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.

Effect of L-arabinose and lactulose combined with Lactobacillus plantarum on obesity induced by a high-fat diet in mice.

L-Arabinose, lactulose, and Lactobacillus plantarum (L. plantarum) have been reported to have glucolipid-lowering effects. Here, the effects of L-arabinose and lactulose combined with L. plantarum on obesity traits were investigated. According to the experimental results, the combination of L-arabinose, lactulose, and L. plantarum was more effective at reducing body weight, regulating glucolipid metabolism, and improving insulin resistance. Besides, this combination showed immunomodulatory activity by adjusting the T lymphocyte subsets and reduced the immune-related cytokine production. Moreover, it improved the gut barrier, ameliorated the disorder of gut microbiota, and upregulated the levels of SCFAs. More importantly, the AL group, LP group, and ALLP group showed different regulatory effects on the abundance of Bifidobacterium and Lactobacillus due to the presence of lactulose and L. plantarum. These findings elucidate that the combination of L-arabinose, lactulose, and L. plantarum constitutes a new synbiotic combination to control obesity by modulating glucolipid metabolism, immunomodulatory activity, inflammation, gut barrier, gut microbiota and production of SCFAs.

Effects of bovine whey protein on exercise-induced gut permeability in healthy adults: a randomised controlled trial.

PURPOSE: Intestinal permeability is a critical component of gut barrier function. Barrier dysfunction can be triggered by certain stressors such as exercise, and if left unmanaged can lead to local and systemic disorders. The aim of this study was to investigate the effects of a specific whey protein fraction in alleviating exercise-induced gut permeability as assessed by recovery of lactulose/rhamnose (L/R) and lactulose/mannitol (L/M) urinary probes. METHODS: Eight males and eight females (aged 18-50) completed two arms of a double-blind, placebo-controlled, crossover study. For each arm participants performed two baseline intestinal permeability assessments, following which they consumed the treatment (2 g/day of milk powder containing 200 mg of whey protein) or placebo (2 g/day of milk powder) for 14 days, before performing a post-exercise permeability assessment. The exercise protocol involved a 20-min run at 80% of maximal oxygen uptake on a 1% incline. RESULTS: Mixed model analysis revealed an increase in L/R (23%; P < 0.001) and L/M (20%; P < 0.01) recovery following exercise. However, there was no treatment or treatment × exercise effect. CONCLUSION: The exercise protocol utilised in our study induces gut permeability. However, consuming whey protein, at the dose and timing prescribed, is not able to mitigate this effect.

Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT3 receptor antagonist, ondansetron.

BACKGROUND: Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron. METHODS: A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content. KEY RESULTS: Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose. CONCLUSION & INFERENCES: Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.

Use of lactulose as a prebiotic in laying hens: its effect on growth, egg production, egg quality, blood biochemistry, digestive enzymes, gene expression and intestinal morphology.

BACKGROUND: The rising popularity of eggs as an alternative source of protein to meat has led to significant increase in egg consumption over the past decade. To meet the increasing demand for eggs, poultry farmers have used antibiotics to treat infections and, to some extent, promote growth and egg production in raising layer. However, the emergence and global spread of antibiotic resistant bacteria has now necessitated antibiotic-free poultry farming. As alternatives to antibiotics, prebiotics are feed additives that can be used to improve the growth and laying performance of poultry which positively impacts their performance and general health. In this study we evaluated the effect of lactulose, formulated as Vetelact, on body weight, egg production, egg quality, blood biochemical parameters and expression of genes associated with reproductive performance in laying hens. RESULTS: Vetelact supplementation improved egg weight, egg production as well as egg quality. Following Vetalact supplementation, the levels of total bilirubin, total protein, globulin and phosphorus were increased, while the activities of alkaline phosphatase and lipase enzymes were increased compared to control. Vetelact at 0.10 ml/kg body weight upregulated OCX-36, OVAL, CALB1, OC-116, OCX-32 and IL8 transcripts while downregulating the transcription of Gal-10, PENK and AvBD9. At this optimal inclusion rate of Vetalect, histomorphologic analyses of intestinal tissue showed increased villi length with more goblet cell distribution and obvious mucus covering a surface, increase in the depth of intestinal crypts produce digestive enzymes, as well as more developed muscle layer that promote improved nutrient absorption. CONCLUSION: Vetelact at a dose of 0.10 ml/ kg body weight was effective in improving productive performance of laying hens. Adding lactulose (0.10 ml/ kg body weight) to layer diet is recommended to promote growth and improve egg laying performance in antibiotics-free poultry production.

Prevention of dextran sulfate sodium (DSS)-induced ulcerative colitis in mice by a synbiotic approach using probiotic and lactulose.

In this research, the synbiotic effects of the probiotic Lactiplantibacillus plantarum YW11 and lactulose on intestinal morphology, colon function, and immune activity were evaluated in a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed that L. plantarum YW11 in combination with lactulose decreased the severity of colitis in mice and improved the structure of the damaged colon, as assessed using colon length and disease condition. Moreover, colonic levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-12, TNF-α, and IFN-γ) were significantly lower and anti-inflammatory factors (IL-10) were significantly higher following the synbiotic supplementation. The synbiotic also exerted antioxidant effects by up-regulating SOD and CAT levels and down-regulating MDA levels in colon tissue. It could also reduce the relative expression of iNOS mRNA and increase the relative expression of nNOS and eNOS mRNA. Western blot confirmed the increased expression of c-Kit, IκBα, and SCF and significantly reduced expression of the NF-κB protein. Therefore, the combination of L. plantarum YW11 and lactulose exerted therapeutic effects mainly through the NF-κB anti-inflammatory pathway, which represented a novel synbiotic approach in the prevention of colonic inflammation.

Effect of early vs. late maturing sire lines and creep feeding on the cortisol response, intestinal permeability, and growth performance of nursery and finishing pigs.

A total of 21 litters (11 early and 10 late maturing Duroc × DNA 241) resulting in 241 pigs were used in 170 d trial to determine the effect of sire lines selected for either early or late maturing growth rates and creep feeding on the cortisol concentration, intestinal permeability, and growth performance of nursery and finishing pigs. Treatments were arranged in a 2 × 2 factorial with main effect of Duroc sire line (early or late maturing) and creep feeding (with or without). Creep feed was provided for 14 d prior to weaning. After weaning (approximately 21 d of age; initially 6.4 kg), no interactions were observed for blood cortisol. However, blood cortisol levels were increased (P = 0.011) in late maturing pigs compared to early maturing pigs. A lower percentage (P < 0.001) of early maturing pigs lost weight 3 d post-weaning compared to late maturing pigs. Likewise, early maturing pigs had improved (P < 0.001) average daily gain (ADG) and average daily feed intake (ADFI) during the first 3 d in the nursery and also had increased ADFI (P < 0.001) from days 2 to 14 in the nursery. Creep feeding had no effect on initial nursery performance. On day 7, after a 2-h fast, a subsample of pigs was administered an oral gavage of lactulose and mannitol dissolved in distilled water. No differences by sire line, creep feeding, or their interactions were observed in lactulose:mannitol ratio. For overall nursery growth performance, an interaction was observed for ADG (P = 0.007) and ADFI (P < 0.001), with creep feed providing a benefit in late maturing pigs, but not in early maturing pigs. Early maturing pigs had poorer gain-to-feed ratio (G:F) (P < 0.001) than late maturing pigs. For overall finishing performance, an interaction was observed for ADG (P = 0.037) and ADFI (P = 0.007), with creep feed providing a benefit in late maturing pigs, but not in early maturing pigs. This resulted in an interaction for final body weight (P = 0.005), with late maturing pigs that did not receive creep feed having decreased market weights (P ≤ 0.003) compared to the other treatments. In summary, early maturing pigs had decreased cortisol concentration at weaning and improved ADG and ADFI until approximately 100 kg, at which point late maturing pigs began to exhibit greater ADG. Late maturing pigs had improved G:F from 46 d of age until market. Interestingly, creep feeding late maturing pigs resulted in increased day 170 weight compared with providing no creep feed, whereas creep feed did not impact early maturing pigs (sire line × creep feed interaction, P < 0.005).

Finishing pig growth potential varies across different genotypes; however, limited research is available on performance of nursery pigs sired from boars selected for different finishing growth patterns. With selection of terminal sires focused on improved lean gain in late finishing, anecdotal or field observations suggest that starting weanling pigs on feed has become more challenging. Hence, our hypothesis that improving post-weaning feed intake by creep feeding may be of greater importance today than in the past due to sire line selection criteria. Therefore, our objective was to determine the possible interaction of Duroc sires selected for early vs. late maturing growth rates and creep feeding on the growth performance of pigs from birth to market. Early maturing pigs had increased feed intake from days 2 to 14 post-weaning compared to late maturing pigs. Likewise, a lower percentage of early maturing pigs lost weight from weaning to 3 d post-weaning. Early maturing pigs had improved average daily gain (ADG) and average daily feed intake until approximately 100 kg, at which point late maturing pigs began to exhibit greater ADG. Overall, offering creep feed to late maturing pigs resulted in improved growth performance compared to no creep feed, whereas creep feed did not impact early maturing pigs.

Effect of Bacillus coagulans Unique IS2 with Lactulose on Functional Constipation in Adults: a Double-Blind Placebo Controlled Study.

In the present double-blind randomised study, the efficacy of combination of Bacillus coagulans Unique IS2 and lactulose was evaluated in the treatment of functional constipation in adults. One-fifty participants diagnosed with functional constipation (Rome III criteria) were randomised (1:1:1) and supplemented daily with 15 mL suspension of probiotic (B. coagulans Unique IS2, 2 × 109 spores) with lactulose (10 g) (group 1) or lactulose (10 g) (group 2) or placebo (water) (group 3) for 4 weeks. The primary (stool frequency) and secondary outome measures (stool consistency, sensation of incomplete evacuation, defecation- and abdominal-pain) were recorded weekly for up to 4 weeks. Bacillus coagulans Unique IS2 with lactulose showed significant changes in stool frequency as compared to lactulose treatment; however, at the end of the trial, it was found insignificant due to the gradual increase of stool frequency score of lactulose treatment. The changes observed in stool consistency were early (2nd week) and remained consistent up to end of the trial. The significant reduction of sensation of incomplete evacuation, defecation-, and abdominal-pain correlated with the strains ability to produce short-chain fatty acids. No adverse events were observed in any of the groups, and all the vital parameters were normal during the course of the study. Overall, results indicated that B. coagulans Unique IS2 addition to lactulose reduced time required to relieve constipation as compared to lactulose alone. In conclusion, B. coagulans Unique IS2 with lactulose is more effective than lactulose alone to relieve symptoms of constipation in a shorter period. Trial registration: CTRI/2018/11/016399, dated 22/11/2018.

The effect of Cassia fistula L. syrup in geriatrics constipation in comparison with the lactulose: A randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia fistula is widely used in traditional Persian Medicine as a mild laxative. The rate of chronic constipation increases above the age of 60. AIM OF THE STUDY: This study aimed to investigate the effect of Cassia fistula syrup (CFS) on geriatric constipation. MATERIALS AND METHODS: This clinical trial study was performed on 70 aged patients who were referred to the clinic of gastroenterology of Rouhani Hospital, Babol, North of Iran. Patients were randomly divided into two groups of CFS or Lactulose with a dose of 30 ccs/day. Patients were visited two weeks after entering the study to evaluate the frequency of defecation, feeling of incomplete emptying after defecation, manual maneuver, consistency of stool, and also the quality of life. RESULTS: The frequency of defecation per week varied from 1.82 ± 1.16 to 8.36 ± 3.44 in the CFS group after 2 weeks of intervention that was significantly more than the Lactulose that changed from 2.16 ± 1.46 to 5.66 ± 2.96 (P-value = 0.023, partial eta square = 0.079, NNT = 4). The quality of life, the percent of straining, lumpy or hard stool, pain during defecation, and the consistency of stool based on VAS were significantly better in the CFS group. The sensation of incomplete defecation, anorectal obstruction, and manual maneuvering were not different significantly between groups. CONCLUSION: CFS can be more effective than Lactulose on geriatric constipation.

Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis.

Lactulose, a galactose-fructose disaccharide, is made from the milk sugar lactose by heating or isomerization processes. Lactulose is proposed to modulate gut microbiota and thus expected to be beneficial in treating inflammatory bowel disease. In the present study, we investigated the therapeutic effect of lactulose on gastrointestinal inflammation and inflammation-related tumorigenesis in a mouse model of colorectal cancer as well as its effect on gut microbiota composition. Azoxymethane (AOM)/dextran sulfate sodium (DSS) model was used in this study. Lactulose treatment was performed by feeding 2% lactulose for 14 weeks. Stool samples collected at 4 time points were used for metagenomic analysis of the microbiota. Pathological analysis was performed 21 weeks after AOM injection. AOM/DSS increased the macrophage counts, inflammatory cytokine expression, colorectal tumorigenesis, and imbalance in gut microbiota composition, as evidenced by increased pathogen abundance (e.g., Escherichia and Clostridium). Lactulose significantly inhibited the inflammatory events, and ameliorated inflammation and tumorigenesis. The composition of the intestinal microbiota was also restored upon lactulose treatment, and lactulose reduced pathogen abundance and increased the abundance of Muribaculum and Lachnospiraceae. Meanwhile, the pathways related to Crohn's disease were downregulated after lactulose treatment. Our findings suggest that lactulose restores the structure and composition of the intestinal microbiota, mitigates inflammation, and suppresses inflammatory tumorigenesis.

Lactulose and Melibiose Inhibit α-Synuclein Aggregation and Up-Regulate Autophagy to Reduce Neuronal Vulnerability.

Parkinson's disease (PD) is a neurodegenerative disease characterized by selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra (SN) and proteinaceous α-synuclein-positive Lewy bodies and Lewy neuritis. As a chemical chaperone to promote protein stability and an autophagy inducer to clear aggregate-prone proteins, a disaccharide trehalose has been reported to alleviate neurodegeneration in PD cells and mouse models. Its trehalase-indigestible analogs, lactulose and melibiose, also demonstrated potentials to reduce abnormal protein aggregation in spinocerebellar ataxia cell models. In this study, we showed the potential of lactulose and melibiose to inhibit α-synuclein aggregation using biochemical thioflavin T fluorescence, cryogenic transmission electron microscopy (cryo-TEM) and prokaryotic split Venus complementation assays. Lactulose and melibiose further reduced α-synuclein aggregation and associated oxidative stress, as well as protected cells against α-synuclein-induced neurotoxicity by up-regulating autophagy and nuclear factor, erythroid 2 like 2 (NRF2) pathway in DAergic neurons derived from SH-SY5Y cells over-expressing α-synuclein. Our findings strongly indicate the potential of lactulose and melibiose for mitigating PD neurodegeneration, offering new drug candidates for PD treatment.

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.

In vitro assessment of prebiotic properties of xylooligosaccharides produced by Bacillus subtilis 3610.

Xylooligosaccharides (XOS) are emergent prebiotics exhibiting high potential as food ingredients. In this work, in vitro studies were performed using human fecal inocula from two healthy donors (D 1 and D2) to evaluate the prebiotic effect of commercial lactulose and XOS produced in a single-step by recombinant Bacillus subtilis 3610. The fermentation of lactulose led to the highest production of lactate (D1: 33.7 ±â€¯0.5 mM; D2:19.7 ±â€¯0.3 mM) and acetate (D1: 77.5 ±â€¯0.6 mM; D2: 81.0 ±â€¯0.7 mM), while XOS led to the highest production of butyrate (D1: 9.0 ±â€¯0.6 mM; D2: 10.5 ±â€¯0.8 mM) and CO2 (D1: 8.92 ±â€¯0.02 mM; D2: 11.4 ±â€¯0.3 mM). Microbiota analysis showed a significant decrease in the relative abundance of Proteobacteria for both substrates and an increase in Bifidobacterium and Lactobacillus for lactulose, and Bacteroides for XOS.

Effects of sialylated lactulose on the mouse intestinal microbiome using Illumina high-throughput sequencing.

Sialylated oligosaccharides are known to have beneficial effects, such as increasing the level of bifidobacteria, reducing the levels of blood endotoxin and blood ammonia, and enhancing the body's immune system. However, it is unknown whether sialylated lactuloses have modulatory effects on the intestinal microbiota. In this study, 60 healthy mice were randomly divided into six groups, namely, a normal control group, a lactulose group, a Kdn-α2,3-lactulose group, a Kdn-α2,6-lactulose group, a Neu5Ac-α2,3-lactulose group, and a Neu5Ac-α2,6-lactulose group. After 14 days of lactulose administration, the feces of three mice from each group were collected, and the intestinal microbiota were detected by Illumina MiSeq high-throughput sequencing targeting the V3-V4 region of the 16S rDNA gene. At the phylum level, the relative abundance of Firmicutes was increased in the sialylated lactulose groups, while the abundance of Bacteroidetes was decreased. At the family level, sialylated lactulose intervention decreased the relative abundance of Bacteroidales S24-7 group and Helicobacteraceae and enhanced the abundance of Lactobacillaceae, which reflects the modulatory effect of sialylated lactulose on intestinal microbiota. Diversity analysis indicated that the index of Chao was higher in the sialylated lactulose groups than in the normal control group, and the Shannon and Simpson diversity indices were higher in the Kdnα-2,6-lactulose group and the Neu5Ac-α2,3-lactulose group than in the normal control group. The results of the intestinal microbiota sample composition indicated that there were differences between the sialylated lactulose groups and the normal control group. Thus, sialylated lactulose could be used as a functional food component with potential therapeutic applications in manipulating intestinal microbiota to exert beneficial effects on the host's health.

Lactulose drives a reversible reduction and qualitative modulation of the faecal microbiota diversity in healthy dogs.

Hepatic encephalopathy is a frequent and debilitating complication of liver disorders. Lactulose is an established and reasonably effective treatment, yet with incompletely understood mechanisms of action. The aims of this study were to examine how the faecal microbiota composition changed before, during and after lactulose treatment in a large animal model. Healthy, privately owned dogs (n = 18) completed a prospective cohort study. Faecal samples were collected weekly, while the subjects were either on their usual diet (week 1), or a standardised diet (weeks 2-9), with added oral lactulose in weeks 6-7. DNA extraction and 16S rRNA gene sequencing were undertaken. Faecal samples from week 7 had a significantly lower microbiota richness/diversity, based on observed operational taxonomic units, Shannon/Chao1 indexes and Pielou's Evenness. Beta diversity based on UniFrac distances was significantly different in week 7 compared to weeks 1, 5 and 9. At the phylum level, week 7 was associated with a significant increase of Firmicutes and Actinobacteria, and a decrease of Bacteroidetes and Fusobacteria, when compared to weeks 5 and 9. In summary, we have shown that lactulose induces a reversible qualitative and quantitative change of the faecal microbiota, which may explain its clinical efficacy in the management of hepatic encephalopathy.

Immunomodulatory influences of sialylated lactuloses in mice.

The aim of this study was to investigate the immune modulatory influences of sialylated lactuloses in mice. The effects of the four sialylated lactuloses by gavage methods on the weight gain rate, organ, serum and spleen immunoglobulin of mice were investigated. Neu5Ac-α2,3-lactulose group and Kdn-α2,3-lactulose group had significantly higher weight gain rate than control group. The weight gain rate, thymus index and spleen index of Kdn-α2,3-lactulose group were significantly higher than control group and lactulose group. Liver and small intestine of Neu5Ac-α2,3-lactulose group, Neu5Ac-α2,6-lactulose group and Kdn-α2,6-lactulose group showed different degree of damage. IgG levels of serum and spleen in Neu5Ac-α2,6-lactulose group and Kdn-α2,6-lactulose group were significantly higher than control group and lactulose group. The contents of IgG in serum and spleen of Kdn-α2,3-lactulose group were significantly lower than that of control group, while the contents of IgA and IgM in serum were significantly higher than those of control group. The IgA level increased by 12.23% and 58.77% comparing with lactulose group and control group, respectively. The IgM level in serum of Kdn-α2,3-lactulose group mice increased by 43.88% and 8.05% comparing with control group and lactulose group, respectively. The IgA level and IgM level in spleen of Kdn-α2,3-lactulose group mice increased by 49.05% and 47.25% comparing with control group. In short, Kdn-α2,3-lactulose is relatively safe and superior to use as a food supplement or potential drug candidate. Our results also indicate that some other sialylated oligosaccharides are potentially harmful to organisms, they may cause some side effects.

Targeting the Gut Microbiota to Investigate the Mechanism of Lactulose in Negating the Effects of a High-Salt Diet on Hypertension.

SCOPE: High-salt diets (HSDs) are widely considered to cause health problems such as gut microecological imbalances, constipation, and hypertension. This study explores how lactulose as a safe molecule can stimulate bodily responses to alleviate salt-sensitive hypertension by regulating the gut microbiotas of HSD-fed mice. METHODS AND RESULTS: After 4 weeks, the blood pressures of mice fed a high-salt plus lactulose diet (HSLD) are significantly lower than those of the HSD-fed mice. The HSD increases the abundances of Alistipes and Ruminococcaceae_UCG_009 and reduced the abundance of Lactobacillus in the gut, while lactulose supplementation increases the abundances of Bifidobacterium, Alloprevotella, and Subdoligranulum. Fecal metabolic profiling shows significant increases in metabolites involved in ATP-binding cassette transporter pathways, and tryptophan metabolism is significantly reduced in the HSLD group compared with the HSD group. Lactulose maintains the intestinal microenvironmental health in the HSD-fed mice by improving glycolipid metabolism, decreasing the small intestinal interleukin-17a (IL-17a) and interleukin-22 (IL-22) mRNA levels and serum IL-17a and IL-22 levels, relieving constipation, increasing fecal sodium, and reducing intestinal permeability. CONCLUSION: Lactulose negates salt-sensitive hypertension. Regulating the gut microbiota is a potential treatment for salt-sensitive hypertension.

Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats.

BACKGROUND: Constipation is frequently observed in patients with chronic kidney disease (CKD). Lactulose is expected to improve the intestinal environment by stimulating bowel movements as a disaccharide laxative and prebiotic. We studied the effect of lactulose on renal function in adenine-induced CKD rats and monitored uremic toxins and gut microbiota. METHODS: Wistar/ST male rats (10-week-old) were fed 0.75% adenine-containing diet for 3 weeks to induce CKD. Then, they were divided into three groups and fed as follows: control, normal diet; and 3.0- and 7.5-Lac, 3.0% and 7.5% lactulose-containing diets, respectively, for 4 weeks. Normal diet group was fed normal diet for 7 weeks. The rats were observed for parameters including renal function, uremic toxins, and gut microbiota. RESULTS: The control group showed significantly higher serum creatinine (sCr) and blood urea nitrogen (BUN) 3 weeks after adenine feeding than at baseline, with a 8.5-fold increase in serum indoxyl sulfate (IS). After switching to 4 weeks of normal diet following adenine feeding, the sCr and BUN in control group remained high with a further increase in serum IS. In addition, tubulointerstitial fibrosis area was increased in control group. On the other hand, 3.0- and 7.5-Lac groups improved sCr and BUN levels, and suppressed tubulointerstitial fibrosis, suggesting preventing of CKD progression by lactulose. Lac groups also lowered level of serum IS and proportions of gut microbiota producing IS precursor. CONCLUSION: Lactulose modifies gut microbiota and ameliorates CKD progression by suppressing uremic toxin production.

Risk factors for upper and lower functional gastrointestinal disorders in Persian Gulf War Veterans during and post-deployment.

BACKGROUND: Gastroenteritis is a risk factor for irritable bowel syndrome (IBS), but its role in other functional gastrointestinal disorders (FGIDs) is less clear. The aim of this study was to determine the prevalence of FGIDs in Gulf War (GW) Veterans before, during, and after deployment and to determine whether gastroenteritis was a risk factor for upper and lower FGIDs. METHODS: The Veterans who served during the Persian GW were mailed validated questionnaires inquiring about their bowel habits, psychological and extra-intestinal symptoms, and quality of life (QOL). The lactulose hydrogen breath test (LBT) was performed for small intestinal bacterial overgrowth. KEY RESULTS: Data were analyzed from 468 GW Veterans. The prevalence of FGID before, during, and 16 years after deployment was 15.7%, 49.9%, and 64.2%, respectively. New FGIDs during deployment was reported by 41.2%, and during 16 years after deployment, 43.7% acquired new FGIDs. FGIDs were associated with psychological disorders, extra-intestinal symptoms, and lower QOL. Gastroenteritis was reported by 44.3% of deployed Veterans and was a risk factor for IBS, dyspepsia, and functional diarrhea post-deployment. The cases and controls did not differ significantly in the frequency of positive LBT. CONCLUSIONS AND INFERENCES: There is an increase in the prevalence of FGIDs during deployment, and it persists after deployment. There is a further increase in the prevalence of FGIDs after deployment. In addition to IBS, gastroenteritis during deployment is a risk factor for dyspepsia and functional diarrhea post-deployment. Therefore, prevention of gastroenteritis during deployment and screening of Veterans for FGIDs post-deployment would be of value for Veterans' long-term health.

Lactulose synergizes with CpG-ODN to modulate epithelial and immune cells cross talk.

Lactulose, a non-digestible oligosaccharide and functional food, promotes Bifidobacteria growth. Here we show that lactulose, beyond its prebiotic action, may have direct immunomodulatory effects as well. In synergy with CpG-ODN, a bacterial DNA mimetic, lactulose enhances basolateral concentrations of IFN-γ, IL-10, and galectin-9 in the co-culture model of epithelial and immune cells.