Inulin-grown Faecalibacterium prausnitzii cross-feeds fructose to the human intestinal epithelium

Raphael R Fagundes; Arno R Bourgonje; Ali Saeed; Arnau Vich Vila; Niels Plomp; Tjasso Blokzijl; Mehdi Sadaghian Sadabad; Julius Z H von Martels; Sander S van Leeuwen; Rinse K Weersma; Gerard Dijkstra; Hermie J M Harmsen; Klaas Nico Faber

doi:10.1080/19490976.2021.1993582

Inulin-grown Faecalibacterium prausnitzii cross-feeds fructose to the human intestinal epithelium

Gut Microbes. 2021 Jan-Dec;13(1):1993582. doi: 10.1080/19490976.2021.1993582.

Authors

Raphael R Fagundes¹, Arno R Bourgonje¹, Ali Saeed^{1

2}, Arnau Vich Vila^{1

3}, Niels Plomp⁴, Tjasso Blokzijl¹, Mehdi Sadaghian Sadabad⁴, Julius Z H von Martels¹, Sander S van Leeuwen⁵, Rinse K Weersma^{1

3}, Gerard Dijkstra¹, Hermie J M Harmsen³, Klaas Nico Faber^{1

5}

Affiliations

¹ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
² Institute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan, Pakistan.
³ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Department of Medical Microbiology and Infection Prevention, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁵ Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Abstract

Many chronic diseases are associated with decreased abundance of the gut commensal Faecalibacterium prausnitzii. This strict anaerobe can grow on dietary fibers, e.g., prebiotics, and produce high levels of butyrate, often associated to epithelial metabolism and health. However, little is known about other F. prausnitzii metabolites that may affect the colonic epithelium. Here, we analyzed prebiotic cross-feeding between F. prausnitzii and intestinal epithelial (Caco-2) cells in a "Human-oxygen Bacteria-anaerobic" coculture system. Inulin-grown F. prausnitzii enhanced Caco-2 viability and suppressed inflammation- and oxidative stress-marker expression. Inulin-grown F. prausnitzii produced excess butyrate and fructose, but only fructose efficiently promoted Caco-2 growth. Finally, fecal microbial taxonomy analysis (16S sequencing) from healthy volunteers (n = 255) showed the strongest positive correlation for F. prausnitzii abundance and stool fructose levels. We show that fructose, produced and accumulated in a fiber-rich colonic environment, supports colonic epithelium growth, while butyrate does not.

Keywords: Faecalibacterium; Gut bacteria; dysbiosis; fructose; intestinal epithelium; inulin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anaerobiosis
Butyrates / analysis
Butyrates / metabolism
Caco-2 Cells
Cell Proliferation
Cell Survival
Coculture Techniques
Faecalibacterium prausnitzii / metabolism*
Feces / chemistry
Feces / microbiology
Fructose / analysis
Fructose / metabolism*
Gastrointestinal Microbiome
Glucose / analysis
Glucose / metabolism
Glucose Transporter Type 5 / genetics
Humans
Inflammation / metabolism
Intestinal Mucosa / cytology
Intestinal Mucosa / metabolism*
Intestinal Mucosa / microbiology
Inulin / metabolism*
Pectins / metabolism
Prebiotics

Substances

Butyrates
Glucose Transporter Type 5
Prebiotics
SLC2A5 protein, human
Fructose
Pectins
Inulin
Glucose

Grants and funding

The research position of RRF was supported by the Graduate School of Medical Sciences (GSMS) of the University of Groningen, the Netherlands. The research position of ARB was supported by a JSM MD-PhD trajectory grant (grant no. 17-57) from the Junior Scientific Masterclass (JSM) of the University of Groningen, the Netherlands. AS was supported by ZonMW-MKMD (grant no. 114021513). The funders had no role in the design of the study, collection, analysis, or interpretation of data or in writing the manuscript.