Key GM-derived metabolites and their impact on metabolic regulation.
| Metabolite | Primary source | Key chemical forms | Main physiological/metabolic roles | Metabolic health implications | References |
|---|---|---|---|---|---|
| Lipopolysaccharides (LPS) | Outer membrane of Gram-negative bacteria | LPS | Activates innate immunity and stimulates the release of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β) used for intercellular communication. | Chronic low-grade inflammation, metabolic endotoxemia, insulin resistance, T2DM, obesity | [46] |
| Short-chain fatty acids (SCFAs) | Fermentation of dietary fiber | Acetate, propionate, butyrate | Maintain gut barrier integrity, modulate immune function, regulate appetite, improve glucose homeostasis. | Protective against obesity, T2DM; imbalance linked to dysmetabolism | [52, 59] |
| Trimethylamine-N-oxide (TMAO) | Dietary choline, carnitine, phosphatidylcholine | TMAO | Modulates cholesterol and bile acid metabolism that regulate fat digestion as well as glucose, lipid, and energy homeostasis. | Elevated levels associated with CVD, atherosclerosis, insulin resistance | [63, 81] |
| Indolepropionic acid (IPA) | Tryptophan metabolism by GM | IPA | Antioxidant, anti-inflammatory; protects pancreatic β-cells. | Higher circulating IPA linked to reduced T2DM risk | [69, 71] |
| Bile acids | Liver synthesis from cholesterol | Cholic acid (CA), chenodeoxycholic acid (CDCA) | Bile acids act as digestive and important signaling molecules. Receptors such as FXR and GPBAR1/TGR5 regulate glucose and lipid metabolism, cholesterol homeostasis, immune responses, and energy balance. | Too much CA can raise blood lipids and worsen insulin resistance | [82, 83] |
The authors extend their sincere gratitude to the Department of Food Science & Technology at Graphic Era (Deemed to be University), Dehradun, Uttarakhand, India, for offering the essential facilities required for the preparation of this review paper.
SJ: Conceptualization, Investigation, Data curation, Writing—original draft. DB: Conceptualization, Writing—review & editing. AD: Conceptualization, Writing—review & editing. RK: Conceptualization, Writing—review & editing. RM: Conceptualization, Writing—review & editing. SK: Writing—review & editing. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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