Indolepropionic Acid, a Gut Bacteria-Produced Tryptophan Metabolite and the Risk of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease

Overview

Journal Nutrients

Date 2022 Nov 11

PMID 36364957

Authors

Ratika Sehgal

Vanessa D de Mello

Ville Mannisto

Jaana Lindstrom

Jaakko Tuomilehto

Jussi Pihlajamaki

Matti Uusitupa

Affiliations

Soon will be listed here.

Abstract

An intricate relationship between gut microbiota, diet, and the human body has recently been extensively investigated. Gut microbiota and gut-derived metabolites, especially, tryptophan derivatives, modulate metabolic and immune functions in health and disease. One of the tryptophan derivatives, indolepropionic acid (IPA), is increasingly being studied as a marker for the onset and development of metabolic disorders, including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). The IPA levels heavily depend on the diet, particularly dietary fiber, and show huge variations among individuals. We suggest that these variations could partially be explained using genetic variants known to be associated with specific diseases such as T2D. In this narrative review, we elaborate on the beneficial effects of IPA in the mitigation of T2D and NAFLD, and further study the putative interactions between IPA and well-known genetic variants (, , and ), known to be associated with the risk of T2D. We have investigated the long-term preventive value of IPA in the development of T2D in the Finnish prediabetic population and the correlation of IPA with phytosterols in obese individuals from an ongoing Kuopio obesity surgery study. The diversity in IPA-linked mechanisms affecting glucose metabolism and liver fibrosis makes it a unique small metabolite and a promising candidate for the reversal or management of metabolic disorders, mainly T2D and NAFLD.

Citing Articles

Indole-3-propionic acid promotes hepatic stellate cells inactivation.

Ilha M, Sehgal R, Matilainen J, Rilla K, Kaminska D, Gandhi S J Transl Med. 2025; 23(1):253.

PMID: 40025530 PMC: 11871697. DOI: 10.1186/s12967-025-06266-z.

Preventive role of Pastinaca sativa in mitigating metabolic dysfunction-associated steatotic liver disease via modulation of metabolic endotoxemia.

Park J, Lee H, Lee Y, Yoo G, Son H, Choi S NPJ Sci Food. 2025; 9(1):20.

PMID: 39915500 PMC: 11803109. DOI: 10.1038/s41538-024-00366-8.

The moderating effect of dietary fiber intake on the association between sleep pattern and liver fibrosis in metabolic dysfunction-associated steatotic liver disease: a study from NHANES.

Jia G, Jia M, Li C BMC Gastroenterol. 2024; 24(1):457.

PMID: 39695427 PMC: 11654364. DOI: 10.1186/s12876-024-03538-8.

Targeting the Gut Microbiota for Prevention and Management of Type 2 Diabetes.

Donati Zeppa S, Gervasi M, Bartolacci A, Ferrini F, Patti A, Sestili P Nutrients. 2024; 16(22).

PMID: 39599740 PMC: 11597803. DOI: 10.3390/nu16223951.

Gut microbiota and gut-derived metabolites are altered and associated with dietary intake in women with polycystic ovary syndrome.

da Silva T, Marchesan L, Rampelotto P, Longo L, de Oliveira T, Landberg R J Ovarian Res. 2024; 17(1):232.

PMID: 39578890 PMC: 11583432. DOI: 10.1186/s13048-024-01550-w.

References

Pan X, Wen S, Kaminga A, Liu A . Gut metabolites and inflammation factors in non-alcoholic fatty liver disease: A systematic review and meta-analysis. Sci Rep. 2020; 10(1):8848. PMC: 7264254. DOI: 10.1038/s41598-020-65051-8. View

Salgaco M, Oliveira L, Costa G, Bianchi F, Sivieri K . Relationship between gut microbiota, probiotics, and type 2 diabetes mellitus. Appl Microbiol Biotechnol. 2019; 103(23-24):9229-9238. DOI: 10.1007/s00253-019-10156-y. View

Menni C, Matey Hernandez M, Vital M, Mohney R, Spector T, Valdes A . Circulating levels of the anti-oxidant indoleproprionic acid are associated with higher gut microbiome diversity. Gut Microbes. 2019; 10(6):688-695. PMC: 6866703. DOI: 10.1080/19490976.2019.1586038. View

Gudmundsdottir V, Pedersen H, Mazzoni G, Allin K, Artati A, Beulens J . Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study. Genome Med. 2020; 12(1):109. PMC: 7708171. DOI: 10.1186/s13073-020-00806-6. View

Nishizawa T, Aldrich C, Sherman D . Molecular analysis of the rebeccamycin L-amino acid oxidase from Lechevalieria aerocolonigenes ATCC 39243. J Bacteriol. 2005; 187(6):2084-92. PMC: 1064027. DOI: 10.1128/JB.187.6.2084-2092.2005. View

Wu W, Zhang L, Xia B, Tang S, Liu L, Xie J . Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin. Microorganisms. 2020; 8(1). PMC: 7022628. DOI: 10.3390/microorganisms8010111. View

Bendheim P, Poeggeler B, Neria E, Ziv V, Pappolla M, Chain D . Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease. J Mol Neurosci. 2002; 19(1-2):213-7. DOI: 10.1007/s12031-002-0036-0. View

Dong T, Mayer E, Osadchiy V, Chang C, Katzka W, Lagishetty V . A Distinct Brain-Gut-Microbiome Profile Exists for Females with Obesity and Food Addiction. Obesity (Silver Spring). 2020; 28(8):1477-1486. PMC: 7494955. DOI: 10.1002/oby.22870. View

Morze J, Wittenbecher C, Schwingshackl L, Danielewicz A, Rynkiewicz A, Hu F . Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care. 2022; 45(4):1013-1024. PMC: 9016744. DOI: 10.2337/dc21-1705. View

10.

Frasinariu O, Serban R, Trandafir L, Miron I, Starcea M, Vasiliu I . The Role of Phytosterols in Nonalcoholic Fatty Liver Disease. Nutrients. 2022; 14(11). PMC: 9182996. DOI: 10.3390/nu14112187. View

11.

Agus A, Planchais J, Sokol H . Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018; 23(6):716-724. DOI: 10.1016/j.chom.2018.05.003. View

12.

Negatu D, Gengenbacher M, Dartois V, Dick T . Indole Propionic Acid, an Unusual Antibiotic Produced by the Gut Microbiota, With Anti-inflammatory and Antioxidant Properties. Front Microbiol. 2020; 11:575586. PMC: 7652848. DOI: 10.3389/fmicb.2020.575586. View

13.

Roager H, Licht T . Microbial tryptophan catabolites in health and disease. Nat Commun. 2018; 9(1):3294. PMC: 6098093. DOI: 10.1038/s41467-018-05470-4. View

14.

OKeefe S . The association between dietary fibre deficiency and high-income lifestyle-associated diseases: Burkitt's hypothesis revisited. Lancet Gastroenterol Hepatol. 2019; 4(12):984-996. PMC: 6944853. DOI: 10.1016/S2468-1253(19)30257-2. View

15.

Wikoff W, Anfora A, Liu J, Schultz P, Lesley S, Peters E . Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009; 106(10):3698-703. PMC: 2656143. DOI: 10.1073/pnas.0812874106. View

16.

Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet A . Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014; 41(2):296-310. PMC: 4142105. DOI: 10.1016/j.immuni.2014.06.014. View

17.

Lindstrom J, Peltonen M, Eriksson J, Louheranta A, Fogelholm M, Uusitupa M . High-fibre, low-fat diet predicts long-term weight loss and decreased type 2 diabetes risk: the Finnish Diabetes Prevention Study. Diabetologia. 2006; 49(5):912-20. DOI: 10.1007/s00125-006-0198-3. View

18.

Liu D, Wang J, Zeng H, Zhou F, Wen B, Zhang X . The metabolic regulation of Fuzhuan brick tea in high-fat diet-induced obese mice and the potential contribution of gut microbiota. Food Funct. 2021; 13(1):356-374. DOI: 10.1039/d1fo02181h. View

19.

Tan Y, Gao Y, Teo G, Koh H, Tai E, Khoo C . Plasma Metabolome and Lipidome Associations with Type 2 Diabetes and Diabetic Nephropathy. Metabolites. 2021; 11(4). PMC: 8069978. DOI: 10.3390/metabo11040228. View

20.

Mazagova M, Wang L, Anfora A, Wissmueller M, Lesley S, Miyamoto Y . Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice. FASEB J. 2014; 29(3):1043-55. PMC: 4422368. DOI: 10.1096/fj.14-259515. View