The synbiotic mixture of lactulose and Bacillus coagulans protects intestinal barrier dysfunction and apoptosis in weaned piglets challenged with lipopolysaccharide

Background Lactulose as an effective prebiotic protects intestinal mucosal injury.Bacillus coagulans is widely used in feed additives because of its ability to promote intestinal health.Our previous study suggests that the combination of lactulose and Bacillus coagulans may be a good candidate as alternative for antibiotic growth promoters.However,the in vivo effects of lactulose and Bacillus coagulans on growth and intestinal health under immune challenge in piglets remains unclear.The objective of this study is to explore the protective effects of synbiotic containing lactu-lose and Bacillus coagulans on the intestinal mucosal injury and barrier dysfunction under immune challenge in weaned piglets.Methods Twenty four weaned piglets were assigned to 4 groups.Piglets in the CON-_(saline)and LPS-_(LPS)group were fed the basal diet,while others were fed either with chlortetracycline(CTC)or synbiotic mixture of lactulose and Bacillus coagulans for 32 d before injection of saline or lipopolysaccharide(LPS).Piglets were sacrificed 4 h after LPS injection to collect samples to determine intestinal morphology,integrity and barrier functions as well as relative genes and proteins.Results Our data showed that no differences were observed in the growth performance of the four test groups.LPS injection induced higher serum diamine oxidase activities,D-lactic acid levels,and endotoxin status,lower villus height and ratio of villus height to crypt depth,greater mRNA and lower protein expression related tight junction in both jejunum and ileum.In addition,a higher apoptosis index,and protein expression of Bax and caspase-3 were also observed in the LPS challenge group.Interestingly,dietary synbiotic mixture with lactulose and Bacillus coagulans protected against LPS-induced intestinal damage,barrier dysfunction and higher apoptosis as well as CTC.Conclusions Our data suggest that dietary supplementation of synbiotic mixture with lactulose and Bacillus coagu-lans showed resilience to LPS-induced intestinal morphological damage,barrier dysfunction and aggressive apoptosis in piglets as well as the protective effects of CTC.These results indicate that synbiotic mixture of lactulose and Bacillus coagulans showed beneficial effects on performance and resilience to acute immune stress in weaned piglets.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth

BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model

AIM： To explore the relationship between changes of intestinal environment and pathogenesis of non-alcoholic steatohepatitis （NASH）. METHODS： Forty-two Sprague-Dawley rats were randomly dMded into model group （n = 24）, treatment group （n = 12）, and control group （n = 6）. The rats of model and treatment groups were given high-fat diet, and those of the control group were given normal diet. Furthermore, the rats of treatment group were given lactulose after 8 wk of high-fat diet. Twelve rats of the model group were killed at 8 wk of high-fat diet. At the 16 wk the rats of treatment group, control group, and the rest of the model group were killed. The serum levels of aminotransferase were measured and the histology of livers was observed by H＆E staining. RESULTS： The livers of rats presented the pathological features of steatohepatitis with higher serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the model group after 16 wk. Compared to the model group, the serum levels of ALT and AST in treatment group decreased significantly and were close to the normal group, and the hepatic inflammation scores also decreased markedly than those in the model group after 16 wk （5.83±2.02 vs 3.63±0.64, P〈0.05）, but were still higher than those in the model group after 8 wk （3.63±0.64 vs 1.98±0.90, P〈0.05）. However, the degree of hepatic steatosis had no changes in treatment group compared to the model group after 16 wk. CONCLUSION： Lactulose could ameliorate the hepatic inflammation of rats with steatohepatitis induced by fat- rich diet, but could not completely prevent the development of steatohepatitis. It is suggested that intestinal environmental changes such as intestinal bacteria overgrowth, are one of the important factors in the pathogenesis of NASH.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n = 28)and control group (n = 20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk,and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA.RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs40%, P＜0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1±4.1 vs 30.2±5.3,31.9±5.1 g/L), prealbumin (79.6±28.0 vs 106.6±54.4,108.4±55.0 g/L), cholesterol (76.3±16.7 vs 85.6±32.3,96.1±38.7 mg/dL), and IGFBP1 (56.8±47.2 vs 89.7±50.3ng/mL after 2 wk) were significantly increased compared to control group (P＜0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed.CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy

Lactulose is known to improve cognitive function in patients with early hepatic encephalopa- thy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cog- nitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.

Morphological and molecular response of small intestine to lactulose and hydrogen-rich water in female piglets fed Fusarium mycotoxins contaminated diet

Background: Following the intake of Fusarium mycotoxin-contaminated feed,small intestines may be exposed to high levels of toxic substances that can potentially damage intestinal functions in livestock.It is well known that Fusarium mycotoxins will lead a breakdown of the normally impeccable epithelial barrier,resulting in the development of a "leaky" gut.H2 administration with different methods has been proved definitely potentials to prevent serious intestinal diseases.The goal of this study is to investigate the roles of lactulose(LAC) and hydrogenrich water(HRW) in preventing intestinal dysfunction in piglets fed Fusarium mycotoxin-contaminated feed.Methods: A total of 24 female piglets were evenly assigned to 4 groups: negative control(NC) group,mycotoxincontaminated(MC) feed group,MC feed with LAC treatment(MC + LAC),and MC feed with HRW treatment(MC +HRW),respectively.Piglets in the NC group were fed uncontaminated control diet,while remaining piglets were fed Fusarium mycotoxin-contaminated diet.For the NC and MC groups,10 mL/kg body weight(BW) of hydrogen-free water(HFW) was orally administrated to piglets twice daily;while in the MC + LAC and MC + HRW groups,piglets were treated with the same dose of LAC solution(500 mg/kg BW) and HRW twice daily,respectively.On d 25,serum was collected and used for biochemical analysis.Intestinal tissues were sampled for morphological examination as well as relative genes and protein expression analysis.Results: Our data showed that Fusarium mycotoxins induced higher serum diamine oxidase(DAO) activities(P < 0.05),D-lactic acid levels(P < 0.01),and endotoxin status(P < 0.01),lower villus height(P < 0.01) and ratio of villus height to crypt depth(P < 0.05) in small intestine,greater apoptosis index and higher mRNA expression related to tight junctions(P < 0.05).In addition,the distribution and down-regulation of claudin-3(CLDN3) protein in the small intestinal was also observed.As expected,oral administrations of HRW and LAC were found to remarkably provide beneficial effects against Fusarium mycotoxin-induced apoptosis and intestinal leaking.Moreover,either HRW or LAC treatments were also revealed to prevent abnormal intestinal morphological changes,disintegrate tight junctions,and restore the expression and distribution of CLDN3 protein in the small intestinal mucosal layer in female piglets that were fed Fusarium mycotoxins contaminated diet.Conclusions: Our data suggest that orally administrations of HRW and LAC result in less Fusarium mycotoxininduced apoptosis and leak in the small intestine.Either HRW or LAC treatments could prevent the abnormal changes of intestinal morphology and molecular response of tight junctions as well as restore the distribution and expression of CLDN3 protein of small intestinal mucosa layer in female piglets that were fed Fusarium mycotoxins contaminated diet.

Comparison of probiotics and lactulose in the treatment of minimal hepatic encephalopathy in rats

AIM: To compare the efficacy of probiotic preparation Golden Bifid and lactulose on rat experimental model of minimal hepatic encephalopathy (MHE) induced by thioactamide (TAA).METHODS: MHE was induced by intraperitoneal injection of TAA (200 mg/kg) every 24 h for two consecutive days.Thirty-six male MHE models were then randomly divided into 3 groups: TAA group (n = 12) received tap water ad libitum only; lactulose group (n = 12) and probiotics group (n = 12) were gavaged, respectively with 8 mL/kg of lactulose and 1.5 g/kg of probiotic preparation Golden Bifid (highly concentrated combination of probiotic)dissolved in 2 mL of normal saline, once a day for 8 d (from the 5th d before the experiment to the 3rd d of the experiment). The latency of brainstem auditory evoked potentials (BAEP) I was used as an objective index of MHE. The incidence of MHE, the level of serum endotoxin,ammonia, liver function and histological grade of hepatic injury of rats were examined individually.RESULTS: There were no overt HE and rat deaths in 3groups. The incidence of MHE, the levels of blood ammonia and endotoxin in TAA group, which were 83.3% (10/12),168.33±15.44 mg/dL and 0.36±0.04 EU/mL, respectively,were significantly higher than those in lactulose group,which were 33.3% (4/12), 110.25±7.39 mg/dL and 0.19±0.02 EU/mL, and probiotics group, which were 33.3% (4/12), 108.58±10.24 mg/dL and 0.13±0.03 EU/mL respectively (P ＜0.001). It showed that either probiotics or lactulose could significantly lower the level of hyperammonemia and hyper-endotoxemia, lighten centrolobular necrotic areas as well as inflammatory reaction in the liver of rats, normalize the latency of BAEP,and decrease the incidence of MHE. However, no significant differences were observed between these two groups (P ＞0.05).CONCLUSION: Probiotic compound Golden Bifid is at least as useful as lactulose for the prevention and treatment of MHE. Probiotic therapy may be a safe, natural, well-tolerated therapy appropriate for the long-term treatment of MHE.

Influence of lactulose on interventional therapy for HCC patients with hepatocirrhosis and hypersplenism

Objective: To investigate the influence of lactulose on immunity of hepatocellular carcinoma(HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. Methods: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 m L/d. Four days before interventional therapies and at day 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count(RBC), and platelet count(PLT). Four days before therapies and at day 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase(SOD), IFN-α, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. Results: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency(P<0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-α and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group(P<0.05), the levels of CD4+/CD8+, SOD and IFN-α were all higher than before and control group(P<0.05). Conclusions: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.

Blood glucose response after oral intake of lactulose in healthy volunteers:A randomized,controlled,cross-over study

AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P < 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.

Lactulose mediates suppression of dextran sulfate sodium-induced colon inflammation

Assessment of digestion colonic flora lactulose can be induced to produce hydrogen and prove lactulose with a potential anti-inflammatory effects. Methods： We established a mouse model of human ulcerative colitis （UC） by supplying mice with water containing dextran sulfate sodium （DSS）. At 7-day, DSS-induced pathogenic outcomes, including loss of body weight, increase of colitis score, pathogenic shortening of colon length, elevated level of TNF-ct, IL-lβ, malondialdehyde （MDA） and myeloperoxidase （MPO） deficiency in colon lesions, were significantly suppressed by lactulose administration and intraperitoneally injected hydrogen water. Results： After eliminating colon microflora by antibiotics, the anti-inflammatory effects of lactulose were significantly compromised. Histological analysis also revealed that the DSS mediated colonic tissue destruction accompanied by neutrophils infiltration was remarkably suppressed by lactulose and hydrogen water. Conclusion：The present study indicated that lactulose can prevent the development of DSS-induced colitis and alleviate oxidative stress state in colitis.

Blood glucose response after oral lactulose intake in type 2 diabetic individuals

BACKGROUND Lactulose is approved for the symptomatic treatment of constipation,a gastrointestinal(GI)complication common in individuals with diabetes.Lactulose products contain carbohydrate impurities(e.g.,lactose,fructose,galactose),which occur during the lactulose manufacturing process.These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus(T2DM)using lactulose for the treatment of mild constipation.A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake.However,it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.AIM To evaluate the blood glucose profile after oral lactulose intake in mildly constipated,non-insulin-dependent subjects with T2DM in an outpatient setting.METHODS This prospective,double-blind,randomized,controlled,single-center trial was conducted at the Clinical Research Center at the Medical University of Graz,Austria,in 24 adult Caucasian mildly constipated,non-insulin-dependent subjects with T2DM.Eligible subjects were randomized and assigned to one of six treatment sequences,each consisting of four treatments stratified by sex using an incomplete block design.Subjects received a single dose of 20 g or 30 g lactulose(crystal and liquid formulation),water as negative control or 30 g glucose as positive control.Capillary blood glucose concentrations were measured over a period of 180 min post dose.The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period[AUC_(baseline_c(0-180 min))].Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose,as well as for liquid lactulose vs crystal lactulose.Safety parameters included GI tolerability,which was assessed at 180 min and 24 h post dose,and adverse events occurring up to 24 h post dose.In 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities(≤3.0%for crystals and approx.30%for liquid).The primary endpoint[AUC_(baseline_c(0-180 min))]was not significantly different between lactulose and water regardless of lactulose dose and formulation.Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level.A minor increase in maximum blood glucose was observed after the 30 g dose,liquid lactulose,in comparison to water with a mean treatment difference of 0.63 mmol/L(95%confidence intervals:0.19,1.07).Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose,respectively(all P<0.0001).No differences in blood glucose response were observed between the different lactulose formulations.As expected,lactulose increased the number of bowel movements and was generally well tolerated.Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.CONCLUSION Blood glucose AUC_(baseline_c(0-180 min))levels in mildly constipated,non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations.

Comparative Analysis of Lactulose and Fructooligosaccharide on Growth Kinetics, Fermentation, and Antioxidant Activity of Common Probiotics

Prebiotics are non-digestible oligosaccharides that selectively stimulate the growth of beneficial bacteria in the human gut. Fructooligosaccharide (FOS) is a common prebiotic found in food products and infant formula. Lactulose is primarily used as a pharmaceutical ingredient but also shows potential prebiotic activities. Our objectives were to determine and compare the effects of FOS and lactulose on: 1) growth kinetics of common probiotics in aerobic condition;2) pH and titratable acidity after fermentation;and 3) antioxidant capacity of the probiotics. Ten probiotic and two non-probiotic strains, representing genera Lactobacillus, Bifidobacterium, Bacillus, and Escherichia were assembled. Media used for prebiotics experiment were modified to contain 2% FOS or lactulose as the sole or main carbohydrate source. All experiments were done in triplicate. In aerobic condition, most strains cultured with FOS or lactulose did not grow optimally compared to dextrose (a non-prebiotic), while all four Bifidobacterium spp. showed little growth regardless of the carbohydrate source. In anaerobic condition, lactulose and FOS fermentation of Bifidobacterium spp. yielded similar pH (p = 0.2723), but percent lactic acid, as determined by titratable acidity, was higher after lactulose fermentation (p = 0.0004). The non-probiotic strains were able to utilize both FOS and lactulose, but displayed weaker acid production and higher pH (p Bifidobacterium spp. (p = 0.0002) and Lactobacillus spp. (p = 0.0447), but not probiotic E. coli and Bacillus spp. (p = 0.2599) or non-probiotics (p = 0.8816). In conclusion, lactulose supported growth activities of probiotics to a similar extent as FOS. Lactulose also stimulated higher acid production for Bifidobacterium spp. than FOS in anaerobic condition, thus it might be considered for incorporation into functional food products containing bifidobacteria.

Pilot Study on Gas Patterns of Irritable Bowel Syndrome and Small Intestinal Bacterial Overgrowth Following Ingestion of Lactulose

Background & Aims: Fermentation site and increasing time of symptomatic gas would be different between irritable bowel syndrome (IBS) and small intestine bacterial overgrowth (SIBO). The aim of this study was to determine the time for increase in abdominal gas following ingestion of lactulose and the possibility of differential diagnosis of SIBO and IBS. Methods: A prospective study was conducted on a series of IBS patients (n = 14) who were referred to the Oroku-Hospital (Okinawa, Japan) from June 6, 2014 to December 30, 2014. Imaging was first performed in early morning after fasting. After ingestion of lactulose, 1 - 4 plain abdominal radiographs were taken for investigation of increased gas during the indicated timeframe. Regions of interest of the gas areas were highlighted on the images obtained. Gas images were divided into three areas, the stomach, small intestine, and large intestine, and each total area was calculated. Results: At a dose of 10 g lactulose and an observation time of two hours, patients displayed no symptoms, and the gas volume was only slightly increased. However, when the dose of lactulose was increased (13 g/50 kg), and the observation time for the lactulose challenge was extended to 240 - 300 minutes, the results clearly demonstrated an increase in the gas produced in IBS patients. Conclusions: An increased dose of lactulose coupled with an extended observation time for the lactulose challenge clearly demonstrated an increase in the gas produced in IBS patients. Alterations in diet rather than antibiotics might reduce IBS symptoms.

The Use of Elobixibat and Lactulose for Bowel Preparation for Colon Capsule Endoscopy

Colon capsule endoscopy was approved for reimbursement under the national health insurance system of Japan in 2014. We decreased quantity of the castor oil and examined an intestinal irrigation degree using Elobixibat and lactulose that could maintain a discharge rate at 100% at a discharge rate and discharge time.

Bowel preparation protocol for hospitalized patients ages 50 years or older:A randomized controlled trial

BACKGROUND The incidence and mortality rate of colorectal cancer progressively increase with age and become particularly prominent after the age of 50 years.Therefore,the population that is≥50 years in age requires long-term and regular colonoscopies.Uncomfortable bowel preparation is the main reason preventing patients from undergoing regular colonoscopies.The standard bowel preparation regimen of 4-L polyethylene glycol(PEG)is effective but poorly tolerated.AIM To investigate an effective and comfortable bowel preparation regimen for hospitalized patients≥50 years in age.METHODS Patients were randomly assigned to group 1(2-L PEG+30-mL lactulose+a lowresidue diet)or group 2(4-L PEG).Adequate bowel preparation was defined as a Boston bowel preparation scale(BBPS)score of≥6,with a score of≥2 for each segment.Non-inferiority was prespecified with a margin of 10%.Additionally,the degree of comfort was assessed based on the comfort questionnaire.RESULTS The proportion of patients with a BBPS score of≥6 in group 1 was not significantly different from that in group 2,as demonstrated by intention-to-treat(91.2%vs 91.0%,P=0.953)and per-protocol(91.8%vs 91.0%,P=0.802)analyses.Furthermore,in patients≥75 years in age,the proportion of BBPS scores of≥6 in group 1 was not significantly different from that in group 2(90.9%vs 97.0%,P=0.716).Group 1 had higher comfort scores(8.85±1.162 vs 7.59±1.735,P<0.001),longer sleep duration(6.86±1.204 h vs 5.80±1.730 h,P<0.001),and fewer awakenings(1.42±1.183 vs 2.04±1.835,P=0.026)than group 2.CONCLUSION For hospitalized patients≥50 years in age,the bowel preparation regimen comprising 2-L PEG+30-mL lactulose+a low-residue diet produced a cleanse that was as effective as the 4-L PEG regimen and even provided better comfort.

Effects of lactulose on intestinal endotoxin and bacterial translocation in cirrhotic rats

Objective To investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats. Methods BT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary 99mTc-diethylenetriamine pentaacetatic acid ( 99mTc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of 51Cr in the intestine. Results BT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT were closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which were closely associated with increased intestinal transit and improved intestinal permeability by lactulose. Conclusions Our study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

A pilot study using lactulose in management of minimal hepatic encephalopathy in children with extrahepatic portal vein obstruction

Background:Minimal hepatic encephalopathy(MHE)is not associated with overt neuropsychiatric symptoms but rather with subtle changes in psychometric and/or neurOphysiolOgic tests.We aimed to diagnose MHE in children with extrahepatic portal vein obstruction fEHPV01 and to evaluate the el№ct of lactulose on MHE.Methods:A prospective study was carried out on 30 patients with EHPVO(21 males;mean age 10+2.5 years).The study was carried out in the Pediatric Hepatology Unit.Cairo University Pediatric Hospital,Cairo,Egypt,between 2011 and 2013.AII patients were subjected to clinical and Iaboratory assessment.neuropsychmetric testin2 using the arabic version of Wechsler intelligence tests.neurophysiological testing by visual electroencephalogram and P300 event related potentials(ERP).

Minimal Hepatic Encephalopathy in Indians:Psychometric Hepatic Encephalopathy Score and Inhibitory Control Test for Diagnosis and Rifaximin or Lactulose for Its Reversal

Background and Aims: Psychometric hepatic encephalop-athy score(PHES)is used widely for diagnosis of minimal hepatic encephalopathy(MHE).This prospective study aimed to determine the utility of the inhibitory control test(ICT)for the diagnosis of MHE.Additionally,the efficacy of rifaximin and lactulose for reversal of MHE was evaluated.Methods:A total of 180 eligible cirrhotic patients underwent testing for MHE.When PHES was ≤ ?5 and ICT lures were ≥ 14,MHE was diagnosed.The 108 patients with MHE were randomized to three groups for treatment with either lactulose,rifaximin,or placebo.Treatment outcomes were measured at the end of 3 months.Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%.The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients,by abnormal ICT and normal PHES in 37 patients,and by abnor-mal PHES and normal ICT in 15 patients.For diagnosis of MHE,ICT had sensitivity of 78.87%,specificity of 66.06%with 60.22%positive predictive value and 82.76%negative predictive value.An area under the curve value of 0.724(95%CI: 0.653–0.788)was obtained for diagnosis of MHE.Reversal of MHE was seen in 71.42%,70.27%and 11.11%of patients in the rifaximin,lactulose and placebo arms(p < 0.001).Rifaximin showed better tolerability compared to lactulose.Conclusions: For the diagnosis of MHE,ICT is a simple tool but has lower sensitivity and better specificity than PHES.Rifaximin is as efficacious as lactulose in the treat-ment of MHE and better tolerated.

Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose

Background Next-generation sequencing has revolutionized our perspective on the gut microbiome composition,revealing the true extent of the adverse effects of antibiotics.The impact of antibiotic treatment on gut microbiota must be considered and researched to provide grounds for establishing new treatment strategies that are less devastating on commensal bacteria.This study investigates the impact on gut microbiome when a commonly used antibiotic,azithromycin is administered,as well as uncovers the benefits induced when it is used in combination with lactulose,a prebiotic known to enhance the proliferation of commensal microbes.Methods 16S rRNA gene sequencing analysis of stool samples obtained from 87 children treated with azithromycin in combination with or without lactulose have been determined.Children's gut microbial profile was established at the pre-and post-treatment stage.Results Azithromycin caused an increase in the relative abundance of opportunistic pathogens such as Streptococcus that was evident 60 days after treatment.While few days after treatment,children who also received lactulose started to show a higher relative abundance of saccharolytic bacteria such as Lactobacillus,Enterococcus,Anaerostipes,Blautia and Roseburia,providing a protective role against opportunistic pathogens.In addition,azithromycin-prebiotic combination was able to provide a phylogenetic profile more similar to the pre-treatment stage.Conclusion It is suggested that during azithromycin treatment,lactulose is able to reinstate the microbiome equilibrium much faster as it promotes saccharolytic microbes and provides a homeostatic effect that minimizes the opportunistic pathogen colonization.