Secondary bile acids and the biliary epithelia: The good and the bad

The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine.Nowadays several researches demonstrated an important role of biliary epithelia(i.e.cholangiocytes)in bile formation.The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases,such as primary biliary cholangitis or primary sclerosing cholangitis.Bile acids(BAs),produced by the liver,are the most represented organic molecules in bile.The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules.In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary(deriving by bacterial manipulation of primary molecules)ones.This class of BAs is demonstrated to have relevant biological effects,ranging from toxic to therapeutic ones.In this family ursodeoxycholic and lithocholic acid present the most interesting features.The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage.These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.

Sugarcane leaves-derived polyphenols alleviate metabolic syndrome and modulate gut microbiota of ob/ob mice

Sugarcane leaves-derived polyphenols(SLP)have been demonstrated to have diverse health-promoting benefits,but the mechanism of action has not been fully elucidated.This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice.In the current study,we prepared the SLP mainly consisting of three flavonoid glycosides,three phenol derivatives,and two lignans including one new compound,and further demonstrated that SLP reduced body weight gain and fat accumulation,improved glucose and lipid metabolism disorders,ameliorated hepatic steatosis,and regulated short-chain fatty acids(SCFAs)production and secondary bile acids metabolism in ob/ob mice.Notably,SLP largely altered the gut microbiota composition,especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens.Oral gavage with the above two strains ameliorated metabolic syndrome(MetS),regulated secondary bile acid metabolism,and increased the production of SCFAs in high-fat diet(HFD)-induced obese mice.These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.

Exploring gut microbes in human health and disease:Pushing the envelope

Humans have coevolved with their microbes over thousands of years,but this relationship,is now being dramatically affected by shifts in the collective human microbiome resulting from changes in the environment and societal norms.Resulting perturbations of intestinal host-microbe interactions can lead to miscues and altered host responses that increase the risk of pathogenic processes and promote“western”disorders such as inflammatory bowel diseases,cancers,obesity,diabetes,autism,and asthma.Given the current challenges and limitations in gene therapy,approaches that can reshape the gut microbiome represent a reasonable strategy for restoring the balance between host and microbes.In this review and commentary,we highlight recent progress in our understanding of the intestinal microbiome in the context of health and diseases,focusing on mechanistic concepts that underlie the complex relationships between host and microbes.Despite these gains,many challenges lie ahead that make it difficult to close the gap between the basic sciences and clinical application.We will discuss the potential therapeutic strategies that can be used to manipulate the gut microbiota,recognizing that the promise of pharmabiotics(“bugs to drugs”)is unlikely to be completely fulfilled without a greater understanding of enteric microbiota and its impact on mammalian physiology.By leveraging the knowledge gained through these studies,we will be prepared to enter the era of personalized medicine where clinical inventions can be custom-tailored to individual patients to achieve better outcomes.

Treatment of recurrent Clostridium difficile colitis:a narrative review

Clostridium difficile is a gram-positive,spore-forming,obligate anaerobic bacillus that was originally isolated from the stool of a healthy neonate in 1935.In high-income countries,C.difficile is the most common cause of infectious diarrhoea in hospitalized patients.The incidence of C.difficile infection in the USA has increased markedly since 2000,with hospitalizations for C.difficile infections in non-pregnant adults doubling between 2000 and 2010.Between 20%and 35%of patients with C.difficile infection will fail initial antibiotic treatment and,of these,40–60%will have a second recurrence.Recurrence of C.difficile infection after initial treatment causes substantial morbidity and is a major burden on health care systems.In this article,current treatments for recurrent C.difficile infection are reviewed and future directions explored.These include the use of antibiotics,probiotics,donor faecal transplants,anion resins,secondary bile acids or anti-toxin antibodies.