Synthetic Glycans Can Change the Composition and Function of the Gut Microbial Community

Complex glycans synthesized in the laboratory can modify the abundance and functioning of human gut bacteria and may be useful for targeted bacterial manipulation, according to a study partly supported by the National Center for Complementary and Integrative Health. The study, from Washington University in St. Louis, Ohio State University, and collaborating institutions, was published in a recent issue of Nature Chemical Biology.

The gut microbiota—the vast, complex community of microorganisms in the intestinal tract—plays important roles in health and disease, but much remains to be learned about exactly how the community functions and how it might be optimized. One approach to enhancing its functioning involves the use of prebiotics—food ingredients that affect the composition or activity of the gut microbiota in ways that are beneficial to health. This study investigated synthetic substances that are similar to certain natural food components to see whether they might have potentially beneficial effects on microorganisms in the digestive tract.

In the study, the investigators evaluated the effects of synthetic glycans on human gut microorganisms, with an emphasis on Bacteroides, an important group of bacteria in the gut. Glycans are complex compounds that include chains of sugar molecules linked together. Many glycans occur in nature, and even more can be synthesized. Creating new glycans makes it possible to capture a wider variety of chemical structures, optimize the types of structures, and produce large enough amounts of glycans for future studies in people.

In the first part of this study, the effects of eight groups of synthetic glycans on the growth of human gut bacteria were assessed. The glycans were incubated with fecal samples from five healthy human donors, and changes in the communities of microorganisms in the feces were measured. Of the eight groups of glycans tested, only one, SG10, caused an increase in the proportion of Bacteroides bacteria. The researchers therefore selected SG10, a structurally complex pool of glycans for further evaluation.

For the next stage of the study, the researchers worked with adult mice that were initially germ free—meaning that they had no microorganisms living in or on them. To give the mice a gut microbial community resembling that of humans eating a Western diet, the researchers introduced a mixture of bacteria derived from the human gut into the digestive tracts of the mice and fed them a diet relatively high in saturated fat and low in fruits and vegetables. One group of mice was given drinking water with added SG10; another group received plain water. After several days, the amounts of different types of bacteria present in feces and in the contents of the first part of the large intestine were measured in both groups. 

The size of the overall gut bacterial community did not increase in the mice that received SG10 treatment. However, the amounts of 30 types of bacteria were found to be significantly different in the SG10-treated mice compared to the mice that drank plain water, with 8 strains showing substantial increases and 20 showing substantial decreases. Three Bacteroides strains were among the bacteria that showed increases in the treated mice, with B. intestinalis increasing the most. The amounts of several other types of Bacteroides showed substantial, rapid decreases after SG10 treatment.

Further analysis showed that in B. intestinalis, SG10 modified the expression of certain groups of genes (called polysaccharide utilization loci or PULs) that are involved in detecting and breaking down naturally occurring glycans. SG10 treatment changed the expression of several B. intestinalis PULs, particularly PUL8, which increased significantly. 

B. intestinalis bacteria in the treated animals showed a modest ability to degrade SG10. In a laboratory experiment, B. intestinalis was able to grow in a medium containing SG10, but not as extensively as in media containing other substrates (sugar beet arabinan or glucose). 

The results of this study show that synthetic glycans can selectively influence the natural carbohydrate utilization machinery in Bacteroides from the human gut. The findings suggest that some synthetic glycans may be useful for precisely manipulating the human gut microbial community in targeted ways that might not be possible with naturally occurring glycans. The reduction in the abundance of some bacterial strains in response to SG10 was particularly interesting because it suggested that synthetic glycans might have useful antimicrobial activity.