Intestinal Surface Area Research Articles

Effect of Using Prickly Pear Seed Cake (Opuntia ficus indica L.) on Growth Performance, Digestibility, Physiological and Histometric Parameters in Rabbits

Prickly pear (Opuntia ficus indica L.) could be used in rabbit nutrition in compliance with circular economy principles, global warming issues, and reduction of production costs. This study aims to evaluate the effects of dietary incorporation of prickly pear seed cake (PPSC) on growth, physiological, and histometric parameters in rabbits. A total of 105 rabbits were divided into three experimental groups (n = 35) and fed different diets: a commercial feed (C group), the same feed with alfalfa replaced by PPSC at 10% (10PP group), and at 20% (20PP group). They were group-housed in cages with 5 animals per cage from weaning until slaughtering. While body weights and weight gains were similar in all groups, the coefficients of nutrient digestibility of dry matter, fibers, and ashes, as well as the characteristics of intestinal villi, were improved in the 10PP group compared to the others (p < 0.05). The 20PP group showed a reduction in perirenal and interscapular fat (p < 0.05), as well as lower plasma concentrations of triglycerides and cholesterol compared to the C group (p < 0.001). In conclusion, PPSC can be incorporated into the diets of growing rabbits up to 20% as a partial substitute for alfalfa without the impairment of growth performance. Additionally, the inclusion of PPSC enhanced nutrient digestibility and increased the intestinal absorption surface area.

Effects of in ovo supplementation of selenium (Se) and zinc (zn) on hatchability and production performance of broiler chickens.

The current research was conducted to assess the effect of in ovo feeding (IOF) of selenium (Se) and zinc (Zn) on hatchability, production performance, liver, intestinal morphology, antioxidant levels and expression levels of immune-related genes in broiler chickens. A total of 400 fertilized eggs were equally divided into four groups: control (non-injected), sham (in ovo injection of 0.75% NaCl), Se (@ 1.5µg/egg in ovo injection) and Zn (500µg/egg in ovo injection) groups respectively. On the seventeenth day of incubation, treatment solutions were administered into amniotic fluid of fertilized eggs. The results revealed that Se and Zn supplementation significantly (P < 0.05) enhanced hatchability, post-hatch growth, organ development, and liver antioxidant capability. Histopathological examination revealed a typical hepatocyte morphology, well-arranged cells, and a significant (P < 0.05) decrease in apoptosis in both selenium and zinc groups. Additionally, selenium and zinc produced auspicious effects on intestinal epithelium and villi surface area. Interestingly, our results revealed that IOF of Se and Zn modulated the expression of immune-related genes in comparison to the control and sham groups. Conclusively, IOF of Se and Zn augmented health and productivity by enhancing the cellular immunity in the broiler chickens, thus IOF can be utilized as an effective strategy to promote health and immunity in broiler chickens.

Growth performance, mucosal immunity and disease resistance in goldfish (Carassius auratus) orally administered with Escherichia coli Strain Nissle 1917.

The current research aimed to shed light on the efficacy of Escherichia coli strain Nissle 1917 (EcN) on goldfish (……) growth, gut immunity, morphology, bacterial nutritional enzyme activity and resistance to Aeromonas hydrophila infection. Fish fed with EcN at 106, 107 and 108CFU/g feed for 80days showed an enhancement in growth better than control fish. The gut innate immunity in terms of lysozyme activity, immunoglobulin and total protein levels was increased in the treatment fish with the best result being observed in fish fed EcN at 108CFU/ g. In addition, an increase was noted in the upregulation of immune-relevant genes, namely lysozyme, interleukin-1β, inducible nitric oxide synthase and tumor necrosis factor α of fish intestine. A marked surge in the number of proteolytic and heterotrophic bacteria was noted in the gut of fish nourished with the probiotic. Histological studies exhibited an improvement in the intestinal absorption surface area, intraepithelial lymphocyte count and goblet cell density. Significantly higher survival rate was obtained in fish fed EcN at 108CFU/g compared with the fish fed with the basal diet. These data exhibited the beneficial effect of EcN on goldfish growth, digestive enzymes, intestine heterotrophic bacteria and resistance against Aeromonas hydrophila challenge. This study confirmed the favorable outcomes resulting from the administration of EcN at108 CFU/g.

The impact of microplastics polystyrene on the microscopic structure of mouse intestine, tight junction genes and gut microbiota.

Microplastics, which are tiny plastic particles less than 5 mm in diameter, are widely present in the environment, have become a serious threat to aquatic life and human health, potentially causing ecosystem disorders and health problems. The present study aimed to investigate the effects of microplastics, specifically microplastics-polystyrene (MPs-PS), on the structural integrity, gene expression related to tight junctions, and gut microbiota in mice. A total of 24 Kunming mice aged 30 days were randomly assigned into four groups: control male (CM), control female (CF), PS-exposed male (PSM), and PS-exposed female (PSF)(n = 6). There were significant differences in villus height, width, intestinal surface area, and villus height to crypt depth ratio (V/C) between the PS group and the control group(C) (p <0.05). Gene expression analysis demonstrated the downregulation of Claudin-1, Claudin-2, Claudin-15, and Occludin, in both duodenum and jejunum of the PS group (p < 0.05). Analysis of microbial species using 16S rRNA sequencing indicated decreased diversity in the PSF group, as well as reduced diversity in the PSM group at various taxonomic levels. Beta diversity analysis showed a significant difference in gut microbiota distribution between the PS-exposed and C groups (R2 = 0.113, p<0.01), with this difference being more pronounced among females exposed to MPs-PS. KEGG analysis revealed enrichment of differential microbiota mainly involved in seven signaling pathways, such as nucleotide metabolism(p<0.05). The relative abundance ratio of transcriptional pathways was significantly increased for the PSF group (p<0.01), while excretory system pathways were for PSM group(p<0.05). Overall findings suggest that MPs-PS exhibit a notable sex-dependent impact on mouse gut microbiota, with a stronger effect observed among females; reduced expression of tight junction genes may be associated with dysbiosis, particularly elevated levels of Prevotellaceae.

Fat malabsorption in short bowel syndrome: A review of pathophysiology and management.

Fat malabsorption is central to the pathophysiology of short bowel syndrome (SBS). It occurs in patients with insufficient intestinal surface area and/or function to maintain metabolic and growth demands. Rapid intestinal transit and impaired bile acid recycling further contribute to fat malabsorption. A significant portion of patients require parenteral nutrition (PN) for their survival but may develop sepsis and liver dysfunction as a result. Despite advancements in the treatment of SBS, fat malabsorption remains a chronic issue for this vulnerable patient population. Peer-reviewed literature was assessed on the topic of fat malabsorption in SBS. Current management of patients with SBS involves dietary considerations, PN management, antidiarrheals, glucagon-like peptide 2 agonists, and multidisciplinary teams. Clinical trials have focused on improving intestinal fat absorption by facilitating fat digestion with pancreatic enzymes. Targeting fat malabsorption in SBS is a potential pathway to improving lifestyle and reducing morbidity and mortality in this rare disease.

Bariatric surgery and secondary hyperparathyroidism; a mini-review

Bariatric surgery is a type of weight loss surgery that is commonly used to treat obesity. However, this surgery can also affect the body’s calcium and PTH metabolism, leading to the development of secondary hyperparathyroidism (SHPT). Several factors contribute to the development of SHPT after bariatric surgery. Malabsorption of calcium due to reduced intestinal surface area, decreased intake of calcium-rich foods, and altered vitamin D metabolism play a significant role. The loss of weight-bearing adipose tissue can also disrupt the balance between bone formation and resorption, leading to increased bone turnover and calcium release from the skeleton. The management of SHPT after bariatric surgery involves a multidisciplinary approach. Calcium and vitamin D supplementation is essential to correct deficiency and maintain bone health. However, achieving optimal calcium and vitamin D levels can be challenging due to malabsorption issues and the need for higher supplementation doses. In some cases, pharmacological interventions such as calcimimetics or PTH analogs may be required to control PTH levels. However, these medications should be used cautiously due to limited data on their safety and efficacy in the bariatric surgery population. Prevention of SHPT is an important aspect of managing patients undergoing bariatric surgery. Nutritional counseling and regular monitoring of calcium, vitamin D, and PTH levels can help identify and address deficiencies early on. Additionally, using procedures that preserve the duodenum and proximal jejunum, such as duodenal switch or biliopancreatic diversion with duodenal switch, may reduce the risk of developing SHPT.

The Effects of Porphyra yezoensis Polysaccharides on Intestinal Health of Spotted Sea Bass, Lateolabrax maculatus

Porphyra yezoensis polysaccharides (PPs) have biological activities such as promoting digestion, functioning as antioxidants, and improving intestinal health. The aim of this study was to investigate the effects of PPs on the intestinal health of spotted sea bass (Lateolabrax maculatus). A total of 360 spotted sea bass (10.53 ± 0.02 g) were randomly divided into six groups. Fish in each group were fed with varying PP concentrations (0, 3, 6, 9, 12, 15 g/kg) for 52 days. The results showed that 12 g/kg PPs significantly increased the body weight gain, specific growth rate, and condition factor, while there was no significant change in the feed conversion ratio. A supplementation dosage of 9 g/kg PPs significantly increased intestinal amylase activity, and 12 g/kg PPs supplementation significantly increased intestinal trypsin activity. In addition, compared with the control group, there was no difference in lipase in the experimental groups. When fed 9 g/kg, the intestinal glutathione content was significantly increased, and the malondialdehyde content was significantly decreased; the effect of PPs on the catalase activity was not significant. PPs improved intestinal morphology, specifically by improving the intestinal villus morphology and increasing the intestinal lining surface area. Compared with the control group, PPs increased the abundance of Firmicutes and Bacteroides. At the genus level, Cyanobacteria, Muribaculaceae, and Lachnospiraceae were the main flora in the intestinal tract of spotted sea bass. In addition, PPs increased ACE and Chao1 indices of the intestinal microorganisms, while the Simpson index and Shannon index did not change significantly, indicating that intestinal microbial composition and abundance had increased to a certain extent. The results indicated that different levels of PPs in feed can improve the intestinal physiological and biochemical indexes, intestinal morphology, and microbial composition, and thus improve the intestinal health of spotted sea bass.

Endoscopic reversal of roux-en-Y gastric bypass prevents worsening of nutritional outcomes in patients with severe malnutrition

Roux-en-Y gastric bypass (RYGB) can precipitate protein-calorie malnutrition and micronutrient deficiencies. Sonographically guided endoscopic reversal (ER) via deployment of a stent from the gastric pouch to the remnant stomach in RYGB anatomy has emerged as a novel option for increasing both intestinal transit time and absorptive surface area. In this investigation, short-term nutritional outcomes after ER of a RYGB in patients (age ≥ 18) with severe protein-calorie malnutrition from a single academic health center in Minneapolis, Minnesota over a seven-year period (2015-2021) were retrospectively reviewed pre-procedurally, and at six and twelve months post-procedurally. 17 patients underwent ER for severe protein-calorie malnutrition, or dependence on tube feeds (TF) or total parenteral nutrition (TPN). At 6 months post-ER, two patients were no longer malnourished and only on oral nutrition; three patients were liberated from TPN. Laboratory markers of protein-calorie malnutrition, renal function, and micronutrients were not significantly different at six- or twelve-month follow-up (P &amp;gt; 0.05). In all patients, access to the gastric remnant was maintained via stent placement through the gastric pouch or proximal Roux limb throughout the study period and no complications were noted after ER. Despite the small sample size, this investigation revealed that ER of RYGB may prevent progressive deleterious weight loss, and worsening macro- and micro-nutrient deficiencies, though improvement in weight and nutritional parameters was not observed. Overall, ER was found to be a nuanced and safe, advanced technique useful for when remnant access is desired in RYGB patients.

Antibiotic-induced microbial depletion enhances murine small intestinal epithelial growth in a serotonin-dependent manner.

Regulation of small intestinal epithelial growth by endogenous and environmental factors is critical for intestinal homeostasis and recovery from insults. Depletion of the intestinal microbiome increases epithelial proliferation in small intestinal crypts, similar to the effects observed in animal models of serotonin potentiation. Based on prior evidence that the microbiome modulates serotonin activity, we hypothesized that microbial depletion-induced epithelial proliferation is dependent on host serotonin activity. A mouse model of antibiotic-induced microbial depletion (AIMD) was employed. Serotonin potentiation was achieved through either genetic knockout of the serotonin transporter (SERT) or pharmacologic SERT inhibition, and inhibition of serotonin synthesis was achieved with para-chlorophenylalanine. AIMD and serotonin potentiation increased intestinal villus height and crypt proliferation in an additive manner, but the epithelial proliferation observed after AIMD was blocked in the absence of endogenous serotonin. Using Lgr5-EGFP-reporter mice, we evaluated intestinal stem cell (ISC) quantity and proliferation. AIMD increased the number of ISCs per crypt and ISC proliferation compared to controls, and changes in ISC number and proliferation were dependent on the presence of host serotonin. Furthermore, western blotting demonstrated that AIMD reduced epithelial SERT protein expression compared to controls. In conclusion, host serotonin activity is necessary for microbial depletion-associated changes in villus height and ISC proliferation in crypts, and microbial depletion produces a functional serotonin-potentiated state through reduced SERT protein expression. These findings provide an understanding of how changes to the microbiome contribute to intestinal pathology and can be applied therapeutically.

THE APPLICATION OF YEAST AND LACTIC ACID BACTERIA IMPROVE GROWTH AND INTESTINAL STRUCTURE OF TIGER SHRIMP LARVAE Penaeus monodon Fab.

This study aims to investigate the effect of the different concentration of RABAL (yeast and lactic acid bacteria) probiotics on the survival, feed conversion, growth and intestinal cells changes of tiger shrimp Penaeus monodon Fab. larvae. This study used a Completely Randomized Design (CRD) method with 4 treatments and 4 replications. Tiger shrimp with average size of 0.02 g was randomly stocked in each container containing RABAL with concentration of 0 ppm (A/control), 75 ppm (B), 150 ppm (C), and 225 ppm (D) with frequency once a day for 30 days. Data were analysed using one way ANOVA. The result showed that the application of RABAL with different doses into the shrimp culture media significantly influences (P0.05) the growth and food conversion ratio of tiger shrimp feed but did not significantly affect (P 0.05) on the survival rate. The value of water quality parameters in this study were still at normal levels for tiger shrimp rearing. As conclusion, the application of probiotics RABAL with different concentrations have positive effect on the absolute weight, absolute length, specific growth rate, feed conversion ratio and intestinal villi surface area of tiger shrimp larvae, without adverse effect on the survival rate of tiger shrimp seed.

Intestinal Farnesoid X Receptor Modulates Duodenal Surface Area but Does Not Control Glucose Absorption in Mice.

Bile acids facilitate the intestinal absorption of dietary lipids and act as signalling molecules in the maintenance of metabolic homeostasis. Farnesoid X receptor (FXR) is a bile acid-responsive nuclear receptor involved in bile acid metabolism, as well as lipid and glucose homeostasis. Several studies have suggested a role of FXR in the control of genes regulating intestinal glucose handling. We applied a novel dual-label glucose kinetic approach in intestine-specific FXR-/- mice (iFXR-KO) to directly assess the role of intestinal FXR in glucose absorption. Although iFXR-KO mice showed decreased duodenal expression of hexokinase 1 (Hk1) under obesogenic conditions, the assessment of glucose fluxes in these mice did not show a role for intestinal FXR in glucose absorption. FXR activation with the specific agonist GS3972 induced Hk1, yet the glucose absorption rate remained unaffected. FXR activation increased the duodenal villus length in mice treated with GS3972, while stem cell proliferation remained unaffected. Accordingly, iFXR-KO mice on either chow, short or long-term HFD feeding displayed a shorter villus length in the duodenum compared to wild-type mice. These findings indicate that delayed glucose absorption reported in whole-body FXR-/- mice is not due to the absence of intestinal FXR. Yet, intestinal FXR does have a role in the small intestinal surface area.

ALTERED ABSORPTION, DISTRIBUTION CHANGES, METABOLIC CONSIDERATIONS, DRUG-DRUG INTERACTION OF PHARMACY KINETICS IN ILL PATIETNS, INFLUENCE OF SEVERAL FACTORS ON DRUG ABSORPTION IN ILL PERSONS

Pharmaco kinetics is a critical branch of pharmacology, emphasizes on how the body operates drugs, along with their absorption, distribution, metabolism and excretion. In all patients, the absorption of orally administered drugs can be influenced by gastro intestinal disturbances, altered pH levels and decreased blood flow to the intestine. In a very few illness, modifications in blood flow, protein levels and tissue binding can changes the distribution of drugs throughout the body. The liver acts as an important organ for metabolizing drugs and when it is compromised due to illness, drug metabolism can slow down or became erratic. Whatever it may be, in ill patients, renal function can be compromised leading to the occurrence of impaired drug excretion. Ill patients often gain multiple interactions to manage their conditions, enhancing the risk of drug drug interactions. Gastro intestinal motility, gastric pH, gastric blood flow and gasro intestinal surface area can influence drug absorption in an ill person. Finally it is concluded that understanding pharmaco kinetics in ill patients is a fundamental aspect of providing safe and effective medical care.

Overexpression of growth hormone improved hepatic glucose catabolism and relieved liver lipid deposition in common carp (Cyprinus carpio L.) fed a high-starch diet.

Growth hormone (GH) is important for regulating insulin secretion and carbohydrate metabolism, and its role in mammalian models of diabetes is relatively worked out. Although some fish species were used as models for diabetes research, the effects of GH on insulin and glucose catabolism and anabolism in these models remain to be clarified. In this study, we investigated the effect of GH on insulin and glucose catabolism and anabolism in an omnivorous fish using GH transgenic (T) common carp that consistently overexpressed GH and wild-type (WT) common carp. We compared the intestinal morphology, and digestive and absorptive capacity of fish fed commercial feed. We also analyzed the growth performance, insulin level, glucose catabolism and anabolism, lipid deposition, and lipid catabolism and anabolism in T carp and WT carp fed diets containing either 30% or 40% starch. In the intestine of T carp, α-amylase activity was enhanced, the number of goblet cells and intestinal villi surface area was increased, and the expression level of glucose transport protein-related genes (glut2 and sglt1) was upregulated when compared to these indicators in WT carp. When fed either a normal or high-starch diet, the growth performance of T carp was better than that of WT carp. Compared with WT carp, serum insulin was increased and glucose was decreased, hepatic expression level of igf-1 and glycolysis-related genes was increased, and the activity level of a hepatic enzyme related to glycolysis was enhanced in T carp. When fed with a high-starch diet, the serum alanine aminotransferase activity, hepatic lipid content, and malondialdehyde content were significantly lower in T carp than in WT carp. These results indicated that overexpression of GH (1) enhanced carbohydrate digestion and absorption in the carp intestine, (2) did not induce insulin resistance and improved glucose catabolism and utilization in carp, and (3) relieved liver lipid deposition. Our data might provide new insights into potential ways to improve glucose utilization in fish and diabetes treatments.

Investigation of murine host sex as a biological variable in epithelial barrier function and muscle contractility in human intestinal organoids.

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male and female mice. tHIOs were harvested after 8-12 weeks in vivo. Reverse transcriptase polymerase chain reaction and immunohistochemistry were conducted to compare tight junctions and contractility-related markers in tHIOs. An Ussing chamber and contractility apparatus were used to evaluate tHIO epithelial barrier and muscle contractile function, respectively. The expression and morphology of tight junction and contractility-related markers from tHIOs in male and female murine hosts is not significantly different. Epithelial barrier function as measured by transepithelial resistance, short circuit current, and fluorescein isothiocyanate-dextran permeability is no different in tHIOs from male and female hosts, although these results may be limited by HIO epithelial immaturity and a short flux time. Muscle contractility as measured by total contractile activity, amplitude, frequency, and tension is not significantly different in tHIOs from male and female hosts. The data suggest that murine host sex may not be a significant biological variable influencing tHIO function, specifically epithelial barrier maintenance and muscle contractility, though limitations exist in our model.

Individual and combined effects of dietary supplementation of probiotic and essential oil on the growth performance, immunity status, gut health and jejunal histomorphology of broiler chickens

The present study was conducted to evaluate the individual and combined effects of probiotic and essential oils on the performance of broilers. Day-old broiler chicks (240) were allocated to 5 groups in completely randomized design to give 6 replications per treatment group with 8 birds in each replicate. The birds of different groups were supplemented with antibiotic growth promoter (CTC 15%) at the level of 335 mg/kg (T1), essential oil formula (TCLVC 1.5×) (T2), L. fermentum NKN51 (107 cfu/g) along with MOS (0.3%) and sodium butyrate (0.03%) (T3), and combination of L. fermentum NKN51 (107 cfu/g) and essential oil formula (TCLVC 1.5×) in presence of MOS (0.3%) and sodium butyrate (0.03%) (T4). The control group was provided basal diet only with no other supplementation. The birds were reared for a period of 6 weeks and examined for growth performance including weekly body weight, average daily gain, weekly FCR, average feed intake, cell mediated and humoral immunity, gut microbiology, jejunal histology and stress parameters including heterophil-lymphocyte ratio and serum corticosterone levels. The group supplemented with combination of probiotic and essential oil formula (TCLVC 1.5×) had significantly better growth performance, cell mediated and humoral immunity and improved jejunal histology in terms of villus height, villus width, VH: CD ratio and intestinal absorptive surface area. No significant difference was observed in stress levels of different groups in terms of heterophil-lymphocyte ratio and serum corticosterone levels. The study depicted that combined supplementation of probiotic and essential oil had affirmative response on performance parameters of broiler chickens.

Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives.

Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.

Adequate levels of dietary sulphur amino acids impart improved liver and gut health in juvenile yellowtail kingfish (Seriola lalandi).

The sulphur amino acids methionine (Met) and cysteine (Cys) and their derivative taurine (Tau) are metabolically active molecules with interlinked roles in nutritional requirements. Deficiencies in these nutrients are linked to poor growth and health; however, the impacts of these deficiencies on organ structure and function are largely unknown. This study examined the effects of dietary Met, Cys and Tau fed at different levels on yellowtail kingfish (YTK) liver histology and surface colour, plasma biochemistry and posterior intestine histology. Samples were collected from two dose-response feeding trials that quantified (1) the Tau requirement and sparing effect of Met by feeding YTK diets containing one of seven levels of Tau at one of two levels of Met and (2) the Met requirement and sparing effect of Cys by feeding YTK diets containing one of five levels of Met at one of two levels of Cys. YTK fed inadequate levels of dietary Met, Cys and Tau exhibited thicker bile ducts, less red livers, more intestinal acidic goblet cell mucus and supranuclear vacuoles and less posterior intestinal absorptive surface area. Further, thicker bile ducts correlated with less red livers (a*, R), whereas increased hepatic fat correlated with a liver yellowing (b*). Our results indicate a shift towards histological properties and functions indicative of improved intrahepatic biliary condition, posterior intestinal nutrient absorption and homoeostasis of YTK fed adequate amounts of Met, Cys and Tau. These findings may assist in formulating aquafeed for optimised gastrointestinal and liver functions and maintaining good health in YTK.

Intestinal Deletion of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion of the Resident Stem Cell Compartment.

The intestine occupies the critical interface between cholesterol absorption and excretion. Surprisingly little is known about the role of de novo cholesterol synthesis in this organ, and its relationship to whole body cholesterol homeostasis. Here, we investigate the physiological importance of this pathway through genetic deletion of the rate-limiting enzyme. Mice lacking 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) in intestinal villus and crypt epithelial cells were generated using a Villin-Cre transgene. Plasma lipids, intestinal morphology, mevalonate pathway metabolites, and gene expression were analyzed. Mice with intestine-specific loss of Hmgcr were markedly smaller at birth, but gain weight at a rate similar to wild-type littermates, and are viable and fertile into adulthood. Intestine lengths and weights were greater relative to body weight in both male and female Hmgcr intestinal knockout mice. Male intestinal knockout had decreased plasma cholesterol levels, whereas fasting triglycerides were lower in both sexes. Lipidomics revealed substantial reductions in numerous nonsterol isoprenoids and sterol intermediates within the epithelial layer, but cholesterol levels were preserved. Hmgcr intestinal knockout mice also showed robust activation of SREBP-2 (sterol-regulatory element binding protein-2) target genes in the epithelium, including the LDLR (low-density lipoprotein receptor). At the cellular level, loss of Hmgcr is compensated for quickly after birth through a dramatic expansion of the stem cell compartment, which persists into adulthood. Loss of Hmgcr in the intestine is compatible with life through compensatory increases in intestinal absorptive surface area, LDLR expression, and expansion of the resident stem cell compartment.

Fecal microbiome and bile acid metabolome in adult short bowel syndrome.

Loss of functional small bowel surface area causes short bowel syndrome (SBS), intestinal failure, and parenteral nutrition (PN) dependence. The gut adaptive response following resection may be difficult to predict, and it may take up to 2 yr to determine which patients will wean from PN. Here, we examined features of gut microbiota and bile acid (BA) metabolism in determining adaptation and ability to wean from PN. Stool and sera were collected from healthy controls and from patients with SBS (n = 52) with ileostomy, jejunostomy, ileocolonic, and jejunocolonic anastomoses fed with PN plus enteral nutrition or who were exclusively enterally fed. We undertook 16S rRNA gene sequencing, BA profiling, and 7α-hydroxy-4-cholesten-3-one (C4) quantitation with LC-MS/MS and serum amino acid analyses. Patients with SBS exhibited altered gut microbiota with reduced gut microbial diversity compared with healthy controls. We observed differences in the microbiomes of patients with SBS with ileostomy versus jejunostomy, jejunocolonic versus ileocolonic anastomoses, and PN dependence compared with those who weaned from PN. Stool and serum BA composition and C4 concentrations were also altered in patients with SBS, reflecting adaptive changes in enterohepatic BA cycling. Stools from patients who were weaned from PN were enriched in secondary BAs including deoxycholic acid and lithocholic aicd. Shifts in gut microbiota and BA metabolites may generate a favorable luminal environment in select patients with SBS, promoting the ability to wean from PN. Proadaptive microbial species and select BA may provide novel targets for patient-specific therapies for SBS.NEW & NOTEWORTHY Loss of intestinal surface area causes short bowel syndrome, intestinal failure, and parenteral nutrition dependence. We analyzed the gut microbiota and bile acid metabolome of a large cohort of short bowel syndrome adult patients with different postsurgical anatomies. We report a novel analysis of the microbiome of patients with ileostomy and jejunostomy. Enrichment of specific microbial and bile acid species may be associated with the ability to wean from parenteral nutrition.

Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel.

Extensive intestinal resection may lead to short bowel (SB) syndrome, resulting in intestinal insufficiency or intestinal failure (IF). Intestinal insufficiency and IF involve deficiency of the proglucagon-derived hormones glucagon-like peptide-1 (GLP-1) and GLP-2. Two major problems of SB are epithelial surface loss and accelerated transit. Standard treatment now targets intestinal adaptation with a GLP-2 analogue to enlarge absorptive surface area. It is possible that additional benefit can be gained from a combination of GLP-1 and GLP-2 activity, with the aim to enlarge intestinal surface area and slow intestinal transit. The GLP-1- and GLP-2-specific effects of the novel dual GLP-1 receptor (GLP-1R) and GLP-2 receptor (GLP-2R) agonist dapiglutide (rINN) were characterized in rodents. Furthermore, in a murine SB model of intestinal insufficiency with 40% ileocecal resection, the influence of dapiglutide on intestinal growth, body weight, food intake, volume status, and stool water content was tested against vehicle and sham-operated male mice. Dapiglutide significantly improves oral glucose tolerance, reduces intestinal transit time, and promotes intestinal growth. In the SB mouse model, dapiglutide promotes body weight recovery, despite unchanged intake of liquid diet. Dapiglutide promotes significant intestinal growth, as indicated by significantly increased villus height as well as intestinal length. Furthermore, dapiglutide reduces stool water losses, resulting in reduced plasma aldosterone. Dapiglutide possesses specific and potent GLP-1R and GLP-2R agonist effects in rodents. In the murine SB model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency and potentially also IF.