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Eat Less and Live Longer?

Mice on a low-calorie diet harbor a distinct population of gut microorganisms that helps prolong life.

By | August 13, 2013

WIKIMEDIA, WUALEXScientists have shown a link between long-living calorie-restricted mice and the types of microbes residing in the guts of those mice. The finding, published last month (July 16) in Nature Communications, suggests a novel mechanism of living longer by establishing the right kind of microbes in our gut through a low-calorie diet.

“[The study] underlined the effectiveness of the healthy modulation of the gut microbiota along with diet specificities,” Jean-Paul Vernoux, a professor of food toxicology at the University of Caen in France who was not involved with the study, said in an email to The Scientist.

Caloric restriction has been known to extend life span in a variety of organisms, including humans, though the molecular mechanisms of this effect are not known. Recent research has begun to outline the role of the apparently innocuous microbes of the gut in modulating metabolism and immunity of their host. Based on these findings, Liping Zhao of Shanghai Jiao Tong University and his colleagues wondered if caloric restriction may prolong life span by modulating the type and composition of gut microbes.

The team fed groups of mice a high- or low-fat reduced-calorie diet. As expected, mice on a low-fat, calorie-restricted diet lived the longest. Additionally, these mice displayed lowest body weight and fat content coupled with other healthy metabolic parameters such as glucose homoeostasis and a favorable serum lipid profile.

Using high-throughput sequencing, the researchers further showed that these calorie-restricted mice harbored a distinct population of beneficial bacteria such as Lactobacillus, as well as lower counts of harmful bacteria. Moreover, the microbial changes in the gut were concomitant with significantly reduced levels of serum lipopolysaccharide-binding protein (LBP), a soluble inflammatory protein that binds to lipopolysaccharide and other antigens and thus can be used as a blood-based biomarker of inflammatory response. This suggests that animals under calorie restriction can establish an optimal composition of gut microbiota, which in turn may lead to a better health by reducing overall inflammation.

Although more research is needed to translate these findings into humans, the study has far-reaching implications, Zhao noted. The idea of a balanced gut microbiota—with more beneficial microbes and fewer harmful ones—is an advantageous factor of a diet low in calories. However, the gut microbiome is also influenced by an individual’s genetic background and lifestyle, as well as environmental factors, he added, so a tailor-made personalized strategy would be the best approach to figure out how many calories to cut to attain an optimal bacterial community in the gut.

The researchers also suggest that such changes in the gut microbiota could be used as early warning signs of aging and age-related increase in inflammatory responses in the host. “We can analyze the composition of gut bacteria as a biomarker,” Zhao said. “We can also analyze serum LBP and see if that is increased or decreased.”

“There was a significant decrease of the negative to positive bacterial ratio correlated with life span in animals under calorie restriction,” said Vernoux. “It also justified the good positive role of probiotic Lactobacilli. The extrapolation to human is plausible, but it needs a lot of more work.”

Zhao’s team now plans to investigate the molecular mechanisms of how reducing caloric intake leads to changes in the gut microbiota, and would eventually like to run clinical trials to confirm these results.

C. Zhang et al., “Structural modulation of gut microbiota in life-long calorie-restricted mice,” Nature Communications, 4: 2163, doi: 10.1038/ncomms3163, 2013.

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Avatar of: Taxpayer

Taxpayer

Posts: 10

August 14, 2013

Apparently the CR-longevity association varies with the strain of mouse used, and microbiome transplants between strains could address this issue.

More importantly, however, microbiome data have not been collected for many epidemiologic studies, and can vary with diet. If this factor is an important predictor of phenotype, perhaps there should not be so many barriers to anonymized human genetic information being freely available to advance research.

Avatar of: mightythor

mightythor

Posts: 43

August 16, 2013

Based on this account, it seems that caloric input was varied with significant effects on several biometric parameters, including life span, body weight, fat content, serum lipids, glucose metabolism, and gut bacteria.  Such a protocol does not justify any conclusion, or even suggestion, of a causal connection among any of the derivative parameters.

Avatar of: W. Boernke

W. Boernke

Posts: 16

August 22, 2013

David Hume told us long ago that you cannot logically conclude that a correlation means a cause and effect.  (Hume went so far as to say that you cannot predict the sun will rise in the east tomorrow simply because it has done so every day in the past.)  Simply observing a correlation betwwen life span and gut microbes does not mean the microbes cause increased life span.

Sunrise is correlated with roosters crowing, but that does not mean roosters cause the sun to rise.

Avatar of: captainhurt

captainhurt

Posts: 1

September 20, 2013

calorie restriction is already a well-proven cause of lengthened life among various animals via controlled experiments.

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