Proton radiation therapy for head and neck cancer demonstrates a safer side effect profile in terms of oral complications, oral microbiome dysbiosis, and functional metabolic status.

Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis?

Background & AimsTurmeric (a source of curcumin) is an excellent food to modulate oxidative stress, inflammation, and gut dysbiosis in patients with chronic kidney disease (CKD). However, no studies report the benefits of curcumin in patients undergoing peritoneal dialysis (PD). This study aims to evaluate the effects of curcuminoid supplementation on oxidative stress, inflammatory markers, and uremic toxins originating from gut microbiota in patients with CKD undergoing PD. MethodsThis longitudinal, randomized, single-blind, placebo-controlled trial evaluated 48 patients who were randomized into two groups: Curcumin (three capsules of 500mg of Curcuma longa extract, with 98.42% total curcuminoids) or placebo (three capsules of 500mg of starch) for twelve weeks. In the peripheral blood mononuclear cells (PBMCs), the transcriptional expression levels of Nrf2, HOX-1 and NF-κB were evaluated by quantitative real-time PCR. Oxidative stress was evaluated by malondialdehyde (MDA) and total Thiol (T-SH). TNF-α and IL-6 plasma levels were measured by ELISA. P-cresyl sulphate plasma level, a uremic toxin, was evaluated by high-performance liquid chromatography (HPLC) with fluorescent detection. ResultsTwenty-four patients finished the study: 10 in the curcumin group (57.5 ± 11.6 years) and 14 in the placebo group (56.5 ± 10.0 years). The plasma levels of MDA were reduced after 12 weeks in the curcumin group (p = 0.01), while the placebo group remained unchanged. However, regarding the difference between the groups at the endpoint, no change was observed in MDA. Still, there was a trend to reduce the p-CS plasma levels in the curcumin group compared to the placebo group (p = 0.07). Likewise, the concentrations of protein thiols, mRNA expression of Nrf2, HOX-1, NF-κB, and cytokines plasma levels did not show significant changes. ConclusionCurcuminoid supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with CKD undergoing PD. This study was registered on Clinicaltrials.gov as NCT 04413266

Uterine microbiome in women with uterine scar defect after cesarean section: Prospective cohort study

Aim. To evaluate the endometrial microbiota in patients with uterine scar defect after cesarean section.
 Materials and methods. The study included 80 women of reproductive age. The main group included 50 patients with a uterus scar defect due to cesarean section; the comparison group included 30 women with a competent uterus scar due to cesarean section. Patients underwent a Pipelle endometrial biopsy on days 2022 of the menstrual cycle using a double-lumen catheter that excludes sample contamination with vaginal and cervical microflora. A molecular genetic study of the endometrium was performed by real-time polymerase chain reaction using the Femoflor 16 reagent kit (DNA-Technology
 Moscow). The DNA content in the specimen was measured using software and expressed in genome equivalent (GE) proportional to the number of microorganisms. The statistical data were processed using the Exсel software package and SPSS Statistics 22.0.
 Results. The study showed the following statistically significant differences: lower count of Lactobacillus spp. 2.600 (1.4303.600) GE/mL vs 3.550 (2.8004.700) GE/mL in patients of the comparison group (p=0.02); higher count of Streptococcus and Staphylococcus spp. 3.270 (3.0003.700) GE/mL and 3.450 (3.2003.600) GE/mL vs 1.030 (0.7601.700) GE/mL and 0.560 (0.1201.200) GE/mL in the comparison group, respectively (p0.00001); higher count of Enterobacteriaceae 2.700 (1.7003.300) GE/mL vs 0.950 (0.6601.120) GE/mL in the comparison group (p0.00001); higher count of Gardnerella/Prevotellabivia/Porphyromonas spp. 2.310 (0.9303.480) GE/mL vs 1.000 (0.0001.860) GE/mL (p=0.003); higher count of Peptostreptococcus spp. 0.195 (0.0001.560) GE/mL vs 0.000 (0.000-0.000) GE/mL (p=0.032); Eubacterium spp. 1.355 (0.1002.460) GE/mL vs 0.000 (0.0001.560) GE/mL (p=0.040).
 Conclusion. Endometrial dysbiosis in patients with a uterus scar defect after cesarean section due to the possible effects of microorganisms can be considered one of the leading causes of the formation of a uterus scar defect in the postoperative period.

Risk factors for malignant oral mucosal lesion development (literature review). Part 1. Endogenous and biological factors

Relevance. Oral mucosal cancer (OMC) is the sixteenth most common cancer worldwide. The high mortality rate is mainly due to the asymptomatic course of the disease in the early stages and late detection when the tumour process poorly responds to treatment. Determining the impact of various risk factors and establishing their relationship are necessary to prevent and diagnose malignant oral mucosal lesions in the early stages.Purpose. Based on the modern literature, the study aimed to determine the impact value of various internal and external risk factors on malignant oral mucosal lesion development and assess the risk factors’ relationship.Material and methods. The research material included the analysis of literature from databases – Elsevier, PubMed, Elibrary, Google Academy, Medline and Cyberleninka. The study included literature sources in Russian and English.Results. Based on modern literature, we have determined endogenous and biological risk factors for malignant oral mucosal lesion development. The study noted the high role of microbiome changes and the presence of dysbiosis in patients with malignant neoplasms and proved the direct involvement of Candida fungi in carcinogenesis. The development of oral mucosal cancer and the presence and severity of oral yeast colonization and human papillomavirus infection showed a positive correlation. Chronic oral diseases, which are susceptible to malignant transformation or contribute to the development of carcinomas, have been identified, and their relationship has been established with biological risk factors, age, sex of the patient and duration of the disease course.Conclusion. The studies considered in this part of the review prove the influence of endogenous and biological factors on the development of malignant neoplasms of the oral cavity and determine their relationship. However, many mechanisms remain unexplored to date. Effective primary and secondary prevention implementation needs improvement and the development of a multidisciplinary approach to research methodology, study the complex impact of all groups of risk factors on the development of malignant oral mucosal lesions.

Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease.

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.

Gut Microbiota Dysbiosis in COVID-19: Modulation and Approaches for Prevention and Therapy.

Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 that contribute to the complications and clinical deterioration of patients. Additionally, COVID-19 has the potential to alter the composition of patients' gut microbiota, characterized by a decreased abundance of bacteria with probiotic effects. Interestingly, certain strains of these bacteria produce metabolites that can target the S protein of other coronaviruses, thereby preventing their transmission and harmful effects. At the same time, the presence of gut dysbiosis can exacerbate inflammation and oxidative stress, creating a vicious cycle that perpetuates the disease. Furthermore, it is widely recognized that the gut microbiota can metabolize various foods and drugs, producing by-products that may have either beneficial or detrimental effects. In this regard, a decrease in short-chain fatty acid (SCFA), such as acetate, propionate, and butyrate, can influence the overall inflammatory and oxidative state, affecting the prevention, treatment, or worsening of COVID-19. This review aims to explore the current evidence regarding gut dysbiosis in patients with COVID-19, its association with inflammation and oxidative stress, the molecular mechanisms involved, and the potential of gut microbiota modulation in preventing and treating SARS-CoV-2 infection. Given that gut microbiota has demonstrated high adaptability, exploring ways and strategies to maintain good intestinal health, as well as an appropriate diversity and composition of the gut microbiome, becomes crucial in the battle against COVID-19.

EVALUATING HUMAN MICROBIOME SIGNATURES ASSOCIATED WITH DEVELOPMENT, OUTCOME, AND TREATMENT RESPONSE IN GLIOMA AND BRAIN METASTASIS: A SCOPING REVIEW

Abstract The human microbiome is made up of over 500 species of bacteria in the body. Microbiome dysbiosis has been implicated in cancer development and treatment response, including in both primary brain tumors and brain metastases, by acting through the gut-brain axis. We conducted a scoping review of the current evidence surrounding the human microbiome and brain tumors. METHODS: A systematic search of relevant studies and abstracts from 5 electronic databases from 1946-2023 was conducted based on a search strategy developed by an information specialist. Eligible studies included human, in vivo, or in vitro studies that focused on the relationship between microbiome and glioma and brain metastasis development, response to therapies, and outcomes. RESULTS: Of 383 citations, 31 studies met inclusion criteria, including 15 articles and 16 conference abstracts. There were 19 human studies and 18 mouse studies, of which 24 studies focused on glioma and 7 studies focused on brain metastases. They either characterized the microbiome in patients with brain tumors (n=19) or its correlation to systemic therapies for glioma (n=12). Changes in the Firmicutes/Bacteroidetes ratio, which is a marker of dysbiosis in patients with brain tumors was observed in 7 studies; however, the direction of change varied. Microbiome dysbiosis seemed to occur in response to both immunotherapy (5 studies) and temozolomide (3 studies), with variable impacts on treatment response. CONCLUSION: Evidence surrounding the impact of the gut-brain axis on brain tumors remains in its infancy with a large amount of heterogeneity.

Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases.

Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T4), L-3,5,3'-triiodothyronine (T3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.

Gut Microbiome Dysbiosis in Patients with Endometrial Cancer vs. Healthy Controls Based on 16S rRNA Gene Sequencing

Metabolic diseases like obesity, diabetes, and hypertension are considered major risk factors associated with endometrial cancer. Considering that an imbalance in the gut microbiome may lead to metabolic alterations, we hypothesized that alteration in the gut microbioma might be an indirect factor in the development of endometrial cancer. Our aim was to profile the gut microbiota of patients with endometrial cancer compared with healthy controls in this study. Thus, we used 16S rRNA high-throughput gene sequencing on the Illumina NovaSeq platform to profile microbial communities. Fecal samples were collected from 33 endometrial cancer patients (EC group) and 32 healthy controls (N group) between February 2021 and July 2021. The total numbers of operational taxonomic units (OTUs) in the N and EC groups were 28,537 and 18,465, respectively, while the number of OTUs shared by the two groups was 4771. This study was the first to report that the alpha diversity of the gut microbiota was significantly reduced in endometrial cancer patients vs. healthy controls. Also, there was a significant difference in the distribution of microbiome between the two groups: the abundance of Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, Faecalibacterium, and Gemmiger_formicis decreased, while that of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae and Shigella increased significantly in the EC group vs. healthy controls (all p < 0.05). The predominant intestinal microbiota of the endometrial cancer patients was Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, and Shigella. These results imply that adjusting the composition of the gut microbiota and maintaining microbiota homeostasis may be an effective strategy for preventing and treating endometrial cancer.

Promising Markers of Inflammatory and Gut Dysbiosis in Patients with Post-COVID-19 Syndrome.

Post-COVID-19 syndrome is a complex of different symptoms, which results in a multisystemic impairment after the suffering from COVID-19 infection. The aim of the study was to reveal the clinical, laboratory, and gut disorders in patients with post-COVID-19 syndrome (n = 39) before and after taking part in the 14-day complex program of rehabilitation. A complete blood count, coagulation test, blood chemistry, biomarkers, and metabolites in serum samples, and gut dysbiosis were revealed in patients on the day of admission and after 14-day rehabilitation, in comparison with the variables of healthy volunteers (n = 48) or with reference ranges. On the day of discharge, patients noted an improvement in respiratory function, general well-being, and mood. At the same time, the levels of some metabolic (4-hydroxybenzoic, succinic, fumaric acids) and inflammatory (interleukin-6) variables, which were increased on admission, did not reach the level of healthy people during the rehabilitation program. Taxonomy disbalance was observed in patients' feces, namely, a high level of total bacterial mass, a decrease in the number of Lactobacillus spp., and an increase in pro-inflammatory microorganisms. The authors suggest that the post-COVID-19 rehabilitation program should be personalized, considering the patient's state together with not only the baseline levels of biomarkers, but also with the individual taxonomy of the gut microbiota.

Gut microbial dysbiosis in patients with Cushing's disease in long-term remission. Relationship with cardiometabolic risk.

Patients with Cushing's disease (CD) in remission maintain an increased cardiovascular risk. Impaired characteristics of gut microbiome (dysbiosis) have been associated with several cardiometabolic risk factors. Twenty-eight female non-diabetic patients with CD in remission with a mean ± SD) age of 51 ± 9 years, mean ( ± SD) BMI, 26 ± 4, median (IQR) duration of remission, 11(4) years and 24 gender-, age, BMI-matched controls were included. The V4 region of the bacterial 16S rDNA was PCR amplified and sequenced to analyse microbial alpha diversity (Chao 1 index, observed number of species, Shannon index) and beta diversity analysis through the Principal Coordinates Analysis (PCoA) of weighted and unweighted UniFrac distances. Inter-group difference in microbiome composition was analysed using MaAsLin2. The Chao 1 index was lower in CD as compared with controls (Kruskal-Wallis test, q = 0.002), indicating lower microbial richness in the former. Beta diversity analysis showed that faecal samples from CS patients clustered together and separated from the controls (Adonis test, p<0.05). Collinsella, a genus form of the Actinobacteria phylum was present in CD patients only, whereas Sutterella, a genus from Proteobacteria phylum, was scarcely detectable/undetectable in CD patients as well as Lachnospira, a genus of the Lachnospiraceae family of the Firmicutes phylum. In CS, the Chao 1 index was associated with fibrinogen levels and inversely correlated with both triglyceride concentrations and the HOMA-IR index (p<0.05). Patients with CS in remission have gut microbial dysbiosis which may be one of the mechanisms whereby cardiometabolic dysfunctions persist after "cure".

The Gut Microbial Metabolite Trimethylamine N-Oxide is Linked to Specific Complications of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare immune-mediated connective tissue disease characterized by fibrosis of the skin and internal organs, whose pathogenesis is not fully understood. Recent studies have revealed dysbiosis in patients with systemic sclerosis and have indicated the possible role of the microbiota and its metabolites in the pathogenesis of the disease. Trimethylamine N-oxide (TMAO) is a compound produced by dysbiotic microbiota observed at higher concentrations in several autoimmune diseases. To determine concentrations of the bacteria-derived metabolite TMAO in patients with systemic sclerosis and to assess possible correlation between TMAO and a specific manifestation of the disease. The study included 63 patients with SSc and 47 matched control subjects. The concentration of TMAO was measured with high-performance liquid chromatography. Plasma TMAO level was significantly increased in patients with SSc (283.0 [188.5-367.5] ng/mL versus 205.5 [101.0-318.0] ng/mL; p < 0.01). An increased concentration of TMAO was observed in patients with concomitant interstitial lung disease (ILD) (302.0 ng/mL [212.0-385.5] ng/mL versus 204.0 [135.5-292.0] ng/mL; p < 0.01) and esophageal dysmotility (289.75 [213.75-387.5] ng/mL versus 209.5 ng/mL [141.5-315.0] ng/mL; p < 0.05) compared to patients without these complications. Furthermore, TMAO concentration exhibited significant correlation with markers of heart involvement (left ventricle ejection fraction, NT-proBNP), marker of ILD severity and Scleroderma Clinical Trials Consortium Damage Index. The concentration of TMAO, gut microbiota-associated metabolite, is increased in systemic sclerosis, particularly in patients with advanced organ involvement. This is the first study evaluating plasma TMAO in systemic sclerosis. Bacterial metabolites may be a link between dysbiosis and organ involvement in the course of the disease. Modulation of gut bacterial-derived metabolites may represent a new therapeutic approach in the management of systemic sclerosis.

On the features of the correction of intestinal dysbiosis in chronic pancreatitis (literature review)

The aim of the literature review was to analyze the modern approach to the correction of intestinal dysbiosis in patients with chronic pancreatitis, including the one combined with metabolic syndrome, coronary heart disease, and especially bacterial overgrowth syndrome.&#x0D; Particular attention is paid to the peculiarities of drug therapy and the pharmacotherapeutic mechanisms of influence of various groups of pro-, pre- and synbiotics on the condition of the intestine, immunity, and inflammatory processes. The requirements for an adequate selection of drugs are considered. They must be useful for the human body; should not cause side effects during long-term use, but should have a minimal ability to translocate from the lumen of the intestine to internal organs; must be resistant to low pH values, the influence of bile acids, and antimicrobial substances produced by endogenous microflora; adhere well to the epithelium of mucous membranes; have a high rate of growth and reproduction in the intestines; and must have a clear physiological, biochemical, and genetic marking. Efficacy criteria are the probiotic effect proven in double-blind placebo-controlled studies. These requirements are met by B. bifidum, Lactobacillus acidophilus, Lactobacillus GG, Lactobacillus fermentum, Strepto(Entero)coccus faecium, Saccharomyces boulardii, which are components of many probiotics.&#x0D; Interesting information is provided about the probiotic with level A evidence, called Enterol by the WHO experts: it is a self-eliminating probiotic, each capsule of which contains 250 mg of lyophilized cells of a selective strain of medicinal yeast, Saccharomyces boulardii. It is crucial that the drug prevents the growth of a wide range of pathogenic microorganisms and fungi and promotes their elimination (Clostridium difficile, Clostridium pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Candida crusei, Candida pseudotropical, Candida albicans, Salmonella typhi, Salmonella enteriditis, Escherichia coli, Shigella dysenteriae, Shigella flexneri, Klebsiella, Proteus, Vibrio cholera, Enthamoeba hystolitica, Enterovirus, Rotavirus).

Возможность применения крема дозированного Ацилакт Дуо при бактериальном вагинозе

Bacterial vaginosis is a clinical condition in which the normal vaginal microflora, predominantly lactobacilli, is replaced by other microorganisms, mainly anaerobes. The goal of treating bacterial vaginosis is to restore the normal microflora of the vagina, to delay the growth of microorganisms that are not characteristic of this vaginal microcenosis. The purpose of the study was to evaluate the effectiveness of various methods of combined two-stage treatment of bacterial vaginosis in women of reproductive age. Material and methods. The study included 50 patients aged 18 to 45 years (mean age 29.6 ± 4.5 years) with bacterial vaginosis. The first group consisted of 25 patients who received Clindamycin 2% cream for 7 days, dose vaginally at night. For the second stage of therapy in this 1 group, acidophilus bacteria + vitamin-mineral-protein-peptide complex Superlimfly (Acylact Duo) were used, suppository time per day at night intravaginally for 10 days. The second group consisted of 25 patients who received Clindacimin cream for 7 days, dose vaginally at night. For the second stage of therapy, a preparation containing a lyophilized culture of lactobacilli L. casei rhamnosus Doderleini was used, at least 1 × 108 CFU, capsule in the vagina at night for 14 days. Results. The effectiveness of BV therapy was 49% (n = 46). The duration of remission was 24.1 ± 2.1 days (n = 24) in the group of women receiving adjuvant therapy with Acilact Duo dosed cream, and 19.9 ± 2 3. days (n = 22) in the comparison group. In all patients, the average vaginal pH before therapy was 5.5 ± 0.4. In group1 participants, after therapy, the pH was 4.54 ± 0.143 , in group 2 patients, the average vaginal pH was 4.976 ± 0.241. Among the patients of both groups, vaginal dysbiosis of varying severity was detected before treatment (normocenosis was not detected). After therapy, in patients of group, normocenosis of the vagina was achieved in 88% (22/25), in participants of group 2, normocenosis was noted in 72% (18/25). At visit (in 45 days) in women of the group 1 84% (21/25), in the participants of the group 2 – normocenosis was noted in 64% (16/25). Conclusions. Acidophilic bacteria + vitamin-mineral-protein-peptide complex Superlymfly (in which dosed Acylact Duo) quickly restores the optimal acidity of the vagina (pH value) and promotes the growth of the number of beneficial lactobacilli, as a result of which it creates an optimal and natural microflora that prevents the appearance of dysbiosis in patients of reproductive age

Gut microbiota alterations in critically Ill patients with carbapenem-resistant Enterobacteriaceae colonization: A clinical analysis.

Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients. Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive (n = 9) and CRE negative (n = 32) patients. The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed. CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera Erwinia, Citrobacter, Klebsiella, Cronobacter, Kluyvera, Dysgomonas, Pantoea, and Alistipes had an upper 2 LDA score in CRE carriers. The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups. Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE.

Effects of Tiaopi Xiezhuo decoction on constipation and gut dysbiosis in patients with peritoneal dialysis

Context A Chinese herbal formula, Tiaopi Xiezhuo decoction (TXD), is developed from a classical Chinese prescription Sanhuang Xiexin decoction. Objective To investigate the regulatory effect of TXD on gut dysbiosis, as a treatment of constipation in patients with peritoneal dialysis (PD). Materials and methods The chemical content of TXD was assessed by high-performance liquid chromatography. A total of 29 PD patients were enrolled and treated with TXD orally (3 g crude drug/each/twice/day) for 3 months. Blood and faecal samples were collected at the beginning and end, to determine the changes in biochemical characteristics and gut microbial composition. The stool conditions were asked to be scored. Additional 30 healthy individuals were recruited as a control for the analysis of gut microbiota. Results Although having no significant effects on serum biochemical characteristics, 3-month TXD intervention improved constipation in PD patients: decreased 80% abdominal distention (p < 0.01), increased 2.6-fold sloppy stools (p < 0.05) and eliminated hard stool completely (p < 0.01). The analysis of gut microbiota showed that, compared to the healthy group, the microbial richness was reduced in PD patients. After a 3-month TXD treatment, this reduced richness was raised, and Paraprevotella clara, Lachnospiraceae bacterium 2-146FA, Phascolarctobaterium succinatutens, Lachnospiraceae bacterium 2-1-58FAA, Fusobacterium mortiferum, and Prevotella copri were accumulated in the intestinal flora. Furthermore, the bacterial species enriched by TXD correlated with the improvement of constipation. Discussion and conclusions TXD treatment may improve constipation by modulating gut dysbiosis in PD patients. These findings provide data to support the further application of TXD in the adjuvant treatment of PD.