Intestinal enterocytes have an elaborate apical membrane of actin-rich protrusions known as microvilli. The organization of microvilli is orchestrated by the intermicrovillar adhesion complex (IMAC), which connects the distal tips of adjacent microvilli. The IMAC is composed of CDHR2 and CDHR5 as well as the scaffolding proteins USH1C, ANKS4B, and Myosin 7b (MYO7B). To create an IMAC, cells must transport the proteins to the apical membrane. Myosin 5b (MYO5B) is a molecular motor that traffics ion transporters to the apical membrane of enterocytes, and we hypothesized that MYO5B may also be responsible for the localization of IMAC proteins. To address this question, we used two different mouse models: 1) neonatal germline MYO5B knockout (MYO5B KO) mice and 2) adult intestinal-specific tamoxifen-inducible VillinCreERT2;MYO5Bflox/flox mice. In control mice, immunostaining revealed that CDHR2, CDHR5, USH1C, and MYO7B were highly enriched at the tips of the microvilli. In contrast, neonatal germline and adult MYO5B-deficient mice showed loss of apical CDHR2, CDHR5, and MYO7B in the brush border and accumulation in a subapical compartment. Colocalization analysis revealed decreased Mander's coefficients in adult inducible MYO5B-deficient mice compared with control mice for CDHR2, CDHR5, USH1C, and MYO7B. Scanning electron microscopy images further demonstrated aberrant microvilli packing in adult inducible MYO5B-deficient mouse small intestine. These data indicate that MYO5B is responsible for the delivery of IMAC components to the apical membrane.NEW & NOTEWORTHY The intestinal epithelium absorbs nutrients and water through an elaborate apical membrane of highly organized microvilli. Microvilli organization is regulated by the intermicrovillar adhesion complexes, which create links between neighboring microvilli and control microvilli packing and density. In this study, we report a new trafficking partner of the IMAC, Myosin 5b. Loss of Myosin 5b results in a disorganized brush border and failure of IMAC proteins to reach the distal tips of microvilli.

Age-related changes in gastrointestinal function have been reported in companion animals, but the impact on digestive efficiency remains uncertain. Healthy dogs (n = 37; 2.6-14.2 years) received four diets varying in total dietary fibre (TDF; 6-29%, as fed). Healthy cats (n = 28; 1-13 years) received four diets with two fat (10-12%; 17-18%) and TDF (9 and 12%) levels. In a crossover design, diets were provided over four consecutive 10-day cycles, including a 4-day faecal collection. Apparent crude protein (CP), ether extract (EE), TDF, calcium (Ca), and phosphorus (P) digestibilities were determined. The effect of age was analysed as a continuous variable in dogs and as differences between adult (1-5 years) and senior (7-13 years) cats. In dogs, EE digestibility was unaffected by age (p > 0.10). Dogs of 6-12 years had higher digestibility of CP (p = 0.032), TDF (p = 0.019), Ca (p = 0.019), and P (p = 0.024) when fed the 6% TDF diet. Senior cats had greater digestibility of TDF (p < 0.01) and Ca (p = 0.024) but had lower EE and CP digestibility with one diet (17% fat; 9%TDF) (age, p > 0.10; diet × age, p < 0.001). Healthy ageing was associated with preserved nutrient digestibility in dogs and cats within the age ranges studied. The effect of ingredient sources in senior cats warrants further investigation.

Crohn's disease (CD) can affect any part of the gastrointestinal tract; however, the frequency of CD lesions differs by location. This work aimed to examine resection rates by location to clarify locational characteristics of the small intestine in surgical CD cases.

This was a single-centre retrospective case note review of patients who had undergone resection for CD affecting the small intestine between January 2014 and February 2020. Operative details, including length of the small intestine, location and extent of the resection, identified the pattern of disease. By normalizing these data the resection rate along the length of the intestine was calculated to create resection rate curves.

One hundred and twenty six surgical cases were identified. The resection rate curves could be divided into two types: exponential and bimodal. For primary surgery, this depended on whether or not surgery was limited to an ileocolic resection. At subsequent surgery, a previous ileocaecal resection influenced the pattern of disease. The peaks of the bimodal curve were located at the proximal and distal ileum.

CD patients requiring resection of the small intestine can be divided into terminal ileum type (exponential type) and proximal ileum type (bimodal type). In the future this analytical method may help predict the site of any recurrent disease but also provides a new perspective on the disease.

Globally, people 65 years of age and older are the fastest growing segment of the population. Physiological manifestations of the aging process include undesirable changes in body composition, declines in cardiorespiratory fitness, and reductions in skeletal muscle size and function (i.e., sarcopenia) that are independently associated with mortality. Decrements in muscle protein synthetic responses to anabolic stimuli (i.e., anabolic resistance), such as protein feeding or physical activity, are highly characteristic of the aging skeletal muscle phenotype and play a fundamental role in the development of sarcopenia. A more definitive understanding of the mechanisms underlying this age-associated reduction in anabolic responsiveness will help to guide promyogenic and function promoting therapies. Recent studies have provided evidence in support of a bidirectional gut-muscle axis with implications for aging muscle health. This review will examine how age-related changes in gut microbiota composition may impact anabolic response to protein feeding through adverse changes in protein digestion and amino acid absorption, circulating amino acid availability, anabolic hormone production and responsiveness, and intramuscular anabolic signaling. We conclude by reviewing literature describing lifestyle habits suspected to contribute to age-related changes in the microbiome with the goal of identifying evidence-informed strategies to preserve microbial homeostasis, anabolic sensitivity, and skeletal muscle with advancing age.

Prebiotic galacto-oligosaccharides (GOS) have an extensively demonstrated beneficial impact on intestinal health. In this study, we determined the impact of GOS diets on hallmarks of gut aging: microbiome dysbiosis, inflammation, and intestinal barrier defects ("leaky gut"). We also evaluated if short-term GOS feeding influenced how the aging gut responded to antibiotic challenges in a mouse model of Clostridioides difficile infection. Finally, we assessed if colonic organoids could reproduce the GOS responder-non-responder phenotypes observed in vivo.

Old animals had a distinct microbiome characterized by increased ratios of non-saccharolytic versus saccharolytic bacteria and, correspondingly, a lower abundance of β-galactosidases compared to young animals. GOS reduced the overall diversity, increased the abundance of specific saccharolytic bacteria (species of Bacteroides and Lactobacillus), increased the abundance of β-galactosidases in young and old animals, and increased the non-saccharolytic organisms; however, a robust, homogeneous bifidogenic effect was not observed. GOS reduced age-associated increased intestinal permeability and increased MUC2 expression and mucus thickness in old mice. Clyndamicin reduced the abundance Bifidobacterium while increasing Akkermansia, Clostridium, Coprococcus, Bacillus, Bacteroides, and Ruminococcus in old mice. The antibiotics were more impactful than GOS on modulating serum markers of inflammation. Higher serum levels of IL-17 and IL-6 were observed in control and GOS diets in the antibiotic groups, and within those groups, levels of IL-6 were higher in the GOS groups, regardless of age, and higher in the old compared to young animals in the control diet groups. RTqPCR revealed significantly increased gene expression of TNFα in distal colon tissue of old mice, which was decreased by the GOS diet. Colon transcriptomics analysis of mice fed GOS showed increased expression of genes involved in small-molecule metabolic processes and specifically the respirasome in old animals, which could indicate an increased oxidative metabolism and energetic efficiency. In young mice, GOS induced the expression of binding-related genes. The galectin gene Lgals1, a β-galactosyl-binding lectin that bridges molecules by their sugar moieties and is an important modulator of the immune response, and the PI3K-Akt and ECM-receptor interaction pathways were also induced in young mice. Stools from mice exhibiting variable bifidogenic response to GOS injected into colon organoids in the presence of prebiotics reproduced the response and non-response phenotypes observed in vivo suggesting that the composition and functionality of the microbiota are the main contributors to the phenotype.

Dietary GOS modulated homeostasis of the aging gut by promoting changes in microbiome composition and host gene expression, which was translated into decreased intestinal permeability and increased mucus production. Age was a determining factor on how prebiotics impacted the microbiome and expression of intestinal epithelial cells, especially apparent from the induction of galectin-1 in young but not old mice. Video abstract.

Two experiments were conducted to investigate the effects of dietary supplementation with protease and phytase on growth performance, serum physiochemical parameters, and activities of digestive enzymes in jejunal digesta of meat ducks. Experiment 1 was carried out to determine the effects of different protease or phytase on growth performance, serum physiochemical parameter, and activities of digestive enzymes in jejunal digesta of meat ducks to select the optimal phytase or protease. According to the hatching age and initial weight, a total of 5040 Cherry Valley ducks (15 days of age) were randomly assigned into six treatments. Treatments included a basal control diet (CON) and 5 basal diets supplemented with different enzyme preparations, which were phytase preparation A (PA, 160 g/t), phytase preparation B (PB, 800 g/t), protease preparation A (PTA, 80 g/t), protease preparation B (PTB, 300 g/t) and protease preparation C (PTC, 200 g/t). The enzyme activities were as follows: Phytase A and B as well as protease A, B, and C were 50,000, 10,000, 250,000, 50,000, and 60,000 U/g, respectively. Each treatment had 7 replicates with 120 meat ducks per replicate. Experiment 1 lasted for 28 days. The results showed that: compared with the CON group, the PA group significantly decreased contents of serum phosphorus and calcium (p < 0.05), and the PTA, PTB, and PTC groups had higher activities of trypsin in jejunal digesta (p < 0.05), and the activity of jejunal chymotrypsin in PTA group was greater (p < 0.05). Experiment 2 was carried out to determine the effects of dietary supplementation with protease and phytase in low-energy and low-protein diet on growth performance, serum physiochemical parameters, and activities of digestive enzymes in jejunal digesta of meat ducks. According to the hatching age and initial weight, a total of 5760 Cherry Valley ducks (15 days of age) were randomly assigned into four treatments on the basis of a trial of 2 × 2 factorial design. Treatments included a basal control diet (PC), basal diet supplemented with enzymes (PCE), low-energy and low-protein diet (LEP), and low-energy and low-protein diet supplemented with enzymes (LEPE), the nutrient levels of energy and CP of basal diet were 2747.2 cal·ME/kg and 16.80%, respectively, and the nutrient levels of energy and CP of low-energy and low-protein diet decreased 45.90 kcal·ME/kg and 0.52% on the basis of basal diet, respectively. According to the results of experiment 1, phytase A and protease A were determined as the optimal enzyme combination of Experiment 2, and additional dosage of which were identical with Experiment 1. Each treatment had 6 replicates with 240 meat ducks per replicate. Experiment 2 lasted for 28 days. The results showed that: compared with PC and LEP groups, PCE and LEPE groups had higher final weight and average daily gain (ADG) (p < 0.05), higher activities of trypsin and chymotrypsin in jejunal digesta (p < 0.05), lower contents of serum calcium and phosphorus as well as higher levels of high-density lipoprotein in the serum (p < 0.05). In conclusion, dietary supplementation with phytase and protease in different energy and protein diets could increase digestive enzymes in jejunal digesta, effect serum physiochemical parameters, improve metabolic status, and increase the growth performance of meat ducks. Meanwhile, with the dietary supplementation with phytase and protease in the lower energy and protein diet, the growth performance could reach to the degree of the higher energy and increased protein diet, but without the addition of phytase and protease.

In the present study, we aimed to evaluate the effect of aging on the absorption of small peptides in spontaneously hypertensive rats (SHRs). Three kinds of dipeptides, glycyl-sarcosine (Gly-Sar), Trp-His, and captopril (a dipeptidomimetic drug), a Gly-Sar-Sar tripeptide, a Gly-Sar-Sar-Sar tetrapeptide, and a Gly-Sar-Sar-Sar-Sar pentapeptide were administered at doses of 10 mg/kg each to 8- and 40-week-old SHRs. The peptides were all detected in their intact forms in the blood. There was a significantly promoted absorption of di/tripeptides in aged SHRs compared with young SHRs. In contrast, the absorption of tetra/pentapeptides was not affected by aging. PepT1 expression in the mid-jejunum was significantly increased in 40-week-old SHRs compared with 8-week-old SHRs, whereas aging did not alter the expression of claudin-1, a tight junction related protein. Thus, the present results suggest that SHR aging may enhance the absorption of di/tripeptides through the enhanced PepT1 transport route, although oligopeptides may be absorbed in an age-independent manner.

The variation of linkage positions in ginsenosides leads to diverse pharmacological efficiencies. The hydrolysis and transglycosylation properties of glycosyl hydrolase family enzymes have a great impact on the synthesis of novel and structurally diversified compounds. In this study, six ginsenoside Rg1-α-glucosides were found to be synthesized from the reaction mixture of maltose as a donor and ginsenoside Rg1 as a sugar acceptor in the presence of rat small intestinal homogenates, which exhibit high α-glucosidase activities. The individual compounds were purified and were identified by spectroscopy (HPLC-MS, (1)H-NMR, and (13)C-NMR) as 6-O-[α-D-glcp-(1→4)-β-D-glcp]-20-O-(β-D-glcp)-20(S)-protopanaxatriol, 6-O-β-D-glcp-20-O-[α-D-glcp-(1→6)-(β-D-glcp)]-20(S)-protopanaxatriol, 6-O-β-D-glcp-20-O-[α-D-glcp-(1→4)-(β-D-glcp)]-20(S)-protopanaxatriol, 6-O-[α-D-glcp-(1→6)-β-D-glcp]-20-O-(β-glcp)-20(S)-protopanaxatriol, 6-O-[α-D-glcp-(1→3)-β-D-glcp]-20-O-(β-D-glcp)-20(S)-protopanaxatriol, and 6-O-β-D-glcp-20-O-[α-D-glcp-(1→3)-(β-D-glcp)]-20(S)-protopanaxatriol. Among these six, 6-O-β-D-glcp-20-O-α-D-glcp-(1→6)-(β-D-glcp)-20(S)-protopanaxatriol and 6-O-α-D-glcp-(1→6)-β-D-glcp-20-O-(β-D-glcp)-20(S)-protopanaxatriol are considered to be novel compounds of alpha-ginsenosidal saponins which pharmacological activities should be further characterized. This is the first report on the enzymatic elaboration of ginsenoside Rg1 derivatives using rat intestinal homogenates. To the best of our knowledge, it is also the first to reveal the sixth and 20th positions of an unusual α-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl sugar chain with 20(S)-protopanaxatriol saponins in Panax ginseng Mayer.

This study evaluated the effects of the supplementation with aqueous extract of Agaricus blazei Murrill (ABM) on biometric and blood parameters and quantitative morphology of the myenteric plexus and jejunal wall in aging Wistar rats. The animals were euthanized at 7 (C7), 12 (C12 and CA12), and 23 months of age (C23 and CA23). The CA12 and CA23 groups received a daily dose of ABM extract (26 mg/animal) via gavage, beginning at 7 months of age. A reduction in food intake was observed with aging, with increases in the Lee index, retroperitoneal fat, intestinal length, and levels of total cholesterol and total proteins. Aging led to a reduction of the total wall thickness, mucosa tunic, villus height, crypt depth, and number of goblet cells. In the myenteric plexus, aging quantitatively decreased the population of HuC/D(+) neuronal and S100(+) glial cells, with maintenance of the nNOS(+) nitrergic subpopulation and increase in the cell body area of these populations. Supplementation with the ABM extract preserved the myenteric plexus in old animals, in which no differences were detected in the density and cell body profile of neurons and glial cells in the CA12 and CA23 groups, compared with C7 group. The supplementation with the aqueous extract of ABM efficiently maintained myenteric plexus homeostasis, which positively influenced the physiology and prevented the death of the neurons and glial cells.

The effect of alloxan-induced maternal diabetes has been studied on the postnatal development of brush border enzymes in rat intestine.

Diabetes was induced by injecting alloxan in rat mothers on day 3 of gestation.

There was no change in gestational period (22 days) in control and diabetic groups; however, the litter size was reduced (P < 0.001) in diabetic mothers compared with controls. Body weight of pups born to diabetic mothers was significantly low up to 45 days of postnatal age compared with controls. Analysis of brush border enzymes revealed elevated levels of lactase (76%), sucrase (46%), maltase (25%), trehalase (38%), alkaline phosphatase (57%), and leucine aminopeptidase (56%) up to 21 days of postnatal age in diabetic group compared with controls. However, in 30- to 45-day-old animals, the enzyme levels were either reduced in diabetic group or there was no change compared with controls. Western blot analysis corroborated the enzyme analysis data in purified brush borders. Also, 45 days after birth, the intestinal uptake of D-glucose and glycine was significantly high (30%-61%) in pups from diabetic dams compared with controls.

These findings indicate that alloxan-induced maternal diabetes influences the postnatal development of intestine and the expression of various brush border enzymes and transport functions in rat intestine. This could affect the growth and development of the offspring during the postnatal period.

Malabsorption of carbohydrates, lipids, amino acids, minerals and vitamins has been described in the elderly. The ability of the intestine to adapt may be impaired in the elderly and this may lead to further malnutrition. Dietary manipulation may prove to be useful to enhance the needed intestinal absorption with ageing. There is an age-associated increase in the prevalence of dyslipidaemia as well as diabetes. These conditions may benefit from nutritional intervention targeted at reducing the absorption of some nutrients. With the continued characterization of the proteins involved in sterol and fatty acid absorption, therapeutic interventions to modify absorption may become available in the future.

Correction of the malnourished state, particularly common and severe in elderly people, is often unsuccessful. To improve the efficiency of realimentation, we evaluated the nutritional effect of a pancreatic extract (PE)-enriched diet in malnourished aged rats. Sprague-Dawley male rats were randomly assigned to 6 groups as follows: 1 group of control rats had free access to the diet for 12 wk (C group) and 5 groups were 50% food restricted for the same period. One food-restricted group was then killed (R group) and the 4 remaining groups were refed for 1 wk using a standard diet enriched either with two different doses of a pancreatic extract (2.4 or 4.8 g/d in PE1 and PE2 groups, respectively) or with an isonitrogenous casein hydrolysate (CH1 and CH2 groups, respectively). Profound alterations induced by food restriction (FR) were moderately corrected by refeeding, except nitrogen balance, which was reestablished in rats refed all diets (P: < 0.01 vs. R). Supplementation of the food ration with a pancreatic extract clearly improved recovery. Indeed, body weight gain, both jejunal and ileal trophicity [jejunum: total height, PE2: 849 +/- 45 microm vs. CH2: 768 +/- 17 microm (P: < 0.05); protein content, PE2: 69.9 +/- 5.7 mg vs. CH2: 56.4 +/- 4.8 mg (P: < 0.01)] and nonspecific immune response in terms of H2O2 production by polymorphonuclear neutrophils and tumor necrosis factor alpha (TNF-alpha) by macrophages (PE2, 20.7 +/- 4.7 vs. CH2, 8.7 +/- 2.3, P: < 0.05) were improved in rats fed PE2. A pancreatic extract could improve the efficiency of realimentation in malnourished aged rats.

Protein energy malnutrition is a common finding in elderly people, increasing morbidity and mortality in aged inpatients. Investigations need to be developed to counteract malnutrition-induced alterations early and to avoid potential irreversible lesions. The aim of this experimental study was to evaluate time-response to severe dietary restriction (DR) initiated in aged rats in terms of protein metabolism and digestive trophicity.

After the acclimatization period, 22-month-old male rats were randomized into six groups: three control groups, fed ad libitum for 3, 6 or 12 weeks with a standard diet and three corresponding dietary-restricted groups fed for the same periods with only 50% of the spontaneous intake. Intestinal mucosa, liver and skeletal muscles (soleus, extensor digitorum longus and tibialis anterior muscle) were removed when the rats were killed.

DR induced dramatic body weight loss (up to 50% of initial body weight after 12 weeks DR). Protein metabolism was affected in terms of nitrogen balance (P < 0.01) and protein content, in particular at the splanchnic level. Morphometrically, the intestine structure was altered after 12 weeks of DR (P < 0.01), and this atrophy was correlated with malabsorption of mannitol (P < 0. 01). Ileal hydrolase activities were decreased throughout the 12 weeks of DR.

Aged rats clearly exhibit a defect of adaptation to long-term DR initiated at an advanced age. Severe DR leads to malnutrition, which becomes of major importance after 12 weeks, in particular at the intestine level. Hence, application of these experimental results to elderly, malnourished people may contribute to a better knowledge of denutrition-induced disorders.

The mouse Cdx1 gene encodes a homeobox-containing transcription factor and is one of the few homeobox genes known to be expressed in endodermally derived tissues of the intestine in fetal and adult mice. A detailed and systematic study of the expression of the Cdx1 protein was carried out during embryonic intestinal development, postnatal cytodifferentiation and in the regenerating (after radiation-induced damage) intestine of the mouse. Using antibodies directed against Cdx1, we show for the first time that the Cdx1 protein is localised in the proliferating immature epithelium during intestinal development. It becomes restricted to the proliferative crypt compartment during postnatal differentiation, as well as in the adult intestine. The mesenchymal layer was completely negative both during embryonic development and in the postnatal intestine. The expression of the protein was first clearly detected throughout the simple columnar epithelium at day 15 of development. This expression progressively became restricted to the regions of epithelial proliferation in the crypts of the adult mouse by day 40 of post-natal development. There were occasional cells that were Cdx1 positive in the villi. During regeneration of the epithelium after radiation-induced damage, Cdx1 expression diminished during the initial phase of cellular regression. The expression was then very strong in the regenerating epithelial foci, but not in the quiescent sterilised crypts between day 4 and 6. The normal pattern was restored between day 6 and 7. The Paneth cells were negative. The physical segregation of Cdx1 with the proliferative compartment and the hierarchy of cell renewal in the intestinal epithelium is an important example of how regulatory genes function in the maintenance and in the dysfunction of renewing tissues.

Taurocholate transport was studied in brush border membrane vesicles (BBMV) isolated from chicken small (duodenum, jejunum, and ileum) and large (proximal cecum and rectum) intestines, using a rapid filtration technique. The purity of the BBMV was verified by the finding that the specific activity of sucrase (a brush border membrane enzyme marker) was severalfold greater in vesicles than corresponding values in mucosal homogenate. The functional integrity of isolated BBMV was evaluated by the uptake of D-glucose, which showed a transient increase in the presence of Na+. A Na+-dependence of taurocholate uptake was shown in BBMV prepared from ileum, cecum, and rectum, as taurocholate transport was transiently increased (accumulation) in the presence of a Na+ gradient between the external medium and intravesicular medium. The magnitude of the accumulation was similar among ileum, cecum, and rectum. In contrast, BBMV prepared from duodenum and jejunum did not show any Na+-dependent taurocholate transport, as the taurocholate uptake was not affected when a Na+ gradient was replaced by a K+ gradient. The use of taurochenodeoxycholate in the incubation medium inhibited Na+-dependent taurocholate transport in the ileum, cecum, and rectum. This study is the first to show the presence of a Na+-dependent bile salt transport in BBMV obtained from chicken ileum, proximal cecum, and rectum.

Lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) are intestinal microvillus membrane hydrolases that play important roles in carbohydrate digestion. Although the expression of these enzymes during postnatal development has been characterized, the effect of old age on disaccharidase activity is poorly understood. In the present investigation, we examined the effect of aging on lactase and sucrase activities and their mRNA levels in the small intestines of 3-, 12- and 24- mo-old rats by sampling from nine equidistant segments of small intestine. Total intestinal disaccharidase activity or mRNA abundance was determined from areas under the proximal-to-distal curves. Rats 24 mo of age had total intestinal lactase and sucrase activities that were 12 and 38% lower, respectively, than the 3-mo-old animals (P < 0.05). In contrast, total LPH and SI mRNA abundance did not change significantly. Thus, total intestinal lactase and sucrase activities decrease with age in a manner that likely involves a posttranscriptional process. The age-related decline in disaccharidase activity, if extrapolated to humans, may have important implications for the digestion of carbohydrate contained in the diet of the elderly.

The effects of aging on intestinal absorption of zinc and L-histidine were investigated in adult (10-month-old) and senescent (30-month-old) Wistar rats' brush-border membrane vesicles isolated from jejunum and ileum. Kinetic parameters of the zinc transport by the jejunal brush-border membrane were Jmax = 126 +/- 24 nmol.min-1.mg-1 protein and Km = 490 +/- 126 microM (10-month-old rats, n = 7). The transport of zinc was the same in the jejunum and the ileum of adult animals. In senescent rats, the zinc uptake was significantly lower in the distal part of the intestine than in the proximal one. A comparison of zinc uptake in 10- and 30-month-old rats showed that the transport capacity of the jejunum did not change with age but the ileal transport capacity decreased by 50%. This reduced uptake was associated with an increased cholesterol content of the brush-border membrane. The major site of L-histidine absorption was the jejunum, in both the 10- and 30-month-old animals. L-Histidine was co-transported with Na+. The kinetic parameters of the L-histidine carrier in the presence of Na+ were Jmax = 6.5 +/- 1.0 nmol.min-1.mg-1 protein and Km = 190 +/- 29 microM in the jejunum of 10-month-old rats (n = 12). Increasing the extra-vesicular concentration of zinc (0 --> 1 mM) reduced the uptake of L-histidine, and conversely increasing the concentration of L-histidine (0 --> 1 mM) reduced that of zinc: there was no evidence of transport of a complexed form [zinc-L-histidine] in brush-border membranes of the small intestine. During aging, the transport capacity of L-histidine by the jejunum decreased, whereas the ileal transport capacity was conserved. The modifications of absorptive capacity for zinc and L-histidine at the membrane level (loss of ileal function for zinc, and loss of jejunal function for amino acid) indicate that the normal aging of intestinal epithelial cells cannot be regarded as a decline in the overall transport of nutriments but as a combination of highly specific modifications of the various transport systems.

Neodiplostomum seoulensis, one of the human intestinal trematodes, was reinfected to albino rats, and worm recovery rates, histopathology and activity changes of the intestinal brush border membrane bound enzymes were observed. The experimental groups were three; uninfected, primary infection and reinfection. The worm recovery rate in the reinfection group was much lower than in the primary infection group 14 days after infection. The duodenal histopathology showed villous atrophy during the first and second week in the primary infection group. In the reinfection group, however, villous changes occurred as early as 3 days after the infection, and the lesion was found healed 7 days after infection. The activities of alkaline phosphatase and sucrase in the duodenum of primary infection rats decreased nearly half of the controls 2 weeks after infection, whereas the activities were unchanged in the reinfection group. However, no changes in the activities were observed in the proximal jejunum between the experimental groups. These findings suggested that a secondary infection of N. seoulensis in rats should make less damage on the intestinal mucosa than a primary infection.

The present experiment was designed to test the hypothesis that ageing modifies the gastrointestinal responses to a change in diet composition. Rats of the Wag/Rij strain, either young adult (4 months of age) or elderly (27 months of age), were given a basal semi-purified diet or a diet of similar major nutrient composition containing 500 g oatmeal/kg for 17-18 d. Elderly rats digested the dry matter (DM) and organic matter (OM) of both diets less well than did their young adult counterparts, with more of this digestion occurring in the distal intestine. The greater flow of OM to the caecum of oats-fed animals was accompanied by significant reductions in caecal pH and increases in caecal total short-chain fatty acids (SCFA) concentration which appeared to be independent of age. However, young adults responded to feeding on oats by showing a much larger increase in the molar proportion of butyrate (332%) than did elderly animals (79%). Elderly rats had longer duodenal villi than did young adults but effects of age or diet were not detectable at other sites. With both age-groups oats consumption was associated with significant stimulation of crypt cell proliferation rate (CCPR) in the small intestine and caecum, but for the colon there was a significant reduction in CCPR with oats feeding. A reduced ability of the aged large bowel (LB) to produce butyrate may contribute to the prevalence of LB disorders in the elderly.

Two groups of male Fisher 344 rats (young: 4 months old; aged: 25 months old) underwent either 70% distal small bowel resection or sham operation (small bowel transection). Rats from each treatment group of each age were sacrificed on the 10th (N = 15: young rats; N = 13: aged rats) or 20th (N = 15: young; N = 13: aged) postoperative day (POD), and the duodenal mucosa was weighed and assayed for DNA, RNA, and protein contents, as well as for specific activities of the disaccharidase, sucrase, maltase, and lactase. Compared to the sham operation, distal small bowel resection significantly increased DNA by 48%, RNA by 122%, and protein by 75% in young rats and DNA by 40%, RNA by 92%, and protein by 71% in aged rats on the 20th POD. Both young and aged rats showed similar adaptive hyperplasia on the 10th POD. On the 20th POD after distal small bowel resection, specific activities of all tested enzymes were significantly increased in young rats (sucrase +86%, maltase +110% and lactase +64%), but showed no significant changes in aged rats. These findings suggest that the duodenum of aged rats may have sufficient proliferative potential to respond to distal small bowel resection, but that the mechanisms governing return of function in response to distal small bowel resection are inhibited in aged rats, compared to those mechanisms in the young.

Duodenal biopsies were collected from 38 subjects (24 female and 14 male) ranging in age from 55 to 91 years. Evidence of bacterial contamination of the small bowel (BCSB) was sought at the same time by bacterial culture of duodenal aspirates and by hydrogen and [14C]glycocholic acid breath tests; subjects were considered to be positive for BCSB if any one of the three tests was abnormal. Biopsies were analyzed for six brush-border membrane enzyme activities: maltase, sucrase, lactase, alkaline phosphatase, leucine aminopeptidase, and alpha-glucosidase. Analysis of covariance with age as the covariate indicated no significant effect of age on the specific activities of these enzymes. Mucosal Na(+)-dependent glucose transport was quantified in brush-border membrane vesicles prepared from the biopsies. In all groups, glucose transport at 20-30 sec was greater (ranging from mean values of 2.45 to 3.66 times) than at 45 min, consistent with Na(+)-coupled glucose transport, and no significant effect of age was observed. BCSB had no significant effect on specific activities of any of the duodenal mucosal hydrolases but was associated with reduced (P = 0.05) brush-border glucose transport. None of the variables studied was significantly affected by the gender of subjects. In conclusion, these biochemical data do not support the contention that reduced capacity for carbohydrate absorption in the elderly is explained by reductions in duodenal brush-border mucosal disaccharidase activities or glucose transport.

1. Lactase, sucrase, maltase, trehalase and alkaline phosphatase activities of rat proximal jejunum were measured in 3, 6, 9, 12, 18 and 24-month-old rats fed with diets differing in their fatty acid composition. 2. A drop of 47-53% of the specific enzyme activity was observed with disaccharidases against a decrease of 71% for alkaline phosphatase in the 24-month-old rats compared to the 3-month-old rats. 3. Changes in dietary fatty acid composition, either in the saturated or monounsaturated ratio, or in the polyunsaturated fatty acid composition, did not significantly interfere with this aging effect.

Leucine uptake in brush-border membrane vesicles purified from rat jejunum is sodium-dependent, sensitive to the membrane electrical potential difference and enhanced by the intravesicular presence of potassium. This last effect is not mediated by the genesis of an electrical potential difference, since potassium activation and electrical potential effects are additive. Sodium-dependent leucine Vmax (1568 +/- 91 pmol/mg per 3 s, is higher in young rats than in adult and old animals. The diffusion component of leucine transport decreases with increasing age. Preloading the vesicles with 100 mM KCl increases leucine Vmax 200% in young animals, 100% in adult and 44% in old animals. The potassium activation is a saturation function of the cation concentration. Leucine uptake in brush border membrane from old animals is less sensitive to the electrical potential difference than in membranes from adult and young animals.

The effect of aging on the intestinal transport of thiamin was studied using small intestinal microvillous vesicles prepared from groups of rats aged 1, 2, 6, 12 and 24 months, respectively. The vesicles (enrichment 14.6-17.8-fold) were incubated with 0.125 to 12.5 microM tritiated thiamin and the radioactivity taken up was measured radiometrically after rapid filtration. The time course and cumulative uptake curves of thiamin and the inhibiting potency of the thiamin structural analogs pyrithiamin, amprolium and oxythiamin on the saturable component of thiamin transport were determined. The vesicle diameter was measured by using a computerized morphometric procedure, and found to be decreased in aged rats. The Km and Jmax values of the saturable component of transport increased with increasing age, the difference with younger groups being statistically significant at 24 and 12 months. The inhibitory potencies of pyrithiamin and amprolium gradually decreased with increasing age, while oxythiamin was devoid of significant inhibitory activity. Passive permeability coefficients decreased with increasing age, reaching their lowest value at 24 months. These results show that aging is associated with intrinsic alterations of the enterocytic plasma membrane resulting in a decrease of the affinity for thiamin, associated with a faster rate of the saturable component of thiamin transport, and with a significant depression of the non-saturable component.

Jejunal brush border membranes were isolated from rats of different ages (very young, young, adult and old); the gamma-GT specific activity and the vesicle volumes were unaffected by ageing, whilst protein content was significantly reduced in brush border from old rats. Vesicles were used to investigate the kinetics of Na-glucose cotransport under voltage-clamped and zero-trans conditions over a wide range of D-glucose concentrations (0.005-70 mM). Results provide evidence that in all the ages tested D-glucose can cross the brush border membrane both by a passive diffusional component and by two Na-dependent saturable transport systems, namely one with high-affinity and low-capacity and the other with low-affinity and high-capacity. However, in some old rats only one saturable and a very small passive component occur. The two Na-dependent transport systems were analyzed to define the stoichiometry of coupling between Na and glucose fluxes. In all the ages tested the Na:glucose ratio is higher in the high-affinity system than in the low-affinity one. Accordingly the effect of a superimposed membrane potential is more evident for the high-affinity transport mechanism. In conclusion, D-glucose transport systems seem to be unaffected by ageing from very young to adult rats; only in old animals age-related alterations can be observed.

The distribution of sodium- and potassium-stimulated ATPase (Na,K-ATPase) along the crypt-villus axis and crypt cytokinetics were examined in an infective model of celiac disease produced by infection of the rat with the nematode Nippostrongylus brasiliensis. In controls, levels of enzyme activity remained stable during enterocyte migration to the villous apex. In the jejunum of infected rats, the structural lesion of villous atrophy and crypt hyperplasia, observed at day 10 of infection, was associated with a three-dimensional expansion of the crypts. Cell cycle time was shortened and this resulted in a markedly increased crypt cell production rate. Enterocytes emerged from the crypts at a faster rate, and this functional immaturity was paralleled by decreased Na,K-ATPase activity. Further decreases in enzyme levels were observed during enterocyte migration along the villi. This may reflect enterocyte damage or increased enzyme turnover. In the ileum of these animals, enterocyte maturation was prolonged and enzyme activity was increased at the level of the crypt villus junction with further increases noted during enterocyte transit. These changes in ileal Na,K-ATPase appear to be adaptive.

The present study intended to evaluate the influences of Metagonimus yokogawai on the activities of brush border membrane bound enzymes of the small intestine. Mice were infected with 500 metacercariae respectively, and the worm recovery, morphological changes and enzyme activities were observed chronologically. A part of them were followed after the treatment. Recovered worms decreased in number continuously after the infection, and they were less than 10% after 2 weeks and almost zero after 28 weeks. Villous atrophy and stromal inflammation were found at two locations of the proximal jejunum from 2 weeks to 4 weeks after the infection. The enzymes, alkaline phosphatase, leucine aminopeptidase and disaccharidases (sucrase, lactase, maltase, and trehalase), showed lowered activities in the duodenum and proximal jejunum of the infected mice but they increased in the distal jejunum for the first two weeks. From three weeks after the infection, the activities were gradually recovered. In one week treated mice, they recovered the activities at 2 weeks from the treatment, but there found no differences of the activities between the 3 week treated group and infected controls. The present data reveal that M. yokogawai infection induces degenerative changes of the host's intestinal mucosa not only morphologically but functionally during the initial phase of infection. The lowered enzyme activities in acute metagonimiasis should be associated with malabsorption and diarrhea.

This study shows the distribution of the messenger RNA for lactase-phlorizin hydrolase during postnatal development and along the longitudinal axis of the rat small intestine. At birth, this messenger RNA was present along the whole length of small intestine, and its concentration remained elevated during the suckling period despite the concomitant decrease in enzyme activity. At weaning, the amount of lactase messenger RNA dropped specifically in the distal ileum. This decrease in lactase messenger RNA was initiated at the ileocecal junction, progressed gradually towards the jejunum, and followed the decrease in lactase activity several days later. Starvation and refeeding were also found to cause modifications of lactase activity and messenger RNA expression that were prominent in the distal part of small intestine. These data support that posttranscriptional and pretranslational levels of regulation are required to define the spatial and temporal expression of lactase in the rat small intestine.

In addition to the well-known (Na,K)-ATPase activity, an ouabain-insensitive Na-ATPase has been evidenced in the basolateral membrane of intestinal and renal cells from different mammals. Basolateral membranes of jejunal enterocytes from rats of different ages, i.e., very young, young, adult and old were separated by self-orienting, Percoll-gradient centrifugation. The total protein content and both Na- and (Na,K)-ATPase activities in initial homogenate and final pellets were analyzed. The dry weight of homogenate and pellet was also determined. The two ATPase activities and the protein content of the basolateral membrane fraction decrease with age when referred to the dry weight of the pellet. This diminution is also evident in the initial homogenate. The activation curve of Na-ATPase, hyperbolic in shape, gives Km and Vmax values unaffected by aging. The same behaviour is true for the kinetic parameters of (Na,K)-ATPase, which has a sigmoidal velocity curve. From these results, it seems that both Na- and (Na,K)-ATPase have the same characteristics in the basolateral membrane of the enterocyte throughout the life span of the animal, but they decrease quantitatively with aging.

In the period 1970 to 1987, 171 patients with small-intestinal mucosal atrophy have been hospitalized in our department. Of these, 132 patients fulfilled the diagnostic criteria of coeliac disease on the basis of histologic findings and clinical improvement on a gluten-free diet. Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) were chosen as markers of hepatic involvement. Elevation above the normal range in one or more of these tests was seen in 62 patients (47.0%, group I). In 70 patients (53.0%, group II) of similar age the levels of these variables were normal. In group I, 14 (10.6%) patients had an elevation of ALP only, leaving 48 (36.4%) patients with pathologic values for one or both transaminases. In group I, 32 patients had their ASAT, ALAT, and ALP reexamined after at least 6 months of gluten-free diet. Among the patients with increased values of one or both transaminases 18 patients were tested before and at least 6 months after start of gluten-free diet. The variables were significantly reduced in all patients. Liver biopsies were performed in 37 patients, and findings were normal in 5. In 25 patients the changes were classified as non-specific. Chronic active hepatitis was demonstrated in five patients. In one of these patients primary sclerosing cholangitis and ulcerative colitis were also diagnosed. Concomitant malignant disease was found in 22 patients, of whom 16 had malignant lymphoma. Malignant disease was seen more often in group I than group II (p less than 0.01). In conclusion, liver lesions were found in a great proportion of the patients with coeliac disease.(ABSTRACT TRUNCATED AT 250 WORDS)

1. Brush border membrane vesicles were prepared from lamb enterocytes. These were used to study the changes in the enzyme contents and the transport capacities which occur during the change from a milk to a roughage diet. 2. Na+-dependent transport of D-glucose was present in all regions of the small intestine of pre-ruminant lambs and absent in ruminants. 3. Na+-dependent transport of L-proline was present in all regions of the small intestine irrespective of the age of the animal. 4. Phosphate transport was seen only in the presence of a transmembrane pH gradient (acid outside). The transport was not stimulated by either Na+ or K+. The transport capacity increases 2-fold as the animal becomes ruminant. 5. The activities of lactase and maltase diminished with age. Alkaline phosphatase and aminopeptidase N activities remain constant. Sucrase activity cannot be detected in lambs of any age.