Resolution of common dietary sugars from probe sugars for test of intestinal permeability using capillary column gas chromatography

BACKGROUND: The most widely accepted method for the evaluation of intestinal barrier integrity is the measurement of the permeation of sugar probes following an oral test dose of sugars. The most-widely used sugar probes are sucrose, lactulose, mannitol and sucralose. Measuring these sugars using a sensitive gas chromatographic (GC) method, we noticed interference on the area of the lactulose and mannitol peaks. METHODS: We tested different sugars to detect the possible makeup of these interferences and finally detected that the lactose interferes with lactulose peak and fructose interferes with mannitol peak. On further developing of our method, we were able to reasonably separate these peaks using different columns and condition for our assay. Sample preparation was rapid and simple and included adding internal standard sugars, derivitization and silylation. We used two chromatographic methods. In the first method we used Megabore column and had a run time of 34 min. This resulted in partial separation of the peaks. In the second method we used thin capillary column and was able to reasonably separate the lactose and lactulose peaks and the mannitol and fructose peaks with run time of 22 min. RESULTS: The sugar probes including mannitol, sucrose, lactulose, sucralose, fructose and lactose were detected precisely, without interference. The assay was linear between lactulose concentrations of 0.5 and 40 g/L (r(2)=1.000, P<0.0001) and mannitol concentrations of 0.01 and 40 g/L (r(2)=1.000). The sensitivity of this method remained high using new column and assay condition. The minimum detectable concentration calculated for both methods was 0.5 mg/L for lactulose and 1 mg/L for mannitol. CONCLUSION: This is the first report of interference of commonly used sugars with test of intestinal permeability. These sugars are found in most of fruits and dairy products and could easily interfere with the result of permeability tests. Our new GC assay of urine sugar probes permits the simultaneous quantitation of sucralose, sucrose, mannitol and lactulose, without interference with lactose and fructose. This assay is a rapid, simple, sensitive and reproducible method to accurately measure intestinal permeability.     

Increased lactulose/rhamnose ratio during fluid load is caused by increased urinary lactulose excretion

Noninvasive assessment of intestinal permeability in vivo is based on the measurement of urinary excretion of orally administered sugar probes. It is expressed as a ratio, usually lactulose/rhamnose or 3-O-methyl-D-glucose (3-OMG)/rhamnose. In both endotoxemic and control rats that were receiving fluid, we observed an increase in the recovery of lactulose and 3-OMG but not rhamnose in both groups, suggesting an enhancement of intestinal permeability. In the measurement of intestinal permeability, all pre- and postmucosal factors are considered equal for all sugars. We hypothesized that postmucosal factors and not changes in intestinal permeability caused the increased urinary lactulose and 3-OMG recoveries observed during fluid loading. Therefore, the effects of fluid loading on urinary excretion of the sugar probes were studied in healthy rats receiving the sugars intravenously. After intravenous injection, fluid loading increased urinary lactulose recovery threefold but not that of 3-OMG and rhamnose. In conclusion, fluid loading increases the lactulose/rhamnose ratio independent of changes in intestinal permeability. The 3-OMG/rhamnose ratio is not influenced by fluid loading.     

Intestinal permeability to lactulose and mannitol in growing rats with iron-deficiency anemia

Iron deficiency can have nonhematological manifestations, some of which may affect the gastrointestinal tract. The aim of this study was to determine if iron-deficiency anemia in growing rats affected small-bowel permeability as assessed by the urinary ratio of lactulose and mannitol. Thirty-seven male Harlan Sprague-Dawley rats (21 d of age) were randomly divided into two groups and fed either an iron-deficient (n=19) or an iron-sufficient diet (n=18) that contained either 13.5 or 43.8 mg of iron/kg diet, respectively. Animals were evaluated between 25 and 38 d of dietary treatment. Intestinal permeability was assessed by measuring the lactulose/mannitol urinary ratio following administration of a solution that contained the two sugars. At the end of the study, the mean body weight of rats fed the low-iron diet was approx 95% that of the controls. The mean hemoglobin (g/dL) was significantly lower in the low-iron diet group (11.2±1.4) than in the control group (16.9±0.8) (p=0.001). The liver iron concentration (μg/g) of the anemic group (41.4±4.7) was also statistically (p=0.001) lower than in the control group (116.6±18.2). The lactulose/mannitol ratio was lower in the anemic rats (2.0±0.7) than in the control group (2.6±0.7) (p=0.008), a finding that is not suggestive of intestinal mucosal atrophy, previously described in anemic children.     

Consumption of sugars by Anastrepha suspensa (Diptera: Tephritidae)

We were interested in determining the feeding response of the Caribbean fruit fly, Anastrepha suspensa Loew (Diptera: Tephritidae), to various sugar concentrations to develop an improved bait for adults. We compared the consumption of 0.01-1.00 M concentrations of glucose, fructose, raffinose, and sucrose in no-choice tests for 24-h- and 6-d-old male and female flies. Sucrose was the most consumed sugar or within the most consumed group of sugars at 0.02-0.20 M concentrations. There were no differences in consumption among sugars at 0.01, 0.40, and 1.00 M. Consumption generally increased with increasing sugar concentration except that sucrose consumption peaked at 0.20 M. Twenty-four-hour females consumed less fructose than other sugars; 24-h males consumed more sucrose than fructose or raffinose, with an intermediate response to glucose. Females in the 6-d group consumed more sucrose than the other three sugars, whereas 6-d males exhibited no difference in consumption among sugars. In choice tests, flies consumed more sugar solution than water, but the difference between 0.20 M fructose and water was not significant for 24-h males or 24-h females. In choice tests between 0.20 M fructose and 0.20 M sucrose, both 24-h and 6-d females showed a preference for fructose. Males of both age classes showed no preference. These results indicate that the responses of flies to different sugars can vary by sugar, gender, and age.     

Intestinal permeability is associated with visceral adiposity in healthy women

Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.     

A comparison of intestinal permeability between humans and three common laboratory animals

Intestinal permeability of humans and three species of experimental animals was assessed by the oral administration of the three non-metabolizable sugars: lactulose, rhamnose and mannitol and collecting all the urine produced in a specified time. The total percentage recovery of the permeability markers was determined by high performance liquid chromatographic assays of urinary aliquots. The permeability of the human gut to mannitol was substantially greater than that of rats, guinea pigs, or hamsters (18-, 6- and 29-fold increases, respectively). The permeability to lactulose in humans was somewhat less than that found in guinea pigs (P less than 0.05), but three times greater than that found in rats or hamsters (P less than 0.001). Human rhamnose permeability was substantially greater than that of rats, guinea pigs or hamsters (6-, 2.5-, and 7-fold increases, respectively). The results suggest that the permeability of the human gut to probe molecules is considerably different from that of three common laboratory rodents, but is closest to that of guinea pigs. Possible species differences in the physiological factors which control permeability are discussed.     

Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls

Mucosal barrier dysfunction contributes to gastrointestinal diseases. Our aims were to validate urine sugar excretion as an in vivo test of small bowel (SB) and colonic permeability and to compare permeability in patients with irritable bowel syndrome-diarrhea (IBS-D) to positive and negative controls. Oral lactulose (L) and mannitol (M) were administered with (99m)Tc-oral solution, (111)In-oral delayed-release capsule, or directly into the ascending colon (only in healthy controls). We compared L and M excretion in urine collections at specific times in 12 patients with IBS-D, 12 healthy controls, and 10 patients with inactive or treated ulcerative or microscopic colitis (UC/MC). Sugars were measured by high-performance liquid chromatography-tandem mass spectrometry. Primary endpoints were cumulative 0-2-h, 2-8-h, and 8-24-h urinary sugars. Radioisotopes in the colon at 2 h and 8 h were measured by scintigraphy. Kruskal-Wallis and Wilcoxon tests were used to assess the overall and pairwise associations, respectively, between group and urinary sugars. The liquid in the colon at 2 h and 8 h was as follows: health, 62 ± 9% and 89 ± 3%; IBS-D, 56 ± 11% and 90 ± 3%; and UC/MC, 35 ± 8% and 78 ± 6%, respectively. Liquid formulation was associated with higher M excretion compared with capsule formulation at 0-2 h (health P = 0.049; IBS-D P < 0.001) but not during 8-24 h. UC/MC was associated with increased urine L and M excretion compared with health (but not to IBS-D) at 8-24 h, not at 0-2 h. There were significant differences between IBS-D and health in urine M excretion at 0-2 h and 2-8 h and L excretion at 8-24 h. Urine sugars at 0-2 h and 8-24 h reflect SB and colonic permeability, respectively. IBS-D is associated with increased SB and colonic mucosal permeability.     

Gas chromatography applied to the lactulose—mannitol intestinal permeability test

Intestinal permeability can be modified by various illnesses, trauma and sepsis. Alterations of the intestinal wall can facilitate the diffusion of potentially harmful substances such as endotoxins, as well as bacterial translocation. We describe the validation of a capillary gas chromatographic method for the determination of mannitol and lactulose, used as intestinal permeability probes. The method is linear up to 3 g/l for mannitol and 300 mg/l for lactulose; recovery from overload samples is between 92 to 110%. Intra-assay coefficients of variation (C.V.s) were 2.7 and 6.8% for mannitol and lactulose, respectively, and inter-assay C.V.s were 8.9 and 9.3%. Normal values for 25 healthy subjects (mean ± S.D.) were 14.5 ± 3.1% and 0.27 ± 0.15% for mannitol and lactulose, respectively. The GC method presented is rapid and precise.     

Novel analytical approach to a multi-sugar whole gut permeability assay

Many pathophysiological conditions are associated with increased gastrointestinal permeability, reflecting an elevated risk of endotoxaemia, inflammation, and sepsis. Permeability tests are increasingly used in clinical practice to obtain information on gastrointestinal functioning, but tests are often restricted to the small intestine, and require large oral sugar doses. Therefore, a novel multi-sugar assay was developed, allowing assessment of whole gut permeability changes in urinary and plasma samples collected at regular intervals from 10 healthy volunteers at baseline and after intake of monosaccharides (rhamnose and erythritol) and disaccharides (sucrose, lactulose, and sucralose). Samples were analyzed by isocratic cation-exchange LC-MS. Sample preparation and detection conditions were optimized. After centrifugation, chromatographic separation was achieved on an IOA-1000 column set at 30°C. Column effluent was mixed with ammonia for sugar-ammonium adduct formation. The lower limit of detection was 0.05 μmol/L for disaccharides and 0.1 μmol/L for monosaccharides. Linearity for each probe was between 1 and 1000 μmol/L (R(2): 0.9987-0.9999). Coefficients of variation were <5% in urine, and <9% in plasma. Recovery data were within the 90% to 110% range at all spiked concentrations. This highly sensitive novel LC-MS approach resulted in a significant decrease of the detection limit for all sugar probes, allowing a 5-fold reduction of the commonly used lactulose dose and the addition of sugar probes to also assess the gastroduodenal and colon permeability. In combination with its extended application in plasma, these features make the novel assay a promising tool in the assessment of site-specific changes in gastrointestinal permeability in clinical practice.     

高压液色谱用于肠通透性的测定

目的 建立一种测定肠通透性的可靠方法。方法 以甘露醇和乳果糖为探测剂,用带脉冲电化学检测器的高压液相色谱仪对２０例健康成人样品中的甘露醇和乳果糖进行检测。结果 ２０个样品中的甘露醇和乳果糖均被检测到,其最低质量浓度分别为０．２０２８ｍｇ／Ｌ和０．１９３０ｍｇ／Ｌ,回收率分别为９８．２％和１０４．３％。结论 用带脉冲电化学检测器的高压液相色谱仪测定尿中的甘露醇和乳果糖是一种灵敏度高,特异性强,操作简     

Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice

Most mammals prefer the sweet taste of sugars, which is mediated by the heterodimeric T1R2+T1R3 taste receptor. Sugar appetite is also enhanced by the post-oral reinforcing actions of the nutrient in the gut. Here, we examined the contribution of gut T1R3 (either alone or as part of the T1R3+T1R3 receptor) to post-oral sugar reinforcement using a flavor-conditioning paradigm. We trained mice to associate consumption of a flavored solution (CS+) with intragastric (IG) infusions of a sweetener, and a different flavored solution (CS-) with IG infusions of water (23 h/day); then, we measured preference in a CS+ vs. CS- choice test. In experiment 1, we predicted that if activation of gut T1R3 mediates sugar reinforcement, then IG infusions of a nutritive (sucrose) or nonnutritive (sucralose) ligand for this receptor should condition a preference for the CS+ in B6 wild-type (WT) mice. While the mice that received IG sucrose infusions developed a strong preference for the CS+, those that received IG sucralose infusions developed a weak avoidance of the CS+. In experiment 2, we used T1R3 knockout (KO) mice to examine the necessity of gut T1R2+T1R3 receptors for conditioned flavor preferences. If intact gut T1R3 (or T1R2+T1R3) receptors are necessary for flavor-sugar conditioning, then T1R3 KO mice should not develop a sugar-conditioned flavor preference. We found that T1R3 KO mice, like WT mice, acquired a strong preference for the CS+ paired with IG sucrose infusions. The KO mice were also like WT mice in avoiding a CS+ flavor paired with IG sucralose infusions These findings provide clear evidence that gut T1R3 receptors are not necessary for sugar-conditioned flavor preferences or sucralose-induced flavor avoidance in mice.     

双歧杆菌四联活菌片联合乳果糖对乙肝肝硬化患者肠道菌群 和肠黏膜屏障功能及肝功能水平的影响

目的研究双歧杆菌四联活菌片联合乳果糖对乙肝肝硬化患者肠道菌群、肠黏膜屏障功能及肝功能水平的影响。方法选择2017年12月至2018年12月于我院感染科住院治疗的乙肝肝硬化患者80例,按照随机数字表法分为试验组和对照组各40例。两组患者常规予以抗病毒及保肝治疗。试验组患者加用双歧杆菌四联活菌片和乳果糖口服液。对照组患者仅给予乳果糖口服液。检测患者肠道肠杆菌、肠球菌、双歧杆菌、乳杆菌和白假丝酵母数量。测定患者血清内毒素和血清二胺氧化酶水平及尿乳果糖/甘露醇(L/M)比值。记录两组患者丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)和总胆红素(TBIL)水平。观察治疗过程中的药物不良反应发生情况。结果治疗4周后,试验组患者肠道肠球菌数量高于治疗1周后(18.41±2.92 vs 18.32±3.06),同时试验组患者肠道双歧杆菌数量与治疗前、治疗1周后以及对照组同时期相比差异也有统计学意义(均P0.05)。试验组患者治疗后肠道乳杆菌和白假丝酵母水平与治疗前相比差异均有统计学意义(均P0.05)。治疗4周后,对照组患者肠道肠杆菌水平高于治疗1周后(F=10.192,P=0.019);而白假丝酵母水平高于治疗前(F=8.567,P=0.024)。治疗前两组患者血清内毒素、血清二胺氧化酶和尿L/M以及AST、ALT、TBIL水平差异无统计学意义(均P0.05)。治疗1个月后,两组患者血清内毒素、血清二胺氧化酶和尿L/M以及AST、ALT、TBIL均较治疗前明显下降(均P0.05),且试验组的下降幅度较对照组更大(均P0.05)。两组患者均未发生不良反应。结论双歧杆菌四联活菌片联合乳果糖可以改善乙肝肝硬化患者肝功能状态,调节失衡的肠道菌群,降低肠黏膜通透性,值得临床推广。     

Lactulose and mannitol intestinal permeability detected by capillary electrophoresis

Aim of this study was to set up a method by capillary electrophoresis to detect lactulose and mannitol in urine after an oral load, and to estimate the intestinal permeability in controls and in type I diabetes patients. The underivatized carbohydrates were monitored by indirect UV detection using sorbate, cetyltrimethylammonium bromide and LiOH as background electrolyte. Urines were purified by solid phase extraction, shaken with cation exchange resin, filtered and analysed. Carbohydrates migrated in <10 min in relation to their pK(a) and M(r). Controls (n = 33) and patients (n = 23) had an excretion ratio lactulose/mannitol 0.025 (0.018-0.051) and 0.067 (0.050-0.127), respectively (p < 0.01, median, interquartile range).     

Studies on intestinal permeability of cirrhotic patients by analysis lactulose and mannitol in urine with HPLC/RID/MS

The method for separation and determination of lactulose (L) and mannitol (M) in urine was developed by HPLC with a refractive index detector (RID). The linearity ranged from 5 to 1000 microg/mL for L and M, respectively. Recoveries ranged from 93.1% to 97.1%. The intra- and inter-day relative standard deviations of peak area were between 0.8-1.4% (n=3) and 1.4-3.6% (n=3). The limits of detection were obtained with 1.40 microg/mL for L and 1.65 microg/mL for M. The ratios of L/M in the urine samples for the spontaneous ascitic fluid infection (SAI), sterile ascitic fluid (SA) patients, and healthy volunteers (HV) were determined. The results showed well the correlations among the L/M ratio, intestinal permeability (IP) and the illness status of patients, and also indicated lactulose could improve the IP of SAI patients. The peaks of L and M in chromatograms were identified by electrospray ionization/mass spectrometry (ESI/MS), which ensured the accurate measurement of the ratio L/M. This method presented a rapid, accurate, and practical technique for determining IP in clinical practice and investigating the pathology of hepatocirrhosis.     

Neutrophil depletion prevents intestinal mucosal permeability alterations in burn-injured rats

Cutaneous thermal injury increases intestinal mucosal permeability. The mechanisms of this functional disturbance are not fully understood. We investigated whether accumulation of neutrophils in the intestine contributes to the increase in mucosal permeability. Labeled and unlabeled lactulose and mannitol were infused into a segment of rat ileum or jejunum. Blood concentrations of [(3)H]lactulose and [(14)C]mannitol were measured after 30, 60, and 90 min. On day 1 postburn, lactulose permeability increased fourfold in the ileum and twofold in the jejunum compared with sham-burned rats; mannitol permeability increased twofold in the ileum and 1. 5-fold in the jejunum. A greater increase in permeability occurred on day 3 postburn in the ileum, but not in the jejunum. The depletion of neutrophils in burned rats prevented the increase in permeability in both segments on day 1 postburn. Histological studies of intestines from burned, with or without neutrophil depletion, and sham-burned rats showed similar morphology. However, numerous neutrophils were found in the extravascular compartment in day 1 postburn, but not in neutrophil-depleted and sham-burned rats. These findings support the concept that the burn-induced increase in mucosal permeability is produced during the accumulation of neutrophils in the intestine and can be abrogated by the depletion of neutrophils.     

谷氨酰胺对脓毒症患者肠粘膜屏障功能和免疫功能的影响

目的:研究谷氨酰胺对脓毒症患者肠道黏膜屏障功能和免疫功能的影响。方法:将2012年10月至2013年10本院收治的40例脓毒症患者随机分为治疗组和对照组,每组20例。两组患者均给予常规对症治疗,治疗组在此基础上加用谷氨酰胺治疗,对照组接受安慰剂治疗。采用分光光度法监测其血清D-乳酸水平,高效液相色谱法监测尿乳果糖/甘露醇(L/M)值。对比两组肠道黏膜屏障功能和免疫功能指标及ARDS、MODS发生率。结果:治疗后,治疗组ARDS和MODS发生率分别为24.1%,17.2%,均低于对照组的38.9%,33.3%,两组比较差异均有统计学意义(P0.05);治疗14 d后,治疗组D-乳酸及尿L/M水平较对照组明显降低,血清Ig G、Ig M、CD4+和CD4+/CD8+水平均增高,两组比较差异均有统计学意义(P0.05)。结论:谷氨酰胺治疗脓毒性患能明显改善肠道黏膜屏障功能,促进患者免疫功能和营养状态的提高,同时还能够降低患者肠道细菌、内毒素移位。     

Assessment of the Effect of Intestinal Permeability Probes (Lactulose And Mannitol) and Other Liquids on Digesta Residence Times in Various Segments of the Gut Determined by Wireless Motility Capsule: A Randomised Controlled Trial

Background

Whilst the use of the mannitol/lactulose test for intestinal permeability has been long established it is not known whether the doses of these sugars modify transit time Similarly it is not known whether substances such as aspirin that are known to increase intestinal permeability to lactulose and mannitol and those such as ascorbic acid which are stated to be beneficial to gastrointestinal health also influence intestinal transit time.

Methods

Gastric and intestinal transit times were determined with a SmartPill following consumption of either a lactulose mannitol solution, a solution containing 600 mg aspirin, a solution containing 500 mg of ascorbic acid or an extract of blackcurrant, and compared by doubly repeated measures ANOVA with those following consumption of the same volume of a control in a cross-over study in six healthy female volunteers. The dominant frequencies of cyclic variations in gastric pressure recorded by the Smartpill were determined by fast Fourier transforms.

Results

The gastric transit times of lactulose mannitol solutions, of aspirin solutions and of blackcurrant juice did not differ from those of the control. The gastric transit times of the ascorbic acid solutions were significantly shorter than those of the other solutions. There were no significant differences between the various solutions either in the total small intestinal or colonic transit times. The intraluminal pHs during the initial quartiles of the small intestinal transit times were lower than those in the succeeding quartiles. This pattern did not vary with the solution that was consumed. The power of the frequencies of cyclic variation in intragastric pressure recorded by the Smartpill declined exponentially with increase in frequency and did not peak at the reported physiological frequencies of gastric contractile activity.

Conclusions

Whilst the segmental residence times were broadly similar to those using other methods, the high degree of variation between subjects generally precluded the identification of all but gross variation between treatments. The lack of any differences between treatments in either total small or large intestinal transit times indicates that the solutions administered in the lactulose mannitol test of permeability had no consistent influence on the temporal pattern of absorption. The negatively exponential profile and lack of any peaks in the frequency spectra of cyclic variation in gastric intraluminal pressure that were consistent with reported physiological frequencies of contractile activity profile suggests that the principal source of this variation is stochastic likely resulting from the effects of external events occasioned by normal daily activities on intra-abdominal pressure.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12615000596505     

Intestinal permeability in children with Crohn's disease and coeliac disease.

Mannitol and lactulose were used as probe molecules to measure intestinal permeability in children with active small-bowel Crohn''s disease and with untreated coeliac disease. Mannitol and lactulose were administered by mouth in a moderately hypertonic solution (580 mmol (mosmol)/l), and results were expressed as the ratio of the molecules excreted in urine over five hours. Patients with Crohn''s disease had a sixfold increase in permeability (due to increased lactulose permeability) and those with coeliac disease a fivefold increase (due to decreased mannitol permeability). From these results the test offers potential as a noninvasive investigation in children with small-bowel disease.     

Catabolite inhibition and sequential metabolism of sugars by Streptococcus lactis.

Growth of galactose-adapted cells of Streptococcus lactis ML(3) in a medium containing a mixture of glucose, galactose, and lactose was characterized initially by the simultaneous metabolism of glucose and lactose. Galactose was not significantly utilized until the latter sugars had been exhausted from the medium. The addition of glucose or lactose to a culture of S. lactis ML(3) growing exponentially on galactose caused immediate inhibition of galactose utilization and an increase in growth rate, concomitant with the preferential metabolism of the added sugar. Under nongrowing conditions, cells of S. lactis ML(3) grown previously on galactose metabolized the three separate sugars equally rapidly. However, cells suspended in buffer containing a mixture of glucose plus galactose or lactose plus galactose again consumed glucose or lactose preferentially. The rate of galactose metabolism was reduced by approximately 95% in the presence of the inhibitory sugar, but the maximum rate of metabolism was resumed upon exhaustion of glucose or lactose from the system. When presented with a mixture of glucose and lactose, the resting cells metabolized both sugars simultaneously. Lactose, glucose, and a non-metabolizable glucose analog (2-deoxy-d-glucose) prevented the phosphoenolpyruvate-dependent uptake of thiomethyl-beta-d-galactopyranoside (TMG), but the accumulation of TMG, like galactose metabolism, commenced immediately upon exhaustion of the metabolizable sugars from the medium. Growth of galactose-adapted cells of the lactose-defective variant S. lactis 7962 in the triple-sugar medium was characterized by the sequential metabolism of glucose, galactose, and lactose. Growth of S. lactis ML(3) and 7962 in the triple-sugar medium occurred without apparent diauxie, and for each strain the patterns of sequential sugar metabolism under growing and nongrowing conditions were identical. Fine control of the activities of preexisting enzyme systems by catabolite inhibition may afford a satisfactory explanation for the observed sequential utilization of sugars by these two organisms.     

空气颗粒物与肠道微生物群及肠道炎症相关性研究进展

颗粒物(particulate matter,PM)是空气污染物中的主要成分,可以通过多种途径进入肠道。研究证实颗粒物进入肠道能够增加肠上皮的通透性,降低肠道免疫屏障功能,也可被代谢为有毒产物进一步引起肠道损伤。颗粒物还能够改变肠道微生物群的组成,目前认为微生物群和机体多个系统的功能密切相关。颗粒物引发的肠道炎症反应影响全身多系统的健康。本文综述了近年来关于空气颗粒物造成的肠道微生物群改变、肠道损伤及其引起的肠道免疫应答反应的研究进展,阐明空气颗粒物进入肠道可能对人体健康产生的影响,为治理空气污染进而改善人群健康提供理论依据。