IsoLife – Stable Isotope Labelled Plant Products for the Life Sciences

Applications  |  Medicine: Starch Metabolism and Prebiotic Effects (SCFA’s )

Tracing metabolites of starch digestion in relation to colon cancer and obesity

Introduction

Relating microbial species to physiological processes like resistant starch fermentation in complex ecosystems like the colon is a major task in nutritional sciences in the context of health and disease (Venema et al., 2010; Egert et al., 2018; Herrmann et al., 2018). The occurrence of colon cancer is increasing in both man and women and an important cause of death in the western society. Starch metabolites are thought to play an essential role in the prevention of colon cancer and obesity (Venema et al., 2010). The potential beneficial effects of starch in the diet probably depend on its digestion and fermentation characteristics (Topping et al., 2003; Conlon & Bird, 2015). Part of the starch, the resistant starch (RS), escapes from digestion and is fermented in the large intestine into short chain fatty acids (SCFA’s) like acetate, propionate, and butyrate. A high rate of SCFA production, especially butyrate, is associated with health promoting activities in the colon. RS may cause these prebiotic effects in the colon by stimulating the growth of specific probiotic bacteria like Bacteroides sp. (Fig. 1).

Figure 1. Bacteroides sp, a (probiotic) bacterium in human intestines (https://alchetron.com).

Stable Isotope Solution: 13C-labelled starches

One of the problems when investigating the effects of prebiotics like RS is how to follow the dynamics of its metabolites e.g. in the blood plasma and to distinguish these from other internal or external sources. The use of uniformly labelled 13C-starch enables tracing of metabolites and linking SCFA production to bacterial species, either in vivo or in vitro systems like TIM-2 (TNO gastro-Intestinal Models).

Results from publications with IsoLife’s 13C Starch

Binsl et al. (2010) found in experiments using TIM-2 that fermentation of U-13C starch resulted in the production of SCFA’s with the following composition 35% acetate, 12% propionate, and 53% butyrate. This was confirmed by Herrmann et al. (2018) who accurately measured digestion and fermentation characteristics for the first time in vivo in mice, also showing that the predominantly produced SCFA was butyrate. Species responsible for the production of SCFA’s were found in the genus Bacteroides and genera affiliated with Prevotellaceae, Ruminococcaceae, and Clostridiales (Kovatcheva-Datchary et al., 2009; Venema et al., 2010; Herrmann et al., 2017, 2018).

References

Binsl TW, AA de Graaf, K Venema, J Heringa, A Maathuis, P de Waard, JHGM van Beek. 2010.
Measuring non-steady-state metabolic fluxes in starch-converting faecal microbiota in vitro.
Beneficial Microbes 1: 391-405.

Conlon M.A. and A.R. Bird. 2015. The impact of diet and lifestyle on gut microbiota and human health. Nutrients 7: 17-44.
The impact of diet and lifestyle on gut microbiota and human health.
Nutrients 7: 17-44.

Herrmann E, W Young, V Reichert-Grimm, S Weis, CU Riedel, D Rosendale, H Stoklosinski, M Hunt, M Egert. 2018.
In vivo assessment of resistant starch degradation by the caecal microbiota of mice using RNA-based Stable Isotope Probing—A proof-of-principle study.
Nutrients 10: 179; doi:10.3390/nu10020179.

Herrmann E, W Young, D Rosendale, R Conrad, CU Riedel, M Egert. 2017.
Determination of resistant starch assimilating bacteria in fecal samples of mice by in vitro RNA-based Stable Isotope Probing.
Frontiers in Microbiology 8: 1331.

Kovatcheva-Datchary P, M Egbert, A Maathuis, M Rajilic-Stojanovic, AA de Graaf, H Smidt, WM de Vos, K Venema. 2009 (Award winning publication).
Linking phylogenetic identities of bacteria to starch fermentation in an in vitro model of the large intestine by RNA-based stable isotope probing.
Environmental Microbiology 11: 914-926.

Topping DL, M Fukushima , AR Bird. 2003.
Resistant starch as a prebiotic and symbiotic: state of the art.
Proceedings of the Nutrition Society 62: 171-176.

Venema K, AA de Graaf, AJH Maathuis, P Kovatcheva-Datchary, H Smidt. 2010.
Fermentation in the large intestine unravelled using 13C-labelled substrates: implications for obesity and gut health.
In: Van der Kamp JW, Jones J, McCleary B, Topping D, eds. Dietary fibre: new frontiers for food and health: 539-554. Wageningen Acad. Publishers.