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      The effect of lactulose supplementation on fecal microflora of patients with chronic kidney disease; a randomized clinical trial

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          Abstract

          Introduction: Lactulose is a prebiotic with bifidogenic and urea reduction effects. It can improve Bifidobacteria and Lactobacilli counts in healthy humans and it may possibly have similar effects in chronic kidney disease (CKD) patients.

          Objectives: To investigate the effect of lactulose on fecal microflora of patients with CKD.

          Patients and Methods: Thirty-two patients with stages 3 and 4 of CKD (43.8% male with mean age of 58.09±12.75 years) were randomly assigned to intervention (n=16) and control (n=16) groups. Patients in intervention group received 30 mm lactulose syrup three times a day for an 8-week period. Control group received placebo 30 mm three times a day. A fecal sample was obtained from all patients at the beginning and at the end of the study and Bifidobacteria and Lactobacilli was counted.

          Results: Creatinine (Cr) significantly decreased in intervention group (3.90±1.43 to 3.60±1.44, P=0.003) and increased in control group (3.87±2.08 to 4.11±1.99, P=0.03). Although Bifidobacterial and Lactobacilli counts were similar before intervention, they were significantly higher at the end of the study in lactulose group ( P=0.01 and P=0.04, respectively). Lactulose led to significant increase in fecal Bifidobacterial counts (3.61±0.54 to 4.90±0.96, P<0.001) and Lactobacilli counts (2.79±1.00 to 3.87±1.13, P<0.001), while the change in placebo group was not significant.

          Conclusion: Lactulose administration will increase Bifidobacteria and Lactobacillus counts in patients with CKD.

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          Most cited references 33

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          Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin.

          Oligofructose and inulin are naturally occurring indigestible carbohydrates. In vitro they selectively stimulate the growth of species of Bifidobacterium, a genus of bacteria considered beneficial to health. This study was designed to determine their effects on the large bowel microflora and colonic function in vivo. Eight subjects participated in a 45-day study during which they ate controlled diets. For the middle 15 days, 15 g.day-1 oligofructose was substituted for 15 g.day-1 sucrose. Four of these subjects went on to a further period with 15 g.day-1 inulin. Bowel habit, transit time, stool composition, breath H2 and CH4, and the predominant genera of colonic bacteria were measured. Both oligofructose and inulin significantly increased bifidobacteria from 8.8 to 9.5 log10 g stool-1 and 9.2 to 10.1 log10 g stool-1, respectively, whereas bacteroides, clostridia, and fusobacteria decreased when subjects were fed oligofructose, and gram-positive cocci decreased when subjects were fed inulin. Total bacterial counts were unchanged. Fecal wet and dry matter, nitrogen, and energy excretion increased with both substrates, as did breath H2. Little change in fecal short-chain fatty acids and breath CH4 was observed. A 15-g.day-1 dietary addition of oligofructose or inulin led to Bifidobacterium becoming the numerically predominant genus in feces. Thus, small changes in diet can alter the balance of colonic bacteria towards a potentially healthier microflora.
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            Probiotics, prebiotics, and synbiotics.

            According to the German definition, probiotics are defined viable microorganisms, sufficient amounts of which reach the intestine in an active state and thus exert positive health effects. Numerous probiotic microorganisms (e.g. Lactobacillus rhamnosus GG, L. reuteri, bifidobacteria and certain strains of L. casei or the L. acidophilus-group) are used in probiotic food, particularly fermented milk products, or have been investigated--as well as Escherichia coli strain Nissle 1917, certain enterococci (Enterococcus faecium SF68) and the probiotic yeast Saccharomyces boulardii--with regard to their medicinal use. Among the numerous purported health benefits attributed to probiotic bacteria, the (transient) modulation of the intestinal microflora of the host and the capacity to interact with the immune system directly or mediated by the autochthonous microflora, are basic mechanisms. They are supported by an increasing number of in vitro and in vivo experiments using conventional and molecular biologic methods. In addition to these, a limited number of randomized, well-controlled human intervention trials have been reported. Well-established probiotic effects are: 1. Prevention and/or reduction of duration and complaints of rotavirus-induced or antibiotic-associated diarrhea as well as alleviation of complaints due to lactose intolerance. 2. Reduction of the concentration of cancer-promoting enzymes and/or putrefactive (bacterial) metabolites in the gut. 3. Prevention and alleviation of unspecific and irregular complaints of the gastrointestinal tracts in healthy people. 4. Beneficial effects on microbial aberrancies, inflammation and other complaints in connection with: inflammatory diseases of the gastrointestinal tract, Helicobacter pylori infection or bacterial overgrowth. 5. Normalization of passing stool and stool consistency in subjects suffering from obstipation or an irritable colon. 6. Prevention or alleviation of allergies and atopic diseases in infants. 7. Prevention of respiratory tract infections (common cold, influenza) and other infectious diseases as well as treatment of urogenital infections. Insufficient or at most preliminary evidence exists with respect to cancer prevention, a so-called hypocholesterolemic effect, improvement of the mouth flora and caries prevention or prevention or therapy of ischemic heart diseases or amelioration of autoimmune diseases (e.g. arthritis). A prebiotic is "a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well being and health", whereas synergistic combinations of pro- and prebiotics are called synbiotics. Today, only bifidogenic, non-digestible oligosaccharides (particularly inulin, its hydrolysis product oligofructose, and (trans)galactooligosaccharides), fulfill all the criteria for prebiotic classification. They are dietary fibers with a well-established positive impact on the intestinal microflora. Other health effects of prebiotics (prevention of diarrhoea or obstipation, modulation of the metabolism of the intestinal flora, cancer prevention, positive effects on lipid metabolism, stimulation of mineral adsorption and immunomodulatory properties) are indirect, i.e. mediated by the intestinal microflora, and therefore less-well proven. In the last years, successful attempts have been reported to make infant formula more breast milk-like by the addition of fructo- and (primarily) galactooligosaccharides.
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              Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients.

              Based on in vitro data, protein-bound uremic retention solutes have increasingly been recognized to play a pathophysiological role in the uremic syndrome. p-Cresol, a representative of this group of molecules, has been shown to be implicated in uremic immunodeficiency and endothelial dysfunction, potentially linking its serum levels to mortality. Thus far, however, no clinical information on this issue is available. To determine the relationship between p-cresol and all-cause mortality, 175 prevalent hemodialysis (HD) patients were enrolled in a prospective study. At baseline, serum levels of the water-soluble solutes urea, creatinine, and phosphate, the middle molecule beta2-microglobulin, total and free concentrations of the protein-bound solute p-cresol, and several risk factors for mortality were evaluated. During a median follow-up of 34 months, 60 patients died. Baseline comorbidity (Davies score) (hazard ratio (HR), 1.49; 95% confidence interval (95% CI), 1.19-1.86), impaired nutritional status (HR, 4.22; 95% CI, 2.15-8.29), time since initiation of dialysis (HR, 0.98; 95% CI, 0.97-1.00), and higher free concentrations of the protein-bound solute p-cresol (HR, 2.28; 95% CI, 1.12-4.64) were independently associated with mortality (multivariate Cox proportional hazards analysis). Our data suggest that free serum levels of p-cresol, a representative of the protein-bound uremic retention solutes, are associated with mortality in HD patients. These findings may encourage nephrologists to widen their field of interest beyond the scope of small water-soluble uremic solutes and middle molecules.
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                Author and article information

                Journal
                J Renal Inj Prev
                J Renal Inj Prev
                J Renal Inj Prev
                JRIP
                Journal of Renal Injury Prevention
                Nickan Research Institute
                2345-2781
                2016
                29 July 2016
                : 5
                : 3
                : 162-167
                Affiliations
                1Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                2Medical Education Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                Author notes
                [* ] Corresponding author: Bahram Niknafs, bahramniknafs@ 123456yahoo.com
                Article
                10.15171/jrip.2016.34
                5040005
                Copyright © 2016 The Author(s); Published by Nickan Research Institute

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Tables: 3, References: 37, Pages: 6
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