## 4 Discussion
### Metabolic Pathways of Top Scoring Enzymes
These findings show that _Bacteroides_ SLs may impact host lipid homeostasis [78]. In animal models, reducing ceramide in the liver improves insulin sensitivity, while inhibition of intestinal ceramide pathways enhances glucose metabolism. Human studies link hepatic or plasma ceramide levels to IR. SL regulation in tissues relies on multiple signaling pathways, controlled by synthesis, recycling, and intestinal uptake. Dietary SLs impact cholesterol absorption, hepatic lipid accumulation, obesity, and insulin sensitivity, partly by altering hepatic ceramide levels. Diet influences gut microbiota-derived SLs, in that way modulate some inflammation related pathways in the colon. However, their impact on the host lipid metabolism pathways remains unknown [78]. Studies indicate that bacterial sphingolipids from Bacteroides are reduced in IBD stool samples and correlate with lower gut inflammation, whereas increased host-derived SLs are associated with reduced Bacteroides levels in IBD patients. Mouse studies have supported these findings, showing disruptions in both bacterial and host sphingolipid pathways during inflammation and IBD. This discovery is crucial, due to the key role of sphingolipid signaling in IBD-related pathways and the notable decrease in Bacteroidetes in various IBD groups [79; 80; 81; 82]. Cer content is linked to inflammation and metabolic diseases. Increasing Cer generation or inhibiting degradation can lead to Cer accumulation, inducing excessive apoptosis. Recent studies using HPLC, GC-MS, and MALDI-MS methods have revealed insights into dietary Cer structures, indicating a more complex role of the sphingolipid metabolite. Higher cellular Cer levels have been found to prevent inflammatory responses, while genetically modified yeast-produced Cers inhibit TNF-\(\alpha\) signaling, maintaining cell viability. Plant-derived Cer-precursor sphingolipids have been used as dietary supplements to restore skin barrier function in humans [73]. C1P, a Cer metabolite, is a bioactive SL metabolite linked to cell proliferation, macrophage migration, and inflammatory response. C1P acts as an extracellular ligand through a G(i) protein-coupled plasma membrane receptor, potentially mediating chemotaxis, and regulates the inflammation in response to Cer stimuli [73]. Recent findings suggest an imbalance in SLs favoring specific types like S1P, C1P, Cers, Sph, and SM over more complex cerebrosides and gangliosides, promoting intestinal inflammation [83]. SLs interact with epithelial cells and immune cells, showing promise for treating immune diseases and as biomarkers. These lipids affect intestinal mucus function, compete with commensals for binding sites, and boost defense against pathogens. Intestinal SL levels are influenced by diet, endogenous production, and SL-producing bacteria. Bacterial and host SLs are structurally alike, affecting the immune responses and signaling pathways. Gut bacteria lacking sphingolipids are linked to inflammatory bowel disease, while human-produced sphingolipids in the gut increase. Gut microbiota metabolites signal to the host, impacting the health outcomes in inflammatory bowel disease [84]. In the literature, it has been also shown that an alteration in the SL metabolism is associated with several inherited human diseases, where defect in the lysosomal SL degradation results in an accumulation of non-degradable storage material in the organs as seen in as seen in GM1-gangliosidosis (GM1 beta-galactosidase deficiency), [PERSON] disease (mutations in \(\beta\)-hexosaminidase), [PERSON] disease (alpha-galactosidase deficiency), [PERSON] disease (\(\beta\)-glucoceramidase I deficiency), and [PERSON] disease (\(\beta\)-galactoceramidase deficiency) [85; 86; 87; 88]. Also, hydro-lyases (EC:4.2.1) and CoA-transferases (EC: 2.8.3) perform metabolic activity together in styrene degradation (Figure 12A), butanoate metabolism (Figure 12B), the citric acid cycle (Figure 12C), and carnitine metabolism (Figure 12D).