Could fasting help fight some infections?

• Fasting and fasting-based therapies are gaining recognition and acceptance as popular tools for promoting health. However, research is inconclusive regarding their value for fighting infections.
• Now, a new study in mice finds that fasting can neutralize Salmonella infections.
• It appears the beneficial bacteria in the gut outcompete Salmonella for scarce nutrients during a fast.

There is some question whether the old saying “feed a cold, starve a fever” has much medical validity. Still, it is certainly the case that loss of appetite is one of the ways the body responds to infection.

While depriving the body of nutrition as it fights off a pathogen may seem unintuitive, a new mouse study from the University of British Columbia (UBC), Canada, finds fasting may help a body keep enteric — referring to intestinal — infections under control.

The study finds that fasting prevents Salmonella enterica serovar Typhimurium, a leading cause of gastroenteritis in humans, from causing inflammation or tissue damage.

The researchers observed similar results with another bacterium, Campylobacter jejuni, suggesting that the study’s conclusions may also apply to other enteric infections.

The study’s senior author Dr. Bruce Vallance, Ph.D., B.Sc., of the UBC, told Medical News Today that since previous research on fasting and infection was inconclusive, he and his colleagues hoped to help resolve the question, even if it turned out that fasting helped bacteria thrive:

“This too would be important to know, as therapeutic fasting is becoming more popular for patients with chronic autoimmune or autoinflammatory diseases.”

“Of course,” he added, “we would want to know if a therapeutic fast would render the patients more susceptible to infections.”

The study appears in PLOS Pathogens.

Demonstrating the value of fasting

The researchers began by treating mice with the antibiotic streptomycin. Previous studies have shown that the antibiotic kills off certain key protective bacteria, helping Salmonella overcome microbiota-based colonization resistance. This creates an environment in which Salmonella can readily expand and cause gastroenteritis.

Researchers fed Salmonella Typhimurium to a group of mice that had been fasting for 24 hours, and also to a group that they fed normally. These rodents can safely fast for up to 48 hours.

After an additional 24 hours, the scientists examined the mice to determine the state of their Salmonella Typhimurium infections. In the fed mice, the infection had expanded through the intestine and invaded the intestinal wall, causing tissue damage.

In contrast, the researchers found almost no Salmonella Typhimurium in 40% of the fasted mice. In the remaining 60%, the bacteria had expanded through the intestine, although it had done little damage.

All the fasted mice exhibited minimal inflammation or tissue damage.

When the team resumed the fasted mice’s normal eating regimen, their Salmonella infections regained their ability to proliferate through the intestine. However, the scientists again observed minimal inflammation or tissue damage.

Investigating how the effect occurs

The researchers investigated the possibility that fasting had altered the stomach’s pH balance, killing Salmonella Typhimurium.

However, they observed no difference in stomach pH between the fasted and fed mice. They also found that the first area in the intestinal tract where levels of Salmonella varied was the cecum, which is far below the stomach in the gastrointestinal tract. This eliminates pH as a possible inhibitor.

The researchers hypothesized that the gut bacteria in the fasted mice were somehow taming Salmonella Typhimurium.

To test this, the scientists repeated their experiments with gnotobiotic mice bred and raised to be completely bacteria-free, including their intestines.

Fasting had no effect on Salmonella Typhimurium in the gnotobiotic mice, indicating to the researchers that gut bacteria in the normal mice were responsible for the effect of fasting.

As further confirmation, the researchers injected Salmonella Typhimurium into other mice. They report that “we saw no protective effect of fasting when Salmonella was injected [intravenously] and spread to the liver and spleen. This emphasizes the key role played by the gut microbiome in mediating the protective effects of fasting.”

What might be happening?

The researchers hypothesize that when nutrients are in short supply during fasting, the gut’s normal, commensal bacteria consume what is available, starving Salmonella Typhimurium of the nutrients it needs to expand and cause damage.

Dr. David A. Butler PharmD, BCPS, AAHIVP of Albany College of Pharmacy and Health Sciences — who was not involved in the study — told MNT:

“In this study, I feel that the effect of fasting clearly prevented the mucosal infection and translocation of the Salmonella, and seems to be complex and multifactorial. As the authors confirm that the virulence was not mitigated in fasting gnotobiotic mice — where we know all the bacteria at play — but the intestinal pathology and inflammatory response was mitigated, though less so than in mice with a microbiome. It is clear that the commensal bacteria play a large role in that immunologic abrogation.”

The location also fits. The authors write:

“Notably, the cecum is also the first site where [orally delivered] Salmonella would encounter a large commensal bacterial community, and thus represents the first place in the [gastrointestinal] tract where the pathogen would face significant competition for nutrients.”

Dr. Butler added:

“A way to confirm the ability of commensals to outcompete pathogens would be if we could pin down which commensals are doing the heavy lifting, and what it is they do that is so beneficial to prevent pathogens from getting a foothold.” He noted that “That’s easier said than done, but as we improve our ability to characterize and study the microbiome, this is certainly an option for the near future.”

Applicability in humans

Dr. Vallance said that one aspect of the study that does not translate to humans is the length of the fast. He notes, “A 2-day fast [such as the fast used in the study] in a mouse is considered a ‘prolonged fast’ akin to 10–14 days of fasting in humans.”

MNT asked Dr. Vallance to suggest ways to test the study’s findings in humans. His reply:

“One [approach] is for [individuals] to undergo a prolonged fast and then be inoculated with a harmless or avirulent bacterial strain to determine if the bacteria would be able to expand to the same degree as in nonfasted humans.”

“Another approach would be to follow [people who] become sick naturally and divide them into two groups — one that keeps up caloric intake (despite loss of appetite) and another group that follows the naturally occurring fasting-response and does not eat or reduces caloric intake significantly.”

“We could then see in which group the infection resolves faster, if there are certain microbiome factors that are associated with either outcome, and in the case of bacterial infections, we could look at the expression of virulence genes as well.”

The future and due caution

Speaking with MNT, Dr. Vallance was keen to make it clear that their study does not show that intermittent fasting can protect against infection. More broadly, he explained:

“There is a lot of exciting data coming out on fasting, but I would encourage people always to check whether the study was done in mice and, if so, how long the mice had been fasting.”

He continued, “Many of the beneficial effects of fasting will not carry over to intermittent fasting or time-restricted eating in humans. A multiple-day fast in humans is very different from an intermittent fast and will trigger different pathways and mechanisms.”

In conclusion, health experts might not be recommending fasting as an anti-infection tool in the clinic any time soon. However, therapeutic fasting and calorie restriction might reveal cues to modulate infectious and potentially noninfectious gastrointestinal diseases beneficially. It certainly warrants further investigation.

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