Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors—genetic, metabolic, and dietary—intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.

Background: To date, most researchhas focused on the bacterial composition of the human microbiota. In this review, we synopsize recent data on the human mycobiome and cancer, highlighting specific cancer types based on current available evidence, presenting interesting perspectives and limitations of studies and laboratory methodologies. Recent findings: Head and neck cancer carcinoma (HNCC), colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDA) have been associated with dissimilarities in the composition of mycobiota between cancer cases and non-cancer participants. Overall, fungal dysbiosis with decreased fungal richness and diversity was common in cancer patients; however, a specific mycobiotic signature in HNSCC or CRC has not emerged. Different strains of Candida albicans have been identified among cases with HNCC, whilst Lichtheimia corymbifera, a member of the Mucoraceae family, has been shown to predominate among patients with oral tongue cancer. Virulence factors of Candida spp. include the formation of biofilm and filamentation, and the secretion of toxins and metabolites. CRC patients present a dysregulated ratio of Basidiomycota/Ascomycota. Abundance of Malassezia has been linked to the occurrence and progression of CRC and PDA, particularly in animal models of PDA. Interestingly, Schizophyllum, a component of the oral mycobiome, may exhibit anti-cancer potential. Conclusion: The human mycobiome, per se, along with its interactions with the human bacteriome and the host, may be implicated in the promotion and progression of carcinogenesis. Fungi may be used as diagnostic and prognostic/predictive tools or treatment targets for cancer in the coming years. More large-scale, prospective, multicentric and longitudinal studies with an integrative multi-omics methodology are required to examine the precise contribution of the mycobiome in the etiopathogenesis of cancer, and to delineate whether changes that occur in the mycobiome are causal or consequent of cancer.

Obesity and obesity-associated disorders pose a major public health issue worldwide. Apart from conventional weight loss drugs, next-generation probiotics (NGPs) seem to be very promising as potential preventive and therapeutic agents against obesity. Candidate NGPs such as Akkermansia muciniphila, Faecalibacterium prausnitzii, Anaerobutyricum hallii, Bacteroides uniformis, Bacteroides coprocola, Parabacteroides distasonis, Parabacteroides goldsteinii, Hafnia alvei, Odoribacter laneus and Christensenella minuta have shown promise in preclinical models of obesity and obesity-associated disorders. Proposed mechanisms include the modulation of gut flora and amelioration of intestinal dysbiosis, improvement of intestinal barrier function, reduction in chronic low-grade inflammation and modulation of gut peptide secretion. Akkermansia muciniphila and Hafnia alvei have already been administered in overweight/obese patients with encouraging results. However, safety issues and strict regulations should be constantly implemented and updated. In this review, we aim to explore (1) current knowledge regarding NGPs; (2) their utility in obesity and obesity-associated disorders; (3) their safety profile; and (4) their therapeutic potential in individuals with overweight/obesity. More large-scale, multicentric and longitudinal studies are mandatory to explore their preventive and therapeutic potential against obesity and its related disorders.

Introduction: Currently, diabetes mellitus (DM) as well as coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are major public health issues worldwide. Background: It has been suggested that patients with DM are more vulnerable to SARS-CoV-2 infection and suffer from more severe forms of the disease. Methods: A literature search was performed using PubMed, Scopus and Google search engines. Results: Angiotensin converting enzyme-2 (ACE2) is the major receptor of SARS-CoV-2 in the human host. The differential expression of ACE2 in the lungs of patients with DM makes them more susceptible to COVID-19. Additionally, acute or chronic hyperglycemia renders individuals in an immune-suppressive state, with impaired innate and adaptive immunity function, contributing also to the severity of COVID-19 infection among patients with DM. Other factors contributing to a more severe course of COVID-19 include the co-existence of obesity in T2DM; the endothelial inflammation induced by the SARS-CoV-2 infection, which aggravates the endothelial dysfunction observed in both T1DM and T2DM; and the hypercoagulability presented in COVID-19 infection that increases the thrombotic tendency in DM. Conclusion: This review summarizes the pathophysiologic mechanisms underlying the co-existence of both pandemics as well as the current recommendations and future perspectives regarding optimal treatment of inpatients and outpatients with DM in the era of SARS-CoV-2 infection. Notably, the current recommended drugs for the treatment of severe COVID-19, dexamethasone and remdesivir, may cause hyperglycemia, an adverse effect that physicians should bear in mind, when caring for patients with DM and COVID-19.

Background Hypertension is the leading risk factor for cardiovascular disease and accounts for approximately 9.4 million deaths globally every year. Hypertension is a complex entity, which is influenced by genetic and environmental factors, such as physical inactivity, obesity, alcohol consumption, tobacco use, stress, diet and why not the microbiome. Methods We searched PubMed using the words ‘microbiome’, ‘microbiota’ and ‘hypertension’ until December 2018. We found information regarding the role of the brain–gut--bone marrow axis, the brain–gut--kidney axis, the high-salt diet, short-chain fatty acids (SCFAs), neurotransitters, such as serotonin, dopamine and norepinephrine, nitric oxide, endothelin and steroids in modulating gut microbiota and in contributing to the pathogenesis of hypertension. The brain--gut--bone marrow axis refers to the hypothesis that hematopoietic stem cells might migrate to the brain or to the gut, and thus, contribute to local inflammation and several immune responses. This migration may further enhance the sympathetic activity and contribute to blood pressure elevation. On the other hand, SCFAs, such as acetate and butyrate, have been shown to exert anti-inflammatory effects on myeloid and intestinal epithelial cells. Also, researchers have noted diminution in microbial richness and diversity in hypertensive patients as well as marked differences in circulating inflammatory cells in hypertensive patients, when compared with controls. In addition, activation of renal sympathetic nerve activity might directly influence renal physiology, by altering body fluid balance and plasma metabolite secretion and retention. These events culminate in the development of chronic kidney disease and hypertension. Conclusion There is a long way ahead regarding the role of gut microbiota in the pathogenesis and as an adjunctive treatment of hypertension. Treatment of dysbiosis could be a useful therapeutic approach to add to traditional antihypertensive therapy. Manipulating gut microbiota using prebiotics and probiotics might prove a valuable tool to traditional antihypertensives.

As the tide of obesity and its complications is on the rise, there is an urgent need for new drugs with weight-lowering and beneficial metabolic properties. Obesity-related disorders, such as metabolic syndrome, prediabetes, type 2 diabetes mellitus (T2DM), cardiovascular disease and non-alcoholic fatty liver disease (NAFLD) make this need more than mandatory. Sodium-Glucose Co-Transporter-2 (SGLT-2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are the latest class of agents to receive approval for the treatment of T2DM. Not long after their marketing, a wide spectrum of target organ-protective and overall beneficial health effects associated with their use began to unveil. An increasing bulk of evidence points towards that these actions are to a great degree independent of glucose lowering, which has led to the broadening of the indications of SGLT-12 inhibitors outside the frame of antihyperglycemic therapy. Additionally, their unique mode of action including an increased renal glucose excretion and hence, net energy loss could render SGLT-2 inhibitors attractive candidates for the treatment of obesity. Very few reviews in the literature have appraised holistically the therapeutic potential of SGLT-2 inhibitors in obesity and its associated complications. Herein, we synopsize the currently available evidence regarding the effects of drugs of this class on body adiposity, together with considerations which accompany their potential use with the aim of weight loss. Furthermore, we attempt an overview of their actions and future perspectives of their use with respect to a range of obesity-related disorders, which include cardiovascular, renal, as well as NAFLD, malignancy, and ovarian dysfunction.

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