Effect of interleukin-2 on intestinal P-glycoprotein expression and functionality in mice

P-glycoprotein (Pgp), an active drug transporter expressed in enterocytes, can reduce intestinal absorption of drugs. Until now, interleukin-2 (IL2) has been reported as a Pgp modulator only in vitro. The present study examines the effects in vivo of IL2 after chronic treatment on intestinal Pgp protein expression and activity. This work also describes the effects of IL2 on the oral bioavailability of a Pgp substrate (digoxin) and of a Pgp/CYP3A cosubstrate (saquinavir). Human recombinant interleukin-2 (rIL2), administered to mice at 9 million international units/kg by intraperitoneal route twice daily for 4 days, led to a decrease in intestinal Pgp protein expression evaluated by Western blot with C219 antibody. In an in vitro everted gut sac model, rIL2 pretreatment decreased the Pgp-mediated transport of rhodamine 123 across mouse intestine by 37%. Moreover, rIL2 pretreatment markedly raised the area under the curve of orally administered digoxin from 3.5 +/- 0.5 to 9.7 +/- 1.5 mg min l(-1) as a consequence of the reduction in intestinal Pgp activity. rIL2 treatment increased saquinavir bioavailability from 2.5 to 4.5%, showing that first-pass metabolism is not affected and that Pgp by itself has only a moderate effect on saquinavir oral bioavailability. In conclusion, rIL2 pretreatment reduces intestinal Pgp protein expression and activity in mice. However, the effect of such a treatment on drug bioavailability depends on the extent of their metabolism by CYP3A.     

Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone

BACKGROUND: The disposition of the long-acting opioid methadone, used to prevent opiate withdrawal and treat short- and long-lasting pain, is highly variable. Methadone undergoes N -demethylation to the primary metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium (EDDP), catalyzed in vitro by intestinal, hepatic, and expressed cytochrome P450 (CYP) 3A4. However, the role of CYP3A4 in human methadone disposition in vivo is unclear.This investigation tested the hypothesis that CYP3A induction (or inhibition) would increase (or decrease) methadone metabolism and clearance in humans. METHODS: Healthy volunteers were studied in a randomized, balanced, 4-way crossover study. They received intravenous (IV) midazolam (to assess CYP3A4 activity) and then simultaneous oral deuterium-labeled and IV unlabeled methadone after pretreatment with rifampin (INN, rifampicin) (hepatic/intestinal CYP3A induction), troleandomycin (hepatic/intestinal CYP3A inhibition), grapefruit juice (selective intestinal CYP3A inhibition), or nothing. Methadone effects were measured by dark-adapted pupil diameter. CYP isoforms catalyzing methadone metabolism by human liver microsomes and expressed CYPs in vitro were also evaluated. RESULTS: Methadone had high oral bioavailability (70%) and low intestinal (22%) and hepatic (9%) extraction, and there was a significant correlation ( r = 0.94, P <.001) between oral bioavailability and intestinal (but not hepatic) availability. Rifampin decreased bioavailability and oral and IV methadone plasma concentrations and increased IV clearance (4.42 +/- 1.00 mL. kg -1. min -1 versus 1.61 +/- 0.67 mL. kg -1. min -1, P <.05) and oral clearance (8.50 +/- 3.68 mL. kg -1. min -1 versus 2.05 +/- 0.92 mL. kg -1. min -1, P <.05), EDDP/methadone area under the curve (AUC) ratios, EDDP formation clearances, and hepatic extraction (0.27 +/- 0.06 versus 0.09 +/- 0.04, P <.05). Troleandomycin and grapefruit juice decreased the EDDP/methadone AUC ratio after oral methadone (0.17 +/- 0.10 and 0.14 +/- 0.06 versus 0.27 +/- 0.20, P <.05) but not IV methadone and had no effect on methadone plasma concentrations, IV clearance (1.29 +/- 0.41 mL. kg -1. min -1 and 1.48 +/- 0.55 mL. kg -1. min -1 ) or oral clearance (2.05 +/- 1.52 mL. kg -1. min -1 and 1.89 +/- 1.07 mL. kg -1. min -1 ), or other kinetic parameters. There was no correlation between methadone clearance and hepatic CYP3A4 activity. Pupil diameter changes reflected plasma methadone concentrations. In vitro experiments showed a predominant role for both CYP3A4 and CYP2B6 in liver microsomal methadone N -demethylation. CONCLUSION: First-pass intestinal metabolism is a determinant of methadone bioavailability. Intestinal and hepatic CYP3A activity only slightly affects human methadone N -demethylation but has no significant effect on methadone concentrations, clearance, or clinical effects. Greater rifampin effects, compared with troleandomycin and grapefruit juice, on methadone disposition suggest a major role for intestinal transporters and for other CYPs, such as CYP2B6. Interindividual variability and drug interactions affecting intestinal transporter and hepatic CYP3A and CYP2B6 activity may alter methadone disposition.     

Evidence for both luminal and systemic factors in the control of rat intestinal epithelial replacement.

1. Isolation of a self-emptying sac of rat small intestine in vivo halved the cell production rate in the crypts of Lieberkühn as measured by colchicine blockade. 2. Starvation for 48 h of rats with isolated intestinal sacs caused a further halving of cell production rate in the sac. 3. Infusion of distilled water into isolated intestinal sacs for 72 h caused a similar degree of stimulation of cell production in sacs in fed and starved rats, suggesting that the fall in cell production rate on starving a rat bearing an isolated sac is not due to t-e non-availability of the substances required for cell synthesis. 4. The possible contribution of innervation of the gut, and of systemic hormonal influences, on intestinal epithelial replacement is discussed.     

Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation

Methadone and levo-alpha-acetylmethadol (LAAM) are opioid agonists used for analgesia and preventing opiate withdrawal. Methadone is sequentially N-demethylated to the inactive metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP). LAAM is essentially a prodrug that undergoes bioactivation via sequential N-demethylation to levo-alpha-acetyl-N-normethadol (nor-LAAM) and levo-alpha-acetyl-N,N-dinormethadol (dinor-LAAM). Methadone and LAAM are metabolized by CYP3A4 in human liver. Since they are administered orally, and CYP3A4 is expressed in human intestine, we tested the hypotheses that human intestine can metabolize methadone and LAAM, and evaluated the participation of CYP3A4. Intestinal microsomal methadone N-demethylation exhibited hyperbolic noncooperative kinetics and biphasic Eadie-Hofstee plots. Using a dual-enzyme Michaelis-Menten model, K(m) values were 11 and 1200 microM for EDDP and 23 and 930 microM for EMDP formation, respectively. CYP3A4 inhibitors (troleandomycin and ketoconazole) inhibited EDDP and EMDP formation by >70%. Methadone N-demethylation by CYP3A4 showed biphasic Eadie-Hofstee plots without evidence of positive cooperativity; K(m) values were 10 and 1100 microM for EDDP and 20 and 1000 microM for EMDP formation. Intestinal microsomal LAAM and nor-LAAM N-demethylation also exhibited hyperbolic kinetics and biphasic Eadie-Hofstee plots. K(m) values were 21 and 980 microM for nor-LAAM from LAAM and 18 and 1200 microM for dinor-LAAM from nor-LAAM. Troleandomycin and ketoconazole inhibited N-demethylation by >70%. LAAM and nor-LAAM metabolism by CYP3A4 showed biphasic Eadie-Hofstee plots without evidence of positive cooperativity; K(m) values were 8 and 1300 microM, 6 and 950 microM, respectively. Predicted in vivo intestinal extraction of methadone and LAAM is 21 and 33%, respectively. We conclude that methadone, LAAM, and nor-LAAM are metabolized by human intestinal microsomes; CYP3A4 is the predominant cytochrome P450 isoform; CYP3A4-catalyzed methadone, LAAM, and nor-LAAM metabolism is characterized by noncooperative, multisite kinetics; and intestinal metabolism may contribute to presystemic methadone inactivation and LAAM bioactivation.     

A study of the intestinal absorption of an ester-type prodrug, ME3229, in rats: active efflux transport as a cause of poor bioavailability of the active drug

The intestinal absorption of a prodrug is affected by a number of factors, such as its membrane permeability, stability in the gut lumen, and conversion to the parent drug in enterocytes. We evaluated the absorption of ME3229, an ester-type prodrug of a hydrophilic glycoprotein IIb/IIIa antagonist. Although the octanol/water distribution coefficient and permeability across a Caco-2 cell monolayer of ME3229 was high enough for us to expect good oral absorption, less than 10% of the dose was absorbed in rats. To clarify this unexpected outcome, we evaluated the rate of its disappearance from the gut lumen (V1), its degradation in the gut lumen (V(deg)), uptake into enterocytes (V(uptake)), and appearance in the mesenteric vein (V2) by using a single-pass perfusion technique in combination with an in vitro metabolism study. Our data suggested that ME3229 crossed the apical membrane and was taken up into enterocytes at a rate compatible with its lipophilicity, but that only a small fraction of the metabolites formed in enterocytes reached the mesenteric vein, primarily attributable to efflux into the intestinal lumen. Transport of the main metabolite across rat intestinal tissue mounted on an Ussing chamber suggested that an active efflux system pumped out any ionic metabolite(s) present.     

Effect of bicarbonate feeding on intestinal absorption of calcium and vitamin D metabolism in rats

The effect of bicarbonate (NaHCO3) feeding on intestinal absorption of calcium and phosphorus and vitamin D metabolism was investigated. Gut sac uptake of 45Ca and [32P]phosphate in vitro, as well as the plasma level of vitamin D metabolites, was determined in rats fed with NaHCO3 for 9 days and their pair-fed controls. Duodenal uptake of 45Ca and [32P]phosphate by alkalotic rats was less than duodenal uptake by controls. 1,25(OH)2D plasma level was much higher in alkalotic rats than in their controls, and 25(OH)D slightly higher than in controls. These data suggest that NaHCO3 feeding causes a substantial increase in 1,25(OH)2D plasma level, but interferes with calcium and phosphorus absorption in the duodenum.     

Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines

As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium could also oxidize long-chain fatty acids, and that luminally delivered acylcarnitines in bile could be consumed via apical absorption by the intestinal epithelium, resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium–induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.     

肠缺血/再灌注时卡巴胆碱对肠上皮细胞凋亡的影响

目的研究肠缺血/再灌注(I/R)时卡巴胆碱对肠上皮细胞凋亡的影响及可能机制。方法雄性Wistar大鼠,戊巴比妥钠腹腔麻醉,结扎肠管造成长约8cm肠袋,采用夹闭肠系膜上动脉(SMA)阻断血流45min后恢复血流的方法,制备肠I/R损伤模型。将动物按随机数字表法分为假手术组(n=40)、I/R模型组(n=40)和卡巴胆碱组(n=40)。卡巴胆碱组在阻断血流的同时向肠袋内注射卡巴胆碱(0.1mg/kg),I/R模型组给予等量生理盐水。分别在再灌注0、30、60、120和240min时,采用病理学方法按Chiu's评分观察肠上皮细胞损伤;原位末端缺刻标记法(TUNEL)检测肠上皮细胞凋亡指数的变化;免疫组化法检测肠上皮细胞凋亡相关半胱氨酸天冬氨酸特异性蛋白酶(caspase-3)和Bcl-2蛋白表达的变化。结果与I/R模型组比较,卡巴胆碱组肠上皮细胞病理学变化较轻,凋亡指数明显降低,caspase-3阳性肠上皮细胞数明显减少,而Bcl-2阳性肠上皮细胞数明显增加(P均<0.01)。结论卡巴胆碱能抑制I/R时肠上皮细胞caspase-3表达,增加Bcl-2表达,减少肠上皮细胞的凋亡。     

基于外翻肠囊法研究乌蕨醇提物的肠吸收特性

目的 研究乌蕨醇提物在肠道中的吸收特性。方法 采用大鼠外翻肠囊实验模型,收集高、中、低质量浓度乌蕨提取物给药后不同时间的肠囊液;采用HPLC检测肠囊液样品中原儿茶酸、原儿茶醛、牡荆苷3种化学成分含量,计算吸收动力学参数（Q、Ka）,考察各成分肠吸收特征。结果 原儿茶酸、原儿茶醛、牡荆苷3种成分在乌蕨醇提物中能被检测出,但在其肠吸收液中未被检测到。结论 在本研究实验条件下,肠道对乌蕨中原儿茶酸、原儿茶醛、牡荆苷3种指标性成分未有吸收,具体原因还有待实验进一步探究。     

Characterization of p-aminobenzoic acid transport across the rat intestine.

The intestinal absorption of PABA, a member of the vitamin B complex, was characterized in vivo and in vitro in the rat by the segmental intestinal perfusion and everted gut sac technique. Net PABA absorption was directly proportional to substrate concentration, and saturation of absorption did not occur with increasing concentrations of PABA (1 to 50 mM), indicating a nonsaturable process. Jejunal and ileal absorption rates were similar and were not influenced by the presence of glucose or the absence of sodium in the test solution. Similarly, 14C-PABA transport in vitro was nonsaturable and proportional to PABA concentration (0.05, 0.5, 1, 10, and 50 mM). It was not inhibited by ouabain or other PABA analogues such as folic acid and benzoic acid. These studies indicate that PABA, a vitamin B cofactor, is absorbed by a nonsaturable, sodium-independent process, which characterizes passive diffusion and is similar to the absorption of other vitamin B members.     

L-阿拉伯糖对肠道微生态的作用及临床应用进展

L-阿拉伯糖是一种天然存在的戊糖,在肠道吸收速率较蔗糖低,能选择性反竞争性抑制小肠黏膜刷状缘的蔗糖酶,抑制人体对蔗糖的代谢和吸收,降低和延缓因蔗糖摄入而导致的血糖升高,具有改善糖耐量和减少脂肪堆积的功效。L-阿拉伯糖促进益生菌增殖改善肠道微生态。肠道微生态由肠道菌群及其生活的环境构成,是影响能量代谢的关键因素,肠道菌群结构和功能的失调将影响糖脂代谢和能量平衡,并引发肠道慢性非特异炎症反应,长期的炎症反应会进一步加剧肠黏膜屏障功能的破坏,形成恶性循环,进而引发代谢综合征。L-阿拉伯糖作为益生元可改善肠道微生态和肠道功能,防治功能性便秘和炎症性肠病。本综述主要介绍L-阿拉伯糖的功能、对肠道微生态的作用及其临床应用,并对L-阿拉伯糖在医学领域的发展前景进行讨论。     

Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone

BACKGROUND AND OBJECTIVES: Cytochrome P450 (CYP) 3A4 is the main CYP isozyme involved in methadone metabolism. We investigated the influence of grapefruit juice, which contains inhibitors of intestinal CYP3A, on the steady-state pharmacokinetics of methadone. METHODS: For 5 days, 8 patients undergoing methadone maintenance treatment received 200 mL water or grapefruit juice 30 minutes before and again together with their daily dose of methadone. Blood sampling for R-, S-, and R,S-methadone plasma determination was performed over a 24-hour period. CYP3A activity was determined by measuring the plasma 1'-hydroxymidazolam/midazolam ratio. RESULTS: A decrease in the midazolam ratio was measured in all patients after grapefruit juice (mean +/- SD before grapefruit juice, 9.3 +/- 5.9; mean +/- SD after grapefruit juice, 3.9 +/- 1.2; P <.05). Grapefruit juice led to a mean 17% increase in the area under the curve extrapolated to 24 hours for both enantiomers of methadone (range, 3% to 29% [P <.005]; range, -4% to 37% [P <.05]; and range, 1% to 32% [P <.01]; for R-, S-, and R,S-methadone, respectively). A similar increase in peak level and decrease in apparent clearance were measured with grapefruit juice, whereas time to peak level, terminal half-life, and apparent volume during the terminal phase of R-, S-, and R,S-methadone were not affected by grapefruit juice. No symptom of overmedication was either detected by the clinical staff or reported by the patients. CONCLUSIONS: Grapefruit juice administration is associated with a modest increase in methadone bioavailability, which is not expected to endanger patients. However, it cannot be excluded that a much stronger effect may occur in some patients, and thus grapefruit juice intake is not recommended during methadone maintenance treatment, in particular in patients initiating such a treatment.     

犬肠缺血/再灌注时小肠对早期肠内营养耐受能力的实验研究

目的研究肠道低灌注状态下实施早期肠内营养(EEN)时小肠功能指标及耐受能力的变化。方法健康雄性杂种犬24只,夹闭肠系膜上动脉(SM A)1 h后恢复灌注造成肠缺血/再灌注(I/R)损伤,复流后4 h实施EEN,将瑞代营养液(4 m l.k-g 1.-h 1)经肠黏膜张力计管持续滴注3 h,如果动物出现肠道不能耐受症状(如呕吐、腹泻等)则停止,间隔6 h后再次实施EEN,直至动物肠道能够耐受为止。按随机数字表法将动物分成单纯EEN组、单纯I/R组、I/R后EEN组(I/R+EEN组),每组8只。检测小肠黏膜二氧化碳分压(P iCO2)、D木糖吸收量、小肠腔内压力判定小肠灌注和功能变化。结果肠I/R+EEN组肠道不能耐受发生率(87.5%)和严重程度均显著高于单纯EEN组(0)和单纯I/R组(12.5%)。实施EEN后,与单纯I/R组和单纯EEN组相比,I/R+EEN组小肠腔内压力及肠P iCO2均显著升高,而血浆D木糖吸收量显著降低(P均<0.01)。结论肠I/R能显著降低小肠对EEN的耐受能力,肠I/R后过早(<12 h)实施EEN能加重小肠I/R损伤,并进一步抑制小肠吸收和运动功能。     

Proinflammatory chemokines in the intestinal lumen contribute to intestinal dysfunction during endotoxemia

Intestinal failure is common in patients with septic shock, with dysfunction of the gut often manifesting as both a cause and consequence of their critical illness. Most studies investigating the pathogenesis of intestinal failure focus on the systemic aspect, although few data examine the inflammatory signaling in the intestinal lumen. Having previously demonstrated apical/luminal chemokine secretion in an in vitro model of intestinal inflammation, we hypothesized that endotoxemia would induce secretion of proinflammatory chemokines into the intestinal lumen. In addition, we examined the contribution of these mediators to intestinal dysmotility. C57/BL6 male mice were injected intraperitoneally with LPS. Serum, intestinal tissue, and intestinal luminal contents were harvested for cytokine analysis. For intestinal motility studies, a transit assay was performed after oral gavage of chemokines. Caco-2 cells grown on Transwell culture inserts were used to examine the role of the intestinal epithelium in chemokine secretion. Monocyte chemoattractant protein 1 (MCP-1/CCL2) and macrophage-derived chemokine (MDC/CCL22) were secreted into the lumen of multiple segments of the gut during endotoxemia in mice. In vitro work showed that the intestinal epithelium participates in monocyte chemoattractant protein 1 and MDC secretion and expresses the CCR2 and CCR4 receptors for these chemokines. Intestinal transit studies show that oral gavage of MDC results in impaired gut motility. This study demonstrates that the intestinal lumen is an active compartment in the gut's inflammatory response. Proinflammatory chemokines are secreted into the intestinal lumen during endotoxemia. These intraluminal chemokines contribute to intestinal dysmotility, complicating intestinal failure.     

Polyamines and the intestinal tract

Owing to their high turnover, the intestinal mucosal cells have a particularly high requirement for polyamines. Therefore, they are an excellent charcol for the study of polyamine function in rapid physiological growth and differentiation. After a cursory introduction to the major aspects of polyamine metabolism, regulation, and mode of action, we discuss the contribution of the polyamines to the maintenance of normal gut function, the maturation of the intestinal mucosa, and its repair after injuries. Repletion of cellular polyamine pools with (D,L)-2-(difluoromethyl)ornithine has considerably improved our understanding of how the polyamines are involved in the regulation of normal and neoplastic growth. Unfortunately, the attempts to exploit polyamine metabolism as a cancer therapeutic target have not yet been successful. However, the selective inactivation of ornithine decarboxylase appears to be a promising chemopreventive method in familial adenomatous polyposis. Presumably, it relies on the fact that ornithine decarboxylase is a critical regulator of the proliferative response of the protooncogene c-myc, but not of its apoptotic response.     

Effect of ischemia on intestinal permeability of lipopolysaccharides

The enteral absorption of endotoxin (lipopolysaccharide, LPS) was studied in vitro and in vivo. The absorption of fluorescence (FITC) labelled LPS was investigated by uptake studies with rabbit jejunal brush-border membrane vesicles (BBMV), the human intestinal cell line Caco-2 and in rats. FITC-LPS from Salmonella typhimurium was taken up into BBMV in a dose-dependent manner. Uptake was neither pH- nor Na+-dependent, nor could it be inhibited by unlabelled LPS. 74.5% of vesicle-associated fluorescence was due to adhesion to the vesicular membranes, 25.5% was taken up into an osmotically-sensitive space. Transport of LPS across Caco-2 cell monolayers was dose-dependent. The permeation rate increased significantly under ischemic conditions, i.e. when the cells were incubated under oxygen-depleted conditions. However, no significant differences in transepithelial electrical resistances were observed between oxygen depleted and control cells. The release of lactate dehydrogenase was only marginally different from control cells, indicating cell integrity. In situ, after gut ischemia, a significantly increased uptake of fluorescent LPS was observed by fluorescence laser scanning microscopy. Conclusion LPS is taken up by the intestinal mucosa, predominantly by passive transcellular diffusion. Under ischemic conditions, the permeability of LPS is increased mainly by an enhanced paracellular permeability and epithelial destruction. The findings partly explain the clinically observed development of multiorgan system failure after temporary malperfusion of the gut during major vascular surgery or thromboembolism.     

Intestinal Cholesterol Metabolism

The handling of cholesterol by the intestine involves a balance between absorption, excretion and metabolism by gut microflora. Between 34–57 % of dietary cholesterol is absorbed from the human intestine. Variables effecting the efficiency of cholesterol absorption include the absolute amount of cholesterol consumed, the presence of plant sterols, the fiber content of the diet, transit time and possibly the relative proportions of fatty acids in the diet. On average, 150 mg/day of cholesterol is excreted in the feces. Fecal cholesterol derives from biliary secretions into the intestine, sloughing of epithelial cells and unabsorbed dietary cholesterol. The major metabolic products of cholesterol in the gut are coprostanol, coprostanone, cholestanol, cholestanone and epicoprostanol. Bacterial metabolism of cholesterol can be influenced by diet as evidenced by significant variations among different population groups with different dietary habits. Altered patterns of intestinal bacterial metabolism of cholesterol may place persons at a higher risk of developing colonic disorders. Dairy products have been reported to influence the bacterial metabolism of cholesterol and possibly plasma cholesterol levels although the significance of these findings to overall cholesterol balance needs to be further defined.     

Intestinal cholesterol metabolism

The handling of cholesterol by the intestine involves a balance between absorption, excretion and metabolism by gut microflora. Between 34-57% of dietary cholesterol is absorbed from the human intestine. Variables effecting the efficiency of cholesterol absorption include the absolute amount of cholesterol consumed, the presence of plant sterols, the fiber content of the diet, transit time and possibly the relative proportions of fatty acids in the diet. On average, 150 mg/day of cholesterol is excreted in the feces. Fecal cholesterol derives from biliary secretions into the intestine, sloughing of epithelial cells and unabsorbed dietary cholesterol. The major metabolic products of cholesterol in the gut are coprostanol, coprostanone, cholestanol, cholestanone and epicoprostanol. Bacterial metabolism of cholesterol can be influenced by diet as evidenced by significant variations among different population groups with different dietary habits. Altered patterns of intestinal bacterial metabolism of cholesterol may place persons at a higher risk of developing colonic disorders. Dairy products have been reported to influence the bacterial metabolism of cholesterol and possibly plasma cholesterol levels although the significance of these findings to overall cholesterol balance needs to be further defined.     

New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease

Intestinal flora plays a key role in nutrient absorption, metabolism and immune defense, and is considered to be the cornerstone of maintaining the health of human hosts. Bile acids synthesized in the liver can not only promote the absorption of fat-soluble substances in the intestine, but also directly or indirectly affect the structure and function of intestinal flora. Under the action of intestinal flora, bile acids can be converted into secondary bile acids, which can be reabsorbed back to the liver through the enterohepatic circulation. The complex dialogue mechanism between intestinal flora and bile acids is involved in the development of intestinal inflammation such as inflammatory bowel disease (IBD). In this review, the effects of intestinal flora, bile acids and their interactions on IBD and the progress of treatment were reviewed.