## 4 Discussion
### Metabolic Pathways of Top Scoring Enzymes
Blood glucose is controlled by the production of insulin, which is a hormon that allows the regulation activity of blood glucose in the body. Bacteria in the gut break down food substances like fiber to synthesize short-chain fatty acids like butyrate and propionate, which can influence pancreatic function and insulin regulation. However, when this balancing act mechanism is blocked, it causes a massive dysregulation in blood glucose levels. When pre-diabetic people consume high fiber diet to stimulate bacteria to produce SCFA, it may enhance their insulin sensitivity and glucose regulation. The surfaces of gastrointestinal (GI) organs have diverse tasks, such as nutritional uptake and defense. The immune cells within the mucosa maintain functional balance to prevent inflammation and uphold barrier function. The rise in GI diseases is linked to dietary changes causing gut microbiome imbalance and chronic inflammation. Gut microbes exhibit a profound connection to host metabolism, although the precise mechanisms underpinning this relationship remain elusive. Understanding immuno-nutrition, nutritional compounds, the role of diet, gut microbiota, and the host immune response is crucial for disease prevention and treatment. Lipids, especially bioactive sphingolipids (SLs) like sphingomyelin (SM), sphingosine (Sph), ceramide (Cer), sphingosine-1-phosphate (S1P), and ceramide-1-phosphate (C1P), from the diet play a key role in GI barrier function and immune homeostasis [73]. As shown in Figure 11B, the galactosylceramidase (EC: 3.2.1.46) enzyme is responsible for the synthesis of Sph from psychosine and Cer synthesis from galacto-sylceramide, while glucosylceramidase (EC: 3.2.1.45) enzymes synthesize Sph from glucosylphingosine and Cer from glucosyl-ceramide. Lactosyl-ceramide is hydrolyzed by beta-galactosidase (EC: 3.2.1.23) to form glucosyl-ceramide. Lactosyl-ceramide formation is performed by sialidase (EC: 3.2.1.18), beta-hexosaminidase (EC: 3.2.1.52), and alpha-galactosidase (EC: 3.2.1.22) enzymes (Figure 11B). SLs, a diverse bioactive lipid class, are present in cellular membranes, lipoproteins, and lipid-rich structures like the skin, influencing apoptosis, cell growth, and migration. They impact pro- and anti-inflammatory immune responses and are regulated through endogenous metabolic pathways. SLs are also in food, affecting immune activation in the GI tract and related diseases. The actions of SLs include inhibiting intestinal lipid uptake, activating inflammatory receptors, and influencing lymphocyte chemotaxis. They neutralize bacterial endotoxins and alter intestinal microbiota, and SL metabolites affect cell functions and can influence the gut microbiota composition [73]. SLs determine cell fate by regulating cell proliferation and growth [74], and they are associated with many cancers, including acute myeloid leukemia [75]. Ceramide, the pivotal apoptotic molecule within the sphingolipid metabolism pathway, is synthesized via the de novo pathway facilitated by serine palmitoyl transferase (SPT) [76]. Studies have shown that targeting ceramide and S1P in SL metabolism for AML treatment regulates the apoptotic mechanisms and cell proliferation [77]. SLs are crucial in mammals, also playing roles in metabolic disorders, ranging from insulin resistance (IR) to hepatic steatosis. While SLs are acquired from the diet and synthesized de novo in mammalian tissues, a yet unexplored potential source of mammalian SLs may be their production by Bacteroidetes, which are a predominant phylum within the gut microbiome. The genomes of _Bacteroides_ spp. and their counterparts encode SPT, enabling them to synthesize SLs [78]. The impact of SL production by gut _Bacteroides_ on host SL homeostasis and related findings underscore the influence of gut-derived bacterial SLs on the host's lipid metabolism. In human cell cultures, bacterial SLs undergo processing by host SL metabolic pathways and, in murine models, lipids derived from Bacteroides are transferred to host epithelial tissue and the hepatic portal vein.