Intestinal-related substances in obesity regulation: A comprehensive review

Table 1 The Role of gut origined indole-3-propionic acid in the weight loss

Affiliation	Method	Result	Conclusion	Ref.
Stanford University, United States	Gene editing using pMTL007C-E2 plasmid with Ll.LtrB group II intron	Identified tryptophan-derived metabolite IPA	Enhances intestinal function: (1) Restores gut barrier integrity; and (2) Attenuates inflammatory responses	[6]
Zhejiang University, China	In vitro pull-down with site mutation to find STAT3 binding site	Trp623 in SH2 domain is key site for IPA binding; IPA enhances leptin sensitivity to combat obesity	Metabolic modulation: (1) Suppresses appetite; and (2) Enhances glucose metabolism	[8]
Shanghai Jiao Tong University, China	Obesity model by high-fat diet; 16S sequencing and LC-MS/MS used for serum IPA quantification	IPA ameliorates hepatic steatosis	Hepatic protection: (1) Suppresses hepatic lipid accumulation; and (2) Promotes intrahepatic lipolysis	[7]
All India Institute of Medical Sciences	Liver histology + LC-MS quantification	Circulating IPA level negatively correlated with liver fibrosis severity	Hepatoprotective effects of IPA. Inhibits liver injury to maintain normal lipid metabolism	[13]
China Agricultural University	High-fat diet mouse model; FMT and microbiome sequencing	IPA + SB + VA combination modulates gut-liver-brain axis and shows anti-obesity potential	Anti-obesity mechanisms: (1) Preserves gut microbiota homeostasis; and (2) Activates hepatic leptin signaling	[14]
King’s College London, United Kingdom	16S rRNA gene sequencing (V3–V4 region)	Gut microbiota composition (esp. butyrate-producers) significantly affects circulating IPA levels	Metabolic function prediction: (1) IPA levels correlate with clinical parameters of metabolic syndrome; and (2) Predicts type 2 diabetes onset	[23]
Southern Medical University, China	IPA administered externally in HFD-induced model	IPA activates tuft cell–IL-25 axis, restores colonic barrier, and prevents obesity/metabolic disorders	Multifunctional effects of IPA: (1) Ameliorates glucose/Lipid metabolic disorders; (2) Attenuates adipose and intestinal inflammation; and (3) Suppresses adipocyte hypertrophy	[24]

16S: 16S ribosomal RNA; 16S-seq: 16S rRNA gene sequencing; FMT: Fecal microbiota transplantation; HFD: High-fat diet; IL-25: Interleukin-25; IPA: Indole-3-propionic acid; LC-MS/MS: Liquid chromatography–tandem mass spectrometry; LC-MS: Liquid chromatography–mass spectrometry; SB: Sodium butyrate; SH2: Src homology 2 domain; VA: Valeric acid.