Fiber-derived butyrate may shape immune cell development, mouse study finds

Researchers reveal that butyrate promotes the development of dendritic cells, which they note are known as the “sentinels” of the immune system. Butyrate is a short-chain fatty acid (SCFA), a secondary metabolite produced by gut bacteria through the fermentation of dietary fibers such as inulin and pectin. 

The team notes that dendritic cells have a specialized set of cell surface molecules that coordinate innate and adaptive immunity. These molecules change as the cells mature. They act as sensors and cellular communicators, and present antigens to trigger immune responses. 

Butyrate modulated the development and expression of these cell surface molecules, details the study. 

“The findings connect dietary conditions, gut microbiota-derived metabolites, and epigenetic regulation, an area of growing interest in immunology,” says lead researcher Chiharu Nishiyama, professor at the Tokyo University of Science, Japan. 

“Since unwarranted immune responses often contribute to allergies, inflammation, and autoimmune diseases, identifying new areas of immunomodulation can aid in the development of strategies to prevent or mitigate immune-related disorders.” 

Since butyrate is produced by gut bacteria by fermenting fibers, the researchers note that understanding how microbiota regulate the production of this SCFA may provide useful directions for future research. They caution that further studies in animal models and humans are needed to validate these findings and their relevance to immune-related diseases. 

SCFAs and immunity

According to the authors, SCFAs act as important signaling molecules that reduce inflammation and help balance the immune system. They can regulate immune-related diseases, such as inflammatory and allergic diseases, by modulating immune-cell gene expression and function. 

Nishiyama says the findings connect dietary fiber, gut microbiota metabolites, and epigenetic regulation.However, the researchers note that the effects of SCFAs on dendritic cell development and expression of its surface molecules had not been clarified prior to their research. 

The research, published in Allergology International, analyzed the effects of SCFAs on the expression levels of surface proteins and messenger RNA in bone marrow-derived dendritic cells, generated from mice. It also assessed how these compounds affected histone modification, an epigenetic process that adds or removes chemical groups from histone proteins that are bound to DNA. 

In addition to butyrate, the team also analyzed the effect of propionate, valerate, and acetate. Among these tested SCFAs, butyrate showed the strongest effect in increasing the expression of cell surface molecules in dendritic cells, note the researchers. 

It also increased the expression of LPAM-1, a receptor protein, which contributes to immune-cell trafficking and localization in the intestinal mucous membrane. 

Moreover, the team found that butyrate affected the balance of dendritic cells in the bone marrow-derived samples, increasing the ratio of conventional dendritic cells (similar to white blood cells) to plasmacytoid ones. The latter group resembles plasma cells and can secrete large amounts of signaling proteins in response to pathogens. 

As the team found that butyrate impacted specific genes, they identified that epigenetic regulation played a role in butyrate’s impact on these cells, highlighting pathways associated with SCFAs.

Meanwhile, the authors caution that the study’s results need to be replicated in human dendritic cells, but say that previous research on SCFAs and their role in immune system shaping implies it is “conceivable” that the metabolites exert a similar effect on human cells. 

“We plan to conduct further experiments using human dendritic cells to determine whether the effects of SCFAs on mouse dendritic cells are similarly observed in humans,” states the team.