The conversion of xylitol in the human colon


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The conversion of xylitol in the human colon

With the food industry’s popular concept of zero sugar, the research and application of sugar substitution has long been attractive to R&D. Xylitol is one of those kinds of sugar substitutes, which can be naturally distributed in fruits, vegetables, and bran but in low fractions.

Chemical structure of xylitol

When xylitol reaches the human digestive system, only a small amount of xylitol can be directly absorbed by the small intestine, and thus over half of the xylitol ingested reaches the colon. However, the effects of xylitol on colonic health are still understudied.

To address the unknown effects of xylitol on colonic health, Xiang et al., first fed mice with different concentrations (2% and 5%) of xylitol in their food for 3 months. The researchers had to address the disparities between human and mouse microbiota composition which cannot fully represent the extent of the human condition. Some researchers would like to use gnotobiotic mice transplanted with human gut microbiota, but their costs are high (check out our article on HMA models to learn more about these models.)

Instead, the research group used cost-effective tools to investigate the human gut microbiota response to xylitol – in vitro colonic simulation system (CDMN). CDMN is a fermentation system which contains three bioreactors with controlled pH to represent different regions of the human colon. Fecal microbiota was used as an inoculum to simulate the gut microbiota composition in the human colon. Because of the lack of host factors in the CDMN, it can not be used to study host-microbiota research. Fortunately, the microbiota composition in CDMN represents 88% of the colonic microbiota, so it is a good tool to study the digestion of food by gut microbiota.  

Interestingly, in both mice and in vitro experiments, the researchers  observed  that xylitol did not significantly change the composition of gut microbiota. Afterwards, they measured the short chain fatty acids (SCFAs), including acetate, propionate, and butyrate. These molecules provide benefits for the host, such as inhibiting pathogens, anti-inflammatory and anticancer activities. Interestingly, they found SCFAs increased in both conditions, especially propionate in the gut lumen of the mice and in the CDMN. Propionate is mainly metabolized in the liver and inhibits cholesterol synthesis after being absorbed. In addition, propionate has been reported to balance the micro-ecosystem in the gut lumen. However, some research demonstrated that mice with excess propionate consumption tended to show anxious behaviour.

The gut microbiota encoding the complex polysaccharides degradation gene, which is much more abundant than the human gene. They analyzed the metatranscriptome to investigate the key enzymes and bacteria responsible for the breakdown of xylitol. At the molecular level, they revealed that enzymes xylitol dehydrogenase, xylulokinase, and xylulose phosphate isomerase were instrumental in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Xylitol was sequentially converted to D-xylulose, D-xylulose-5-phosphate, and D-ribulose-5-phosphate. Therefore, Bacteroides and Lachnospiraceae are considered as keystone bacterium in xylitol digestion.

Summary of xylitol conversion, enzyme and bacterium integral to the process. Adapted from Xiang et al.

Cross-feeding, a relationship in which one organism consumes metabolites excreted by another, allows certain bacteria to work as a team to degrade and produce metabolites. The results of expressed key enzyme distribution in human gut microbiota indicated there might be cross feeding in the gut bacteria to degrade xylitol. To confirm the cross feeding of bacteria to digest xylitol. They tested the five representative gut bacteria species. And the cross-feeding relationship was observed among the Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol.

This research explores the role of gut microbiota in degrading xylitol in the human colon. Moreover, It be considered as a reference for xylitol further studies on the mechanisms of prebiotics and the modulation of the gut microbiota

Link to the original post:

Xiang, S., Ye, K., Li, M. et al. Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota. Microbiome 9, 62 (2021).

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