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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 × 10 9 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.

Objective: Faecal bifidobacteria and lactobacilli, perceived as exerting health-promoting properties, may be increased by ingestion of high-dose lactulose in humans. The effects of low and well-tolerated doses of lactulose are not well known. The aim of the study was to assess the effects of prolonged low-dose lactulose administration on faecal bifidobacteria and selected metabolic indexes potentially involved in colonic carcinogenesis. Subjects and methods: In all, 16 healthy volunteers were included in this controlled, randomised, double-blind, parallel group trial. Participants ingested lactulose or placebo (sucrose) at a dose of 5 g b.i.d. for 6 weeks. Stools were regularly collected at baseline (d0), and after 3 (d21) and 6 (d42) weeks of sugar ingestion. Tolerance was evaluated using a daily chart. Results: Faecal bifidobacterial counts were higher in lactulose than in sucrose group (P=0.03). Lactulose ingestion led to a significant increase in faecal bifidobacteria counts from d0 to d21 and d42 ((m+/-s.e.m.) 8.25+/-0.53, 8.96+/-0.40 and 9.54+/-0.28 log colony-forming units/g wet wt (CFU/g), respectively (P=0.048)). Placebo ingestion did not lead to any faecal bifidobacterial count change. Total anaerobes, Lactobacillus and pH were not significantly changed throughout the study in the two groups. Neither faecal bile acids nor neutral sterols were modified by lactulose. Excess flatus was more common in the lactulose group (P=0.03), but was very mild. Bloating and borborygmi did not differ between both the groups. Conclusions: A measure of 10 g lactulose/day increases faecal bifidobacterial counts, and lactulose fulfils the criteria requested to be considered as a prebiotic.

Objective: To investigate the influence of different pre- and probiotics on faecal β-glucuronidase and β-glucosidase activity, as one of the claimed beneficial effects of pre- and probiotics is the hypothesis that these substrates are able to reduce the production of toxic and carcinogenic metabolites by suppressing specific enzyme activities in the colon. Setting: Department of Gastrointestinal Research, University Hospital Gasthuisberg, KU Leuven, Belgium. Design and subjects: The effect was evaluated in a randomized, crossover study in 53 healthy volunteers who were randomly assigned to one of five treatment groups. Interventions: At the start and after a 4-week treatment period, the healthy volunteers collected faeces during 72 h. Lactulose and oligofructose-enriched inulin (OF-IN) were chosen as prebiotics, whereas Lactobacillus casei Shirota, Bifidobacterium breve and Saccharomyces boulardii were selected as probiotics. Two synbiotic combinations were evaluated as well. The enzyme activity was assessed spectrophotometricly. Results: Lactulose and OF-IN significantly decreased β-glucuronidase activity, whereas a tendency to a decreased β-glucuronidase activity was observed after L. casei Shirota and B. breve intake. To the contrary, B. breve increased β-glucosidase levels. Supplementation with the synbiotic did not appear to be more beneficial than either compound alone. No influence of S. boulardii was noted. Conclusions: Administration of lactulose, OF-IN, L. casei Shirota or B. breve resulted in a decrease of the β-glucuronidase activity, which is considered beneficial for the host.

The H2 breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H2 which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of 13C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85·3 (sd 42·8) min) compared with L-S (162·4 (sd 62·6) min) and inulin (292·4 (sd 66·7) min; P = 0·007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0·005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0·05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H2 breath test.

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.

The principal therapeutic agents for minimal hepatic encephalopathy (MHE), which focus on the modulation of the gut microbiota, include lactulose and rifaximin; however, the precise mechanisms through which they operate remain unclear. This study aimed to investigate the effects of rifaximin and lactulose on the gut-liver-brain axis in a rat model of MHE and to clarify the underlying mechanisms involved. A rat model of MHE was established by subcutaneous carbon tetrachloride (CCl4) injection. The Morris water maze (MWM) test was used to assess cognitive function in MHE rats following treatment with rifaximin and lactulose. Serum and cerebrospinal fluid ammonia levels were quantified, along with measurements of portal lipopolysaccharide (LPS) and various serum inflammatory markers. Furthermore, the expression of Toll-like receptor 4 (TLR4) in the liver was examined by histopathological evaluation. Additional analyses included the detection of tight junction proteins in the intestinal mucosa as well as colon fecal 16S rRNA sequencing and metabolic pathway assessments. Both rifaximin and lactulose were effective in reducing ammonia concentrations in MHE rats and ameliorating cognitive deficits, although they exhibited a minimal impact on hepatic function. Post-treatment assessments revealed significant reductions in portal LPS, serum interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). The expression of TLR4 in the liver and hepatic inflammatory infiltration were notably diminished. Rifaximin administration led to increased occludin expression in the intestinal tissues of MHE rats. Despite no significant alterations in the diversity or composition of the gut microbiota, metabolic pathway analyses indicated a downregulation of glycometabolism pathways following treatment. Rifaximin and lactulose may enhance cognitive performance in MHE rats by modulating gut microbiota metabolism and preserving the intestinal barrier integrity. This modulation is associated with lowered ammonia levels, decreased translocation of LPS to the liver, and reduced inflammatory response, both in the liver and systemically.

PurposeIntestinal 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.MethodsEight 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.ResultsMixed 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.ConclusionThe 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.

Although low-dose lactulose has shown a good theoretical foundation for the treatment of ulcerative colitis (UC) in previous studies, the exact effects and mechanism remain unclear. The rats were randomly distributed into 5 groups, i.e., normal drinking water was provided for an initial 14 days in blank control group, 4% dextran sulfate sodium was used for modeling in the remaining 4 groups. During the 15-24th day, rats in the blank control group were administered with 0.9% saline (0.5 ml/d) by gavage. In the rest 4 groups, rats were administered 0.9% saline (0.5 ml/d, UC model), mesalazine (400 mg/kg/d), lactulose (1000 mg/kg/d), and lactulose + mesalazine (two-drug combination) by gavage. In addition to symptoms and pathological changes, serum IL-6, TNF-α, and High-sensitivity C-reactive protein(Hs-CRP) by ELISA analysis, mRNA and protein expression levels of TLR-2, TLR-4, Nuclear factor-κB(NF-κB), IL-6, and TNF-α in colon tissues by RT-qPCR and WB analyses respectively. Meanwhile, short-chain fatty acid(SCFAs) and intestinal flora were analyzed. Low-dose lactulose improved symptoms (diarrhea, blood in stool, weight loss) and pathological inflammation. In addition to serum IL-6, TNF-α, and Hs-CRP, the mRNA and protein expression levels of TLR-2, TLR-4, NF-κB, IL-6 and TNF-α in the colon were down-regulated with the intervention of lactulose.Meanwhile, lactulose decreased the ileocecal PH, increased SCFAs and altered the intestinal flora. Low-dose lactulose may be beneficial to UC by regulating TLRs/NF-κB pathway, reducing ileocecal PH, increasing SCFAs, regulating intestinal flora and improving the intestinal mucosal barrier. Meanwhile, low-dose lactulose and mesalazine may have additive effects upon combination.

In recent years, the escalating incidence of goose gout has inflicted severe economic losses on the goose industry. This research aimed to investigate the impact of lactulose on both intestinal health and uric acid metabolism in geese, as well as to elucidate its possible mechanisms through RNA-seq analysis. A total of 180 one-day-old Yangzhou geese were assigned to three different groups: the control group (CG), which received a standard diet; the high-protein model group (MG), which was provided a diet with 21% crude protein; and the lactulose group (LS), which had a diet containing 21% crude protein along with 0.3% lactulose. The findings indicated that the LS group exhibited significantly reduced serum uric acid levels and an intact ileal mucosal structure when compared to both the CG and MG groups. Through bioinformatics analyses of the transcriptome, including GO and KEGG enrichment analyses, Gene Set Enrichment Analysis, and trend analysis, key pathways and genes closely related to intestinal health and uric acid metabolism were identified. These key findings encompass the biological process of zinc ion import across the plasma membrane, the ABC Transporters pathway, the Wnt signaling pathway, the key uric acid transport gene ABCG2 , and genes closely associated with intestinal structural integrity ( KLF2 , LRP6 , TJP1 , TJP3 , PROM1 ). The results indicated that lactulose can effectively reduce the serum uric acid level in geese by improving intestinal morphology.

The purpose of this review is to highlight the importance of whey as a source of new-generation functional ingredients. Particular interest is given to probiotic growth in the presence of whey derivatives such as lactulose, a lactose derivative, which is a highly sought-after prebiotic in functional feeding. The role of sugar/nitrogen interactions in the formation of Maillard products is also highlighted. These compounds are known for their antioxidant power. The role of bioactive peptides from whey is also discussed in this study. Finally, the importance of an integrated valuation of whey is discussed with an emphasis on functional nutrition and the role of probiotics in the development of novel foods such as synbiotics.