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Simple Summary Saccharin sodium (SS) is one of the commonly used artificial sweeteners (AS) in the food industry, but the mechanisms mediating the physiological effects of sweeteners in the gut-brain axis is still unclear. The aim of this study was to explore the regulatory effect of SS on the microbiota-gut-hypothalamus axis on guinea pigs. We found that SS treatment may alter the growth and glucose metabolism of guinea pigs by activating sweet receptor signaling in the gut and growth hormone-releasing peptide (GHRP) hormone secretion. Besides, SS treatment increased the abundance of Firmicutes and Lactobacillasceae-Lactobacillus in the ileum, and subsequently increased levels of lactic acid and short-chain fatty acids (SCFAs). Adding 1.5 mM SS to drinking water alters the growth of guinea pigs by regulating the microbiota-hypothalamus-gut axis. This conclusion has theoretical implications for the comprehensive assessment of the biological effects of appropriate SS in the food industry. Abstract The effects of saccharin, as a type of sweetener additive, on the metabolism and development of mammals are still controversial. Our previous research revealed that saccharin sodium (SS) promoted the feed intake and growth of guinea pigs. In this experiment, we used the guinea pig model to study the physiological effect of SS in the microbiota-gut-hypothalamus axis. Adding 1.5 mM SS to drinking water increased the serum level of glucose, followed by the improvement in the morphology and barrier function of the ileal villus, such as SS supplementation which increased the villus height and villus height/crypt depth ratio. Saccharin sodium (SS) treatment activated the sweet receptor signaling in the ileum and altered GHRP hormone secretion. In the hypothalamus of SS and control (CN) group, RNA-seq identified 1370 differently expressed genes (796 upregulated, 574 downregulated), enriching into the taste signaling transduction, and neuroactive ligand–receptor interaction. LEfSe analysis suggested that Lactobacillaceae-Lactobacillus was the microbe with significantly increased abundance of ileum microorganisms in the SS-treated group, while Brevinema-Andersonii and Erysipelotrichaceae-Ilebacterium were the microbes with significantly increased abundance of the control. Furthermore, SS treatment significantly enhanced the functions of chemoheterotrophy and fermentation of ileal microflora compared to the CN group. Accordingly, SS treatment increased levels of lactic acid and short-chain fatty acids (acetic acid, propionic acid and N-valeric acid) in the ileal digesta. In summary, drinking water with 1.5 mM SS activated sweet receptor signaling in the gut and altered GHRP hormone secretion, followed by the taste signaling transduction in the hypothalamus.

Sexual hormones are essential for the process of spermatogenesis in the testis. However, the effect of maternal genistein (GEN) on the pups&rsquo, testicular development remain-unclear. Our present study evaluated the effects of supplementing GEN for parental and offspring mice on the reproductive function and growth performance of the male pups. Mothers during gestation and lactation period were assigned to a control diet (CON group), low dose GEN (LGE group) diet (control diet +40 mg/kg GEN), and high dose of GEN (HGE group) diet (control diet +800 mg/kg GEN). Their male offspring underwent the same treatment of GEN after weaning. LGE treatment (40 mg/kg GEN) significantly increased body weights (p &lt, 0.001), testes weights (p &lt, 0.05), diameters of seminiferous tubule (p &lt, 0.001) and heights of seminiferous epithelium (p &lt, 0.05) of offspring mice. LGE treatment also increased serum testosterone (T) levels and spermatogenesis scoring (p &lt, 0.05). However, HGE treatment (800mg/kg GEN) significantly decreased body weights (p &lt, 0.05) and testis sizes (p &lt, 0.001). Furthermore, mRNA expressions of ESR2 (p &lt, 0.05), CYP19A1 (p &lt, 0.001), SOX9 (p &lt, 0.001) and BRD7 (p &lt, 0.001) in testis of mice were increased in the LGE group. Similarly, HGE treatment increased mRNA expressions of ESR2 (p &lt, 0.05) and CYP19A1 (p &lt, 0.001). However, mRNA expressions of SOX9 and BRD7 were decreased significantly in the HGE group (p &lt, 0.001). Meanwhile, higher ratio apoptotic germ cells and abnormal sperms were detected in the HGE group (p &lt, 0.001). In conclusion, exposure to a low dose of GEN during fetal and neonatal life could improve testicular development of offspring mice, whereas, unfavorable adverse effects were induced by a high dose of GEN.

The sense of taste which tells us which prospective foods are nutritious, poisonous and harmful is essential for the life of the organisms. Denatonium benzoate (DB) is a bitter taste agonist known for its activation of bitter taste receptors in different cells. The aim of the current study was to investigate the mRNA expressions of bitter taste, downstream signaling effectors, apoptosis-, autophagy- and antioxidant-related genes and effector signaling pathways in the heart/kidney of chickens after DB dietary exposure. We randomly assigned 240, 1-day-old Chinese Fast Yellow chicks into four groups with five replicates of 12 chicks and studied them for 28 consecutive days. The dietary treatments consisted of basal diet and feed containing DB (5, 20 and 100 mg/kg). The results revealed that dietary DB impaired (p &lt, 0.05) the growth performance of the chickens. Haemotoxylin and eosin staining and TUNEL assays confirmed that medium and high doses of DB damaged the epithelial cells of heart/kidney and induced apoptosis and autophagy. Remarkably, the results of RT-PCR and qRT-PCR indicated that different doses of DB gradually increased (p &lt, 0.05) mRNA expressions of bitter taste, signaling effectors, apoptosis-, autophagy- and antioxidant- related genes on day 7 in a dose-response manner, while, these expressions were decreased (p &lt, 0.05) subsequently by day-28 but exceptional higher (P &lt, 0.05) expressions were observed in the high-dose DB groups of chickens. In conclusion, DB exerts adverse effects on the heart/kidney of chickens in a dose-response manner via damaging the epithelium of the heart/kidney by inducing apoptosis, autophagy associated with bitter taste and effector gene expressions. Correlation analyses for apoptosis/autophagy showed agonistic relationships. Our data provide a novel perspective for understanding the interaction of bitter taste, apoptosis, autophagy and antioxidative genes with bitter taste strong activators in the heart/kidney of chicken. These insights might help the feed industries and pave the way toward innovative directions in chicken husbandry.

The present study was conducted to investigate the responsiveness expressions of ggTas2Rs against denatonium benzoate (DB) and genistein (GEN) in several organs of the Chinese Fast Yellow Chicken. A total of 300 one-day-old chicks that weighed an average of 32 g were randomly allocated into five groups with five replicates for 56 consecutive days. The dietary treatments consisted of basal diet, denatonium benzoate (5 mg/kg, 20 mg/kg, and 100 mg/kg), and genistein 25 mg/kg. The results of qRT-PCR indicated significantly (p &lt, 0.05) high-level expressions in the heart, spleen, and lungs in the starter and grower stages except for in bursa Fabricius. The responsiveness expressions of ggTas2Rs against DB 100 mg/kg and GEN 25 mg/kg were highly dose-dependent in the heart, spleen, lungs, and kidneys in the starter and grower stages, but dose-independent in the bursa Fabricius in the finisher stage. The ggTas2Rs were highly expressed in lungs and the spleen, but lower in the bursa Fabricius among the organs. However, the organ growth performance significantly (p &lt, 0.05) increased in the groups administered DB 5 mg/kg and GEN 25 mg/kg, meanwhile, the DB 20 mg/kg and DB 100 mg/kg treatments significantly reduced the growth of all the organs, respectively. These findings indicate that responsiveness expressions are dose-dependent, and bitterness sensitivity consequently decreases in aged chickens. Therefore, these findings may improve the production of new feedstuffs for chickens according to their growing stages.