Fermentation Of Lactulose Research Articles

Co-Administration of Lactulose Crystals with Amoxicillin Followed by Prolonged Lactulose Treatment Promotes Recovery of the Human Gut Microbiome In Vitro.

The validated SHIME model was used to assess the effect of repeated administration of two different lactulose dosages (5 g/d and 10 g/d) on the human gut microbiome during and following amoxicillin–clavulanic acid treatment. First, antibiotic treatment strongly decreased Bifidobacteriaceae levels from 54.4% to 0.6% and from 23.8% to 2.3% in the simulated proximal and distal colon, respectively, coinciding with a marked reduction in butyrate concentrations. Treatment with lactulose enhanced acetate and lactate levels during antibiotic treatment, likely through lactulose fermentation by Lachnospiraceae and Lactobacillaceae. One week after cessation of antibiotic treatment, Bifidobacteriaceae levels re-increased to 20.4% and 7.6% in the proximal and distal colon of the 5 g lactulose/d co-administered unit, as compared with 1.0% and 2.2% in the antibiotic-treated unit, and were even further stimulated upon extension of lactulose administration. Marked butyrogenic effects were observed upon prolonged lactulose supplementation, suggesting the establishment of cross-feeding interactions between Bifidobacteriaceae and butyrate producers. Furthermore, a limited Enterobacteriaceae outgrowth following antibiotic treatment was observed upon dosing with 10 g lactulose/d, indicating inhibition of pathogenic colonization by lactulose following antibiotic therapy. Overall, lactulose seems to be an interesting candidate for limiting the detrimental effects of amoxicillin–clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings.

Colonic Lactulose Fermentation Has No Impact on Glucagon-like Peptide-1 and Peptide-YY Secretion in Healthy Young Men

The colon houses most of humans' gut microbiota, which ferments indigestible carbohydrates. The products of fermentation have been proposed to influence the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) from the many endocrine cells in the colonic epithelium. However, little is known about the colonic contribution to fasting or postprandial plasma levels of L-cell products. To determine the impact of colonic lactulose fermentation on gut peptide secretion and to evaluate whether colonic endocrine secretion contributes to gut hormone concentrations measurable in the fasting state. Ten healthy young men were studied on 3 occasions after an overnight fast. On 2 study days, lactulose (20 g) was given orally and compared to water intake on a third study day. For 1 of the lactulose visits, participants underwent a full colonic evacuation. Over a 6-h study protocol, lactulose fermentation was assessed by measuring exhaled hydrogen, and gut peptide secretion, paracetamol, and short-chain fatty acid levels were measured in plasma. Colonic evacuation markedly reduced hydrogen exhalation after lactulose intake (P = 0.013). Our analysis suggests that the colon does not account for the measurable amounts of GLP-1 and PYY present in the circulation during fasting and that fermentation and peptide secretion are not acutely related. Whether colonic luminal contents affect colonic L-cell secretion sufficiently to influence circulating concentrations requires further investigation. Colonic evacuation markedly reduced lactulose fermentation, but hormone releases were unchanged in the present study.

Low-Dose Lactulose as a Prebiotic for Improved Gut Health and Enhanced Mineral Absorption.

Although medium and high doses of lactulose are used routinely for the treatment of constipation and hepatic encephalopathy, respectively, a wealth of evidence demonstrates that, at low doses, lactulose can also be used as a prebiotic to stimulate the growth of health-promoting bacteria in the gastrointestinal tract. Indeed, multiple preclinical and clinical studies have shown that low doses of lactulose enhance the proliferation of health-promoting gut bacteria (e.g., Bifidobacterium and Lactobacillus spp.) and increase the production of beneficial metabolites [e.g., short-chain fatty acids (SCFAs)], while inhibiting the growth of potentially pathogenic bacteria (e.g., certain clostridia). SCFAs produced upon microbial fermentation of lactulose, the most abundant of which is acetate, are likely to contribute to immune regulation, which is important not only within the gut itself, but also systemically and for bone health. Low-dose lactulose has also been shown to enhance the absorption of minerals such as calcium and magnesium from the gut, an effect which may have important implications for bone health. This review provides an overview of the preclinical and clinical evidence published to date showing that low-dose lactulose stimulates the growth of health-promoting gut bacteria, inhibits the growth of pathogenic bacteria, increases the production of beneficial metabolites, improves mineral absorption, and has good overall tolerability. Implications of these data for the use of lactulose as a prebiotic are also discussed.

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 ± 0.5 mM; D2:19.7 ± 0.3 mM) and acetate (D1: 77.5 ± 0.6 mM; D2: 81.0 ± 0.7 mM), while XOS led to the highest production of butyrate (D1: 9.0 ± 0.6 mM; D2: 10.5 ± 0.8 mM) and CO2 (D1: 8.92 ± 0.02 mM; D2: 11.4 ± 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.

Screening of autochthonous lactic acid bacteria strains from artisanal soft cheese: probiotic characteristics and prebiotic metabolism

Today's growing interest in functional foods is due to their positive impacts on human health. The aim of this study was to evaluate the probiotic properties and prebiotic metabolism of autochthonous lactic acid bacteria from artisanal Serpa cheese. Twenty strains presented better tolerance to stress conditions found in the gastrointestinal tract, highlighting Lactobacillus brevis C1Lb21 for its adequate auto-aggregating ability and significantly higher hydrophobicity. However, eight strains were discarded for their antibiotic resistance and biogenic amine production. Finally, prebiotic fermentation study showed that lactulose supported better growth of lactobacilli and induced the production of short-chain fatty acids (SCFA). During lactulose fermentation, Lb. pentosus G4Lb7 produced statistically more SCFA, and Lb. plantarum G1Lb5 lactic acid. Thus, Lb. brevis C1Lb21, Lb. plantarum G1Lb5 and Lb. pentosus G4Lb7 are promising probiotic candidates, and in combination with lactulose could be used for developing a symbiotic cheese.

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen

ObjectiveTo study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied. MethodsThe study included 31 patients with abdominal pain (11 with functional dyspepsia, 10 with irritable bowel syndrome, and 10 with functional abdominal pain). The hydrogen breath test was used to investigate fructose malabsorption and lactulose fermentation in the intestinal lumen. Food consumption was assessed by food registry. Weight and height were measured. ResultsFructose malabsorption was characterized in 21 (67.7%) patients (nine with irritable bowel syndrome, seven with functional abdominal pain, and five with functional dyspepsia). Intolerance after fructose administration was observed in six (28.6%) of the 21 patients with fructose malabsorption. Fructose malabsorption was associated with higher (p<0.05) hydrogen production after lactulose ingestion, higher (p<0.05) energy and carbohydrate consumption, and higher (p<0.05) body mass index z‐score value for age. Median estimates of daily fructose intake by patients with and without fructose malabsorption were, respectively, 16.1 and 10.5g/day (p=0.087). ConclusionFructose malabsorption is associated with increased lactulose fermentability in the intestinal lumen. Body mass index was higher in patients with fructose malabsorption.

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 < 0.0001) relative to the probiotic strains. Antioxidant activity of spent medium was measured with Trolox as the reference standard. Overall, the antioxidant activity of probiotics was strain-dependent. FOS enhanced the antioxidant activity of 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.

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen

ObjectiveTo study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied. MethodsThe study included 31 patients with abdominal pain (11 with functional dyspepsia, 10 with irritable bowel syndrome, and 10 with functional abdominal pain). The hydrogen breath test was used to investigate fructose malabsorption and lactulose fermentation in the intestinal lumen. Food consumption was assessed by food registry. Weight and height were measured. ResultsFructose malabsorption was characterized in 21 (67.7%) patients (nine with irritable bowel syndrome, seven with functional abdominal pain, and five with functional dyspepsia). Intolerance after fructose administration was observed in six (28.6%) of the 21 patients with fructose malabsorption. Fructose malabsorption was associated with higher (p<0.05) hydrogen production after lactulose ingestion, higher (p<0.05) energy and carbohydrate consumption, and higher (p<0.05) body mass index z-score value for age. Median estimates of daily fructose intake by patients with and without fructose malabsorption were, respectively, 16.1 and 10.5g/day (p=0.087). ConclusionFructose malabsorption is associated with increased lactulose fermentability in the intestinal lumen. Body mass index was higher in patients with fructose malabsorption.

Lactulose accelerates liver regeneration in rats by inducing hydrogen

BackgroundOxidative stress and inflammation are implicated in the process of liver regeneration. Lactulose orally administered can be bacterially fermented and induces dramatic amounts of endogenous hydrogen. Hydrogen has been confirmed to have antioxidant and anti-inflammatory properties. This study investigated the potential influence of lactulose administration on liver regeneration. Materials and methodsAntibiotics were used to suppress bacterial fermentation of lactulose, and hydrogen-rich saline was used as a supplementary measure of exogenous hydrogen. The liver regeneration model was produced in Sprague–Dawley rats through 70% partial hepatectomy. ResultsCompared with non–lactulose-treated group, lactulose administration remarkably increased the weights of remnant liver and inhibited increases in serum levels of transaminases more notably. In the lactulose-treated group, increases of markers for regeneration, such as proliferating cell nuclear antigen and cyclin D1, were highly elevated. Biochemically, lactulose administration increased liver superoxide dismutase activity and decreased malondialdehyde content. In the lactulose-treated group, excessive increases in inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, were inhibited significantly. Increased heme oxygenase-1 and superoxide dismutase 2 expression were also observed after lactulose treatment. The antibiotics suppressed the regeneration-promoting effect of lactulose by reducing hydrogen production, whereas supplementing hydrogen by hydrogen-rich saline would get a similar regeneration-promoting effect as lactulose administration. ConclusionsLactulose administration accelerates posthepatectomized liver regeneration in rats by inducing hydrogen, which may result from attenuation of the oxidative stress response and excessive inflammatory response.

Lactulose ameliorates cerebral ischemia–reperfusion injury in ratsby inducing hydrogen by activating Nrf2 expression

Molecular hydrogen has been proven effective in ameliorating cerebral ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen species. Lactulose can produce a considerable amount of hydrogen through fermentation by the bacteria in the gastrointestinal tract. To determine the neuroprotective effects of lactulose against cerebral I/R injury in rats and explore the probable mechanisms, we carried out this study. The stroke model was produced in Sprague–Dawley rats through middle cerebral artery occlusion. Intragastric administration of lactulose substantially increased breath hydrogen concentration. Behavioral and histopathological verifications matched biochemical findings. Behaviorally, rats in the lactulose administration group won higher neurological scores and showed shorter escape latency time in the Morris test. Morphologically, 2,3,5-triphenyltetrazolium chloride showed smaller infarction volume; Nissl staining manifested relatively clear and intact neurons and TUNEL staining showed fewer apoptotic neurons. Biochemically, lactulose decreased brain malondialdehyde content, caspase-3 activity, and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine concentration and increased superoxide dismutase activity. The effects of lactulose were superior to those of edaravone. Lactulose orally administered activated the expression of NF-E2-related factor 2 (Nrf2) in the brain as verified by RT-PCR and Western blot. The antibiotics suppressed the neuroprotective effects of lactulose by reducing hydrogen production. Our study for the first time demonstrates a novel therapeutic effect of lactulose on cerebral ischemia/reperfusion injury and the probable underlying mechanisms. Lactulose intragastrically administered possessed neuroprotective effects on cerebral I/R injury in rats, which could be attributed to hydrogen production by the fermentation of lactulose through intestinal bacteria and Nrf2 activation.

Rise in Hydrogen Production During Lactulose Breath Test Does Not Represent Oro-Cecal Transit Due to Lag in Peak Fermentation

Purpose: Small bowel bacteria plays a role in the pathophysiology of irritable bowel syndrome (IBS) recently proven by small bowel culture. However, questions remain about the role of breath testing in IBS. A recent study suggested that hydrogen production reflects oro-cecal transit time rather than bacterial overgrowth based on 5% arrival of lactulose/technetium in the cecum in IBS (Yu et. al., 2011). The study's conclusions are misleading due to 2 unknowns: 1) time to reach peak H2 production and 2) whether 5% of lactulose is sufficient to produce fermentation. We evaluated the first issue by measuring hydrogen production after combining lactulose with fresh stool. Methods: Healthy subjects were recruited based on no complaints of bloating, gas, diarrhea, abdominal pain or constipation. Exclusion criteria were abdominal surgery other than cholecystectomy or appendectomy, use of antibiotics or prokinetic/antikinetic agents within 30 days, or if a single breath test had ≥3ppm of methane. Stool samples were processed within two hours of passage. Every 20g of stool was mixed with 30mL of PBS. Preliminary study showed 2.5g of stool was ideal for hydrogen detection. Thus, 2.5g of stool was placed in five separate flasks with vented stoppers and incubated at 37C while 0g, 0.5g, 2.5g, 5g or 10g of lactulose was added to each. Twenty cc of gas was withdrawn from each flask at intervals up to 90 minutes and analyzed by gas chromatograph for hydrogen and methane. Results: Seven subjects provided stool samples (3 female, 4 male, mean age=31 years). The amount of hydrogen produced was greatest with 0.5g of added lactulose. This happens to represent the expected quantity of lactulose arrival to the colon in Yu et al. Using 0.5g, peak hydrogen production occurred at 60 minutes in all cases with median peak hydrogen level of 210ppm. Although all subjects were breath methane negative, five had increasing methane in their stool. In 4 of the 5, the peak methane production (median=15ppm) occurred at 60 minutes. Thus, even low methane production did not inhibit the production and detection of hydrogen in this experiment. Conclusion: The arrival of 0.5g of lactulose to the colon would produce hydrogen. However, after mixing with colon flora, maximum hydrogen production does not occur until 60 minutes later. Given this large time lag, the time to rise in H2 does not indirectly measure oro-cecal transit. In fact, breath H2 production at a given moment appears to reflect lactulose fermentation by bacteria that started up to 60 minutes earlier (i.e in small intestine).

In vitro fermentation of carbohydrates by porcine faecal inocula and their influence on Salmonella Typhimurium growth in batch culture systems

The aim of this study was to evaluate in vitro the influence of fermentable carbohydrates on the activity of porcine microbiota and survival of Salmonella Typhimurium in a batch culture system simulating the porcine hindgut. The carbohydrates tested were xylooligosaccharides, a mixture of fructooligosaccharides/inulin (FIN), fructooligosaccharides (FOS), gentiooligosaccharides (GEO) and lactulose (LAC). These ingredients stimulated the growth of selected Bifidobacterium and Lactobacillus species in pure cultures. In batch cultures, the carbohydrates influenced some fermentation parameters. For example, GEO and FIN significantly increased lactic acids compared with the control (no added carbohydrate). With the exception of LAC, the test carbohydrates increased the production of short-chain fatty acid (SCFA) and modified SCFA profiles. Quantitative analysis of bacterial populations by FISH revealed increased counts of the Bifidobacterium group compared with control and, with exception of FOS, increased Lactobacillus, Leuconostoc and Weissella spp. counts. Salmonella numbers were the lowest during the fermentation of LAC. This work has looked at carbohydrate metabolism by porcine microbiota in a pH-controlled batch fermentation system. It provides an initial model to analyse interactions with pathogens.

Effects of therapeutic doses of lactulose vs. polyethylene glycol on isotopic colonic transit

Lactulose and polyethylene glycol are osmotic agents used to treat idiopathic chronic constipation. To compare the effects of low doses of lactulose and PEG 4000 on transit time measured by scintigraphy in normal subjects. For 5 days, 10 healthy subjects received either 10 g b.d. of lactulose or PEG 4000 in a randomized, double-blind, crossover study. On the evening of day 4, they took a capsule containing Amberlite resin pellets labelled with (111)In. On day 5, after a 1000 kcal test meal labelled with 99 Tcm, gastric, small bowel and colonic transits were measured. Gastric emptying and small bowel transit time were not different. Ascending colon emptying curve was significantly accelerated with lactulose in comparison with polyethylene glycol (P = 0.001) and, respectively, 50 +/- 18% vs. 35 +/- 18% of the radioactivity had left the ascending colon at the end of the study (P < 0.05). The descending colon filling curves, variations in the geometric centre and numbers of scintigraphic movements were not different. In healthy subjects, in comparison to PEG 4000, usual therapeutic doses of lactulose significantly accelerate ascending colon emptying. This result supports a stimulating motor effect of colonic fermentation of lactulose.

Solid‐phase microextraction method for carbon isotopic analysis of volatile carboxylic acids in human plasma by gas chromatography/combustion/isotope ratio mass spectrometry

A new analytical method is described for the determination of the physiological concentration and low-level enrichment of (13)C-short-chain volatile organic acids (SCVAs) (e.g. (13)C-acetate and (13)C-butyrate) in human plasma. This two-step method involves solid-phase microextraction (SPME) coupled to gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) without any organic solvents or derivatizing agents. Two SCVA extraction methods were compared using a carboxen/polydimethylsiloxane fiber: headspace sampling (HS) and liquid sampling (LS) SPME. The influences of extraction temperature and time were tested to optimize the adsorption of SCVAs onto the fiber. The comparison of the peak area responses of the acids in the two adsorption methods showed better sensitivity in the human physiological concentration range in the LS mode than in the HS mode. The accuracy of isotopic enrichment measurement was determined using plasma spiked with (13)C-acetate and (13)C-butyrate solution from 0 to 1 mol percent excess (MPE). The linearity and repeatability (RSD < 5%) were measured in LS mode. Plasma SCVA concentrations were also determined relative to 3-methylvalerate (internal standard). Linearity and repeatability were observed from 0 to 400 microM for acetate, from 0 to 20 microM for propionate, and from 0 to 10 microM for butyrate. This method was also used to determine plasma acetate production obtained from lactulose (an undigestible disaccharide) fermentation in one healthy volunteer over 3 h. The acetate concentration increased twofold, 2 h after oral lactulose intake. These results are in agreement with the data obtained by GC/MS in healthy volunteers and obese adults following a lactulose intake by using higher amounts of labelled tracers.SPME coupled with GC/C/IRMS can be used to analyze (13)C-SCVAs at low enrichment (<0.5 MPE) within the physiological concentration measured in human plasma.

Comparison of Inulin and Lactulose as Reference Standards in the Breath Hydrogen Test Assessment of Carbohydrate Malabsorption in Patients with Chronic Pancreatic Exocrine Insufficiency

Although often used as a reference standard in the breath hydrogen test (BHT), lactulose fermentation produces more hydrogen, compared to starch, and may therefore not be ideal. This study compares inulin with lactulose as reference standard in the study of carbohydrate malabsorption. Seventeen patients with malabsorption due to chronic pancreatitis and 15 normal controls were studied. Following overnight fasts, BHTs were performed after ingesting 10 g lactulose, 10 g inulin, and 200 g (16 g highly resistant starch) maize meal. Lactulose fermentation produced significantly more hydrogen than inulin in patients with malabsorption (97 +/- 20 vs 45 +/- 22 ppm x hr; P < 0.05) and controls (43 +/- 18 vs 21 +/- 10 ppm x hr; P < 0.05). Patients produced more hydrogen than controls with both standards (lactulose, 97 +/- 20 vs 43 +/- 18 ppm x hr, P < 0.05; inulin 45 +/- 22 vs 21 +/- 10 ppm x hrs; P < 0.05), suggesting adaptation of the colonic flora. Calculated CHO malabsorption was 2.5 +/- 0.8 vs 5.2 +/- 3.8 g with lactulose and 5.2 +/- 3.1 vs 11.2 +/- 9.6 g with inulin as standards in controls and patients, respectively (P < 0.05). Lactulose produces more breath hydrogen than inulin. Calculation of CHO malabsorption using these standards is therefore not comparable.

The Effect of Lactulose on the Composition of the Intestinal Microbiota and Short-chain Fatty Acid Production in Human Volunteers and a Computer-controlled Model of the Proximal Large Intestine

The objective of this study was to compare the in vivo effect of lactulose on faecal parameters with the effect in a dynamic, computer-controlled in vitro model of the proximal large intestine (TIM-2). Faecal samples from 10 human volunteers collected before (non-adapted) and after 1 week of treatment (10 g/day) with lactulose (lactulose-adapted) were investigated. Parameters were compared immediately in the faecal samples, and after incubation in the in vitro model of the large intestine. After an adaptation period of the faecal microbiota in the in vitro model of the proximal colon, lactulose (10 g/day) was fed to the microbiota over a 48-h period. Samples taken from the model were investigated for microbiota composition and metabolite production (short-chain fatty acids (SCFAs) and lactate). No changes in the faecal parameters pH, dry weight or SCFA ratio were observed in the in vivo samples. However, the results show a major change in the ratio of SCFAs produced in the in vitro model, with a drastic reduction of butyrate production on lactulose. This was clear in the non-adapted microbiota by the observed arrest in butyrate production 24 h after the start of lactulose feeding. However, in the adapted microbiota butyrate production was already low from the start of the experiment. In fact, only the microbiota of one of the 10 individuals still produced significant amounts of butyrate after lactulose adaptation, the concentration in the other samples was extremely low. Similarly, in the in vitro model lactate production of the non-adapted microbiota started after approximately 24 h, whereas the adapted microbiota produced lactate from the start. In faecal (in vivo) samples no changes in microbiota composition were obvious, except for a significant increase in Bifidobacterium counts after lactulose feeding. With classic plating techniques, the in vitro samples showed an increase in Lactobacillus and Enterococcus species. With denaturing gradient gel electrophoresis, a clear change in banding pattern was observed, indicating a shift in microbiota composition. When the major bands that appeared after lactulose feeding in the in vitro model were excised and sequenced, the sequences showed homology to Lactobacillus and Enterococcus species. This is in agreement with the classic plating technique as well as with the observed increase in lactate production. Sampling in vivo at ‘the site where it all happens’ (the proximal colon) is difficult and inconvenient. We conclude that the in vitro model for the proximal colon reflects much better the fermentation of lactulose, in both metabolite production and changes in microbiota composition, than do faecal samples from an in vivo experiment. Therefore, the in vitro model is an excellent tool with which to study bioconversion of functional food components and/or drugs.

Abdominal distension after colonic lactulose fermentation recorded by a new extensometer.

Colonic lactulose fermentation induces bloating, but whether it also causes abdominal distension is not known. The aim of this study was to assess the effect of colonic lactulose fermentation on abdominal girth using a new extensometer. We recorded abdominal girth in 24 healthy subjects by means of an extensometer that measures the phase shift of an ultrasound wave propagating in a tube encircling the abdomen. The recordings were continuously made for 3 h after the ingestion of 100 mL of tap water with (16 subjects) or without (eight subjects) 10 g of lactulose. Every 10 min, H2 in the breath was analysed and the intensity of bloating was recorded. Bloating was never reported after water ingestion, whereas it was reported by 10 subjects after lactulose ingestion (P = 0.002). The mean +/- SD changes in abdominal girth in comparison with resting conditions were statistically significant after lactulose ingestion (3 +/- 2.9 mm; P = 0.002) but not after water ingestion (-0.2 +/- 2.7 mm; P = 0.82). The area under the curve of the changes in abdominal girth after lactulose were significantly greater than after water ingestion (P = 0.03). In conclusion, colonic lactulose fermentation induces bloating and abdominal distension. The new extensometer is useful for continuously recording changes in abdominal girth.

The fermentation of lactulose in rats inoculated with Clostridium paraputrificum influences the activities of liver and intestinal xenobiotic‐metabolising enzymes

AbstractOne of the most recent hypotheses concerning the protective effect of some dietary fibres against colon cancer implicates butyrate. Very few publications have addressed its possible influence on the phase II enzymes and on the bacterial enzymes involved in the enterohepatic recirculation of toxic compounds. We used an original model of monoxenic rats oriented towards the preferential production of butyrate. Fischer male germ‐free rats were mono‐associated with a strain of Clostridium paraputrificum. They were fed either a control diet or a lactulose‐enriched diet for 6 weeks. In the caeco‐colon the specific activities (SAs) of the microsomal enzymes (glutathione‐S‐transferase and UDP‐glucuronosyl‐transferase) were 1.7‐fold those of the control rats. In the intestine and liver the SAs of the phase II enzymes were not altered, nor was the hepatic cytochrome P450. In the caecum of the lactulose‐fed rats the SA of β‐glucuronidase decreased by 27% and that of β‐glucosidase doubled. The chronic consumption of lactulose doubled the total caecal short‐chain fatty acids, and the production of butyrate was enhanced. Since the germ‐free rats behaved differently when fed the same diets, we concluded that the fermentation products of lactulose (and not the lactulose itself) were involved in the effects we describe. The involvement of butyrate in this phenomenon is discussed.© 2001 Society of Chemical Industry

Continuous recording of abdominal girth by a new ultrasound bell before and after colonic lactulose fermentation

Continuous recording of abdominal girth by a new ultrasound bell before and after colonic lactulose fermentation

Continuous recording of abdominal girth by a new ultrasound bell before and after colonic lactulose fermentation

Continuous recording of abdominal girth by a new ultrasound bell before and after colonic lactulose fermentation