Short-, medium-, and long-chain fatty acid profiles and signaling is responsive to dietary phytase and lactic acid treatment of cereals along the gastrointestinal tract of growing pigs

Abstract

Dietary and microbially derived fatty acids (FA) play important roles in gut mucosal inflammatory signaling, barrier function and oxidative stress response. Nevertheless, little information is available about gastrointestinal FA profiles and receptor distribution in pigs, especially for long-chain FA (LCFA). Therefore, the present pilot study aimed to 1) investigate the gastrointestinal FA profiles; 2) link the luminal FA profiles to the mucosal expression of genes related to FA sensing and signaling; and 3) assess potential dietary effects on gut and systemic lipid metabolism in pigs. Gut, liver and serum samples were obtained from barrows (13.1 ± 2.3 kg) fed diets containing either phytase (500 phytase units/kg diet) or cereals treated with 2.5% lactic acid (LA) (n = 8/diet) for 18 days. Results showed gut regional and diet-related differences in luminal FA profiles and mucosal receptor expression, whereas diet little affected hepatic expression levels and serum lipids. Short-chain fatty acids (SCFA) increased from stomach, jejunum and ileum to the cecum (P < 0.05), whereas LCFA were higher in stomach, cecum and colon than in jejunum and ileum (P < 0.05). LA-treated cereals enhanced cecal acetate and butyrate, whereas phytase and LA treated cereals decreased the LCFA by 35.9 and 14.4%, respectively (P < 0.05). Gut regional differences suggested stronger signaling via FFAR1 expression in the ileum, and via FFAR2, FFAR4 and HCAR1 expression in cecum and colon (P < 0.05). Expression of AMPK, FASN, PPARG, SREBP1 and SREBP2 was higher in the cecum and colon compared to the small intestine (P < 0.05), with stronger sensing via FASN and SREBP2. Phytase decreased expression of FFAR2 and FFAR4, whereas it increased that of FFAR3 and MCT1 in the cecum (P < 0.05). LA-treated cereals raised cecal expression of FFAR3 and HCAR1 (P < 0.05). Pearson’s correlations (|r| > 0.35; P < 0.05) supported that FA receptor- and nuclear transcription factor-dependent pathways were involved in the mucosal regulation of gut incretin expression but differed across gut regions. In conclusion, results support regional differences in SCFA, lactate and LCFA sensing and absorption capacities in the small and large intestines of pigs. Effects of phytase and the LA-treated cereals on intestinal FA levels and signaling can be explained by differences in nutrient flows (e.g. phosphorus and carbohydrate fractions). This overview provides a solid basis for future intestinal FA sensing in pigs.

Short-Chain Fatty Acids Modulate Permeability, Motility and Gene Expression in the Porcine Fetal Jejunum Ex Vivo

“…SCFA are absorbed transcellularly via carrier proteins and paracellularly via pores formed by tightjunction proteins [23]. Postnatally, the sodium-coupled transporters (SMCT) are the major SCFA transporters in the porcine jejunum, whereas monocarboxylate transporter (MCT)-1 dominates in the large intestine [24]. According to the present results for absolute gene expression, MCT-1 seems to play an equally important role in SCFA absorption in the fetal jejunum to SMCT-1.…”

The Role of Dietary and Microbial Fatty Acids in the Control of Inflammation in Neonatal Piglets

“…Against this background, intestinal production of conjugated LA and other FA derivatives by the gut microbiota may be thinkable, even in very young piglets. In this respect, we recently found increased long-chain FA concentrations including C18:1 n-9, C18:2 n-6, and C18:3 n-3 in the cecal and colonic digesta of 10-to 11-week-old pigs, which were, at least partially, attributable to microbial FA synthesis [31].…”

“…At this age, GPRs and HCAR-1, which responds to lactate, were highly expressed in the small and large intestines, emphasising the importance of dietary and microbial FA sensing along the intestinal tract. Gene expression data further suggested a stronger signalling via FFAR-1 in the ileum, as well as via FFAR-2, FFAR-4 and HCAR-1 in the cecum and colon regions which was likely attributable to substrate affinities and luminal exposure to SCFA, MCFA and long-chain FA [31]. Likewise, gene copy abundances for nuclear transcription factors suggested a greater role of FA synthase (FASN) and sterol regulatory element-binding protein (SREBP)-2 in gut mucosal signalling in young growing pigs [31].…”

“…Gene expression data further suggested a stronger signalling via FFAR-1 in the ileum, as well as via FFAR-2, FFAR-4 and HCAR-1 in the cecum and colon regions which was likely attributable to substrate affinities and luminal exposure to SCFA, MCFA and long-chain FA [31]. Likewise, gene copy abundances for nuclear transcription factors suggested a greater role of FA synthase (FASN) and sterol regulatory element-binding protein (SREBP)-2 in gut mucosal signalling in young growing pigs [31]. However, information about the development of gut region-specific FA receptor expression and signalling in the first weeks of life is still missing.…”

“…GPRs, HCARs and nuclear transcription factors are involved in signalling related to insulin and incretin hormone secretion, adipocyte differentiation, anti-inflammatory effects, neuronal responses, and appetite and thus are involved in energy and immune homeostasis. Recently, we have been able to demonstrate the regional specificities for gut mucosal SCFA, lactate and long-chain FA sensing capacities (i.e., receptor activation and FA signal transduction) in the small and large intestines of 10-week-old pigs towards luminal FA concentrations, leading to the differential expression of the downstream targets of these receptors, i.e., gastric inhibitory polypeptide (GIP) and glucagon-like peptide (GLP)-1, in the small and large intestines [31]. At this age, GPRs and HCAR-1, which responds to lactate, were highly expressed in the small and large intestines, emphasising the importance of dietary and microbial FA sensing along the intestinal tract.…”