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.
Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ...ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients. Interestingly, a role of intestinal bacteria in maintaining muscle health has been hypothesized through the translocation of bacteria and bacterial products into the bloodstream triggering the production of muscle wasting-related cytokines. Sarcopenia is associated with severe outcomes in patients with liver cirrhosis, mostly due to the incidence of disease complications. Furthermore, sarcopenia may represent an important prognostic factor for patients with hepatocellular carcinoma and for those undergoing liver transplantation and can be considered a useful additional tool in the global assessment of patients with advanced liver disease.
The gut microbiota is involved in the maintenance of the homeostasis of the human body and its alterations are associated with the development of different pathological conditions. The liver is the ...organ most exposed to the influence of the gut microbiota, and recently important connections between the intestinal flora and hepatocellular carcinoma (HCC) have been described. In fact, HCC is commonly associated with liver cirrhosis and develops in a microenvironment where inflammation, immunological alterations, and cellular aberrations are dramatically evident. Prevention and diagnosis in the earliest stages are still the most effective weapons in fighting this tumor. Animal models show that the gut microbiota can be involved in the promotion and progression of HCC directly or through different pathogenic mechanisms. Recent data in humans have confirmed these preclinical findings, shedding new light on HCC pathogenesis. Limitations due to the different experimental design, the ethnic and hepatological setting make it difficult to compare the results and draw definitive conclusions, but these studies lay the foundations for a pathogenetic redefinition of HCC. Therefore, it is evident that the characterization of the gut microbiota and its modulation can have an enormous diagnostic, preventive, and therapeutic potential, especially in patients with early stage HCC.
The number of effective systemic therapies for the treatment of advanced hepatocellular carcinoma (HCC) is rapidly increasing, and the advent of immunotherapy has changed the treatment paradigm for ...these patients, leading to significantly improved survival outcomes. However, many patients with HCC will continue to receive tyrosine kinase inhibitors, partly because of contraindications to immune checkpoint inhibitors. Currently, the best sequential first- and second-line systemic treatment remains elusive. Maintenance of optimal liver function is crucial, it is likely to impinge on temporary or permanent treatment discontinuation, and should also be considered when defining the treatment sequence. Hepatic decompensation, which does not always coincide with disease progression, is part of this complex dynamically evolving system, and must be promptly recognized and adequately managed to allow the patient to continue in the therapeutic course. The purpose of this review is to highlight and summarize the evidence on the efficacy and safety of systemic agents, with a focus on the impact of underlying cirrhosis, and to suggest new clinical outcomes for randomized controlled trials for advanced HCC to better assess the net health benefit in this specific setting.
Preliminary studies suggested a possible correlation of microbiota with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), where the need for tools to ameliorate its poor prognosis is ...mandatory. We explored the potential signature of esophageal microbiota and its predicted functional profile along the continuous spectrum from BE to EAC. We analyzed through 16S-based amplicon sequencing the mucosal microbiota and the microbiota-related functional predictions in 10 BE and 6 EAC patients compared with 10 controls, exploring also potential differences between the metaplastic mucosa (BEM) and the adjacent normal areas of BE patients (BEU). BEM and EAC showed a higher level of α and β-diversity. BEM evidenced a decrease of Streptococcus and an increase of Prevotella, Actinobacillus, Veillonella, and Leptotrichia. EAC displayed a striking reduction of Streptococcus, with an increase of Prevotella, Veillonella and Leptotrichia. LefSe analysis identified Leptotrichia as the main taxa distinguishing EAC. BEM showed a decreased α-diversity compared with BEU and a reduction of Bacteroidetes, Prevotella and Fusobacterium. Functional predictions identified peculiar profiles for each group with a high potential for replication and repair in BEM; an upregulated energy, replication and signaling metabolisms, with the fatty-acids biosynthesis and nitrogen and D-alanine pathways down-regulated in EAC. Our pilot study identifies a unique microbial structure and function profile for BE and EAC, as well as for metaplastic and near-normal areas. It proposes a new concept for BE, which could be intended not only as the histological, but, also, as the microbial closest precursor of EAC. This requires further larger follow-up studies, but opens intriguing horizons towards innovative diagnostic and therapeutic options for EAC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The intestinal barrier, with its multiple layers, is the first line of defense between the outside world and the intestine. Its disruption, resulting in increased intestinal permeability, is a ...recognized pathogenic factor of intestinal and extra-intestinal diseases. The identification of a gut-vascular barrier (GVB), consisting of a structured endothelium below the epithelial layer, has led to new evidence on the etiology and management of diseases of the gut-liver axis and the gut-brain axis, with recent implications in oncology as well. The gut-brain axis is involved in several neuroinflammatory processes. In particular, the recent description of a choroid plexus vascular barrier regulating brain permeability under conditions of gut inflammation identifies the endothelium as a key regulator in maintaining tissue homeostasis and health.
Weight loss is a therapeutic solution for many metabolic disorders, such as obesity and its complications. Bariatric surgery aims to achieve lasting weight loss in all patients who have failed after ...multiple dietary attempts. Among its many benefits, it has been associated with the regression of non-alcoholic fatty liver disease (NAFLD), which is often associated with obesity, with evidence of substantial improvement in tissue inflammation and fibrosis. These benefits are mediated not only by weight loss, but also by favorable changes in systemic inflammation and in the composition of the gut microbiota. Changes in microbial metabolites such as short-chain fatty acids (SCFAs), capable of acting as endocrine mediators, and bile acids (BAs) as well as modifications of the gut-brain axis, are among the involved mechanisms. However, not all bariatric surgeries show beneficial effects on the liver; those leading to malabsorption can cause liver failure or a marked worsening of fibrosis and the development of cirrhosis. Nevertheless, there are still many unclear aspects, including the extent of the benefits and the magnitude of the risks of bariatric surgery in cirrhotic patients. In addition, the usefulness and the safety of these procedures in patients who are candidates to or who have undergone liver transplant need solid supporting evidence. This paper aims to review literature data on the use of bariatric surgery in the setting of chronic liver disease.
Portal vein thrombosis (PVT) represents a well-known complication during the natural course of liver cirrhosis (LC), ranging from asymptomatic cases to life-threating conditions related to portal ...hypertension and hepatic decompensation. Portal flow stasis, complex acquired hypercoagulable disorders and exogenous factors leading to endothelial dysfunction have emerged as key factors for PVT development. However, PVT occurrence remains unpredictable and many issues regarding its natural history, prognostic significance and treatment are still elusive. In particular although spontaneous resolution or disease stability occur in most cases of PVT, factors predisposing to disease progression or recurrence after spontaneous recanalization are not clarified as yet. Moreover, PVT impact on LC outcome is still debated, as PVT may represent itself a consequence of liver fibrosis and hepatic dysfunction progression. Anticoagulation and transjugular intrahepatic portosystemic shunt are considered safe and effective in this setting and are recommended in selected cases, even if the safer therapeutic option and the optimal therapy duration are still unknown. Nevertheless, their impact on mortality rates should be addressed more extensively. In this review we present the most debated questions regarding PVT, whose answers should come from prospective cohort studies and large sample-size randomized trials.
The gut microbiota plays a critical role in the modulation of host metabolism and immune response, and its impairment has been implicated in many gastrointestinal and extraintestinal diseases. ...Current evidence shows the well-documented role of
in maintaining the integrity of the intestinal barrier, modulating the host immune response, and improving several metabolic pathways, making it a key element in the pathogenesis of several human diseases. In this scenario,
is the most promising next-generation probiotic and one of the first microbial species suitable for specific clinical use when compared with traditional probiotics. Further studies are needed to provide more accurate insight into its mechanisms of action and to better elucidate its properties in several major areas, paving the way for a more integrated and personalized therapeutic approach that finally makes the most of our knowledge of the gut microbiota.
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