The Impact of Fasting on Mucosal Immunity

In addition to being an effective weight loss strategy, past research has suggested that fasting has wide-ranging benefits, from increased insulin sensitivity to protection from neurodegenerative diseases. However, a study in mice suggests that nutritional signals are important for maintaining the immune cell population in the gut, and that fasting can negatively impact this group of cells.

According to the research published in the journal Cell, fasting resulted in the loss of antigen-producing B cells responsible for protecting the gut against infection. This led to a weakened immune response when the mice were challenged with foreign antigen. Unlike other immune cells, which migrated to the bone marrow during fasting, the aforementioned B cells were not recovered when the mice began feeding again.

Should the benefits of fasting be reconsidered in light of this research? The answer is almost certainly no. As the study was carried out in juvenile mice, it is not yet known whether the impact in adult humans would be significant. Even then, the benefits of fasting would likely still outweigh any disadvantages.

This study may be more relevant to the field of vaccination, as vaccine effectiveness relies on the recipient mounting an immune response. The response to vaccination in malnourished children is thought to be impaired, although the long term health implications are not clear. However, this study suggests that even a short term lack of nutrition might influence the quality of vaccination. Further research would be needed to confirm this.

Herein, we report that temporary fasting drastically reduces the number of lymphocytes by ∼50% in Peyer’s patches (PPs), the inductive site of the gut immune response. Subsequent refeeding seemingly restored the number of lymphocytes, but whose cellular composition was conspicuously altered. A large portion of germinal center and IgA⁺ B cells were lost via apoptosis during fasting. Meanwhile, naive B cells migrated from PPs to the bone marrow during fasting and then back to PPs during refeeding when stromal cells sensed nutritional signals and upregulated CXCL13 expression to recruit naive B cells. Furthermore, temporal fasting before oral immunization with ovalbumin abolished the induction of antigen-specific IgA, failed to induce oral tolerance, and eventually exacerbated food antigen-induced diarrhea. Thus, nutritional signals are critical in maintaining gut immune homeostasis.

Nagai, M., Noguchi, R., Takahashi, D., Morikawa, T., Koshida, K., & Komiyama, S. et al. (2019). Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses. Cell, 178(5), 1072-1087.e14. doi:10.1016/j.cell.2019.07.047