Role Of Gut Microflora Research Articles

Altered colonic microflora and its metabolic profile in mice with acute viral myocarditis induced by coxsackievirus B3.

Mounting evidence suggests that the gut-heart axis is critical in the pathogenesis of cardiovascular diseases. The gut serves as the primary pathway through which Coxsackievirus B3 (CVB3) infects its host, leading to acute viral myocarditis (AVMC). However, little is known about the role of gut microflora and its metabolites in the development of AVMC. The AVMC model was established by intraperitoneal injection of CVB3 in mice. Then, 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) untargeted metabolomics profiling were performed to analyze the microflora composition and metabolic profile of colonic contents. Compared to the Control mice, the AVMC mice displayed a significant reduction in gut microflora richness and diversity, as revealed by an increased abundance of Proteobacteria and a decreased abundance of Cyanobacteria and Desulfobacterota. LEfSe analysis indicated that the main genera differing between the two groups were Escherichia-Shigella, Lactobacillus, Clostridium_sensu_stricto_1, Prevotellaceae_UCG-001, and Odoribacter. Based on the criterion of OPLS-DA VIP ≥ 1.0 and p-value < 0.05, a total of 198 differential metabolites (DMs) were identified in the gut, including 79 upregulated and 119 downregulated metabolites, of which lipids and lipid-like molecules accounted for the largest proportion. Notably, both altered gut bacterial taxa and metabolites were significantly enriched in the Lipid metabolism pathway, with Traumatic acid (TA), Alpha-Linolenic acid (ALA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) being the key DMs in the pathway. Additionally, significant positive correlations (|r| > 0.80 and p < 0.05) were found between TA levels and Anaerotruncus and Bilophila abundance, between EPA levels and Clostridium_sensu_stricto_1 abundance, and between DHA levels and Escherichia-Shigella abundance, respectively. CVB3 infection leads to notable alterations in gut microflora composition and its metabolic profile, which may participate in AVMC development. Our findings provide important clues for future in-depth studies on AVMC etiology.

The importance of the genital tract microflora in the endometriosis development

Endometriosis is a common pathology among women of reproductive age. In the pathogenesis of its development a great importance is paid to the process of regulation of estrogens and other sex hormones, the implementation of the immune response at the general and local levels, the inflammatory response, and genetic background. In recent years, the role of the microbiota in different parts of the genital tract of the female organism has been studied not only from the standard approach of inflammatory diseases research of the reproductive organs and pathological vaginal discharge, but its contribution into the development of other gynecological diseases, in particular endometriosis, is presented.The article is devoted to a review of scientific publications about researches devoted to the significance of the genital tract microflora in the pathophysiology of endometriosis. The article presents the concepts of states of eubiosis and dysbiosis, describes the features of the microflora of the lower (vagina, cervix) and upper parts (uterus, fallopian tubes) of the genital tract in healthy women. The data on the importance of Lactobacillus in maintaining an optimal state of acidity in the vaginal environment are presented. The difference in the composition of the microbiota of the vagina, cervical mucus, uterine cavity and peritoneal fluid in women with and without endometriosis is revealed. The pathogenetic mechanisms of the role of the microbiota in the processes of endometriosis pathogenesis, namely, the regulation of the immune response and inflammation processes in this pathology, are described. It has been shown that in women with endometriosis there are differences in the microflora composition of the vagina, cervix, uterine cavity, peritoneal fluid, manifested by a decreased concentration of Lactobacillus and the presence of a variety of other microorganisms in relation to healthy women. The data about the role of gut microflora in patients with this pathology are also presented. The results of research about the diagnosis of various stages of endometriosis by studying the composition of the genital tract microbiota are described.

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.

The role of gut microflora in mucosal immunity

The role of gut microflora in mucosal immunity

Gut micro flora in genesis of methilthyo metabolites of paracetamol

Gut micro flora represents a system of extensive metabolic capacity which is quite different when compared to other cells of body and organs. In recent times, there has been an evidence of very important role of gut cysteine conjugate beta-lyases in metabolism of cystein conjugates. A lot of studies are dedicated to exploration of the role of gut micro flora in formation of methylthio adducts from paracetamol in conventional mice and those treated with neomycin as our study. A highly significant reduction in urinary excretion of 3-methylthioparacetamol in group of neomycin-treated mice was confirmed as well its glucuronic acid and sulphate conjugates. Following the principal role of gut flora in the C-S cleavage of paracetamol l-3-cyctein it is clear that highest concentration of methylthio adducts from paracetamol are presented in pretreated mice.

Gut Microbial Signatures Underline Complicated Crohn's Disease but Vary Between Cohorts; An In Silico Approach.

Microflora dysbiosis is implicated in the pathophysiology of Crohn's disease. This work analyzes differences in microbial communities and relevant metabolic pathways among the nonstricturing nonpenetrating (B1), stricturing (B2), and penetrating (B3) subphenotypes of Crohn's disease vs healthy controls. We conducted a bioinformatics analysis using the QIIME pipeline and the Calypso, linear discriminant analysis effect size, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and STAMP tools on publicly available 16S bacterial rRNA sequencing data from terminal ileum mucosal biopsies of healthy controls and the 3 subphenotypes of Crohn's disease. We analyzed differences in microbial diversity and taxonomy, inferred active metabolic pathways via relevant genes' abundance, and detected bacterial families that could serve as biomarkers. Microbiota α-diversity was decreased within all 3 Crohn's disease subphenotypes vs control samples, with more significant reductions in B2 and B3 compared with B1. β-diversity analysis identified similar microbial patterns in B2 and B3 samples, different from those of B1 and from those of healthy controls. Abundance analysis of microbial families in cohorts, beyond altered abundances compared with healthy controls, highlighted significant differences between the B2 and B3 subphenotypes and the B1 subphenotype. A similar pattern was observed in the inference of microbial metabolomics: the B2 and B3 cohorts had different predicted metabolotypes from the B1 cohort, in addition to differences observed in Crohn's disease vs healthy controls. Our findings indicate distinct microbiome signatures in complicated Crohn's disease subphenotypes and provide the basis for further investigation into the role of gut microflora in the natural course of Crohn's disease.

Abstract 636: Gut Microflora Influences Pathology in the Kawasaki Disease (KD) Vasculitis Mouse Model

Background: KD is the leading cause of acquired heart disease in the US. We have demonstrated the critical role of innate immune responses via IL-1R/MyD88 signaling in the Lactobacillus casei cell wall extract (LCWE)-induced KD mouse model. The diversity and composition of microflora (both bacterial and fungal) have been associated with the regulation and alterations of immune responses and various pathologies. However, the role of gut microbiota in immunopathology of KD has not been investigated. Objective: To evaluate the role of gut microflora in development of coronary arteritis, and vascular abnormalities in KD mouse model. Methods and Results: We investigated the role of gut microflora in the LCWE-induced KD mouse model, using Specific-Pathogen Free (SPF) and Germ Free (GF) mice (C57BL/6). GF mice showed a significant decrease of KD lesions, including coronary arteritis compared with SPF mice. The development of LCWE-induced AAA, which we recently discovered in this mouse model, was also markedly diminished in GF mice. In addition to GF mice, we also investigated the specific role of commensal bacteria and/or fungi, and determined whether altered microorganism burden in this KD mouse model contributes to disease severity. To deplete bacteria and/or fungi in the gut microflora, we exposed pregnant SPF mice and their offspring to antibiotics cocktail (Abx) or antifungal drug (fluconazole; Fluc) in their drinking water for 5 wks and induced KD. The mice treated with Abx or Fluc had significantly reduced coronary arteritis and AAA compared to controls. The Abx plus Fluc administration showed marked decrease of KD vasculitis. Conclusions: We demonstrate here that gut microflora play a critical role in the development of KD vasculitis in LCWE-induced mouse model. Our results suggest that both bacteria and fungi in the intestinal microbiota may control the induction and severity of KD vasculitis. These findings provide a new perspective on the potential role of the microbiome in KD pathogenesis and may offer new diagnostic and therapeutic strategies for KD patients.

Abstract O.24: Gut Microflora Influences Pathology in the Kawasaki Disease Vasculitis Mouse Model

Background: Kawasaki Disease (KD) is the leading cause of acquired heart disease in the US. We have demonstrated the critical role of innate immune responses via IL-1R/MyD88 signaling in the Lactobacillus casei cell wall extract (LCWE)-induced KD mouse model. The diversity and composition of microflora (both bacterial and fungal) have been associated with the regulation and alterations of immune responses and various pathologies. However, the role of gut microbiota in immunopathology of KD has not been investigated. Objective: To evaluate the role of gut microflora in development of coronary arteritis, and vascular abnormalities in KD mouse model. Methods and Results: We investigated the role of gut microflora in the LCWE-induced KD mouse model, using Specific-Pathogen Free (SPF) and Germ Free (GF) mice (C57BL/6). GF mice showed a significant decrease of KD lesions, including coronary arteritis compared with SPF mice. The development of LCWE-induced AAA, which we recently discovered in this mouse model, was also markedly diminished in GF mice. In addition to GF mice, we also investigated the specific role of commensal fungi, and determined whether altered fungal burden in this KD mouse model contributes to disease severity. To deplete fungi in the gut microflora, we exposed pregnant SPF mice and their offspring to fluconazole (antifungal) in their drinking water for 5 wks and induced KD. The fluconazole treated mice had significantly reduced coronary arteritis, and AAA compared to controls. Since Dectin-1 has emerged as a key receptor that recognizes β-1,3-glucans found in the cell wall of nearly all fungi, we next induced KD in Dectin-1 deficient mice. Dectin-1 deficient mice also had significantly reduced KD lesions such as coronary arteritis compared with WT mice. Conclusions: We demonstrate here that gut microflora play a critical role in the development of KD vasculitis in LCWE-induced mouse model. Our results suggest that fungi in the intestinal microbiota may specifically control the induction and severity of KD vasculitis, which may be mediated by Dectin-1. These findings provide a new perspective on the potential role of the microbiome in KD pathogenesis and may offer new diagnostic and therapeutic strategies for KD patients.

More on Current Evidences on Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease

Dear Editor, In their recent article Kelishadi et al. (1) analyzed in a clear and concise way a number of key aspects of obesity-related NAFLD, deepening in particular the role of gut microflora and its potential therapeutic modulation by probiotics. From their paper it is apparent that most promises still derive from a relevant number of studies conducted in different NAFLD animal models. When interpreting data obtained in these models one should however remind that other factors like physical activity, social and chemical environment, psychological stress factors and genetics are also important contributors to the development of human NAFLD and to its incredible resistance to treatments as well (2). In this respect Dr. Kelishadi and colleagues' review of four available clinical trials on human population is therefore particularly welcomed. In three studies probiotic treatments appear to improve somehow NAFLD related parameters. The fourth study, published in 2008 by doctor Diehl’s group, instead warned versus probiotics treatment of NAFLD, reporting that steatosis measured by proton magnetic resonance spectroscopy increased in three out of four patients treated with VSL#3 for 4 months (3). In addition to these meagre evidences, in recent times, Malguarnera et al. showed in histologically monitored NAFLD patients that Bifidobacterium longum + fructo-oligosaccharides (FOS) treatment and lifestyle modification, when compared to lifestyle modification alone, significantly reduced a number of serum inflammatory, metabolic, toxinic and cytolitic parameters, along with improved histological steatosis, and NASH activity index (4). Even more recently, a further open label randomized controlled trial in 20 obese adult patients with biopsy proven NAFLD appeared fairly promising. Patients received a six month formula containing five strains of bacteria (4 lactobacilli + Bifidobacterium bifidum) + FOS. Treatment resulted in reduction of liver fat (P = 0.034) and AST level (absolute change P = 0.021; percentage of baseline value P = 0.008) (5). In all cases, it should be emphasized that the hitherto available study designs are not homogeneous and data results cannot be easily compared. Study population of two examined series by dr Kelishadi and colleagues for example included different chronic liver diseases in addition to NAFLD (6, 7); probiotics preparations often contained different bacteria strains, and sometimes confounding prebiotics (FOS) and/or vitamins cocktails (4-6); study duration was quite different, and it is still not clear if longer study may be affected by a number of biases like concurrent unpredictable major life style modifications, and at which extent. Last, but not least, although the Authors reminded the seriousness of epidemiologic data of pediatric NAFLD, they do not refer further to pediatric therapeutic studies targeting gut microbiota. In this regard we think therefore it might be valuable to the discussion completeness also the inclusion of our 2011 study published in Journal of Pediatric Gastroenterology and Nutrition (8). In that double-blind, placebo-controlled pilot study the effects of a short-term (8 weeks) probiotic treatment in 20 children with obesity-related liver disease were evaluated. Patients received Lactobacillus Rhamnosus strain GG (12 billion CFU/day): this probiotic strain was chosen because of the proven safety and efficacy profile in previous pediatric studies. Consistently with available adult data, in our population a multivariate analysis after probiotic treatment revealed a significant decrease in alanine aminotransferase (average variation vs. placebo P = 0.03), with normalization in most (80%) cases, irrespective of changes in BMI z score and visceral fat. We measured anti peptidoglycan-polysaccharide (PGPS) antibodies, an indirect indicator of intestinal bacterial overgrowth. PGPS is a ubiquitous bacterial antigen found in both gram-positive and gram-negative bacteria wall, and anti PGPS production is a sign of bacteria or bacterial membrane translocation through intestine barrier. Interestingly PGPS antibodies were significantly reduced after probiotic treatment (average variation vs. placebo P = 0.03). Serum levels of tumor necrosis factor-alpha, and US bright liver parameters remained stable during the study frame. Summing up, taking into account also the above additional evidences, we agree with Dr. Kelishadi and colleagues that available animal and human studies altogether may authorize to further support the view of a reasonable therapeutic role of probiotics in adult and also pediatric NAFLD patients not compliant to lifestyle changes, also because of minimal adverse effects and low cost (9). For better clarifying these aspects, future studies still need to be planned on well characterized larger populations, possibly with single probiotic agents, followed by a wash out period, and/or with gut microbiota characterization. The latter, much interestingly, has been defined only very recently both in adult (10)and in pediatric NAFLD (11).

Pharmacokinetics of Dietary Isoflavones

Dietary isoflavones are reported to have significant influences on human health. The beneficial effects reported include reduced risk of cancers, decreased menopausal symptoms, reduced osteoporosis etc. Most of these benefits have been deduced from epidemiological studies involving soy bean as the source of dietary isoflavones, since soy bean is an important food crop in several parts of the world. Over the last 30 years, considerable progress has been made in understanding the fate of dietary isoflavones in humans. Now we understand that the pharmacokinetics of dietary isoflavones is a complex phenomenon and involving multifaceted biological processes. The role of gut micro flora in deciding the bioavailability of isoflavones is quite significant. This review examines various pharmacokinetic aspects of dietary isoflavones and factors influencing the systemic bioavailability of isoflavones. This review also attempts to identify important factors which may contribute to the inter-person differences in the effects of isoflavones.

Role of gut microflora in the development of obesity and insulin resistance following high-fat diet feeding

A recent growing number of evidences shows that the increased prevalence of obesity and type 2 diabetes cannot be solely attributed to changes in the human genome, nutritional habits, or reduction of physical activity in our daily lives. Gut microflora may play an even more important role in maintaining human health. Recent data suggests that gut microbiota affects host nutritional metabolism with consequences on energy storage. Several mechanisms are proposed, linking events occurring in the colon and the regulation of energy metabolism. The present review discusses new findings that may explain how gut microbiota can be involved in the development of obesity and insulin resistance. Recently, studies have highlighted some key aspects of the mammalian host-gut microbial relationship. Gut microbiota could now be considered as a "microbial organ" localized within the host. Therefore, specific strategies aiming to regulate gut microbiota could be useful means to reduce the impact of high-fat feeding on the occurrence of metabolic diseases.

Rifaximina nel trattamento della malattia diverticolare: potenziale terapeutico ed economico

Antibiotics are commonly used to treat major inflammatory complications of diverticular disease, but apparently there is no rationale for the use of antibiotic therapy in uncomplicated disease, where an inflammatory component is by definition excluded. Some observations suggest a possible role of gut microflora in determining some symptoms related to diverticular disease: bacterial overgrowth, amplifying gas production and bacterial degradation of fibres, could determine bloating, pain and high fecal density. Therefore a beneficial antibiotic action on diverticular disease symptoms can be hypothesized. In this paper pharmacokinetic, pharmacodinamic and therapeutic potential of an intestinal antibiotic, rifaximin, are reviewed. Rifaximin is a rifamycin derivative which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration and in vitro data indicate it to possess a broad spectrum of action; bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. The results of placebo-controlled clinical trials show that cyclic administration of rifaximin is more effective in reducing symptoms and in preventing complications than fibre supplementation alone; the drug appears to be well tolerated and safe. We consider the clinical implications and economical impact of diverticulosis on the Italian National Health System and the patient, with a particular attention on the cost of hospitalization, surgery and global management of diverticulitis and other common disease complications. The hypothetic savings correlated to the reduction of complications incidence, attainable with rifaximin use have been calculated and the comparison between the different acquisition costs of the drug frequently used to treat the diverticular disease is provided. Finally we reviewed some quality of life trials in which the psychological and sociological influence of the disease symptoms and treatments on the patient are assessed.

Role of probiotics in the management of patients with food allergy

This review will concentrate on the potential use of probiotics in treating or preventing allergic disorders of the gastro-intestinal tract. In small infants, most reactions to foods are manifested in the gastro-intestinal tract. As children get older, cutaneous and even systemic or respiratory manifestations of food intolerances may be more common. In most instances, allergic disorders in the gut cause inflammation in the mucosa. Recently, the role of gut microflora in allergic disease has gained increasing interest with reports of probiotics being used to treat food allergy. Pertinent scientific reports on the role of probiotics in the management of patients with food allergy will be reviewed. A recent study to determine the effect of very early probiotic colonization will be extensively reviewed as it presents an intriguing concept of a preventive strategy related to food allergy development Significant improvement has been noted in infants receiving Lactobacillus GG in their extensively hydrolyzed formula. It is likely more studies will be forthcoming with different probiotic organisms in the prevention and treatment of allergic disorders in children and adults.

Determinants of serum enterolactone concentration

The lignan enterolactone, which is produced by the intestinal microflora from dietary precursors, may protect against hormone-dependent cancers and cardiovascular diseases. We examined the cross-sectional associations between the serum enterolactone concentration and variables related to diet and health in Finnish adults. Serum enterolactone was measured by using time-resolved fluoroimmunoassay in 2380 Finnish men and women aged 25-64 y who were participating in a cross-sectional national survey in 1997. Background information was collected with self-administered questionnaires and the diet was assessed with a food-frequency questionnaire. The median serum enterolactone concentration was 13.8 nmol/L (range: 0-95.6 nmol/L) in men and 16.6 nmol/L (range: 0-182.6 nmol/L) in women. Multiple regression analyses showed positive associations in men between the serum enterolactone concentration and constipation, consumption of whole-grain products, and intake of fruit and berries. In women, the serum enterolactone concentration was positively and independently associated with consumption of vegetables, subject age, and constipation and was negatively associated with smoking. Furthermore, female subjects of normal weight had significantly higher serum enterolactone concentrations than did their underweight or obese peers. The serum enterolactone concentration varies widely in the population. Of the variables we examined, the most important determinants of the serum enterolactone concentration were consumption of lignan-containing foods and constipation; however, these appeared to explain only a small part of the variation. Therefore, the role of gut microflora in the metabolism of lignans might be very important. Further studies will also be needed to determine the bioavailability and absorption rate of lignans.

The presence, nature, and role of gut microflora in aquatic invertebrates: A synthesis

This review of the literature concerns the gut microbiota of aquatic invertebrates and highlights the questions and processes that merit attention if an understanding of the role of gut microbes in the physiology of host invertebrates and nutrient dynamics of aquatic systems is to be gained. A substantial number of studies report the presence of gut microbes in aquatic invertebrates. Crustacea, Mollusca, and Echinodermata have received the most attention, with few studies involving other invertebrate groups. Different types of associations (e.g., ingestion, contribution of exoenzymes, incubation, parasitism) are reported to occur between gut microbes and aquatic invertebrates, and it is clear that gut bacterial communities cannot be treated as single functional entities, but that individual populations require examination. In addition, gut microbes may be either ingested transients or residents, the presence of which have different implications for the invertebrate. The most commonly reported genera of gut bacteria are Vibrio, Pseudomonas, Flavobacterium, Micrococcus, and Aeromonas. Quite a number of authors report the physiological properties of gut microbes (including enzyme activities and attributes such as nitrogen fixation), while less attention has been given to consideration of the colonization sites within the digestive tract, the density and turnover of gut bacteria, and the factors affecting the presence and nature of gut microflora. In addition, although a few studies have demonstrated a positive relationship between invertebrates and their gut microbiota, particularly with regard to nutrient gain by the invertebrate, very little conclusive evidence exists as to the role of bacteria in the physiology of host invertebrates. This has resulted from a lack of process-oriented studies. The findings for aquatic gut microbes are compared to those of gut bacteria associated with terrestrial invertebrates, where gut microbes contribute significantly to nutrient gain by the host in some environments.

Ascorbic acid catabolism by gut microflora: studies in germ-free and conventional guinea pigs

The role of gut microflora in ascorbic acid catabolism was investigated in both conventional and germ-free guinea pigs. In vitro studies demonstrated extensive degradation of the vitamin by fresh feces, cecal, and colonic contents of conventional guinea pigs. Direct injection of [1- 14C] ascorbic acid into the cecum of conventional guinea pigs in vivo yielded a 70% recovery of the label as respiratory 14CO 2 within 6 hr compared with only 5% recovery following injection into the virtually sterile peritoneum in a comparable group of conventional guinea pigs. Thus, ascorbic acid not absorbed prior to reaching the lower gastrointestinal tract stands to be extensively decarboxylated by microflora in the cecum. In a companion study of germ-free guinea pigs, 10% of an administered dose of [1- 14C] ascorbic acid was expired as 14CO 2 within 36 hr post-injection following intraperitoneal injection compared with 16% recovery in a matched group of conventional animals injected at the same site. Results of this series of studies suggest that hepatic decarboxylation and gut microflora, in tandem, contribute to ascorbic acid decarboxylation in this species.

Specificities of nitrogen metabolism in the chicken and the role of gut microflora - A review.

Specificities of nitrogen metabolism in the chicken and the role of gut microflora - A review.