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Scientifically Speaking | Can a chemical made by your gut bacteria help you live longer?

ByAnirban Mahapatra
Dec 31, 2024 07:10 PM IST

Two new studies reveal how a compound produced by gut bacteria during digestion might mirror fasting benefits without drastically cutting calories.

For thousands of years, healers across cultures believed fasting and bile (the bitter fluid aiding in fat digestion) held special powers to restore health and vitality. Now, pioneering research published in Nature suggests they may have been right without knowing exactly why.

Two new studies reveal how a compound produced by gut bacteria during digestion might mirror fasting benefits without drastically cutting calories. This finding could hold clues to slowing ageing and improving health.

Scientists have long known that eating about 40% less than normal, a practice called caloric restriction, can extend lifespan and improve health in creatures ranging from yeast to monkeys. By activating ancient survival mechanisms within our cells, caloric restriction promotes repair and renewal throughout the body. But the challenges are steep and include muscle loss, constant hunger, trouble staying warm, and the sheer difficulty of sustaining such a strict diet in today's food-filled world.

Sheng-Cai Lin and his team at Xiamen University in China set out to find an alternative. Could the benefits of caloric restriction be captured in a single molecule? To find out, they sifted through hundreds of compounds in the blood of calorie-restricted mice. Among these, one molecule stood out, lithocholic acid, or LCA, a compound produced when gut bacteria break down bile.

To explore LCA's effects, the researchers turned to organisms commonly used to study ageing. They started with microscopic worms and fruit flies—creatures that share basic biological processes with humans but age much faster. LCA extended their lifespan and improved their stress resilience. Encouraged by these results, they tested LCA in mice, with remarkable outcomes.

Older mice treated with LCA showed striking improvements in health. Their muscles grew stronger and repaired themselves better. They ran farther, gripped harder, and managed blood sugar more effectively, all without the muscle loss typically associated with calorie-restricted diets. These results suggest that LCA can deliver fasting-like benefits while avoiding its most punishing drawbacks.

To understand how LCA works, the team mapped its journey inside cells. The molecule binds to a protein called TULP3, which initiates a chain reaction that enhances energy management and repair, mirroring the benefits of fasting without dietary restrictions.

The study adds to growing evidence linking gut microbes to health. The research underscores how gut bacteria might influence healthy ageing. These microbes produce LCA by breaking down bile acids, suggesting a deeper connection between the microbiome and ageing. This might help explain why some people age more gracefully than others and why transplanting gut bacteria from younger to older animals can improve health.

Yet scientists are quick to caution against rushing to take LCA supplements. While the compound improved health markers in mice, it didn't significantly extend their lifespans as it did in simpler organisms. At high doses, LCA can harm the liver, with the line between helpful and harmful still unclear.

Human biology adds another layer of complexity. Laboratory animals live in controlled environments, eat standardised diets, and share similar genetic backgrounds. Humans, in contrast, have diverse diets, unique genetics, and longer lifespans, making treatments both harder to design and riskier to test. Additionally, gut bacteria vary dramatically between individuals, influenced by diet, medications, and health. Since LCA production depends on these microbes, responses could differ widely from person to person.

To address these challenges, the researchers are now studying primates, whose biology and lifespans are closer to ours. They're also exploring whether dietary changes or microbiome-targeted therapies could naturally boost LCA production, avoiding the risks of supplementation.

The journey from laboratory discovery to human treatment is long and unpredictable. Many promising compounds fail during clinical trials, either because they don't work in humans or because side effects emerge over time. Still, this research offers a window into the mechanisms of ageing and hints at ways to improve health in later life.

What makes this discovery remarkable is how it validates age-old beliefs about fasting and bile while unravelling the molecular processes behind their effects. As humans live longer than ever, understanding how our bodies' natural processes affect ageing could pave the way for new treatments for age-related diseases. While there's no miracle pill yet, these findings mark an exciting step toward learning more about how we might age better.

Anirban Mahapatra is a scientist and author, most recently of the popular science book, When The Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.

For thousands of years, healers across cultures believed fasting and bile (the bitter fluid aiding in fat digestion) held special powers to restore health and vitality. Now, pioneering research published in Nature suggests they may have been right without knowing exactly why.

Two new studies reveal how a compound produced by gut bacteria during digestion might mirror fasting benefits without drastically cutting calories. This finding could hold clues to slowing ageing and improving health.

Scientists have long known that eating about 40% less than normal, a practice called caloric restriction, can extend lifespan and improve health in creatures ranging from yeast to monkeys. By activating ancient survival mechanisms within our cells, caloric restriction promotes repair and renewal throughout the body. But the challenges are steep and include muscle loss, constant hunger, trouble staying warm, and the sheer difficulty of sustaining such a strict diet in today's food-filled world.

Sheng-Cai Lin and his team at Xiamen University in China set out to find an alternative. Could the benefits of caloric restriction be captured in a single molecule? To find out, they sifted through hundreds of compounds in the blood of calorie-restricted mice. Among these, one molecule stood out, lithocholic acid, or LCA, a compound produced when gut bacteria break down bile.

To explore LCA's effects, the researchers turned to organisms commonly used to study ageing. They started with microscopic worms and fruit flies—creatures that share basic biological processes with humans but age much faster. LCA extended their lifespan and improved their stress resilience. Encouraged by these results, they tested LCA in mice, with remarkable outcomes.

Older mice treated with LCA showed striking improvements in health. Their muscles grew stronger and repaired themselves better. They ran farther, gripped harder, and managed blood sugar more effectively, all without the muscle loss typically associated with calorie-restricted diets. These results suggest that LCA can deliver fasting-like benefits while avoiding its most punishing drawbacks.

To understand how LCA works, the team mapped its journey inside cells. The molecule binds to a protein called TULP3, which initiates a chain reaction that enhances energy management and repair, mirroring the benefits of fasting without dietary restrictions.

The study adds to growing evidence linking gut microbes to health. The research underscores how gut bacteria might influence healthy ageing. These microbes produce LCA by breaking down bile acids, suggesting a deeper connection between the microbiome and ageing. This might help explain why some people age more gracefully than others and why transplanting gut bacteria from younger to older animals can improve health.

Yet scientists are quick to caution against rushing to take LCA supplements. While the compound improved health markers in mice, it didn't significantly extend their lifespans as it did in simpler organisms. At high doses, LCA can harm the liver, with the line between helpful and harmful still unclear.

Human biology adds another layer of complexity. Laboratory animals live in controlled environments, eat standardised diets, and share similar genetic backgrounds. Humans, in contrast, have diverse diets, unique genetics, and longer lifespans, making treatments both harder to design and riskier to test. Additionally, gut bacteria vary dramatically between individuals, influenced by diet, medications, and health. Since LCA production depends on these microbes, responses could differ widely from person to person.

To address these challenges, the researchers are now studying primates, whose biology and lifespans are closer to ours. They're also exploring whether dietary changes or microbiome-targeted therapies could naturally boost LCA production, avoiding the risks of supplementation.

The journey from laboratory discovery to human treatment is long and unpredictable. Many promising compounds fail during clinical trials, either because they don't work in humans or because side effects emerge over time. Still, this research offers a window into the mechanisms of ageing and hints at ways to improve health in later life.

What makes this discovery remarkable is how it validates age-old beliefs about fasting and bile while unravelling the molecular processes behind their effects. As humans live longer than ever, understanding how our bodies' natural processes affect ageing could pave the way for new treatments for age-related diseases. While there's no miracle pill yet, these findings mark an exciting step toward learning more about how we might age better.

Anirban Mahapatra is a scientist and author, most recently of the popular science book, When The Drugs Don’t Work: The Hidden Pandemic That Could End Medicine. The views expressed are personal.

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