Serotonin (5-HT) produced by enterochromaffin (EC) cells in the digestive tract is crucial for maintaining gut function and homeostasis. Nutritional and non-nutritional stimuli in the gut lumen can modulate the ability of EC cells to produce 5-HT in a temporal- and spatial-specific manner that toning gut physiology and immune response. Of particular interest, the interactions between dietary factors and the gut microbiota exert distinct impacts on gut 5-HT homeostasis and signaling in metabolism and the gut immune response. However, the underlying mechanisms need to be unraveled. This review aims to summarize and discuss the importance of gut 5-HT homeostasis and its regulation in maintaining gut metabolism and immune function in health and disease with special emphasis on different types of nutrients, dietary supplements, processing, and gut microbiota. Cutting-edge discoveries in this area will provide the basis for the development of new nutritional and pharmaceutical strategies for the prevention and treatment of serotonin homeostasis-related gut and systematic disorders and diseases.

Early colonization of intestinal microbiota during the neonatal stage plays an important role on the development of intestinal immune system and nutrients absorption of the host. Compared to the normal birth weight (NBW) piglets, intrauterine growth restricted (IUGR) piglets have a different intestinal microbiota during their early life, which is related to maternal imprinting on intestinal microbial succession during gestation, at birth and via suckling. Imbalanced allocation of limited nutrients among fetuses during gestation could be one of the main causes for impaired intestinal development and microbiota colonization in neonatal IUGR piglets. In this review, we summarized the potential impact of maternal imprinting on the colonization of the intestinal microbiota in IUGR piglets, including maternal undernutrition, imbalanced allocation of nutrients among fetuses, as well as vertical microbial transmission from mother to offspring during gestation and lactation. At the same time, we give information about the current maternal nutritional strategies (mainly breastfeeding, probiotics and prebiotics) to help colonization of the advantageous intestinal microbiota for IUGR piglets.

Lactobacillus species have been shown to alleviate gut inflammation and oxidative stress. However, the effect of different lactobacilli components on gut inflammation has not been well studied. This study aims to identify the differences in the effect and mechanisms of different forms and components of Limosilactobacillus mucosae (LM) treatment in the alleviation of gut inflammation using a colitis mouse model that is induced by dextran sodium sulfate (DSS). Seventy-two C57BL/6 mice were divided into six groups: control, DSS, live LM+DSS (LM+DSS), heat-killed LM+DSS (HKLM+DSS), LM cell-free supernatant + DSS (LMCS+DSS), and MRS medium + DSS (MRS+DSS). The mice were treated with different forms and components of LM for two weeks before DSS treatment. After that, the mice were sacrificed for an assessment of their levels of inflammatory cytokines, serotonin (5-HT) receptors (HTRs), and tryptophan metabolites. The results showed that, compared to other treatments, LMCS was more effective (p < 0.05) in the alleviation of DSS-induced body weight loss and led to an increase in the disease activity index score. All three forms and components of LM increased (p < 0.05) the levels of indole-3-acetic acid but reduced (p < 0.05) the levels of 5-HT in the colon. HKLM or LMCS reduced (p < 0.05) the percentages of CD3⁺CD8⁺ cytotoxic T cells but increased (p < 0.05) the percentages of CD3⁺CD4⁺ T helper cells in the spleen. LM or HKLM increased (p < 0.05) abundances of CD4⁺Foxp3⁺ regulatory T cells in the spleen. The LM and LMCS treatments reduced (p < 0.05) the expression of the pro-inflammatory cytokines Il6 and Il17a. The mice in the HKLM+DSS group had higher (p < 0.05) mRNA levels of the anti-inflammatory cytokine Il10, the cell differentiation and proliferation markers Lgr5 and Ki67, the 5-HT degradation enzyme Maoa, and HTRs (Htr1a, Htr2a, and Htr2b) in the colon. All three forms and components of LM reduced the phosphorylation of STAT3. The above findings can help to optimize the functionality of probiotics and develop new dietary strategies that aid in the maintenance of a healthy gut.

Sows usually suffer oxidative stress during gestation, and this limits the growth of fetuses via placenta. Gamma-aminobutyric acid (GABA) is a functional nonessential amino acid engaged in regulating the physiological status of animals. However, the effects of GABA on the oxidative homeostasis of sows and their offspring remain unclear. Eighteen late gestating sows (85 d) were divided into the CON and GABA groups and fed the basal diet and the GABA diet (200 mg/kg GABA), respectively, until farrowing. At parturition, the sows’ litter characteristics, the plasma antioxidant parameters of sows, and their offspring were evaluated. The results showed that GABA supplementation had no marked effect on the reproductive performance of sows (p > 0.10) but had a trend of reducing the amount of intrauterine growth restriction (IUGR) in piglets (0.05 < p < 0.10). At the same time, the addition of GABA elevated the plasma superoxide dismutase (SOD) level of sows and enhanced the glutathione peroxidase (GSH-Px) activity of newborn piglets (p < 0.05). Based on the H₂O₂-induced oxidative stress in pTr-2 cells, GABA elevated intracellular GSH-Px, SOD, catalase (CAT), and total antioxidant capacity (T-AOC, p < 0.01) and upregulated the gene expressions of CAT, gamma-aminobutyric acid receptor (GABRP), and nuclear factor-erythroid 2-related factor-2 (Nrf2) in H₂O₂-treated pTr-2 cells (p < 0.05). Taken together, GABA improved the antioxidant capacity of sows and alleviated the placental oxidative stress by upregulating the GABRP and Nrf2 genes, which have the potential to promote oxidative homeostasis in newborn piglets.

Tryptophan (Trp) has been shown to improve the growth and gut function of weaned piglets. Whether the growth-promoting effect of Trp is due to the improvement in nutrient transport and absorption during weaning or under conditions of inflammation has not been fully characterized. The objective of this study was to determine the effects of Trp on lipopolysaccharide (LPS)-induced changes in glucose and amino acid (AA) transport in the rat jejunum. Twenty-four 7-week-old Sprague Dawley rats were randomly divided into one of three groups: control, LPS, and Trp + LPS. Rats were supplemented with 0 or 0.1 mg Trp per gram body weight/d in drinking water for 7 days and were intraperitoneally injected with LPS (5 mg/kg BW) on day 8. After 24 h, rats were sacrificed, and jejunum samples were isolated for the analysis of glucose and AA transport using an Ussing chamber and the expression of glucose and AA transporters. The results showed that Trp alleviated the LPS-induced increase in jejunal permeability (p < 0.05) and decrease in changes in the short-circuit current of glucose, arginine, glutamine, glutamate, glycine, histidine, leucine, lysine, taurine, threonine, and Trp (p < 0.05). Trp reversed (p < 0.05) the LPS-induced downregulation of expression of the glucose transporter SGLT1 and AA transporters solute carrier family 38 member 2 (SNAT2) and solute carrier family 7 member 8 (LAT2), as well as ATPase Na⁺/K⁺ transporting subunit alpha 2 (ATP1A2). However, Trp increased (p < 0.01) the LPS-induced upregulation of acidic AA transporter solute carrier family 1 member 1 (EAAT3) expression. The above findings may help to develop nutritional interventions for the differential targeting of gut nutrient transporters, aiming to improve gut function and health in the presence of inflammation in both humans and animals.