Drinking Water with Saccharin Sodium Alters the Microbiota-Gut-Hypothalamus Axis in Guinea Pig

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.

Effects of non‐nutritive sweeteners on growth and intestinal health by regulating hypothalamic RNA profile and ileum microbiota in guinea pigs

“…Furthermore, our findings indicated that the RA and SS groups exhibited significantly higher serum levels of GHRP and the TGS group had an increased serum levels of CCK in comparison with the CN group. Consistent with our previous reports, dietary supplementation with 1.5 mM SS in drinking water initiated sweet receptor signaling within the gastrointestinal tract and altered the secretion of GHRP hormones 17 . Growth hormone‐releasing peptide, a brain‐gut peptide responsible for stimulating appetite, is known for its role in increasing gastric acid production, as well as promoting gastric motility and emptying 32 .…”

“…Consistent with our previous reports, dietary supplementation with 1.5 mM SS in drinking water initiated sweet receptor signaling within the gastrointestinal tract and altered the secretion of GHRP hormones. 17 Growth hormone-releasing peptide, a brain-gut peptide responsible for stimulating appetite, is known for its role in increasing gastric acid production, as well as promoting gastric motility and emptying. 32 The hypothalamus functions as a central brain structure that processes information regarding overall energy levels and metabolic status through hormones or nutrients.…”

“…The arcuate nucleus (ARC) within the hypothalamus plays a crucial role in sensing the body's overall energy status 14 . The ARC contains various neuron groups related to energy homeostasis, including orexin neuropeptide Y (NPY)/agouti‐related peptide (AgRP) neurons and orexin opiomelanocortin (POMC) neurons 15‐17 . The addition of dietary additives such as non‐nutritive sweeteners may influence the production of these appetite‐regulating neuropeptides, potentially altering animal feed intake.…”

“…14 The ARC contains various neuron groups related to energy homeostasis, including orexin neuropeptide Y (NPY)/agoutirelated peptide (AgRP) neurons and orexin opiomelanocortin (POMC) neurons. [15][16][17] The addition of dietary additives such as non-nutritive sweeteners may influence the production of these appetite-regulating neuropeptides, potentially altering animal feed intake. However, the specific effects of non-nutritive sweeteners on the production of ARC-related appetite-related neurons in the hypothalamus remain unknown.…”

Effects of lactoferrin on intestinal flora of metabolic disorder mice

“…We found that Ileibacterium -valens was significantly increased in the gut microbiota of mice in the LF intervention group compared to the control group. The study [33] had confirmed that abundance of Erysipelotrichaceae-Ileibacterium was associated with obesity. It may affect the host metabolism and inflammatory diseases and is closely related to obesity [34].…”