Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis

Sehgal, Ratika; Ilha, Mariana; Vaittinen, Maija; Kaminska, Dorota; Männistö, Ville; Kärjä, Vesa; Tuomainen, Marjo; Hanhineva, Kati; Romeo, Stefano; Pajukanta, Päivi; Pihlajamäki, Jussi; de Mello, Vanessa D.

doi:10.3390/nu13103509

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Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis

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^1,4,

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^1,8,† and

^1,*,†

Department of Clinical Nutrition, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211 Kuopio, Finland

Departments of Medicine, University of Eastern Finland and Kuopio University Hospital, 70211 Kuopio, Finland

Department of Pathology, University of Eastern Finland and Kuopio University Hospital, 70211 Kuopio, Finland

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Department of Life Technologies, Food Chemistry and Food Development Unit, University of Turku, 20500 Turku, Finland

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Department of Molecular and Clinical Medicine, University of Gothenburg, 40530 Gothenburg, Sweden

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Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA

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Institute for Precision Health, School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA

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Department of Medicine, Endocrinology and Clinical Nutrition, Kuopio University Hospital, 70211 Kuopio, Finland

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Academic Editor: Alberto Dávalos

Nutrients 2021, 13(10), 3509; https://doi.org/10.3390/nu13103509

Received: 25 August 2021 / Revised: 28 September 2021 / Accepted: 30 September 2021 / Published: 5 October 2021

(This article belongs to the Special Issue Dietary Biomarkers in Human Nutrition)

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Abstract

Background and Aims: Gut microbiota-derived metabolites play a vital role in maintenance of human health and progression of disorders, including obesity and type 2 diabetes (T2D). Indole-3-propionic acid (IPA), a gut-derived tryptophan metabolite, has been recently shown to be lower in individuals with obesity and T2D. IPA’s beneficial effect on liver health has been also explored in rodent and cell models. In this study, we investigated the association of IPA with human liver histology and transcriptomics, and the potential of IPA to reduce hepatic stellate cell activation in vitro. Methods: A total of 233 subjects (72% women; age 48.3 ± 9.3 years; BMI 43.1 ± 5.4 kg/m²) undergoing bariatric surgery with detailed liver histology were included. Circulating IPA levels were measured using LC-MS and liver transcriptomics with total RNA-sequencing. LX-2 cells were used to study hepatoprotective effect of IPA in cells activated by TGF-β1. Results: Circulating IPA levels were found to be lower in individuals with liver fibrosis compared to those without fibrosis (p = 0.039 for all participants; p = 0.013 for 153 individuals without T2D). Accordingly, levels of circulating IPA associated with expression of 278 liver transcripts (p < 0.01) that were enriched for the genes regulating hepatic stellate cells (HSCs) activation and hepatic fibrosis signaling. Our results suggest that IPA may have hepatoprotective potential because it is able to reduce cell adhesion, cell migration and mRNA gene expression of classical markers of HSCs activation in LX-2 cells (all p < 0.05). Conclusion: The association of circulating IPA with liver fibrosis and the ability of IPA to reduce activation of LX-2 cells suggests that IPA may have a therapeutic potential. Further molecular studies are needed to investigate the mechanisms how IPA can ameliorate hepatic fibrosis. View Full-Text

Keywords: indole-3-propionic acid; non-alcoholic fatty liver disease; hepatic fibrosis; hepatic stellate cells; gut microbiota

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MDPI and ACS Style

Sehgal, R.; Ilha, M.; Vaittinen, M.; Kaminska, D.; Männistö, V.; Kärjä, V.; Tuomainen, M.; Hanhineva, K.; Romeo, S.; Pajukanta, P.; Pihlajamäki, J.; de Mello, V.D. Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis. Nutrients 2021, 13, 3509. https://doi.org/10.3390/nu13103509

AMA Style

Sehgal R, Ilha M, Vaittinen M, Kaminska D, Männistö V, Kärjä V, Tuomainen M, Hanhineva K, Romeo S, Pajukanta P, Pihlajamäki J, de Mello VD. Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis. Nutrients. 2021; 13(10):3509. https://doi.org/10.3390/nu13103509

Chicago/Turabian Style

Sehgal, Ratika, Mariana Ilha, Maija Vaittinen, Dorota Kaminska, Ville Männistö, Vesa Kärjä, Marjo Tuomainen, Kati Hanhineva, Stefano Romeo, Päivi Pajukanta, Jussi Pihlajamäki, and Vanessa D. de Mello. 2021. "Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis" Nutrients 13, no. 10: 3509. https://doi.org/10.3390/nu13103509

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Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis

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