(P40-14-26) Metabolic Functional Guilds Drive Fiber-Specific Xenometabolite Signatures From Human Gut Microbiota

Objectives: Most gut microbiome research has focused on community structures and/or production of a very limited set of bioactive metabolites produced by gut bacteria (e.g., butyrate), often testing a single fiber type. These approaches have major limitations in terms of understanding mechanisms driving the health and functional outcomes associated with the diet-gut microbiome-host nexus. Wider assessment of the xenometabolome (microbe-derived compounds in the body) addresses these limitations and characterizes metabolic functional guilds. We previously demonstrated consistency in xenometabolite signatures in stool cultures provided differently-sized inulins, despite high variability in microbial taxonomy across human donors. Herein, we tested if this same principle of metabolic functional guilds applies to additional fiber types and sources provided as substrates.

Methods: An untargeted GC-TOF/MS metabolomics platform was applied to human stool culture supernatants derived from 3 healthy adults (3 anerobic culture lineages/each/treatment sampled after culture d7). Soluble/insoluble fibers of wheat bran, sorghum bran, wheat arabinoxylan [AX], and sorghum AX were the fiber substrates, representing diverse polysaccharide structures/matrices.

Results: > 500 metabolites were detected. Principal Component Analysis explained >78% of the total variance using the first three components and identified clusters that separated fiber groups. There were statistically significant (p < 0.05) main effects of grain source or AX vs. bran and individual contrasts across sources and fiber types. Hundreds of metabolites contributed to these differences, indicating that fiber substrates drive substantial shifts in xenometabolism. Tight grouping of metabolite patterns in the statistical models supports the presence of metabolic functional guilds, despite variable donor microbe taxa.

Conclusions: Despite highly variable microbiota community structures across the adult population, dietary fibers are known to promote health and reduce disease risk. We speculate that this is due to a myriad of fiber-specific xenometabolites that are produced by metabolic functional guilds in the gut microbiome.

Funding Sources: NIH-NIDDK 1R01DK137173