Functional Heterogeneity in the Fermentation Capabilities of the Healthy Human Gut Microbiota

By Dr. Katie E Golden, MD

The research community is working tirelessly to elucidate the microbiome’s influence on host immune pathways in the hope to develop more effective treatment interventions for a range of human diseases. Inflammatory Bowel Disease (IBD) is at the forefront of this effort, as the current treatment regimens are invasive, come with significant side effects, and are frequently ineffective for the patient. Current research objectives hold the promise of uncovering how we can effectively manipulate the human diet or intestinal flora to alter disease development and progression.

A new study by Gurry and fellow CMIT colleagues takes us one step closer to understanding the relationship between fiber intake and anti-inflammatory pathways.¹ In their study, the authors show the inter-individual variability in microbial production of Short Chain Fatty Acids (SFCA), which is thought to be protective against intestinal inflammation. They subsequently investigate the relationship between fiber intake and SCFA production, proposing a possible therapeutic strategy to treat microbiome-associated disease.

SFCAs are the by-product of gut microbial fermentation of dietary fiber, and have been shown to play an important role in host physiology. They exert anti-inflammatory properties by modulating T cell differentiation, cytokine production, and even colonic epithelium immune response. Prior studies have shown how SFCAs affect insulin resistance and plasma glucose levels, and SFCA abnormalities have been associated with increased risk of diabetes. Given the population variability in microbiome composition, the researchers here wanted to understand whether this translates to variable SFCA levels, and the relationship between fiber ingestion and SFCA production.

The authors started with ex vivo measurements of SFCA quantities in stool samples from healthy donors. As expected, they found that there is significant variability in the SFCA production capacity of an individual’s microbiota. Subsequent genetic sequencing studies showed that SFCA production could also be predicted by their microbiome composition, and this production is relatively stable over time. They then sought to understand in vivo microbial production, and developed a quantitative model to study an individual’s SFCA production and absorption with varying fiber supplementation. They found that ingested fiber is almost entirely consumed by the microbiota on passage through the intestine, and furthermore, that SFCA absorption rates directly correlate with that individual’s SFCA production.

If we can indeed prevent and treat autoimmune disease by modifying SFCA production pathways, then these findings suggest a treatment strategy that would include personalized fiber supplementation based on a patient’s microbiome profile. This study is an elegant example of how our advanced understanding of the microbiome has the potential to yield low impact, personalized treatment for inflammatory-mediated diseases.

1. Thomas Gurry, Le Thanh Tu Nguyen, Xiaoqian Yu, Eric J Alm. Functional heterogeneity in the fermentation capabilities of the healthy human gut microbiota. bioRxiv 2020.01.17.910638.