Multiple Regulatory Mechanisms Synergistically Control the Soluble Expression of CsCE for Enhanced Enzymatic Productivity of Lactulose in E. coli.

The limited expression of cellobiose 2-epimerase poses a significant constraint on the industrial enzymatic production of lactulose. Extensive modifications to the expression cassette offer a means to enhance the yield of recombinant proteins. In this study, an integrated strategy, combining individual and collaborative approaches, is proposed to fine-tune each stage of the CsCE overexpression program. This strategy involves the multidimensional integration of standardized genetic elements at various levels, including transcription, translation, folding, and three-dimensional structure. The volumetric activity of the final recombinant strain was markedly increased by 12-fold compared to the wild-type strain, reaching 2260.62 U/L. The protein expression in the newly developed high-yield recombinant strain exhibited a significant enhancement, with a higher proportion of soluble protein compared to that of inclusion bodies. Our findings offer insights into the multifaceted synergistic regulation of protein expression processes, holding promising implications for the production of heterologous recombinant proteins.

The prebiotic effect of 1-kestose in low-birth-weight neonates taking bifidobacteria: a pilot randomized trial in comparison with lactulose.

Probiotics such as bifidobacteria have been given to low-birth-weight neonates (LBWNs) at risk for a disrupted gut microbiota leading to the development of serious diseases such necrotizing enterocolitis. Recently prebiotics such as lactulose are used together with bifidobacteria as synbiotics. However, faster and more powerful bifidobacteria growth is desired for better LBWN outcomes. The prebiotic 1-kestose has a higher selective growth-promoting effect on bifidobacteria and lactic acid bacteria in vitro among several oligosaccharides. Twenty-six premature neonates (less than 2,000 g) admitted to a neonatal intensive care unit (NICU) were randomly assigned to receive Bifidobacterium breve M16-V with either 1-kestose or lactulose once a day for four weeks from birth. A 16S rRNA gene analysis revealed similar increases in alpha-diversity from 7 to 28 days in both groups. The most dominant genus on both days was Bifidobacterium in both groups, with no significant difference between the two groups. Quantitative PCR analysis revealed that the number of Staphylococcus aureus tended to be lower in the 1-kestose group than in the lactulose group at 28 days. The number of Escherichia coli was higher in the 1-kestose group at 7 days. The copy number of total bacteria in the 1-kestose group was significantly higher than that in the lactulose group at 3 time points, 7, 14, and 28 days. No severe adverse events occurred in either group during the study period. l-Ketose may offer an alternative option to lactulose as a prebiotic to promote the development of gut microbiota in LBWNs.

Lactulose with synergists supplementation improving a health of chicks and reducing the environmental burden in poultry industry.

Objective: The study aims to understand the effect of new antibiotic-substituting supplements in feeding chickens of the Hisex Brown cross in industrial conditions. Materials and Methods: A total of 216 hatched chicks were randomly selected and distributed into Control, Test I, and Test II groups, with 3 replicates of 24 birds in three treatments. Results: At the end of the experiment, BW of T1/T2 birds was higher by 6.12% (p <0.01) and 10.29% (p <0.001) than CON. In comparison with the control hens, T1/T2 birds had a higher feed conversion rate and digestibility of nutrients. The blood indicators of T1/T2 hens exceeded those in control. Prebiotic supplementations were positively influenced in the immune indices of birds. IgA, IgG, IgM increased in groups T1/T2. Similar regularity was found in the natural resistance of chicks fed S1/S2. In the caecum, the Lactobacilli number was higher than in CON by 17.03% (p <0.01) in T1 and by 18.47% (p <0.01)-in T2; Bifidobacteria-by 17.94 (p <0.001) and 19.09% (p <0.01), respectively; at the same time, the number of E. coli decreased by 21.05% (p <0.01) and 24.21% (p <0.01). The concentration of emitted excreta noxious gases decreased: ammonia by 22.40%-24.95% (p <0.01); hydrogen sulfide by 10.67%-16.00% (p <0.01); and mercaptans by 12.90%-17.74% (p <0.05). Conclusion: These findings support the use of lactulose-based supplements as antibiotic alternatives to improve production in poultry farming and to reduce the toxic load on the environment.

Urinary excretion of gluten immunoreactive peptides as an indicator of gastrointestinal function after fasting and dietary provocation in healthy volunteers.

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability. Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed. Results: The majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability. Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems.

A Rapid and Reliable Spectrofluorimetric Method to Measure the Urinary Lactulose/Mannitol Ratio for Dysbiosis Assessment.

Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn's disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis.

The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [18F]PBR146 in-vivo neuroinflammation imaging study.

INTRODUCTION: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro-PET/CT. METHODS: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. RESULTS: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. CONCLUSIONS: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.

Methane gas in breath test is associated with non-alcoholic fatty liver disease.

Although the associations between a patient's body mass index (BMI) and metabolic diseases, as well as their breath test results, have been studied, the relationship between breath hydrogen/methane levels and metabolic diseases needs to be further clarified. We aimed to investigate how the composition of exhaled breath gases relates to metabolic disorders, such as diabetes mellitus, dyslipidemia, hypertension, and nonalcoholic fatty liver disease (NAFLD), and their key risk factors. An analysis was performed using the medical records, including the lactulose breath test (LBT) data of patients who visited the Ajou University Medical Center, Suwon, Republic of Korea, between January 2016 and December 2021. The patients were grouped according to four different criteria for LBT hydrogen and methane levels. Of 441 patients, 325 (72.1%) had positive results for methane only (hydrogen < 20 parts per million [ppm] and methane ⩾ 3 ppm). BMIs and NAFLD prevalence were higher in patients with only methane positivity than in patients with hydrogen and methane positivity (hydrogen ⩾ 20 ppm and methane ⩾ 3 ppm). According to a multivariate analysis, the odds ratio of only methane positivity was 2.002 (95% confidence interval [CI]: 1.244-3.221,P= 0.004) for NAFLD. Our results demonstrate that breath methane positivity is related to NAFLD and suggest that increased methane gas on the breath tests has the potential to be an easily measurable biomarker for NAFLD diagnosis.

Technological and sensory characteristics in development of innovative symbiotic boneless dry-cured lamb meat snack.

Novel shelf-stable and high-protein meat products that are affordable, convenient, and healthy are hot topic in current food innovation trends. To offer technological databases for developing new functional lamb meat products, this study aimed to evaluate the technological and sensory aspects of dry-cured lamb meat snacks incorporated with the probiotic culture Lactobacillus paracasei and the prebiotic lactulose. Four formulations were analyzed: control (without prebiotic or probiotic); PREB (with 2% lactulose); PROB (with 107 CFU/g of L. paracasei); and SYMB (with 2% lactulose and 107 CFU/g of L. paracasei). Fitted curves revealed that weight-loss behavior during snack ripening was not affected (P > 0.05) by treatments. Snack moisture, water activity, pH, titratable acidity, lipid oxidation, and residual nitrite were affected (P < 0.05) only by ripening time. The target probiotic strain stood out against competitive flora and was detected at 107 CFU/g in the snack-supplemented formulations (PROB and SYMB). In snacks supplemented with prebiotics (PREB and SYMB), the lactulose content was maintained at 2.17%. Significant differences were not observed in the chemical composition, texture profiles, and CIE color indices between the proposed functional snacks and the control. In addition to texture, flavor, and overall impression evaluation, only color attributes were positively impacted (P < 0.05) in the acceptance and multiple comparison tests against the control. The proposed formulation and bench process parameters produced potential nutritionally and sensory-appreciated, microbiologically stable, and safe (multi-hurdle perspective) functional high-protein restructured lamb snacks.

Promotion of lactose isomerization to fructose and lactulose in one batch by immobilized enzymes on bacterial cellulose membranes.

The production of the sugars fructose and lactulose from lactose using the enzymes ß-galactosidase and glucose isomerase immobilized on bacterial cellulose (BC) membranes has been investigated. Lactose is hydrolyzed by ß-galactosidase at 30 °C to glucose and galactose at a high conversion rate, while at the same temperature, glucose isomerase is not effective in converting the produced glucose to fructose. The rate of the isomerization reaction of glucose to fructose at 70 °C has been studied. Two types of enzyme immobilization were investigated: immobilization in one stage and immobilization in two stages. The results showed that BC membrane increased three-fold the yield and the reaction rate of fructose and lactulose production from lactose. The noteworthy enhancement of BC membranes' impact on the isomerization reaction by immobilized enzymes grants permission for a novel research avenue within the context of white biotechnology development. Additionally, this effect amplifies the role of BC in sustainability and the circular economy.

Production of lactulose from lactose using a novel cellobiose 2-epimerase from Clostridium disporicum.

Lactulose is a semisynthetic nondigestive sugar derived from lactose, with wide applications in the food and pharmaceutical industries. Its biological production routes which use cellobiose 2-epimerase (C2E) as the key enzyme have attracted widespread attention. In this study, a set of C2Es from different sources were overexpressed in Escherichia coli to produce lactulose. We obtained a novel and highly efficient C2E from Clostridium disporicum (CDC2E) to synthesize lactulose from lactose. The effects of different heat treatment conditions, reaction pH, reaction temperature, and substrate concentrations were investigated. Under the optimum biotransformation conditions, the final concentration of lactulose was up to 1.45 M (496.3 g/L), with a lactose conversion rate of 72.5 %. This study provides a novel C2E for the biosynthesis of lactulose from low-cost lactose.

Critical appraisal of the SIBO hypothesis and breath testing: A clinical practice update endorsed by the European society of neurogastroenterology and motility (ESNM) and the American neurogastroenterology and motility society (ANMS).

BACKGROUND: There is compelling evidence that microbe-host interactions in the intestinal tract underlie many human disorders, including disorders of gut-brain interactions (previously termed functional bowel disorders), such as irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) has been recognized for over a century in patients with predisposing conditions causing intestinal stasis, such as surgical alteration of the small bowel or chronic diseases, including scleroderma and is associated with diarrhea and signs of malabsorption. Over 20 years ago, it was hypothesized that increased numbers of small intestine bacteria might also account for symptoms in the absence of malabsorption in IBS and related disorders. This SIBO-IBS hypothesis stimulated significant research and helped focus the profession's attention on the importance of microbe-host interactions as a potential pathophysiological mechanism in IBS. PURPOSE: However, after two decades, this hypothesis remains unproven. Moreover, it has led to serious unintended consequences, namely the widespread use of unreliable and unvalidated breath tests as a diagnostic test for SIBO and a resultant injudicious use of antibiotics. In this review, we examine why the SIBO hypothesis remains unproven and, given the unintended consequences, discuss why it is time to reject this hypothesis and its reliance on breath testing. We also examine recent IBS studies of bacterial communities in the GI tract, their composition and functions, and their interactions with the host. While these studies provide important insights to guide future research, they highlight the need for further mechanistic studies of microbe-host interactions in IBS patients before we can understand their possible role in diagnosis and treatment of patient with IBS and related disorders.

Engineering Bacillus subtilis for highly efficient production of functional disaccharide lactulose from lactose.

Bioconversion of lactose to functional lactose derivatives attracts increasing attention. Lactulose is an important high-value lactose derivative, which has been widely used in pharmaceutical, nutraceutical, and food industries. Lactulose can be enzymatically produced from lactose by cellobiose 2-epimerase (CEase). Several studies have already focused on the food-grade expression of CEase, but they are all aimed at the biosynthesis of epilactose. Herein, we reported for the first time the biosynthesis of lactulose using the recombinant food-grade Bacillus subtilis. Lactulose biosynthesis was optimized by varying lactulose-producing CEases and expression vectors. Caldicellulosiruptor saccharolyticus CEase and pP43NMK were determined to be the optimal CEase and expression vector. Fine-tuning of CEase expression was investigated by screening a beneficial N-terminal coding sequence. After fed-batch cultivation, the highest fermentation isomerization activity reached 11.6 U/mL. Lactulose was successfully produced by the broth of the engineered B. subtilis with a yield of 52.1 %.

Key Insights and Clinical Pearls in the Identification and Management of Cirrhosis and Its Complications.

Cirrhosis is a prevalent, chronic condition with an asymptomatic compensated phase, in which patients may feel well, and a decompensated phase that begins with the onset of complications (eg hepatic encephalopathy, ascites, and/or variceal bleeding). Because patients with cirrhosis may appear healthy with normal liver enzymes, alkaline phosphatase, and serum bilirubin levels, awareness of clinical signals is important. For example, patients with thrombocytopenia should be evaluated for chronic liver disease and cirrhosis. Early recognition and management of cirrhosis-related complications (eg hepatic encephalopathy, ascites, and/or variceal bleeding) are important, given their association with hospitalization and poor prognosis (eg increased odds of short-term mortality). Hepatic encephalopathy can be the most subtle cirrhosis-related complication and associated cognitive impairment may be misdiagnosed. Because hepatic encephalopathy can be associated with hospital readmissions, reducing readmission rates after hepatic encephalopathy-related hospitalizations is critical. This includes incorporating ongoing therapy (eg rifaximin plus lactulose) in postdischarge management plans to reduce the risk of hepatic encephalopathy recurrence. Strategies that mitigate cirrhosis progression and prevent the development of cirrhosis-related complications are key to improving patient outcomes.

The effects of lactulose on constipation in patients with Parkinson's disease: An exploratory pilot study.

Introduction: Constipation is one of the most common non-motor symptoms of Parkinson's disease (PD) and is associated with reduced quality of life in patients with PD. The aim of this study was to evaluate the effect of lactulose on defecation status in patients with PD. Methods: In this open-label, single-center, exploratory pilot study, twenty-nine patients with PD received lactulose for three weeks for the treatment of constipation. The primary endpoint was the number of spontaneous bowel movements (SBMs). The secondary endpoints were stool consistency (Bristol Stool Form Scale [BSFS]) and the number of rescue laxatives used. Results: Twenty-five patients with PD completed the study. The number of SBMs recorded during the lactulose intervention period was significantly increased compared with that recorded during the pre-intervention period. During the intervention period, the BSFS scores of the patients increased significantly, whereas the number of rescue laxatives they used decreased significantly. No serious adverse events were observed during the study period. Lactulose was well-tolerated. Conclusions: The results of this study suggest that lactulose may be effective in improving defecation status in patients with PD. Further randomized controlled trials are needed to confirm the effects of lactulose on constipation in patients with PD.

Factors associated with stunting in under-five children with environmental enteropathy in slum areas of Jimma town, Ethiopia.

Introduction: Stunting is a major public health issue with a significant influence on the health and development of children in low-income countries, where it affects up to 32% of children. Nutritional intake is impacted by alterations in intestinal permeability and underlying chronic inflammation, which hinder children's normal linear growth. Environmental enteropathy is a poorly understood condition with chronic intestinal inflammation. The purpose of this study was to identify the magnitude of stunting, change in growth, and factors associated with stunting and change in height for the age Z-score of children with an elevated lactulose-to-mannitol ratio. Methods: An observational follow-up study was conducted to follow children with an elevated lactulose-to-mannitol ratio for changes in their linear growth. A lactulose-mannitol test was performed to identify children with elevated lactulose-to-mannitol ratios, indicative of environmental enteropathy. After a 1-year follow-up, anthropometry was repeated to assess their linear growth. A multivariable logistic regression analysis was performed to identify the independent predictors for stunting in children with elevated lactulose-to-mannitol ratios. All tests were two-sided, and a p-value of <0.05 was considered significant. Results: The prevalence of stunting in children with an elevated L:M at baseline and end line was found to be 72.4% (95% CI: 60.3, 84.5) and 78.4% (95% CI: 66.7, 90.2), respectively. In a multivariate analysis, a low dietary diversity score (<4 food groups), presence of flies and insects in the toilet area, poor handwashing practices during a critical time, and MUAC z < -2 were significantly associated with stunting. Flies and insects in the toilet area and unsafe disposal of feces were significantly associated with changes in HAZ in children with elevated lactulose-to-mannitol ratios, an indicator of environmental enteropathy. Conclusion: Most of the children with an elevated lactulose-to-mannitol ratio in the study population were stunted, and no significant change in their linear growth was observed after 1-year follow-up. Therefore, further investigation and urgent intervention are needed to prevent environmental enteropathy and stunting among under-five children in this community who are exposed to very poor sanitary conditions and other risk factors for malnutrition.

Prophylaxis of hepatic encephalopathy: current and future drug targets.

Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.

Cinnamaldehyde/lactulose combination therapy alleviates thioacetamide-induced hepatic encephalopathy via targeting P2X7R-mediated NLRP3 inflammasome signaling.

AIMS: Cinnamaldehyde (CA), the main active constituent of cinnamon oil, is reported to have neuroprotective effects. However, the potential benefits of CA for brain protection in hepatic encephalopathy (HE) are still not understood. Thus, the present study investigates the possible ameliorative effect of CA (70 mg/kg/day, I.P.) either alone or in combination with lactulose (Lac) (5.3 g/kg/day, oral) against thioacetamide (TAA)-induced hepatic encephalopathy in rats. MATERIALS AND METHODS: For induction of HE, TAA (200 mg/kg) was intraperitoneally administered for 1 week at alternative days. CA, Lac and Lac+CA were administered for 14 days prior to and for further 7 days together with TAA injection. KEY FINDINGS: CA, Lac and Lac+CA combination effectively attenuated TAA-induced HE; as indicated by the improvement in behavioral tests, mitigation of pathological abnormalities in both liver and brain, the significant reduction in serum hyperammonemia and amelioration in liver function biomarkers; ALT and AST. This was accompanied with a substantial restoration of redox state in liver and brain; MDA and GSH levels. Moreover, CA, Lac and Lac+CA combination reduced neuroinflammation as demonstrated by the notable attenuation of P2X7R, NLRP3, caspase-1, IL-1ß, GFAP and Iba1 brain levels, as well as the amelioration of brain edema as manifested by reduction in AQP4 levels in brain. SIGNIFICANCE: Our study has demonstrated that CA in combination with Lac possesses a superior neuroprotective effect over Lac alone against TAA-induced HE by attenuation of P2X7R/NLRP3 mediated neuroinflammation and relieving brain edema.

Pharmacologic Management of Hepatic Encephalopathy.

Hepatic encephalopathy is a common cause of morbidity and mortality among patients with decompensated liver cirrhosis. In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate.

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 low-residue 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.

Polyethylene glycol compared to lactulose for constipation in pregnancy: A randomized controlled trial.

OBJECTIVE: To compare polyethylene glycol 4000 versus lactulose in chronic constipation during pregnancy. METHODS: Women at 28-32 weeks' gestation attending antenatal clinic for routine care were screened using the Rome IV chronic constipation criterion. Eligible women were approached and consented. Participants were randomized to oral polyethylene glycol (10 g/day) or lactulose (10 g/day) for 4 weeks. A bowel movement diary was kept and outcomes using the Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM), Patient Assessment of Constipation Quality of Life questionnaire (PAC-QoL) and Bristol Stool Form Scale (BSFS), which were evaluated at the start and end of the four-week period. Relative risks (RR) were determined for the coprimary outcomes of complete spontaneous bowel movement (CSBM) and PAC-SYM mean score improvement (decrease in score of >1 from the baseline). RESULTS: A total of 4323 women underwent screening, of which 780 fulfilled the Rome IV criterion, and 360 consented to participate (180 randomized to PEG and lactulose, respectively). Data from 247 women who completed the study were analyzed. CSBM was achieved in 107/124 (86.3%) versus 102/123 (82.9%) (RR 1.04, 95% CI: 0.93-1.16, P = 0.464) for PEG and lactulose trial arms, respectively. PAC-SYM mean score improvement was 62/118 (52.5%) in the PEG arm versus 44/118 (37.3%) in the lactulose arm (RR 1.40, 95% CI: 1.05-1.88). Of secondary outcomes, a significant difference was found in favor of PEG, with respect to PAC-SYM abdominal symptoms subscale, normal stool versus loose stool consistency and side effects of vomiting and diarrhea. After controlling for parity, baseline PAC-SYM, PAC-QoL scores, characteristics different at baseline, only diarrhea and loose stools remained significant. CONCLUSION: Both PEG 4000 and lactulose are effective laxatives in pregnancy with similar performance after adjusted analysis. Diarrhea and loose stools are less frequently reported with PEG.