Intestinal Absorptive Function Research Articles

Characterization of glucagon-like peptide 2 pathway member expression in bovine gastrointestinal tract

Glucagon-like peptide 2 (GLP-2), secreted by enteroendocrine cells, has several physiological effects on the intestine of monogastric species, including promotion of growth of intestinal epithelium, reduction of epithelial cell apoptosis, and enhancement of intestinal blood flow, nutrient absorption, and epithelial barrier function. The regulatory functions of GLP-2 in the ruminant gastrointestinal tract (GIT) have not been well studied. The objectives of this investigation were to characterize the mRNA expression of 4 members of the GLP-2 pathway throughout the bovine GIT, including (1) proglucagon (GCG), the parent peptide from which GLP-2 is derived through cleavage by prohormone convertase; (2) prohormone convertase (PCSK1); (3) GLP-2 receptor (GLP2R); and (4) dipeptidyl peptidase IV (DPP4), the enzyme that inactivates GLP-2. Gene expression was evaluated in rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum, and rectum collected at slaughter from prepubertal heifers, mature cows in early, mid, and late lactation, and nonlactating cows (n=3 per stage) by a gene expression profiling assay. In addition, mRNA expression of 14 genes involved in nutrient transport, enzyme activity, blood flow, apoptosis, and proliferation were evaluated in the 9 GIT tissues for their association with GCG and GLP2R mRNA expression. Immunohistochemistry was used to localize GLP2R protein in tissues of the lower GIT. Results indicated that mRNA expression of GCG, PCSK1, GLP2R, and DPP4 varies across the 9 GIT tissues, with greatest expression in small and large intestines, and generally nondetectable levels in forestomachs. Expression of DPP4 and GLP2R mRNA varied by developmental stage or lactational state in intestinal tissues. Expression of GCG or GLP2R mRNA was correlated with molecular markers of proliferation, apoptosis, blood flow, enzyme activity, and urea transport, depending on the tissue examined, which suggests a potential for involvement of GLP-2 in these physiological processes in the ruminant GIT. The GLP2R protein was expressed in intestinal crypts of the bovine GIT, which is consistent with the distribution in monogastric species. Our findings support a functional role of the GLP-2 pathway in bovine GIT and the potential for use of GLP-2 as a therapy to improve intestinal function and nutrient absorption in ruminants.

Early use of probiotics is important therapy in infants with severe congenital anomaly

Infants with severe congenital anomaly often need to undergo operation followed by antibiotic therapy. As a result they inevitably acquire abnormal intestinal microbiota, which cause severe infections such as necrotizing enterocolitis. Also, intestinal function deteriorates and their nutritional state is very poor. In order to prevent these situations probiotic therapy is proposed as an effective supporting treatment. Probiotic therapy were therefore applied to infants with severe congenital anomaly as early as possible to ascertain its efficacy. As probiotics, two bacteria were used: Bifidobacterium breve Yakult and Lactobacillus casei Shirota. Probiotic therapy was used in four infants with severe congenital anomaly as early as possible after surgery. Their intestinal microbiota and physical growth were followed through the treatment course. Two patients suffered from meconium peritonitis with ileal atresia. One patient was born with complex anomalies (omphalocele, bladder exstrophy, myelomeningocele). The fourth patient suffered from complete urorectal septum malformation. The intestinal microbiota of these four patients was first induced to be probiotic dominant and finally changed to commensal anaerobe dominant that was similar to normal intestinal microbiota. Pathogenic bacteria were seldom detected. The patients' physical growth was excellent despite short bowel and pulmonary hypoplasia. Probiotic therapy was effective in inducing probiotic dominant intestinal microbiota and normal intestinal microbiota in infants with severe congenital anomalies. As a result their intestinal absorptive functions were activated and severe infections were completely prevented. All of the infants grew well despite their physical disadvantages.

Medical management of pediatric intestinal failure

The outcome for children with congenital enteropathies or massive surgical resections has improved significantly over the past two decades. Advances in understanding of the pathophysiology of intractable diarrhea and of the mutations causing many of the congenital enteropathies have enabled initiation of preventive measures for intractable diarrhea, and have enabled clinicians to provide focused treatment of immune-mediated congenital diarrheal illnesses. Children with surgical short bowel syndrome also face an improved outcome because of improvements in the composition of parenteral nutrition (TPN) and in enteral alimentation strategies. It is now recognized that, through adaptation, small intestinal surface area and absorptive function may improve over time to facilitate emancipation from parenteral nutrition. Beyond provision of enteral nutrition, ancillary therapies such as judicious use of acid suppression, antibiotics, prokinetic agents, and soluble fiber seem to accelerate the rate of adaptation in young children. In the future, trophic hormones such as epidermal growth factor (EGF) or glucagon-like peptide 2 (GLP-2) may become routine members of the therapeutic armamentarium for surgical short bowel syndrome, thus further improving outcomes.

4．入浴による肝・腎・腸管吸収機能の定量的分析

4．入浴による肝・腎・腸管吸収機能の定量的分析

Plasma citrulline is a marker of absorptive small bowel length in patients with transient enterostomy and acute intestinal failure

Small bowel disruption is often complicated by acute intestinal failure and can be corrected by chyme reinfusion (CR). Plasma citrulline ([Cit]) is a biomarker of the enterocyte mass. Our aim was to determine whether [Cit] could be a marker of absorptive intestinal mass or function by assessing whether CR could affect intestinal absorptive function and [Cit]. Twenty-six patients with small bowel disruption and double enterostomy were treated with CR. Fecal wet weight, nitrogen and fat absorption, parenteral nutrition delivery and [Cit] were measured before and after the initiation of CR with a median follow-up of 30 days. CR decreased the intestinal wet weight output (median+/-IQ, 2384+/-969 vs. 216+/-242mLd(-1), P<0.0001) and parenteral nutrition dependence (65% vs. 8%, P<0.01). CR was associated with a rise in net nitrogen and fat digestive absorption and [Cit] (17.0+/-10.0 vs. 31.0+/-12.0micromolL(-1), P=0.0001). Before the initiation of CR, [Cit] correlated positively with the absorptive post-duodenal small bowel length (r=0.39, P=0.04), but not with the total post-duodenal small bowel length (r=0.11, P=0.60). CR allows for a dramatic improvement of intestinal absorptive function and a near doubling in [Cit] level. [Cit] is not a marker of overall intestinal mass, but of the absorptive small bowel function.

Intestinal barrier function is modulated by short-term exposure to fumonisin B1 in Ussing chambers

Fumonisin B₁ (FB1) alters intestinal epithelial cell cycle, absorptive, secretory and barrier properties of intestinal epithelial cells in vitro but data with intestinal mucosa are lacking. Therefore, we tested the hypothesis that acute exposure to FB1 alters indices of intestinal absorptive and secretory physiology and barrier function ex vivo. Eighteen non-littermates pigs (n=18) weaned at 28 d were slaughtered 7 d post-weaning. Jejunal tissue was collected immediately, the mucosa was mounted in Ussing chambers (UC) and short-term (2 h) effects of pure FB1 were investigated. Increased transepithelial resistance (TER) (P=0.05) and macromolecular passage (P=0.06) were observed after 60-90 min of incubation of jejunal mucosa with FB1. FB1 did not alter the jejunal absorptive and secretory physiology. In conclusion, 2h-exposure to FB1 tended to increase the trans- cellular permeability and increased para-cellular permeability of pig small intestine.

Intestinal Physiology and Peptidase Activity in Male Pigs Are Modulated by Consumption of Corn Culture Extracts Containing Fumonisins1–3

Fumonisin B1 (FB1) alters intestinal epithelial cell cycle and absorptive, secretory, and barrier properties in vitro, but in vivo data are lacking. Therefore, we tested the hypothesis that repeated intake of a corn culture extract rich in fumonisins, mainly in FB1, alters indices of intestinal absorptive and secretory physiology and barrier function in vivo. Intra-litter pairs of pigs (n = 36) weaned at 28 d, were fed the vehicle (control) or the extract (providing 1.5 mg FB1/kg body weight) daily for 9 d starting 7 d postweaning. After slaughter, the jejunal mucosa of pigs was mounted in Ussing chambers (UC). Extract consumption for 9 d decreased the gain:feed ratio (P = 0.04) and increased liver weight (P = 0.01). Basal net ion secretion (P = 0.02), sodium-dependent glucose absorption (P = 0.02), and theophylline-induced secretion (P < 0.01) of the jejunal mucosa determined in UC were higher in pigs fed the extract than in controls. By contrast, jejunal permeability to the horseradish peroxidase model protein in UC was not influenced by extract consumption. Ileal villi tended to be longer (P = 0.07) and jejunal aminopeptidase N activity was lower (P < 0.01) in pigs fed the extract. In conclusion, consumption of an extract rich in fumonisins for 9 d has the potential to alter intestinal physiology, villous architecture, and enzyme activities. Underlying mechanisms remain to be investigated.

Nutrition in heart failure: an update

Chronic heart failure (CHF) is increasingly recognized as a multisystem disease with important comorbidities such as anemia, insulin resistance, autonomic dysbalance, or cardiac cachexia. Apart from these perturbations, increasing evidence points to alterations in intestinal morphology, permeability, and absorption function in patients with CHF. This review provides an overview of the sonographic, histological, and functional abnormalities of different gastrointestinal regions. This intestinal dysfunction and disturbed intestinal barrier may lead to both the chronic inflammatory state and catabolic/anabolic imbalance as seen in cardiac cachexia, as a terminal stage of CHF, which carries a particularly poor prognosis. This review highlights the current knowledge of nutritional abnormalities that may occur in CHF, including fat, carbohydrates, proteins, water, and micronutrients. The regulation of feeding is discussed, as are nutritional strategies with potentially anti-inflammatory effects in the treatment of CHF. The gut and its role for inflammation and dietary interventions in heart failure patients are a crucial target of further heart failure research.

Growth hormone deficiency and antipituitary antibodies in a patient with common variable immunodeficiency

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and T-lymphocytes dysfunction. Autoimmune diseases are frequent. A 10.7-yr-old female, diagnosed with CVID when 7 yr old, was referred because of short stature. She was pre-pubertal and short (height -2.86 SD score) with delayed bone age. Her intestinal absorption, routine biochemistry, heart, renal, liver, and thyroid functions were normal. Two stimulation tests for GH showed a maximum peak of 1.9 ng/ml (IGF-1: 154 ng/ml, 147-832). When the patient was 13 yr old (height -4.23 SD score, telarche and pubarche stage 2, bone age 6.25 yr), GH treatment was initiated. Despite poor compliance, the growth velocity showed improvement. Anti-thyrogobulin, anti-thyroperoxidase, anti-21-hydroxylase, and anti-tyrosine-phosphate antibodies were negative while anti- pituitary antibodies (APA) were positive. For the first time, the presence of APA (previously associated with GH deficiency in non-CVID subjects) is reported in a CVID patient. The possibility of an autoimmune involvement of the pituitary gland was previously debated for CVID patients, but had never been demonstrated. This case suggests that in CVID, the pituitary gland can be targeted by autoantibodies and thus a more comprehensive follow-up of these patients should be performed.

A shift in microvillus membrane fucosylation to sialylation by ethanol ingestion in rat intestine

The luminal surface of enterocytes is covered with glycocalyx which is rich in glycoproteins. Ethanol ingestion is shown to induce morphological and biochemical changes in the intestine. In this study, the effect of ethanol ingestion on membrane glycoproteins has been investigated. Chemical analysis of microvillus membranes revealed an increase in hexose and sialic acid contents, but a reduction in fucose levels in ethanol-fed rats compared with controls. The observed changes were apparent in animals fed with ethanol for 35-56 days compared with controls. Lectin-binding assay indicated an increase in Wheat germ agglutinin (affinity for GlcNAc/sialic acid) and a decrease in Aleuria aurantia (affinity for alpha-L: -fucose) reactivity of brush borders in ethanol-fed animals for 4-8 weeks. Western blot analysis using biotin-labeled Wheat germ agglutinin revealed increased binding to proteins of M(r) 66-205 kDa in ethanol-fed rats compared with controls. The binding of Aleuria aurantia to membrane proteins of M(r) 97-185 kDa was reduced in ethanol-fed animals. These findings suggest that long-term ethanol feeding modulates the sialylation and fucosylation processes of microvillus membrane proteins in rat intestine. This could affect the intestinal digestive and absorptive functions in chronic alcoholism.

Development of animal model of early oral fluid resuscitation of burn shock

Objective To establish an animal model for study on early oral fluid resuscitation of burn shock so as to provide experimental basis for oral fluid resuscitation of burn shock in wars, accidents or disasters. Methods Male Beagle dogs weighing 11-13 kg were used in the study and the carotis, jugular and duodenum were cannulated respectively for measurement of homodynamics, tissue perfusion and gastrointestinal function. Dogs were subjected to a 35% TBSA full thickness flame injury with 10-mi-nute anesthesia by intravenous injection of propofol 24 hours later, and then randomly and equally divided into two groups(8 dogs in each group) : no fluid resuscitation group (NR group) undergoing no treatment in the first 24 hours post burn and oral fluid resuscitation group ( OR group) undergoing gastric infusion of glucose electrolyte solution (GES) according to Parkland formula. From the second 24 hours post burn, animals in two groups were given delayed Ⅳ fluid resuscitation, and then intravenous nutritional support was initiated at the 72nd hour. The mean arterial pressures (MAP), cardiac output (CO), dp/dt max of left ventricular contractility (dp/dtmax) and plasma volume (PV) were monitored continuously. The pa-rameters of gastrointestinal tissue peffusion, the rates of gastric emptying and intestinal absorption of GES were determined, the morbidity was also recorded at the end of 5-day experiment. Results After 35% TBSA burn injury, MAP, CO,dp/dt max and PV dropped markedly and gastrointestinal tissue perfusion reduced obviously. CO and PV in OR group were significantly higher than those in NG group at 4, 8 and 24 hours after burn. Homodynamic parameters and gastrointestinal tissue perfusion in OR group were pro-moted to pre-injury level at 48 and 72 hours respectively, while homodynamic parameters in NR group did not return to pre-injury level till 72 hours, and gastrointestinal tissue perfusion kept lower than pre-injury till 120 hours post burn. Rates of gastric emptying and intestinal absorption of GES significantly reduced to the lowest level (42% and 37% of pre-injury) at about 4 hours post bum, but did not return to pre-in-jury level till eight hours post bum. Over five days, two out of eight dogs (25%) died in NG group but none in OR group. Conclusions The animal model can exactly simulate the actual circumstance, where oral resuscitation is superior to Ⅳ resuscitation in some aspects in treating early bum shock in wars, accidents and disasters, and provide practical and reliable method for measurement of homodynamic parameters, tissue perfusion, gastric emptying and intestinal absorptive function. Key words: Bums; Shock; Fluid therapy; Animal model

Clinical Evidence for Immunomodulatory Effects of Probiotic Bacteria

Close, tightly orchestrated interactions between the intestinal epithelium and the mucosa-associated immune system are critical for normal intestinal absorptive and immunological functions. Recent data indicate that commensal intestinal microbiota represents a major modulator of intestinal homeostasis. This review analyzes the process of intestinal colonization and the interaction of microbiota with the intestinal epithelium and mucosal immune system, with special reference to the first years of extrauterine life. Dysregulation of the symbiotic interaction between intestinal microbiota and the mucosa may result in a pathological condition with potential clinical repercussions. Based on the concept that there is a beneficial and symbiotic relation between the host and endogenous microbiota, strategies aimed at directly modulating intestinal microbiota with regard to disease prevention or treatment have been developed. One strategy involves administering viable probiotic bacteria. Clinical evidence for the beneficial effect of probiotics in the prevention and/or treatment of necrotizing enterocolitis, infectious and antibiotic-associated diarrhea, allergic diseases, and inflammatory bowel disorders is reviewed herein.

Preservation of extracorporeal tissue in closing gastroschisis augments intestinal length

Background Prenatal closure of the umbilical ring in gastroschisis may result in an amorphous, nonviable appearing extracorporeal tissue that is resected during the repair. However, it is unclear whether such remnant intestine is truly nonviable. Methods and Results We examined the outcomes of patients when this tissue is preserved. We identified 8 patients who presented with a closing gastroschisis and a mass of tissue connected by a vascular pedicle. Four patients underwent abdominal exploration with resection of the mass and gastroschisis closure. Histologic examination revealed normal intestinal wall architecture. All patients in this group developed short bowel syndrome, requiring long-term parenteral nutrition. Conversely, 4 patients underwent abdominal exploration with internalization of the remnant tissue, a maneuver referred to as “parking,” along with either silo placement, or primary closure of the gastroschisis. At re-exploration, 3 of 4 patients were found to have viable intestine, and bowel continuity was reestablished. The mean parenteral nutrition requirement for this group was significantly shorter than the resected group. Conclusion In this series, we show that this amorphous tissue, when preserved, may exhibit normal intestinal architecture and absorptive function. Therefore, such remnant tissue should be preserved as it may significantly increase bowel length and minimize parenteral nutrition requirement.

Intermediate outcomes after serial transverse enteroplasty in children with short bowel syndrome

Background Serial transverse enteroplasty (STEP) is a novel intestinal lengthening procedure introduced in 2003. To date, no human studies exist that report objective assessment of intestinal absorptive capacity. The aim of this study was to report intermediate outcomes in patients who have received the STEP at our institution using clinical and biochemical assessment of intestinal function. Methods All 14 patients who received the STEP since May 2003 were reviewed. Clinical (weight gain, enteral tolerance, stool frequency) and biochemical (citrulline levels, d-xylose absorption, alpha-1 antitrypsin clearance, and fecal fat content) outcomes were performed pre-STEP and post-STEP at 1, 6, and 12 months, respectively. Data are presented as means with standard deviation. Paired t tests were used to compare post-STEP outcomes with pre-STEP values ( P < .05 was significant). Three patients had a STEP as a newborn and are analyzed separately. Main Results There were 14 patients (3 females; mean age, 24.8 months; range, 1 day-14 years). Serial transverse enteroplasty resulted in a mean increase in length of dilated bowel segment of 94% ± 30% and increase in total small bowel length of 49% ± 42% with mean application of 16 ± 9 cartridges and cost of Can$2878.51 ± 1406.22. Patients demonstrated improvement in both clinical parameters, as well as intestinal absorptive function. Complications included 2 patients with staple line leak and 1 patient with gastrointestinal bleeding from staple line ulcers. Three patients died (2 from liver failure and 1 from sepsis and congenital heart disease). Two patients received liver-intestinal transplants at 4 and 5 months post-STEP. Mean follow-up was 23 ± 9 months, with 7 patients followed more than 2 years. Of 8 patients with post-STEP follow-up of more than 1 year, 7 have weaned from parenteral nutrition. Conclusion Clinical and objective biochemical outcomes of intestinal function after the STEP procedure show promise after intermediate follow-up.

Intestinal secretory and absorptive function in Trichinella spiralis mouse model of postinfective gut dysfunction: role of bile acids

Objective:Observations showing that bile acid malabsorption is frequent in irritable bowel syndrome (IBS) suggest that alterations in bile acid-induced secretion and absorption could contribute to IBS-associated diarrhoea. The secretory response...

Influence of dietary tannic acid and polyethylene glycol on growth and intestinal D-xylose absorption of broiler cockerels and activity of serum enzymes

1. In an experiment on broiler cockerels, the influence of tannic acid (TA) and polyethylene glycol (PEG) on body weight gain (BWG), feed conversion ratio (FCR), weight of intestine and liver, the activities of serum enzymes LDH, AST, ALT and intestinal absorption function were investigated. 2. Broiler cockerels were given either a commercial diet alone (control group) or a commercial diet with TA (20 g/kg), PEG (10 g/kg) or TA plus PEG (20 + 10 g/kg), for 10 d. 3. On the last day of the experiment, all birds and remaining feed were weighed individually and a sample of blood was taken to measure the serum activities of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The capacity of intestinal cells for the absorption of D-xylose was measured. Finally all birds were killed humanely and the intestine and liver were weighed. 4. The results showed that TA significantly reduced BWG and FCR, as well as the activity of LDH, AST and ALT. 5. TA also increased the relative weight of the intestine. Adding PEG alone had no effect on any of the measured parameters. 6. However, PEG improved significantly BWG, FCR and the activity of LDH and AST of TA-fed birds. 7. The plasma D-xylose concentration of experimental birds was similar for all dietary treatments most likely because of temporal separation between feeding the dietary TA and administering the D-xylose. 8. It was concluded that the presence of tannins in the GI lumen of the bird was necessary to affect the processes involved in the absorption of simple sugars such as D-xylose, at the level of intestinal absorptive cells.

Probiotiques et pathologies digestives de l’enfant

The intestinal mucosa is continuously exposed to a magnitude of foreign antigenic structures of alimentary but also microbial origin. Interactions between the intestinal epithelium and the gut immune system is critical to develop and maintain (normal) intestinal (absorptive and immunological) functions. Commensal intestinal microflora is a major player in the homeostasis of the intestinal tract. The process of intestinal colonization and interaction of the microflora with the intestinal epithelium and (mucosal) immune system (is especially crucial and) starts during the first days of life. Any dysregulation of this symbiotic interaction between microflora and intestinal mucosa might impede tolerance acquisition towards food or bacterial antigens and cause a pathological state, resulting in clinical disorders. Based on the concept of beneficial and symbiotic interaction between the host and its endogenous microflora, it is logical to develop strategies to directly modulate the intestinal microflora in the prevention or treatment of certain pathological states. One such strategy is in the form of administering viable probiotic bacteria. Here, we review the clinical evidence for beneficial use of probiotics in infants and children of different ages, to prevent or treat, (infectious and antibiotic-associated) acute diarrhoea, allergic diseases and necrotizing enterocolitis.

Are Plasma Citrulline and Glutamine Biomarkers of Intestinal Absorptive Function in Patients With Short Bowel Syndrome?

Sensitive biomarkers for intestinal absorptive function would be clinically useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is produced almost exclusively by the gut, which is also a major site of Gln metabolism. The goals of this study were to examine whether plasma Cit and Gln concentrations are biomarkers of residual small intestinal length and nutrient absorptive functions in adult SBS patients followed prospectively. We studied 24 stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a double-blind, randomized trial of individualized dietary modification +/- recombinant human growth hormone (GH). During a baseline week, intestinal absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate, sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and Gln concentrations determined. Individualized dietary modification and treatment with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days, then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4 and continued as tolerated for 24 weeks. Repeat plasma amino acid determination and nutrient absorption studies were performed at weeks 4 and 12. Residual small bowel length at baseline was positively correlated with baseline plasma Cit (r = 0.467; p = .028). However, no significant correlations between absolute Cit or Gln concentrations and the percent absorption of nutrient substrates at any time point were observed. Similarly, no correlation between the change in Cit or GLN concentration and the change in % nutrient absorption was observed (baseline vs weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned completely from PN, respectively. However, baseline plasma Cit or Gln did not predict PN weaning at these time points. We concluded that plasma Cit (but not Gln) concentrations appeared to be an indicator of small intestinal length in adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal absorptive function in this cohort of patients with SBS.

Effects of dietary sodium butyrate supplementation on the intestinal morphological structure, absorptive function and gut flora in chickens

A study was carried out to investigate the effects of dietary sodium butyrate (SB) on the intestine and growth performance in chickens. Three hundred and thirty six day-old AA broiler chicks were allocated at random into four groups with six replicates each. Four groups were fed with basal diet (control) or diets supplemented with SB at the level of 500, 1000, 2000 mg/kg. Body weight gain increased linearly during the period from 0 to 21 days as the dietary supplementation of SB increased (P<0.05). Dietary supplementation of SB influenced feed conversion ratio (FCR) in a positive quadratic fashion during the period from 0 to 42 days (P<0.05). Dietary SB did not influence the absorptive function of jejunum (P>0.05). The concentrations of DNA, RNA, and protein in duodenal mucosa showed negative quadratic responses to the increase of dietary SB supplementation level (P<0.05). The ratio of villus height to crypt depth increased linearly with the increase of dietary SB supplementation (P<0.01). The Lactobacillus count decreased linearly with the increase of dietary SB supplementation (P<0.01).

Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis

Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.