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Sensing of nutrients by chemosensory cells in the gastrointestinal tract plays a key role in transmitting food-related signals, linking information about the composition of ingested foods to digestive processes. In recent years, a number of G protein-coupled receptors (GPCR) responsive to a range of nutrients have been identified. Many are localised to intestinal enteroendocrine (chemosensory) cells, promoting hormonal and neuronal signalling locally, centrally and to the periphery. The field of gut sensory systems is relatively new and still evolving. Despite huge interest in these nutrient-sensing GPCR, both as sensors for nutritional status and targets for preventing the development of metabolic diseases, major challenges remain to be resolved. However, the gut expressed sweet taste receptor, resident in L-enteroendocrine cells and responsive to dietary sweetener additives, has already been successfully explored and utilised as a therapeutic target, treating weaning-related disorders in young animals. In addition to sensing nutrients, many GPCR are targets for drugs used in clinical practice. As such these receptors, in particular those expressed in L-cells, are currently being assessed as potential new pathways for treating diabetes and obesity. Furthermore, growing recognition of gut chemosensing of microbial-produced SCFA acids has led further attention to the association between nutrition and development of chronic disorders focusing on the relationship between nutrients, gut microbiota and health. The central importance of gut nutrient sensing in the control of gastrointestinal physiology, health promotion and gut-brain communication offers promise that further therapeutic successes and nutritional recommendations will arise from research in this area. [ABSTRACT FROM AUTHOR]

Summary Dietary carbohydrates, when digested and absorbed in the small intestine of the horse, provide a substantial fraction of metabolisable energy. However, if levels in diets exceed the capacity of the equine small intestine to digest and absorb them, they reach the hindgut, cause alterations in microbial populations and the metabolite products and predispose the horse to gastrointestinal diseases. We set out to determine, at the molecular level, the mechanisms, properties and the site of expression of carbohydrate digestive and absorptive functions of the equine small intestinal brush-border membrane. We have demonstrated that the disaccharidases sucrase, lactase and maltase are expressed diversely along the length of the intestine and D-glucose is transported across the equine intestinal brush-border membrane by a high affinity, low capacity, Na [ABSTRACT FROM AUTHOR]

Introduction Based on morphological and physiological differences in their digestive systems Hofmann and Stewart (1972) classified ruminants into three feeding types: concentrate selectors (CS), grass and roughage eaters (GR) and intermediate, opportunistic, mixed feeders (IM). In evolutionary terms CS most closely resemble the original ruminants (Hofmann 1989). They have a relatively small forestomach with large openings between the different parts of the stomach. The retention time of ingesta is short and therefore less suited to optimizing cellulose digestion. They have relatively large saliva glands, producing high volumes of saliva (Fickel et al. 1998), which may facilitate the passage of soluble nutrients down their highly developed ventricular groove. The CS ruminants choose easily digestible forage, especially dicotyledons, which are rich in soluble plant cell contents (PCC, Tixier et al. 1997; Duncan et al. 1998). With evolution, the forestomach of the ruminants became larger relative to body size, and also more subdivided. These evolutionary adaptations optimized the selective retention of feed particles and increased retention time, leading to improvement of cellulose digestion. Large GR are well adapted to digest plant cell walls (PCW), i.e. structural carbohydrates (cellulose); they consequently feed mainly on monocotyledons. Roe deer (Capreolus capreolus) are very small ruminants which select concentrated feed. As energy requirements increase proportional to metabolic body weight (Kleiber 1961) roe deer require relatively more energy per unit body mass for maintenance compared to that required by large ruminants (Van Soest 1994; Duncan et al. 1998). Easily digestible forage is not sufficient to satisfy the energy requirements of roe deer. It is proposed therefore that these animals may have other methods of avoiding energy losses due to microbial fermentation, either bypassing nutrients down the ventricular groove (rumen bypass) or by ruminal... [ABSTRACT FROM AUTHOR]

Absorption of glucose from the lumen of the intestine into enterocytes is accomplished by sodium-glucose co-transporter 1 (SGLT1). In the majority of mammalian species, expression (this includes activity) of SGLT1 is upregulated in response to increased dietary monosaccharides. This regulatory pathway is initiated by sensing of luminal sugar by the gut-expressed sweet taste receptor. The objectives of our studies were to determine (1) if the ruminant intestine expresses the sweet taste receptor, which consists of two subunits [taste 1 receptor 2 (T1R2) and 3 (T1R3)], and other key signaling molecules required for SGLT1 upregula-tion in nonruminant intestines, and (2) whether T1R2-T1R3 sensing of artificial sweeteners induces release of glucagon-like peptide-2 (GLP-2) and enhances SGLT1 expression. We found that the small intestine of sheep and cattle express T1R2, T1R3, G-protein gustducin, and GLP-2 in enteroendocrine L-cells. Maintaining 110-d-old ruminating calves for 60 d on a diet containing a starter concentrate and the artificial sweetener Sucram (consisting of saccharin and neohesperidin dihydrochalcone; Pancosma SA, Geneva, Switzerland) enhances (1) Na+-dependent d-glucose uptake by over 3-fold, (2) villus height and crypt depth by 1.4- and 1.2-fold, and (3) maltase- and alkaline phosphatase-specific activity by 1.5-fold compared to calves maintained on the same diet without Sucram. No statistically significant differences were observed for rates of intestinal glucose uptake, villus height, crypt depth, or enzyme activities between 50-d-old milk-fed calves and calves maintained on the same diet containing Sucram. When adult cows were kept on a diet containing 80:20 ryegrass hay-to-concentrate supplemented with Sucram, more than a 7-fold increase in SGLT1 protein abundance was noted. Collectively, the data indicate that inclusion of this artificial sweetener enhances SGLT1 expression and mucosal growth in ruminant animals. Exposure of ruminant sheep intestinal segments to saccharin or neohesperidin dihydrochalcone evokes secretion of GLP-2, the gut hormone known to enhance intestinal glucose absorption and mucosal growth. Artificial sweeteners, such as Sucram, at small concentrations are potent activators of T1R2-T1R3 (600-fold > glucose). This, combined with oral bioavailability of T1R2-T1R3 and the understanding that artificial sweetener-induced receptor activation evokes GLP-2 release (thus leading to increased SGLT1 expression and mucosal growth), make this receptor a suitable target for dietary manipulation. [ABSTRACT FROM AUTHOR]

Provides information on a study examining the effect of adaptation to a low-NaCl diet on the activity of two epithelial exchangers in the colonic brush borders (BBs) of chicken colon and ileum. Methodology and materials used to conduct the study; Kinetics of D-glucose uptake into brush border membrane vesicles (BBMV) from colon of chickens fed either a high- or low-NaCl diet; Findings of the study.

Toll-like receptors (TLRs) play a key role in the recognition of microbes via detection of specific and conserved microbial molecular features. TLRs, mainly expressed in immune cells, interact with intestinal microbiome. Little is known about mechanism(s) of sensing of bacteria by the intestinal surface enteroendocrine cells (EECs). We show here that TLR9 is expressed by the EECs of proximal intestine in a range of species and is co-expressed with the satiety hormone cholecystokinin (CCK). CCK secreted in excess induces emesis (vomiting). Using an EEC model cell line, STC-1, we demonstrate that in response to the TLR9 agonist, DNA containing unmethylated CpG dinucleotide motifs, STC-1 cells secrete CCK and that this secretion is inhibited by specific inhibitors of TLR9. Exposure of STC-1 cells to heat-inactivated pathogenic bacteria, Escherichia coli O55/H7, Shigella flexneri 2457T, Salmonella typhimurium ST4/74, and non-pathogenic Lactobacillus amylovorus GRL1112, results to an increase in CCK secretion compared to untreated control. The magnitudes of CCK release are higher in response to pathogenic bacteria and lowest in response to the non-pathogenic L. amylovorus. The pathogenic strains not only have substantially bigger genomes than L. amylovorus, they also have significantly higher numbers/frequency of RR/CG/YY stimulatory CpG hexamers in their genomic DNA. Pathogen-induced excessive secretion of the gut hormone CCK, provoking emesis can serve as a protective mechanism against development of enteric infections., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Glucose transport across the enterocyte brush border membrane by sodium/glucose cotransporter-1 (SGLT1, coded by Slc5a1) is the rate-limiting step for intestinal glucose transport. The relevance of SGLT1 expression in predisposition to diabetes mellitus and to obesity was investigated in dogs. Cultured Caco-2/TC7 cells were shown to express SGLT1 in vitro. A 2-kbp fragment of the Slc5a1 5' flanking region was cloned from canine genomic DNA, ligated into reporter gene plasmids, and shown to drive reporter gene expression in these cells above control (P < 0.001). To determine the effect of the 3 known SNPs in this region on promoter function, new promoter/reporter constructs (all permutations of these 3 SNPs) were created by site-directed mutagenesis. No significant differences in promoter function were seen, suggesting that these SNPs do not have a significant effect on the constitutive transcription of SGLT1 mRNA in dogs. A search for novel SNPs in this region in dogs was made in 2 breeds predisposed to diabetes mellitus (Samoyed and cairn terrier), 2 breeds that rarely develop diabetes (boxer and German shepherd), and 2 breeds predisposed to obesity (Labrador retriever and cocker spaniel). The Slc5a1 5' flanking region was amplified from 10 healthy individuals of each of these breeds by high-fidelity PCR with the use of breed-labeled primers and sequenced by pyrosequencing. The sequence of the Slc5a1 5' flanking region in all individuals of all breeds tested was identical. On this evidence, variations in Slc5a1 promoter sequence between dogs do not influence the pathogenesis of diabetes mellitus or obesity in these breeds., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The domestic cat (Felis catus), a carnivore, naturally eats a very low carbohydrate diet. In contrast, the dog (Canis familiaris), a carno-omnivore, has a varied diet. This study was performed to determine the expression of the intestinal brush border membrane sodium/glucose cotransporter, SGLT1, sweet receptor, T1R2/T1R3, and disaccharidases in these species adapted to contrasting diets. The expression (this includes function) of SGLT1, sucrase, maltase and lactase were determined using purified brush border membrane vesicles and by quantitative immunohistochemistry of fixed tissues. The pattern of expression of subunits of the sweet receptor T1R2 and T1R3 was assessed using fluorescent immunohistochemistry. In proximal, middle, and distal small intestine, SGLT1 function in dogs was 1.9- to 2.3-fold higher than in cats (P = 0.037, P = 0.0011, P = 0.027, respectively), and SGLT1 protein abundance followed an identical pattern. Both cats and dogs express T1R3 in a subset of intestinal epithelial cells, and dogs, but not cats, express T1R2. In proximal and middle regions, there were 3.1- and 1.6-fold higher lactase (P = 0.006 and P = 0.019), 4.4- and 2.9-fold higher sucrase (both P < 0.0001), and 4.6- and 3.1-fold higher maltase activity (P = 0.0026 and P = 0.0005), respectively, in the intestine of dogs compared with cats. Dogs have a potential higher capacity to digest and absorb carbohydrates than cats. Cats may suffer from carbohydrate malabsorption following ingestion of high-carbohydrate meals. However, dogs have a digestive ability to cope with diets containing significant levels of carbohydrate.

SGLT1 (Na(+)/glucose co-transporter 1) transports the dietary sugars, D-glucose and D-galactose, from the lumen of the intestine into enterocytes. SGLT1 regulation has important consequences for the provision of glucose to the respiring tissues and is therefore essential for maintaining glucose homoeostasis. SGLT1 expression is directly regulated in response to changes in the sugar content of the diet. To monitor these variations, there is a requirement for a glucose-sensing system located on the luminal membrane of gut cells. This short review focuses on recent findings on intestinal sugar sensing and the downstream mechanisms responsible for enhancement in SGLT1 expression.

The transition from normality to malignancy in colorectal cancer is characterized by alterations in the expression of genes associated with the maintenance of tissue homoeostasis. Butyrate, a product of microbial fermentation of dietary fibre in the colon, is known to regulate a number of genes associated with the processes of proliferation, differentiation and apoptosis of colonic epithelial cells, and, hence, homoeostasis of colonic tissue. We have shown previously that the transport of butyrate into colonocytes is of fundamental importance to butyrate's regulatory ability, and therefore sought to assess the expression profile of butyrate-responsive genes in colon cancer tissue, where the expression of the colonic luminal-membrane butyrate transporter, MCT1 (monocarboxylate transporter 1), is significantly down-regulated. In the present paper, we first employed microarray analysis to assess global changes in butyrate-responsive genes using HT29 human colon carcinoma cells treated with butyrate. There was consistency in the butyrate response of selected genes in two other human colonic cell lines (HCT116 and AA/C1) using quantitative real-time PCR. Furthermore, we report that expression levels of selected butyrate-responsive genes involved in the processes of proliferation, differentiation and apoptosis, are deregulated in colon cancer tissue, correlating with decreased expression of MCT1. These findings support our hypothesis that a reduction in MCT1 expression, and hence butyrate transport, can lead to a reduction in the intracellular butyrate levels required to regulate gene expression. Collectively, our results highlight the important contribution of butyrate transport to the maintenance of tissue homoeostasis and disease prevention.

The composition of the intestinal luminal content varies considerably with diet. It is important therefore that the intestinal epithelium senses and responds to these significant changes and regulates its functions accordingly. Although it is becoming evident that the gut epithelium senses and responds to luminal nutrients, little is known about the nature of the nutrient sensing molecule and the downstream cellular events. A prototype example is the modulation in the capacity of the gut to absorb monosaccharides via the intestinal luminal membrane Na(+)/glucose cotransporter, SGLT1. The experimental evidence suggests that luminal sugar is sensed by a glucose sensor residing on the luminal membrane of the gut epithelium and linked to a G-protein-coupled receptor, cAMP/PKA (protein kinase A) pathway, resulting ultimately in modulation of intestinal monosaccharide absorption. Here we report the expression, at mRNA and protein levels, of members of the T1R sweet taste receptors, and the alpha-subunit of the G-protein gustducin, in the small intestine and the enteroendocrine cell line, STC-1. In the small intestine, there is a highly coordinated expression of sweet taste receptors and gustducin, a G-protein implicated in intracellular taste signal transduction, throughout the gut. The potential involvement of these receptors in sugar sensing in the intestine will facilitate our understanding of intestinal nutrient sensing, with implications for better nutrition and health maintenance.