1
The short-term control of feed intake in pigs relies on the signals from the upper gastrointestinal tract (mouth and stomach) while the long-term control of feed intake comes after the integration of post-gastric (from small or large intestines) signals to the brain. The harmonization of the two mechanisms requires a finely tuned chemosensory system capable of communicating with the brain.
The chemosensory system in the gut
The main function of the digestive system is to obtain all nutrients essential to maintain physiological homeostasis. This requires a network of organs and tissues consisting of highly differentiated cell-types with complementary functions ranging from enzymatic secretion, gut motility or immunity among others. In particular, the epithelium of the gastrointestinal tract (GIT) has emerged as a complex cell system consisting of a diversity of functional cell types of epithelial origin including enterocytes (for nutrient absorption) and several cell-types specialised in sensing nutrients (sensory), mucous secretion (goblet), and defence against microbes or parasites (Paneth and tuft cells, respectively). All of these cell-types rely on chemosensory receptors (some originally identified as taste receptors) to align their function to the rest of the functions in an orderly/synchronised manner. The role of synchronising the digestive and nutrient absorption functions in the GIT relies on the entero-endocrine cells (EEC). EEC account for roughly 1% of the digestive epithelial cells only. However, EEC release gut peptides to amplify their signals to a local (paracrine) or systemic (endocrine) levels facilitating the steering role in digestive functions and integrating the signals to and the feedback from the brain (the gut-brain axis). The structured network of gastrointestinal cells (including EEC) and afferent and efferent nerves and their synchronised function has been referred to as the gut chemosensory system.
In brief, the chemosensory system functions by monitoring nutrients and potential toxicants present in the orogastric and intestinal contents (primarily of dietary origin). It allows pigs to discriminate between nutrient sources present in the environment and integrate incoming signals from the brain relevant to nutritional status (appetite) or other senses (i.e. smell, sound, vision). Carbohydrates and fats (energy) and amino acids are sensed by taste sensory cells in the mouth eliciting the hedonic sensing of foods, and by EEC in the gut which respond with gut peptide secretion (Table 1).
Table 1. Main chemosensory cells, nutrient affinity and gut hormones released in pigs
(adapted from Roura and Navarro 2018; Fothergill and Furness 2018; Steenles and Depoortere, 2018)
| GIT organ | Cell type | Hormone | Dietary ligands described | Main effects described relevant to feed intake |
|---|---|---|---|---|
| Mouth (taste papillae) | Type I or III sensory cells | 5-HT | Salt (Type I) or acids (Type III) | Short-term anorexigenic role (↓appetite); stimulates gustatory cortex; determines feed rejection. |
| Mouth (taste papillae) | Type II sensory cells (subtype 1) | 5-HT | Sugars, sweeteners, amino acids and fatty acids | Short-term orexigenic role (↑appetite); stimulates gustatory cortex; ↑insulin secretion (cephalic peak) determines feed preference. |
| Mouth (taste papillae) | Type II sensory cells (subtype 2) | 5-HT | Bitter compounds | Short-term anorexigenic role (↓appetite); stimulates gustatory cortex. Identification of toxicants causing feed rejection. |
| Stomach |
P/D1 cells (X/A in mice) |
Ghrelin | Stimulated by peptones, L-Trp, L-Phe, L-Ala, L-Glu, Sugars, LCFA; inhibited by acetate or propionate | Short-term effect on hunger. Initiates feed intake and determines the timing of meals. Reduces the sensitivity of gastric vagal afferents and to gastric distension; ↑insulin |
| Stomach | G cells | Gastrin | Stimulated by peptones, L-Trp, L-Phe, L-Ala; SCFA (C1-C5) | Secretion of digestive agents (gastric acid, hormones); ↑Plasma CCK |
| Stomach and small intestine | D cells | Somatostatin | Stimulated by peptones, L-Trp, L-Phe, L-Ala; LCFA (C14-C22) | Initiates the protein-induced satiety pathway more relevant at intestinal level; ↓Gastrin secretion |
| Proximal small intestine | I cells | CCK | Stimulated by L-Trp, L-Phe, L-Glu and L-Lys(1); SCFA, MCFA and LCFA; Bitterants | Shor-term and long-term inhibition of feed intake (↑satiation) part of the protein-induced satiety and fermentation-driven satiety; ↓Gastrin secretion and emptying; ↑ pancreatic enzyme secretion |
| Proximal small intestine | K cells | GIP | Glucose | Long-term inhibition of feed intake; ↑Insulin secretion (post-cephalic) and satiety; ↑ Glucose uptake and storage and fatty acids uptake into adipocytes. |
| Distal small & large intestine | L cells | GLP-1 / PYY | Stimulated by L-Ala and L-Glu; Sugars; SCFA, MCFA and LCFA; Bile acids; Bitterants | Long-term inhibition of feed intake with ↓gastrointestinal motility; part of the protein-induced satiety pathway; ↑Insulin release (GLP-1) and satiety; ↑Glucose uptake and storage |
Abbreviations: GIT=Gastrointestinal tract; LCFA/MCFA/SCFA= Long (L), Medium (M) or Short (S) Chain Fatty Acids; 5-HT=Serotonin; G cells=Gastrin-producing cells; P/D1 cells= Pancreatic D1-like cells; D cells=Pancreatic D-like cells; I, or L cells refer to the size of intracellular vesicles (Small, Intermediate or Large, respectively); K cells=cells with large vesicles but different from L cells; M cells=Motilin-producing cells; N cells=Neurotensin-producing cells; CCK=Cholecystokinin; GIP=Glucose-dependent Insulinotropic Peptide; GLP-1=Glucagon-like Peptide-1; PYY=Polypeptide Tyrosine Tyrosine. (1)Roura et al (unpublished data).
Orogastric and intestinal sensing mechanisms in the control of feed intake in pigs
The control of appetite and feed intake is complex. In brief, it integrates at least two mechanisms that relate to the short term (within a meal) or long term (between meals) control of appetite (Table 1).
Short-term effects on feed intake
Meal duration has been related to feedback mechanisms conveyed to the brain by the upper digestive system (mainly oral cavity or stomach). Based on preference models, pigs have the capacity to taste compounds which have been described as sweet, starchy, umami, fatty, salty, sour or bitter by humans. Taste perception occurs in the mouth after the signal has been conveyed to the gustatory cortex of the brain through dedicated neuronal fibres of cranial nerves (VII, IX and X). In brief, hedonic tastes (sweet, starchy, umami and fatty tastes) are related to essential nutrients and will stimulate feed intake, while unpleasant tastes are related to potential toxic compounds (bitter), excess salt (salty) or bacterial fermentation (sour) will reduce consumption (Table 1). The stomach is a decision-making organ equipped with extraordinary nutrient sensing capabilities. EEC cells have been related to the release of Ghrelin, Gastrin or Somatostatin among others (Table 1) in response to nutrients. In particular, peptones, L-Trp, L-Phe, L-Ala, L-Glu, sugars, and long-chain fatty acids (LCFA) exert a positive stimulatory effect on appetite through P/D1 and D cells. In contrast, appetite inhibiting signals are released by G cells in response to short-chain fatty acids (SCFA) among other ligands.
Long-term effects on feed intake
The interval between meals and beyond is determined mainly by an integration of signals originated in the small and/or large intestines. Nutrient sensors (including taste receptors) are abundantly expressed in EEC and other gut-associated epithelial cells. This nutrient sensors are co-expressed with gut peptides (such as CCK, GLP-1 or PYY) in EEC and are associated with their release serving paracrine (local) or endocrine (systemic) functions relevant to appetite. The type of co-expression patterns (nutrient receptor/gut peptide) and location of the sensory cells will determine how the sensing of a nutrient will be translated into a complex dialogue between gut and brain which will determine feed intake behaviour (Table 1). Recent evidences point at three functionally distinctive sites: a) intestinal pre-enzymatic digestion which affects gut motility and CCK release eliciting satiety; b) intestinal post-enzymatic digestion relates to feed digestibility and linked to the release of GLP-1, GIP and PYY with insulinotropic effects; and c) bacterial fermentation associated with the release of short-chain-fatty-acids (SCFA) which in turn may reach the small intestine and elicit CCK release (Table1).
Application of chemosensory principles
The principles of how the chemosensory system affects short-term and long-term mechanisms on feed intake have the potential to improve practical feeding/formulation practices. Firstly, hedonic feed ingredients (including flavours) can improve short-term feed intake. Some of these ingredients have abundant simple molecules (maybe as a result of pre-hydrolysed material such as hydrolysed protein sources) that improve the hedonic value of feeds. Secondly, in order to avoid a depression on feed intake feeds should be formulated not only to meet the essential amino acid requirement but also avoid excess of synthetic amino acids which will strongly elicit CCK release from the upper small intestine. Thirdly, low digestibility ingredients (resistant- starch) will slow down gastric emptying and passage rate, decrease the insulinotropic response (inhibiting GLP-1 release) and increase hindgut fermentation and SCFA production all resulting in decreased feed intake.
