Abstract Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, ...yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut “virome” composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut “virome” in the larger microbial ecosystem.
Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been ...reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in
,
and
abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.
Lipopolysaccharides (LPSs) are bacterial surface glycolipids, produced by Gram-negative bacteria. LPS is known to determine acute inflammatory reactions, particularly in the context of sepsis. ...However, LPS can also trigger chronic inflammation. In this case, the source of LPS is not an external infection, but rather an increase in endogenous production, which is usually sustained by gut microbiota (GM), and LPS contained in food. The first site in which LPS can exert its inflammatory action is the gut: both GM and gut-associated lymphoid tissue (GALT) are influenced by LPS and shift towards an inflammatory pattern. The changes in GM and GALT induced by LPS are quite similar to the ones seen in IBD: GM loses diversity, while GALT T regulatory (Tregs) lymphocytes are reduced in number, with an increase in Th17 and Th1 lymphocytes. Additionally, the innate immune system is triggered, through the activation of toll-like receptor (TLR)-4, while the epithelium is directly damaged, further triggering inflammation. In this review, we will discuss the importance of the crosstalk between LPS, GM, and GALT, and discuss the possible implications.
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•Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma.•Addition of selective internal radiation therapy did not significantly ...improve overall survival compared to sorafenib alone.•Subgroup analyses provided results that will guide future clinical trial designs for this combination therapy.
Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of a combination of sorafenib and selective internal radiation therapy (SIRT) – with yttrium-90 (90Y) resin microspheres – to sorafenib alone in patients with advanced HCC.
SORAMIC is a randomised controlled trial comprising diagnostic, local ablation and palliative cohorts. Based on diagnostic study results, patients were assigned to local ablation or palliative cohorts. In the palliative cohort, patients not eligible for TACE were randomised 11:10 to SIRT plus sorafenib (SIRT + sorafenib) or sorafenib alone. The primary endpoint was overall survival (OS; Kaplan-Meier analysis) in the intention-to-treat (ITT) population.
In the ITT cohort, 216 patients were randomised to SIRT + sorafenib and 208 to sorafenib alone. Median OS was 12.1 months in the SIRT + sorafenib arm, and 11.4 months in the sorafenib arm (hazard ratio HR 1.01; 95% CI 0.81–1.25; p = 0.9529). Median OS in the per protocol population was 14.0 months in the SIRT + sorafenib arm (n = 114), and 11.1 months in the sorafenib arm (n = 174; HR 0.86; p = 0.2515). Subgroup analyses of the per protocol population indicated a survival benefit of SIRT + sorafenib for patients without cirrhosis (HR 0.46; 0.25–0.86; p = 0.02); cirrhosis of non-alcoholic aetiology (HR 0.63; p = 0.012); or patients ≤65 years old (HR 0.65; p = 0.05). Adverse events (AEs) of Common Terminology Criteria for AE Grades 3–4 were reported in 103/159 (64.8%) patients who received SIRT + sorafenib, 106/197 (53.8%) patients who received sorafenib alone (p = 0.04), and 8/24 (33.3%) patients who only received SIRT.
Addition of SIRT to sorafenib did not result in a significant improvement in OS compared with sorafenib alone. Subgroup analyses led to hypothesis-generating results that will support the design of future studies.
Sorafenib given orally is the recommended treatment for patients with advanced hepatocellular carcinoma (HCC). In selective internal radiation therapy (SIRT), also known as radioembolisation, microscopic, radioactive resin or glass spheres are introduced into the blood vessels that feed the tumours in the liver. This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafenib treatment alone. However, the results give an indication of how future studies using this combination therapy in people with advanced HCC could be designed.
Study Registration: EudraCT 2009-012576-27, NCT0112 6645.
The stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of drugs such as proton pump inhibitors (PPIs), or bacterial infection such as Helicobacter ...pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in early phase and rely principally on linear techniques for multivariate analysis. Here we disclose the importance of complementing linear dimensionality reduction techniques with nonlinear ones to unveil hidden patterns that remain unseen by linear embedding. Then, we prove the advantages to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of bacterial network re-organizations which emerge from perturbations induced by a medical treatment (PPIs) or an infectious state (H. pylori). Finally, we show how to build bacteria-metabolite multilayer networks that can deepen our understanding of the metabolite pathways significantly associated to the perturbed microbial communities.
Over the past recent years, a great number of studies have been directed toward the evaluation of the human host-gut microbiota interaction, with the goal to progress the understanding of the ...etiology of several complex diseases. Alterations in the intestinal microbiota associated with inflammatory bowel disease are well supported by literature data and have been widely accepted by the research community. The concomitant implementation of high-throughput sequencing techniques to analyze and characterize the composition of the intestinal microbiota has reinforced the view that inflammatory bowel disease results from altered interactions between gut microbes and the mucosal immune system and has raised the possibility that some form of modulation of the intestinal microbiota may constitute a potential therapeutic basis for the disease. The aim of this review is to describe the changes of gut microbiota in inflammatory bowel disease, focusing the attention on its involvement in the pathogenesis of the disease, and to review and discuss the therapeutic potential to modify the intestinal microbial population with antibiotics, probiotics, prebiotics, synbiotics and fecal microbiota transplantation.
Alterations of intestinal microflora may significantly contribute to the pathogenesis of different inflammatory and autoimmune disorders. There is emerging interest on the role of selective ...modulation of microflora in inducing benefits in inflammatory intestinal disorders, by as probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation(FMT). To summarize recent evidences on microflora modulation in main intestinal inflammatory disorders, Pub Med was searched using terms microbiota, intestinal flora, probiotics, prebiotics, fecal transplantation. More than three hundred articles published up to 2015 were selected and reviewed. Randomized placebo-controlled trials and meta-analysis were firstly included, mainly for probiotics. A meta-analysis was not performed because of the heterogeneity of these studies. Most of relevant data derived from studies on probiotics, reporting some efficacy in ulcerative colitis and in pouchitis, while disappointing results are available for Crohn’s disease. Probiotic supplementation may significantly reduce rates of rotavirus diarrhea. Efficacy of probiotics in NSAID enteropathy and irritable bowel syndrome is still controversial. Finally, FMT has been recently recognized as an efficacious treatment for recurrent Clostridium difficile infection. Modulation of intestinal flora represents a very interesting therapeutic target, although it still deserves some doubts and limitations. Future studies should be encouraged to provide new understanding about its therapeutical role.
A number of double, triple, and quadruple therapies have been proposed as first-line empiric treatments for Helicobacter pylori infection. However, knowledge of their worldwide and regional ...comparative efficacy is lacking. We examined the comparative effectiveness of all empirically used first-line regimens tested against standard triple treatment using a network meta-analysis of published randomized controlled trials.
Data extracted from eligible randomized controlled trials were entered into a Bayesian network meta-analysis to investigate the comparative efficacy of H pylori infection empiric first-line regimens and to explore their effectiveness rank order. The ranking probability for each regimen was evaluated by means of surfaces under cumulative ranking values.
Sixty-eight eligible randomized controlled trials were included, giving a total of 92 paired comparisons with 22,975 patients randomized to 8 first-line regimens. The overall results showed that only vonoprazan triple therapy and reverse hybrid therapy achieved cure rates of >90%. Levofloxacin triple therapy performed best in Western countries (eradication rate 88.5%). The comparative effectiveness ranking showed that vonoprazan triple therapy had the best results, whereas standard triple therapy was the least efficacious regimen (surfaces under cumulative ranking 92.4% vs 4.7% respectively; odds ratio, 3.80; 95% credible interval, 1.62–8.94).
For first-line empiric treatment of H pylori infection, vonoprazan triple therapy and reverse hybrid therapy achieved high eradication rates of >90%. Levofloxacin triple therapy achieved the highest eradication rates in Western countries. Standard triple therapy was the least efficacious regimen in this network meta-analysis.
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This network meta-analysis, examining the comparative effectiveness of Helicobacter pylori first-line dual, triple, and quadruple therapies showed that vonoprazan-based triple therapy was the most effective worldwide and standard triple therapy was the least efficacious.
Helicobacter pylori and Extragastric Diseases Franceschi, Francesco; Tortora, Annalisa; Gasbarrini, Giovanni ...
Helicobacter (Cambridge, Mass.),
September 2014, Volume:
19, Issue:
s1
Journal Article
Peer reviewed
While Helicobacter pylori infection was initially revealed to be associated only with some gastroduodenal diseases, further studies have shown its possible role in several extragastric diseases. For ...idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency, the diagnosis of H. pylori infection is recommended, and there are many other conditions such as cardiovascular, neurological, dermatological, and respiratory diseases in which H. pylori may possibly play a role. Interestingly, a potential role has also been described for GI neoplastic diseases, including colorectal and pancreatic cancer. Different mechanisms of action have been proposed, ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic over the last year.
The micro-organisms residing within the gastrointestinal tract, namely gut microbiota, form a dynamic population proper of each individual, mostly composed by bacteria which co-evolved symbiotically ...with human species. The advances of culture-independent techniques allowed the understanding of the multiple functions of the gut microbiota in human physiology and disease, the latter often recognising a predisposing condition in an imbalanced intestinal microbial ecosystem (dysbiosis). A complex mutual interconnection between the central nervous system (CNS), the intestine and the gut microbiota, known as “microbiota-gut-brain axis”, has been hypothesized to play a pivotal role in maintaining central and peripheral functions, as well as mental health. Thus, dysbiosis with specific microbiota imbalances seems to be strongly associated with the onset psychiatric disorders by altering neurodevelopment, enhancing neurodegeneration, affecting behaviour and mood. Fecal microbiota transplantation (FMT) consists of transferring the fecal matter from a donor into the gastrointestinal tract of a recipient, and it is used to quickly modulate the gut microbiota. This review focuses on the uses of FMT in psychiatric disorders. FMT has been used to induce dysbiosis and to study the disease development, or to heal dysbiosis-related mental disorders. Overall, FMT of impaired microbiota resulted effective in enhancing psychiatric-like disturbances (mainly depression and anxiety) in recipient animals, plausibly by impairing immune system, inflammatory and metabolic pathways, neurochemical processes and neuro-transmission. On the other side, preclinical and clinical data suggest that reversing or mitigating dysbiosis seems a promising strategy to restore behavioural impairments or to obtain psychiatric symptom relief. However, current evidence is limited by the lack of procedural standardization, the paucity of human studies in the vastity of psychiatric conditions and the need of a microbiota-targeted donor-recipient matching.
•Imbalances of the gut microbiota are related to psychiatric disorders.•Fecal microbiota transplantation can impair mental health in recipient animals.•Fecal microbiota transplantation is promising in relieving psychiatric symptoms.
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