Science is only beginning to understand the role that the gut microbiome—the collection of bacteria and other microbes that live in our intestines—plays in our overall health. For one thing, these tiny tenants of our digestive system metabolize various components of our diets to produce beneficial fatty acids (FAs) that help keep our bodies healthy and in balance.
For example, metabolites originating from polyunsaturated fatty acids—found in nuts, seeds, and fatty fish—and influenced by probiotics such as Lactobacillus plantarum, exhibit potent effects on inflammation and immune responses. And, not surprisingly, manipulating these metabolites and the bacteria that produce them shows promise in treating metabolic and inflammatory disorders.
Despite recent advances in our understanding of the structure and function of the gut microbiome, however, the precise mechanisms governing the immunomodulatory properties of microbe-derived metabolites remained a mystery. To address this issue, a team of researchers led by Chiharu Nishiyama, PhD, from the Tokyo University of Science conducted a series of experiments using both in vitro and in vivo mouse models to understand exactly how bacteria-generated FAs regulate immune responses. The results of their research were published in the journal Frontiers in Immunology.
The Study
The researchers focused their study on metabolites of linoleic acid, a common dietary fat found in vegetable oils such as sunflower, safflower, soybean, corn, and canola oils. They first tested the impact of different linoleic acid derivatives on spleen cells that had been stimulated to produce an enhanced immune response. Their results showed that the linoleic acid metabolites significantly reduced levels of interleukin 2—a key protein that triggers the expansion of immune cells and inflammation—while unmetabolized linoleic acid produced no effect, thus showing the critical role that intestinal probiotics play in activating the FAs’ immunomodulatory properties. The metabolites also suppressed prolonged T-cell proliferation and dendritic cell activation, which can lead to inflammation and autoimmune diseases.
These effects were most prominent in a metabolite known as gKetoC, which is where the researchers focused the in vivo phase of their study. Using a mouse model of inflammatory bowel disease, the researchers examined immune and inflammatory responses prompted by gKetoC treatment. Analysis showed that the treatment significantly reduced fibrosis-induced tissue damage in the colon, reduced colitis-induced weight loss, and improved stool scores.
Conclusions
By identifying gKetoC as a specific FA metabolite with beneficial properties, this study has the potential to open up whole new avenues of treatment for intestinal diseases. While further studies are needed, the researchers emphasized that their results show that anti-inflammatory FA metabolites hold therapeutic promise in the treatment of intestinal inflammatory diseases and maintenance of gut health.
“Our findings demonstrate that the compounds of dietary oils are converted into useful metabolites with anti-inflammatory effects by gut bacteria,” said Nishiyama. “By conducting detailed analyses at the individual, cellular, and genetic levels, we hope to understand how the food we eat daily influences the function of immune cells, and how these effects can be targeted for the prevention and mitigation of inflammatory diseases.”
In the long run, the researchers said, these findings can help improve the quality of life for patients suffering from inflammatory diseases and increase the possibility of developing functional foods, supplements, and nutraceuticals based on microbial metabolites. The researchers also suggest that these developments could help in the development of compounds that are capable of preventing or alleviating immune-related diseases.
