The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and ...The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.展开更多
OBJECTIVES Parkinson disease(PD)is the second most common neurodegener⁃ative disease,but none of the current treatments for PD could halt the progress of the disease due to the limited understanding of the pathogenesi...OBJECTIVES Parkinson disease(PD)is the second most common neurodegener⁃ative disease,but none of the current treatments for PD could halt the progress of the disease due to the limited understanding of the pathogenesis.Increasing evidence proves that the close com⁃munication between the brain and the gastroin⁃testinal system is influenced by gut microbiota in PD pathogenesis,known as microbiota-gut-brain axis.However,the explicit mechanisms of micro⁃biota dysbiosis in PD development have not been well elucidated yet.FLZ,a novel squamosamide derivative,has been proved to be effective in many PD models and is undergoing the phaseⅠclinical trial to treat PD in China.The aims of our study are to assess the neuroprotective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool.METHODS Chronic administration of rotenone(30 mg·kg-1 per day)was utilized to induce a mouse model to mimic the pathological process of PD.Behavioral tests and gastrointestinal function tests were conduct⁃ed to evaluate the PD symptoms.Gut microbiota alterations were analyzed by 16s rRNA sequenc⁃ing.The intestinal permeability and blood-brain barrier structures were assessed by various methods.The pro-inflammatory cytokines and LPS levels in the colon,serum,and brain were detected by ELISA.Furthermore,the levels of in⁃flammation and TLR4/MyD88/NF-κB pathway in the substantia nigra(SN)and colon were mea⁃sured.RESULTS Behavioral tests and gastroin⁃testinal function tests found that rotenone-in⁃duced mice showed gastrointestinal dysfunctions(week 3)prior to the motor deficits(week 4).However,FLZ treatment significantly alleviated these PD symptoms.16S rRNA sequencing illus⁃trated that PD-related microbiota alterations in⁃duced by rotenone were reversed by FLZ treatment at various taxa levels.Especially,we identified an increased genus Akkermansia in the Rotenone group(P=0.0006),which could be reversed by FLZ administration(P=0.0070).By reducing micr展开更多
基金Supported by(in part)FARB-ex 60%2012 of the University of Salerno grant to Vajro P
文摘The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.
文摘OBJECTIVES Parkinson disease(PD)is the second most common neurodegener⁃ative disease,but none of the current treatments for PD could halt the progress of the disease due to the limited understanding of the pathogenesis.Increasing evidence proves that the close com⁃munication between the brain and the gastroin⁃testinal system is influenced by gut microbiota in PD pathogenesis,known as microbiota-gut-brain axis.However,the explicit mechanisms of micro⁃biota dysbiosis in PD development have not been well elucidated yet.FLZ,a novel squamosamide derivative,has been proved to be effective in many PD models and is undergoing the phaseⅠclinical trial to treat PD in China.The aims of our study are to assess the neuroprotective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool.METHODS Chronic administration of rotenone(30 mg·kg-1 per day)was utilized to induce a mouse model to mimic the pathological process of PD.Behavioral tests and gastrointestinal function tests were conduct⁃ed to evaluate the PD symptoms.Gut microbiota alterations were analyzed by 16s rRNA sequenc⁃ing.The intestinal permeability and blood-brain barrier structures were assessed by various methods.The pro-inflammatory cytokines and LPS levels in the colon,serum,and brain were detected by ELISA.Furthermore,the levels of in⁃flammation and TLR4/MyD88/NF-κB pathway in the substantia nigra(SN)and colon were mea⁃sured.RESULTS Behavioral tests and gastroin⁃testinal function tests found that rotenone-in⁃duced mice showed gastrointestinal dysfunctions(week 3)prior to the motor deficits(week 4).However,FLZ treatment significantly alleviated these PD symptoms.16S rRNA sequencing illus⁃trated that PD-related microbiota alterations in⁃duced by rotenone were reversed by FLZ treatment at various taxa levels.Especially,we identified an increased genus Akkermansia in the Rotenone group(P=0.0006),which could be reversed by FLZ administration(P=0.0070).By reducing micr
