Fasting before and during exposure to Salmonella enterica bacteria protects mice from developing a full-blown infection, in part due to changes in the animals’ gut microbiomes, according to new research published in PLOS Pathogens by Dr. Bruce Vallance and colleagues at BC Children’s Hospital and University of British Columbia (UBC).
When people or animals develop an infection, they often lose their appetite. However, it remains controversial whether fasting protects a host from infection, or increases their susceptibility. In the new study, mice were fasted for 48 hours before and during oral infection with the bacteria Salmonella enterica serovar Typhimurium, a common cause of foodborne illness in people. Food poisoning can be particularly dangerous for young children because illness can lead to diarrhea and dehydration. Children younger than five are three times more likely to be hospitalized if they get a Salmonella infection.
Fasting decreased the signs of bacterial infection compared to fed mice, including nearly eliminating all intestinal tissue damage and inflammation. When fasted animals were re-fed for a day after their fast, there was a dramatic increase in Salmonella numbers and invasion into the intestinal walls, although the associated inflammation was still reduced compared to normal.
The results did not hold true when mice were exposed to Salmonella intravenously instead of orally, and analyses of the microbiomes of mice showed significant changes associated with fasting and protection against infection.
Moreover, fasting did not fully protect germ-free mice—bred to lack a normal microbiome—from Salmonella, suggesting that some of the protection was due to fasting’s effect on the microbiome. Experiments using the bacteria Campylobacter jejuni confirmed that the effect of fasting was not limited to Salmonella, with similar results seen.
“These results indicate that the gut microbiome helps protect us from gut infections either by directly competing with the invasive bacteria for nutrients or due to the presence or absence of specific gut bacteria,”
said Franziska Graef, a PhD student in Dr. Vallance’s team and first author on the study. “We also show that fasting itself decreases gut inflammation during infection, independent of the gut microbiome.”
The study was made possible by computational analysis provided by the Gut4Health microbiome facility at BC Children’s Hospital Research Institute. Gut4Health helps facilitate microbiome studies for the research community in B.C.
“Our research highlights the important role that food plays in regulating interactions between the host, intestinal pathogens and the gut microbiome,”
said Dr. Bruce Vallance. “When food is limited, the microbiome appears to sequester the nutrients that remain, preventing pathogens from acquiring the energy they need to infect the host. While more research is needed, fasting or otherwise adjusting food intake could be exploited therapeutically to modulate infectious diseases in the future.”