And are considered the main enactor of neural degradation in the condition [80]. An incredible success in the treatment of hepatic encephalopathy occurred in 1966 with the introduction of prebiotic lactulose to manage gut ammonia [81]. Since its employment, lactulose has been widely regarded for its broad benefits to cognition and quality of life in encephalopathy patients [82]. Two recent meta-analyses of randomized human trials concluded that lactulose can effectively prevent and treat hepatic encephalopathy, and also improve underlying liver dysfunction [83,84]. Early studies recognized several probable mechanisms of lactulose’s benefits on elevated blood ammonia. Fermentation of lactulose into fatty acids such as lactate reduces fecal pH by Necrostatin-1 web releasing protons into the colonic lumen. It was proposed that these protons convert ammonia into ammonium to create a concentration gradient that increases ammonia reuptake from blood into the gastrointestinal tract [85]. Concurrently, lactulose provides fermentable energy to colonic bacteria, diverting them from producing ammonia by amino acid metabolism, and can even directly inhibit glutaminases which degrade glutamine into ammonia [83]. Lastly, lactulose can flush out metabolites such as ammonia by shortening colonic transit time. Many of these properties are shared by a number of prebiotics–colonic acidification, fermentation, and stool softening–and have provided the basis for testing other indigestible saccharides for this purpose. In fact, a number of other order MK-8742 compounds can also benefit hepatic encephalopathy, particularly lactitol [86]. Lactitol is equally as effective as lactulose in treating encephalopathy, and actually has fewer negative side effects such as diarrhea [87,88]. The success of using these prebiotics for treating a liver and brain related disorder further provides evidence for prebiotic compounds impacting distant sites. 4. Immune Function It has been well documented that prebiotics can modulate immune functioning locally in Peyer’s patches, but an increasing body of evidence suggests that these compounds also exert immunological benefits throughout the body. Although isolated immune systems are generally unaffected by prebiotics such as fructans [89,90], clear benefits are observable in response to immune challenges. Since we are constantly exposed to a range of foreign stimuli, prebiotics could therefore be effective to downplay their effects. We will review here the immunomodulatory benefits of prebiotics in the context of challenges from pathogens, atopic dermatitis, and chronic inflammation, as well as their ability to improve mounted responses against vaccinations. Key human interventions studying prebiotic benefits on immune function will be summarized in Table 3. The immunostimulatory properties of prebiotics can, in some cases, improve mounted memory development against vaccinations and pathogens. Oligofructose administered to infants several weeks leading up to measles vaccination elevates their measles-specific IgG response [91]. Even later in life, -fructan prebiotics promote adaptive responses against influenza vaccination. In a study by Lomax et al. [92], four weeks of 8 g daily oligofructose/inulin mix prior to and following immunization was sufficient to increase circulating antibodies for influenza in a cohort of middle-aged adults. Unfortunately, this mounted immune response was limited to the H3 N2 -like strain, despiteNutrients 2016, 8,8 ofthe vaccine.And are considered the main enactor of neural degradation in the condition [80]. An incredible success in the treatment of hepatic encephalopathy occurred in 1966 with the introduction of prebiotic lactulose to manage gut ammonia [81]. Since its employment, lactulose has been widely regarded for its broad benefits to cognition and quality of life in encephalopathy patients [82]. Two recent meta-analyses of randomized human trials concluded that lactulose can effectively prevent and treat hepatic encephalopathy, and also improve underlying liver dysfunction [83,84]. Early studies recognized several probable mechanisms of lactulose’s benefits on elevated blood ammonia. Fermentation of lactulose into fatty acids such as lactate reduces fecal pH by releasing protons into the colonic lumen. It was proposed that these protons convert ammonia into ammonium to create a concentration gradient that increases ammonia reuptake from blood into the gastrointestinal tract [85]. Concurrently, lactulose provides fermentable energy to colonic bacteria, diverting them from producing ammonia by amino acid metabolism, and can even directly inhibit glutaminases which degrade glutamine into ammonia [83]. Lastly, lactulose can flush out metabolites such as ammonia by shortening colonic transit time. Many of these properties are shared by a number of prebiotics–colonic acidification, fermentation, and stool softening–and have provided the basis for testing other indigestible saccharides for this purpose. In fact, a number of other compounds can also benefit hepatic encephalopathy, particularly lactitol [86]. Lactitol is equally as effective as lactulose in treating encephalopathy, and actually has fewer negative side effects such as diarrhea [87,88]. The success of using these prebiotics for treating a liver and brain related disorder further provides evidence for prebiotic compounds impacting distant sites. 4. Immune Function It has been well documented that prebiotics can modulate immune functioning locally in Peyer’s patches, but an increasing body of evidence suggests that these compounds also exert immunological benefits throughout the body. Although isolated immune systems are generally unaffected by prebiotics such as fructans [89,90], clear benefits are observable in response to immune challenges. Since we are constantly exposed to a range of foreign stimuli, prebiotics could therefore be effective to downplay their effects. We will review here the immunomodulatory benefits of prebiotics in the context of challenges from pathogens, atopic dermatitis, and chronic inflammation, as well as their ability to improve mounted responses against vaccinations. Key human interventions studying prebiotic benefits on immune function will be summarized in Table 3. The immunostimulatory properties of prebiotics can, in some cases, improve mounted memory development against vaccinations and pathogens. Oligofructose administered to infants several weeks leading up to measles vaccination elevates their measles-specific IgG response [91]. Even later in life, -fructan prebiotics promote adaptive responses against influenza vaccination. In a study by Lomax et al. [92], four weeks of 8 g daily oligofructose/inulin mix prior to and following immunization was sufficient to increase circulating antibodies for influenza in a cohort of middle-aged adults. Unfortunately, this mounted immune response was limited to the H3 N2 -like strain, despiteNutrients 2016, 8,8 ofthe vaccine.
