Research News

A Cleveland Clinic study recently published in Cell Host & Microbe indicates a diet enriched in a modified, digestible form of the dietary fiber pectin is associated with strong immune response supported by gut microbes. The findings identify a new connection between diet and gut immunity.

The research team, led by Thaddeus Stappenbeck, MD, PhD, chair of the Department of Inflammation & Immunity, identified a small group of gut bacteria capable of enhancing production of an antibody called Immunoglobulin A (IgA). These antibodies form a barrier to prevent disease, protecting our intestinal and respiratory systems from germs, viruses and bacteria.

"Dysregulation to small intestine IgA can lead to infections and hyper-inflammation in response to intestinal damage," Dr. Stappenbeck says. "Our research showed that a single diet modification can enhance this all-important immune protection in the body. If we investigate how specific foods can shape our immune system, we have another tool for understanding the susceptibility of patients to certain diseases." 

Post-doctoral fellows and co-authors Shanshan Zhang, PhD, and Yi Han, PhD, first observed pectin oligosaccharide (pec-oligo) caused significantly high levels of IgA in the intestines of preclinical models. Pec-oligo is defined as molecular weight chains of microbe-digestible complex sugar residues derived from pectin that are normally indigestible. Pectin is found in sources like citrus peels and sugar beet pulp. 

The surprise finding was that the intestinal IgA remained at high levels even after researchers stopped administering pec-oligo. This suggests that specific microbes that were altered in response to pec-oligo drove and maintained high levels of IgA in the intestines. 

The investigators first looked for individual microbes that were enriched by pec-oligo and were bound by IgA. However, there were no such microbes in the initial screen done through microbial DNA sequencing. Instead, a functional approach led to the identification of a small group of microbes, dominated by Lachnospiraceae A2, that promoted IgA levels to all microbes in the intestine. The finding suggests the possible presence of a dietary factor induced a small group of microbes that controls the general adaptive immune response in the intestine. Importantly, the original dietary factor was not required to maintain this effect.

"The microbiome is a huge ecosystem and scientists are only now beginning to understand the rules of how it is governed," Dr. Stappenbeck says. "Studies like this give functional roles to specific microbes that are instrumental in furthering our understanding of the wide-reaching roles that microbes play in protecting the human body." 

In addition to identifying more microbes that promote immunity through a similar process to Lachnospiraceae A2, researchers plan to translate their findings so far to humans. Some patients show higher levels of IgA, but researchers still need to determine why, and whether higher amounts grant better protection from disease. Isolating dietary factors in preclinical work provides a lead so investigators can map out these pathways in human patients, Dr. Stappenbeck says. 

Funding for the work was supported by the Crohn's & Colitis Foundation and conducted in partnership with the Lerner Research Institute Gnotobiotic Facility and Imaging Core.