A new mouse study published in Nature showed that intermittent fasting changes gut bacteria, and increases the ability to recover from nerve damage. The fasting led to gut bacteria increasing production of 3-Indolepropionic acid (IPA), a metabolite which is required for regenerating axons.
The bacteria that produces IPA, Clostridium sporogenesis, is found naturally in the guts of humans as well as mice and IPA is found in human bloodstreams too, the researchers said.
“There is currently no treatment for people with nerve damage beyond surgical reconstruction, which is only effective in a small percentage of cases, prompting us to investigate whether changes in lifestyle could aid recovery,” said study author Professor Simone Di Giovanni at Imperial College London.
“Intermittent fasting has previously been linked by other studies to wound repair and the growth of new neurons – but our study is the first to explain exactly how fasting might help heal nerves.”
The study assessed nerve regeneration of mice where the sciatic nerve, the longest nerve running from the spine down the leg, was crushed. Half of the mice underwent intermittent fasting (one day with food, one day without), while the other half ate freely. These diets continued for a period of 10 days or 30 days before their operation, and the mice’s recovery was monitored 24 to 72 hours after the nerve was severed. The regrown axons were about 50% greater in mice that had been fasting.
Prof Di Giovanni said, “I think the power of this is that opens up a whole new field where we have to wonder: is this the tip of an iceberg? Are there going to be other bacteria or bacteria metabolites that can promote repair?”
The researchers also studied how fasting led to this nerve regeneration. They found that there were significantly higher levels of specific metabolites, including IPA, in the blood of diet-restricted mice.
To confirm whether IPA led to nerve repair, the mice were treated with antibiotics to remove gut bacteria. They were then given gene-edited of Clostridium sporogenesis that could or could not produce IPA.
“When IPA cannot be produced by these bacteria and it was almost absent in the serum, regeneration was impaired. This suggests that the IPA generated by these bacteria has an ability to heal and regenerate damaged nerves,” Prof Di Giovanni said.
Importantly, when IPA was administered to the mice orally after a sciatic nerve injury, regeneration and increased recovery was observed between two and three weeks after injury.
The next step is investigating spinal cord injuries in mice, along with seeing if more frequent IPA administrations increase its efficacy.
“One of our goals now is to systematically investigate the role of bacteria metabolite therapy.” Prof Di Giovanni said.
More studies will need to investigate whether IPA increases after fasting in humans and the efficacy of IPA and intermittent fasting as a potential treatment in people.
He said: “One of the questions that we haven’t explored fully is that, since IPA lasts in blood for four to six hours in high concentration, would administering it repeatedly throughout the day or adding it to a normal diet help maximise its therapeutic effects?”
Source: Imperial College